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1
Ferrannini, E., E. J. Barrett, S. Bevilacqua, R. Jacob, M. Walesky, R. S. Sherwin, and R. A. DeFronzo. "Effect of free fatty acids on blood amino acid levels in human." American Journal of Physiology-Endocrinology and Metabolism 250, no. 6 (June 1, 1986): E686—E694. http://dx.doi.org/10.1152/ajpendo.1986.250.6.e686.
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Raised plasma free fatty acid (FFA) levels effectively impede glucose uptake in vivo, thereby conserving plasma glucose and sparing glycogen. To test whether FFA have any effect on blood amino acid levels, we infused Intralipid plus heparin or saline into healthy volunteers under four different experimental conditions: A) overnight fast; B) euglycemic hyperinsulinemia (approximately 100 microU/ml); C) hyperglycemic (approximately 200 mg/100 ml) hyperinsulinemia (approximately 50 microU/ml); and D) hyperglycemic (approximately 300 mg/100 ml) normoinsulinemia (approximately 20 microU/ml). In the fasting state (A), lipid infusion was associated with lower blood levels of most amino acids, both branched chain and glucogenic. This effect, however, could not be ascribed to lipid infusion alone, because plasma insulin levels were also stimulated. The clamp studies (B, C, and D) allowed to assess the influence of lipid on blood amino acid levels at similar plasma insulin and glucose levels. It was thus observed that lipid infusion has a significant hypoaminoacidemic effect of its own under both euglycemic (B) and hyperglycemic (C) conditions; this effect involved many glucogenic amino acids (alanine, glycine, phenylalanine, serine, threonine, and cystine) but none of the branched-chain amino acids (leucine, isoleucine, and valine). In marked contrast, normoinsulinemic hyperglycemia (D), with or without lipid infusion, caused no change in the blood level of any measured amino acid. We conclude that lipid infusion has a hypoaminoacidemic action. We also suggest that this action is permitted by insulin and may involve specific metabolic interactions (e.g., reduced availability of glucose-derived pyruvate or glycerophosphate) as well as enhanced uptake by the liver.
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Hodenius, Michael A. J., Thoralf Niendorf, Gabriele A. Krombach, Walter Richtering, Thomas Eckert, Heiko Lueken, Manfred Speldrich, et al. "Synthesis, Physicochemical Characterization and MR Relaxometry of Aqueous Ferrofluids." Journal of Nanoscience and Nanotechnology 8, no. 5 (May 1, 2008): 2399–409. http://dx.doi.org/10.1166/jnn.2008.18276.
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The synthesis and characterization of ferrofluid based MR contrast agents, which offer R2* versatility beyond that of ferucarbotran, is described. Ferrofluids were formed after stabilizing magnetite cores with dodecanoic acid (a), oleic acid (b), dodecylamine (c), citric acid (d) or tartaric acid (e). Core sizes were deduced from TEM micrographs. Magnetic properties were determined by SQUID magnetometry. Hydrodynamic particle diameters were determined by dynamic light scattering measurements. Zeta potentials were measured by combining laser Doppler velocimetry and phase analysis light scattering. Iron contents were evaluated colorimetrically. MR relaxometry including R1 and R2* was conducted in vitro using homogeneous ferrofluid samples. The average core diameters of ferrofluids a, b and c equaled 9.4±2.8 nm and approximately 2 nm for ferrofluids d and e. Magnetization measurements at 300 K revealed superparamagnetic behaviour for the dried 9 nm diameter cores and paramagnetic-like behaviour for the dried cores of ferrofluids d and e. Iron contents were between 32–75 mg Fe/mL, reflecting the ferrofluids' high particle concentrations. Hydrodynamic particle diameters equaled 100–120 nm (a, b and c). For the ferrofluids a, b, d and e coated with anions, strong negative zeta potential values between −27.5 mV and −54.0 mV were determined and a positive zeta potential value of +33.5 mV was found for ferrofluid c, covered with cationic dodecylammonium ions. MR relaxometry yielded R1-values of 1.9±0.3 (a), 4.0±0.8 (b), 5.2±1.0 (c), 0.124±0.002 (d) and 0.092±0.005 s−1 mM−1 (e), and R2*-values of 856±24 (a), 729±16 (b), 922±29 (c), 1.7±0.05 (d) and 0.49±0.05 s−1 mM−1 (e). Thus, the synthesized ferrofluids reveal a broad spectrum of R2* relaxivities. As a result, the various MR contrast agents have a great potential to be used in studies dealing with malignant tissue targeting or molecular imaging.
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Conway, A. M., and C. Valvatne. "The Boulton Field, Block 44/21a, UK North Sea." Geological Society, London, Memoirs 20, no. 1 (2003): 671–80. http://dx.doi.org/10.1144/gsl.mem.2003.020.01.53.
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AbstractThe Boulton Field was discovered in 1984 when gas was tested from the Lower Ketch Unit, Carboniferous Westphalian C/D, in well 44/21-2. Following appraisal drilling in 1990, the Boulton 'B' structure was delineated and a trap confirmed by a combination of up-dip seal against basal Permian shales, and salts and lateral seal against sealing faults and impermeable Westphalian C sediments. A second structure was drilled in the same year, Boulton 'F', with gas discovered in the deeper Murdoch Sand Interval of the Westphalian C/D. The two separate structures collectively form the Boulton Field.Current deliverability from the 'B' structure, Lower Ketch Sands is approximately 100 MMSCFD from a single producer. Developed with a minimal platform facility, the gas is delivered to Theddlethorpe Gas Terminal via offshore compression at the nearby Murdoch Field. The reservoir in Boulton 'B' comprises a series of channel sands deposited in a braided stream complex flowing predominantly from north to south across an Upper Carboniferous alluvial plain. Sandbody connectivity within the complex fluvial architecture of the Westphalian C is a key control on gas production.
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Kotzer, T. G., T. K. Kyser, and E. Irving. "Paleomagnetism and the evolution of fluids in the Proterozoic Athabasca Basin, northern Saskatchewan, Canada." Canadian Journal of Earth Sciences 29, no. 7 (July 1, 1992): 1474–91. http://dx.doi.org/10.1139/e92-118.
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In the Athabasca Basin, diagenetic hematite of variable paragenesis occurs throughout the sandstones and underlying paleoregolith. This hematite carries three distinct, single-component magnetizations: A (D = 158°, I = 62°, α95 = 5°, n = 21); B (D = 11°, I = −36°, α95 = 7°, n = 6); and C (D = 18°, I = 79°, α95 = 3°, n = 27). In some areas of the sandstones, such as near reactivated fault zones, the diagenetic hematite has been altered to goethite which yields a very low-intensity, incoherent D magnetization. Ages for the A, B, and C magnetizations, inferred from comparisons with paleomagnetic directions in Precambrian rocks whose ages are known approximately, are 1750–1600, 1600–1450, and about 900 Ma, respectively. The A magnetization is carried by the earliest formed hematite, and its estimated age compares well with U–Pb ages of 1650–1700 Ma for early diagenetic apatite. U–Pb and Rb–Sr ages of approximately 1500 and 900 Ma for uraninite and illite coeval with hematite that carries the B and C magnetizations compare well with their ages estimated from paleomagnetism. The development of B magnetization appears to be coeval with high-grade, unconformity-type uranium mineralization.Petrographic and field relationships indicate that the A magnetization is carried by hematite formed during initial diagenesis of the Athabasca sandstones, the B magnetization is carried by hematite formed during peak diagenesis, and the C magnetization is carried by hematite formed during subsequent high-temperature hydrothermal alteration. The incoherent D magnetizations have resulted from degradation of hematite to goethite as a result of incursion of low-temperature meteoric waters along fault zones that have been continuously reactivated since the late Precambrian. δ18O values of clay minerals and of the coeval hematite which carries the B and C magnetization indicate that they were formed from a fluid having temperatures of 150–200 °C and δ18O values near 1.0‰. Fluids that deposited the early formed hematite carrying the A magnetism are relatively 18O depleted, with values of approximately 0.8‰ and somewhat lower temperatures of 120–160 °C. Intermingling of A, B, and C magnetizations indicates either that hematite may be deposited by one fluid and reprecipitated by a subsequent fluid, or that fluid flow was controlled by local variations in permeability. Evidently, fluid flow has been episodic and basin wide and has occurred over a time span on the order of 108 years. It is suggested that the stratigraphy of the sandstones controlled the basin-wide lateral migration of the basinal fluids and that faults facilitated interformational fluid flow.
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COHEN, R. D. H., H. H. NICHOLSON, and E. D. JANZEN. "EFFECT OF REPEATED IMPLANTATION WITH ZERANOL FROM BIRTH OR WEANING ON GROWTH AND REPRODUCTION IN BEEF HEIFERS." Canadian Journal of Animal Science 67, no. 1 (March 1, 1987): 37–42. http://dx.doi.org/10.4141/cjas87-005.
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Liveweight, pregnancy rate, skeletal development and carcass characteristics were measured on 52 crossbred beef heifers implanted with zeranol at birth then at 110, 204 and 314 d of age (B); at weaning (204 d of age) and at 314 d of age (W); or not implanted (C). At 14 mo of age, the heifers were bred for 6 wk in corrals by natural service. Six weeks later they were slaughtered and their reproductive tracts collected. Height at the withers and pelvic area were measured before slaughter. Mean weaning weights ± SD, corrected to 200 d and for age of dam, were 249 ± 20 kg for group B and 226 ± 22 kg for groups W and C (P < 0.001). At breeding, the heifers weighed 434 ± 24, 416 ± 29 and 392 ± 31 kg for groups B, W and C, respectively (P < 0.001). At slaughter, their liveweights were 531 ± 26, 508 ± 32 and 483 ± 36 kg, respectively (P < 0.001) and carcass weights were 304 ± 17, 286 ± 21 and 270 ± 20 kg, respectively (P < 0.001). Rib eye area was 84.3 ± 8.47, 76.5 ± 8.89 and 72 ± 7.81 cm2, respectively (P < 0.001) but there were no significant differences between groups for cutability (58.2 ± 1.85%), average fat cover (9.4 ± 0.84 mm) or grade (90.3% ± A1/A2 and 9.7% A3/A4). Height at the withers did not differ between groups (46.7 ± 1.61 cm) but zeranol increased pelvic area (186.4 ± 19.54, 178.6 ± 21.84 and 165.3 ± 21.14 cm2 zeranol for groups B, W and C, respectively; (P < 0.05). Pregnancy rate was significantly reduced (P < 0.05) in group B (42.9%) compared with groups W and C (84.2 and 77.8%, respectively). However, examination of the reproductive tracts indicated that only one nonpregnant heifer in each of groups B and C was not cycling and no other abnormalities were found. It was concluded that zeranol will increase live and carcass weights, rib eye area and pelvic area of heifers but that four implants given at birth and at approximately 100-d intervals to 314 d of age will reduce reproductive rate in comparison to heifers implanted twice postweaning or not implanted. Key words: Zeranol, heifer, growth, reproduction, pelvimetry, carcass
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Spriet, L. L. "ATP utilization and provision in fast-twitch skeletal muscle during tetanic contractions." American Journal of Physiology-Endocrinology and Metabolism 257, no. 4 (October 1, 1989): E595—E605. http://dx.doi.org/10.1152/ajpendo.1989.257.4.e595.
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Rat fast-twitch muscles were tetanically stimulated in situ with an occluded circulation to examine ATP utilization and provision during isometric tension production. Plantaris (PL) and gastrocnemius (G) muscles were stimulated for 60 s in four conditions: A) 1.0-Hz train rate, 200-ms train duration at 80 Hz, B) 1.0 Hz (100 ms, 80 Hz), C) 0.5 Hz (100 ms, 80 Hz), and D) 1.0 Hz (200 ms, 40 Hz). Muscles were sampled pre- and post-stimulation for pH, high-energy phosphates, and glycolytic intermediates. Contributions to total ATP utilization (all muscles and conditions) were 64-67% glycolysis, 24-28% phosphocreatine, and 8-9% endogenous ATP. Glycogenolysis and glycolysis were greatest in white G (WG), 40% lower in red G (RG), and intermediate in PL muscles. Average energy costs in conditions A and D were approximately 0.60 mumol ATP/(N.s). Decreasing the train duration to 100 ms in B and the number of tetani to 30 in C increased energy costs to 0.93 +/- 0.05 and 1.26 +/- 0.07 mumol ATP/(N.s). Despite a lower pH, WG glycogenolytic (phosphorylase) activity was constant during condition A, whereas RG activity decreased in the final 30 contractions. Larger accumulations of Pi and inosine monophosphate may account for the maintained phosphorylase activity. Glycolytic (phosphofructokinase, PFK) activity was highest in WG and associated with higher fructose 6-phosphate concentration, greater depletion of ATP and, in later contractions, a higher NH4+ concentration. During tetanic in situ stimulation of fast-twitch muscle, the H+ profiles of phosphorylase and PFK are extended beyond in vitro predictions via the accumulation of positive modulators. This permits significant anaerobic ATP production via the glycolytic pathway despite increasing [H+]. The findings also suggest that lengthening the duration of tetani, generating lower peak tensions, and prolonging relaxation time all contribute to lower energy costs in fast-twitch muscle.
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Triandi, Rachmat, and Johannes Beck. "Synthesis and Crystal Structures of Silver Thianthrene Complexes with Weakly Coordinating Anions." Zeitschrift für Naturforschung B 62, no. 10 (October 1, 2007): 1291–97. http://dx.doi.org/10.1515/znb-2007-1010.
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Two novel silver complexes with thianthrene (TA) as a ligand have been synthesized in the poorly coordinating solvent liquid sulfur dioxide, using silver salts with weakly coordinating anions [BF4]− and [SbF6]−. Both colorless compounds contain discrete molecular entities and SO2 molecules included in the crystal structure. Selection of crystals and the diffraction data collection were performed at low temperatures (123 K). The tris(μ-thianthrene-κ2S)disilver(I) bis(hexafluoroantimonate) sulfur dioxide solvate [Ag2(TA)3][SbF6]2·5SO2 (1) (monoclinic, P21/c, a = 21.644(3), b = 12.4216(4), c = 21.934(3) Å , β = 115.04(1)°, Z = 4) is made up of complexes bearing three TA units acting as bridging ligands with both S atoms towards two Ag+ ions with d(Ag+-Ag+) = 2.911 Å giving the [Ag2(TA)3]2+ unit approximately D3h molecular symmetry. The bis(μ-thianthrene-κ2S)disilver(I) bis(tetrafluoroborate) sulfur dioxide solvate [Ag2(TA)2][BF4]2・3SO2 (2) (monoclinic, C2/c, a = 21.0045(6), b = 7.4553(2), c = 22.6024(6) A° , β = 109.65(0)°, Z = 4) is made up of [Ag2(TA)2]2+units with two bridging TA units coordinating two Ag+ ions with d(Ag+-Ag+) = 2.925 Å giving the complexes approximately D2h molecular symmetry. Weak, secondary bonds between Ag+ and the F atoms of the anions, such as Ag···F-SbF5 = 2.862(4) Å in 1 or Ag···F-BF3 = 2.773(2) Å in 2, and with O atoms of SO2 molecules link the complexes with the anions and the solvate molecules, respectively.
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Kwon, Su Yeon, Jung Hee Shim, Yu Ha Kim, Chang Su Lim, Seong Bae An, and Inbo Han. "Efficacy for Whitlockite for Augmenting Spinal Fusion." International Journal of Molecular Sciences 22, no. 23 (November 28, 2021): 12875. http://dx.doi.org/10.3390/ijms222312875.
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Whitlockite (WH) is the second most abundant inorganic component of human bone, accounting for approximately 25% of bone tissue. This study investigated the role of WH in bone remodeling and formation in a mouse spinal fusion model. Specifically, morphology and composition analysis, tests of porosity and surface area, thermogravimetric analysis, an ion-release test, and a cell viability test were conducted to analyze the properties of bone substitutes. The MagOss group received WH, Group A received 100% beta-tricalcium phosphate (β-TCP), Group B received 100% hydroxyapatite (HAp), Group C received 30% HAp/70% β-TCP, and Group D received 60% HAp/40% β-TCP (n = 10 each). All mice were sacrificed 6 weeks after implantation, and micro-CT, hematoxylin and eosin (HE) staining, and Masson trichome (MT) staining and immunohistochemistry were performed. The MagOss group showed more homogeneous and smaller grains, and nanopores (<500 nm) were found in only the MagOss group. On micro-CT, the MagOss group showed larger fusion mass and better graft incorporation into the decorticate mouse spine than other groups. In the in vivo experiment with HE staining, the MagOss group showed the highest new bone area (mean: decortication group, 9.50%; A, 15.08%; B, 15.70%; C, 14.76%; D, 14.70%; MagOss, 22.69%; p < 0.0001). In MT staining, the MagOss group demonstrated the highest new bone area (mean: decortication group, 15.62%; A, 21.41%; B, 22.86%; C, 23.07%; D, 22.47%; MagOss, 26.29%; p < 0.0001). In an immunohistochemical analysis for osteocalcin, osteopontin, and CD31, the MagOss group showed a higher positive area than other groups. WH showed comparable bone conductivity to HAp and β-TCP and increased new bone formation. WH is likely to be used as an improved bone substitute with better bone conductivity than HAp and β-TCP.
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Reinke, W., P. Gaehtgens, and P. C. Johnson. "Blood viscosity in small tubes: effect of shear rate, aggregation, and sedimentation." American Journal of Physiology-Heart and Circulatory Physiology 253, no. 3 (September 1, 1987): H540—H547. http://dx.doi.org/10.1152/ajpheart.1987.253.3.h540.
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Apparent viscosity was determined in vertical glass tubes (ID 30.2-132.3 microns) with suspensions of human red cells in A) serum, B) saline containing 0.5 g/100 ml albumin, C) plasma, and D) plasma containing Dextran 250 at a feed hematocrit of 0.45. Pressure-flow relationships were obtained in a range of pseudo-shear rates (mu) between 0.15 and 250 s-1. Relative viscosities in the nonaggregating suspensions (A and B) were found to increase monotonically with decreasing mu. The Fahraeus-Lindqvist effect was present in the entire range of mu. In the two aggregating suspensions (C and D), viscosities increased initially in larger but not small tubes with declining mu and fell in all tubes at some characteristic mu (usually below 10 s-1). Viscosity reduction was greater in the larger tubes and in suspensions with greater aggregation tendency. With suspension D, the Fahraeus-Lindqvist effect was eliminated in the lowermost shear-rate range. The cell-free marginal zone increased in width (to a maximum of approximately 40% of tube radius) as viscosity declined. Measurements of viscosity and cell-free marginal zone were also performed with suspension C in tubes mounted in horizontal position. In contrast to vertical tubes, a monotonic increase in viscosity was found with decreasing mu, associated with cell sedimentation and development of a cell-free layer only in the upper portion of the tubes.
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Nasir-Naeem, Khadeejah O., Sarah A. Akande, Rahinat Garba, and Jubril O. Akolade. "Assessment of milling as an alternative to chemical additives in processing of jute mallow (Corchorus olitorius)." AROC in Food and Nutrition 1, no. 2 (October 25, 2021): 10–17. http://dx.doi.org/10.53858/arocfn01021017.
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Background: Jute mallow is a widely consumed vegetable because of its enormous nutritional benefits. The mode of preparation of this vegetable differs across sub-Saharan Africa. In Nigeria, it is commonly cooked with potash. This study was designed to assess the milling of jute mallow leaves before cooking as an alternative to chemical additives in its preparation into “ewedu” soup. Methods: The experiment was divided into four groups. Group A (jute mallow leaves cooked alone), Group B (jute mallow leaves cooked with 1 g of potash), Group C (jute mallow leaves cooked with 1 g of baking soda) and Group D (jute mallow leaves pulverized before cooking). Proximate, mineral and Vitamin C content, as well as the viscosity of the soups, were determined using standard analytical procedures. Results: The results showed that there was no significant difference (p>0.05) in the moisture, ash, fibre and lipid contents. However, the protein (4.29 %) content of group B and carbohydrate (2.4 %) content of group C were significantly lower (p>0.05) than that of the other groups. Potassium content (235.88 mg/100g) in group B, was significantly higher (p<0.05) than those of the other groups. There was no significant difference (p>0.05) in the calcium and magnesium contents. Group C (13.54 mg/100g) and B (12.15 mg/100g) showed a significantly higher (p<0.05) sodium content than A (10.44 mg/100g) and D (10.37mg/100g). There was no observed significant difference (p>0.05) in the vitamin C content of the groups. Viscosity was significant (p<0.05) in this order, A>B>D>C. Group A recorded the highest viscosity of approximately 9 cP compared to 2.7, 1.6 and 2.1 cP in groups B, C and D respectively. Conclusion: This study shows that milling before cooking can be promoted as against the use of potash and baking soda in processing jute mallow leaves into “ewedu” soup
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Pereira, Rita de Cassia Ribeiro, Carolina Augusta Modena Heming, Thiago Ramos Tejo, Thais Cristina Lima de Oliveira, Rita do Socorro Uchoa da Silva, and Daniella Braz Parente. "Use of the LI-RADS classification in patients with cirrhosis due to infection with hepatitis B, C, or D, or infected with hepatitis B and D." Radiologia Brasileira 53, no. 1 (February 2020): 14–20. http://dx.doi.org/10.1590/0100-3984.2018.0077.
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Abstract Objective: To evaluate liver lesions, in accordance with the LI-RADS classification, using contrast-enhanced multiphase dynamic computed tomography in patients with hepatitis B, coinfected or not with hepatitis D, or with chronic hepatitis C, as well as to determine the level of agreement between radiologists. Materials and Methods: We evaluated 38 patients with hepatitis B, coinfected or not with hepatitis D, or with chronic hepatitis C, all of whom underwent contrast-enhanced multiphase dynamic computed tomography. For each examination, two radiologists selected up to three hepatic lesions, categorizing them in accordance with the LI-RADS classification and evaluating signs of chronic liver disease and portal hypertension. To determine the level of agreement between radiologists, we calculated the kappa statistic (κ) . Results: Radiologist 1 and radiologist 2 selected 56 and 48 liver lesions, respectively. According to radiologist 1 and radiologist 2, respectively, 27 (71%) and 23 (61%) of the 38 patients had at least one liver lesion; 13 (34%) and 12 (32%) had a LI-RADS 5 lesion (κ = 0.821); 19 (50%) and 16 (42%) had a hypervascular lesion (κ = 0.668); and 30 (79%) and 24 (63%) had splenomegaly (κ = 0.503). Both radiologists identified chronic liver disease in 31 (82%) of the patients (κ = 1.00). Conclusion: Lesions categorized as LI-RADS 5 were detected in approximately 32% of the patients, with almost perfect agreement between the radiologists. The level of agreement was substantial or moderate for the other LI-RADS categories.
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Kortt, A. A., J. B. Caldwell, G. G. Lilley, R. Edwards, J. Vaughan, and D. J. Stewart. "Characterization of a basic serine proteinase (pI ∼ 9.5) secreted by virulent strains of Dichelobacter nodosus and identification of a distinct, but closely related, proteinase secreted by benign strains." Biochemical Journal 299, no. 2 (April 15, 1994): 521–25. http://dx.doi.org/10.1042/bj2990521.
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An extracellular serine proteinase with a PI approximately 9.5 (referred to as ‘basic proteinase’) was purified to homogeneity, from strains of Dichelobacter nodosus that cause virulent foot-rot, by gel filtration of concentrated culture supernatant on Sephadex G-100 and chromatography on sulphopropyl-Sephadex C-25 at pH 8.6 D. nodosus strains that cause benign foot-rot do not secrete a corresponding basic proteinase with a pI of approximately 9.5. Benign strains secrete a closely related, but distinct, proteinase which has the same molecular mass and N-terminal sequences as the ‘virulent’ basic proteinase, but a lower pI of approximately 8.6. The basic proteinases from both strains appear to interact with other proteins present in the culture medium, which results in anomalous behavior on gel filtration. Pure D. nodosus ‘virulent’ basic proteinase has a molecular mass of 36 kDa and showed a low solubility at I < 0.05 precipitating quantitatively from solution as microcrystals. The proteinase shows optimal activity at pH 8.0 and is stable to heating to 55 degrees C for 30 min, but at higher temperatures activity is rapidly lost. Bivalent-metal ions (e.g. Ca2+) are required to maintain the structural integrity and stability of the proteinase; in the presence of EDTA or conditions that cause protein unfolding, the proteinase undergoes rapid and complete autolysis. Cleavage of oxidized insulin A- and B-chain showed that the basic proteinase has a broad specificity, including cleavage at lysine and arginine bonds.
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Sheridan, G. J., H. B. So, and R. J. Loch. "Improved slope adjustment functions for soil erosion prediction." Soil Research 41, no. 8 (2003): 1489. http://dx.doi.org/10.1071/sr02029.
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Numerous studies in the last 60 years have investigated the relationship between land slope and soil erosion rates. However, relatively few of these have investigated slope gradient responses: (a) for steep slopes, (b)�for specific erosion processes, and (c) as a function of soil properties. Simulated rainfall was applied in the laboratory on 16 soils and 16 overburdens at 100 mm/h to 3 replicates of unconsolidated flume plots 3 m long by 0.8 m wide and 0.15 m deep at slopes of 20, 5, 10, 15, and 30% slope in that order. Sediment delivery at each slope was measured to determine the relationship between slope steepness and erosion rate. Data from this study were evaluated alongside data and existing slope adjustment functions from more than 55 other studies from the literature. Data and the literature strongly support a logistic slope adjustment function of the form S = A + B/[1 + exp (C – D sin θ)] where S is the slope adjustment factor and A, B, C, and D are coefficients that depend on the dominant detachment and transport processes. Average coefficient values when interill-only processes are active are A –1.50, B 6.51, C 0.94, and D 5.30 (r2 = 0.99). When rill erosion is also potentially active, the average slope response is greater and coefficient values are A –1.12, B 16.05, C 2.61, and D 8.32 (r2 = 0.93). The interill-only function predicts increases in sediment delivery rates from 5 to 30% slope that are approximately double the predictions based on existing published interill functions. The rill + interill function is similar to a previously reported value. The above relationships represent a mean slope response for all soils, yet the response of individual soils varied substantially from a 2.5-fold to a 50-fold increase over the range of slopes studied. The magnitude of the slope response was found to be inversely related (log–log linear) to the dispersed silt and clay content of the soil, and 3 slope adjustment equations are proposed that provide a better estimate of slope response when this soil property is known. Evaluation of the slope adjustment equations proposed in this paper using independent datasets showed that the new equations can improve soil erosion predictions.
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Kim, Sangwoo, Yong Hwan Kim, and Kyung-Jin Kim. "Cloning, expression, purification, crystallization and X-ray crystallographic analysis ofD-lactate dehydrogenase fromLactobacillus jensenii." Acta Crystallographica Section F Structural Biology Communications 70, no. 8 (July 23, 2014): 1046–48. http://dx.doi.org/10.1107/s2053230x14012606.
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The thermostable D-lactate dehydrogenase fromLactobacillus jensenii(LjD-LDH) is a key enzyme for the production of the D-form of lactic acid from pyruvate concomitant with the oxidation of NADH to NAD+. The polymers of lactic acid are used as biodegradable bioplastics. TheLjD-LDH protein was crystallized using the hanging-drop vapour-diffusion method in the presence of 28%(w/v) polyethylene glycol 400, 100 mMTris–HCl pH 9, 200 mMmagnesium sulfate at 295 K. X-ray diffraction data were collected to a maximum resolution of 2.1 Å. The crystal belonged to space groupP3121, with unit-cell parametersa=b= 90.5,c= 157.8 Å. With two molecules per asymmetric unit, the crystal volume per unit protein weight (VM) is 2.58 Å3 Da−1, which corresponds to a solvent content of approximately 52.3%. The structure was solved by single-wavelength anomalous dispersion using a selenomethionine derivative.
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Palmer, L. G., I. Corthesy-Theulaz, H. P. Gaeggeler, J. P. Kraehenbuhl, and B. Rossier. "Expression of epithelial Na channels in Xenopus oocytes." Journal of General Physiology 96, no. 1 (July 1, 1990): 23–46. http://dx.doi.org/10.1085/jgp.96.1.23.
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Epithelial Na channel activity was expressed in oocytes from Xenopus laevis after injection of mRNA from A6 cells, derived from Xenopus kidney. Poly A(+) RNA was extracted from confluent cell monolayers grown on either plastic or permeable supports. 1-50 ng RNA was injected into stage 5-6 oocytes. Na channel activity was assayed as amiloride-sensitive current (INa) under voltage-clamp conditions 1-3 d after injection. INa was not detectable in noninjected or water-injected oocytes. This amiloride-sensitive pathway induced by the mRNA had a number of characteristics in common with that in epithelial cells, including (a) high selectivity for Na over K, (b) high sensitivity to amiloride with an apparent K1 of approximately 100 nM, (c) saturation with respect to external Na with an apparent Km of approximately 10 mM, and (d) a time-dependent activation of current with hyperpolarization of the oocyte membrane. Expression of channel activity was temperature dependent, being slow at 19 degrees C but much more rapid at 25 degrees C. Fractionation of mRNA on a sucrose density gradient revealed that the species of RNA inducing channel activity had a sedimentation coefficient of approximately 17 S. Treatment of filter-grown cells with 300 nM aldosterone for 24 h increased Na transport in the A6 cells by up to fivefold but did not increase the ability of mRNA isolated from those cells to induce channel activity in oocytes. The apparent abundance of mRNA coding for channel activity was 10-fold less in cells grown on plastic than in those grown on filters, but was increased two- to threefold by aldosterone.
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Yoshida, R., H. W. Murray, and C. F. Nathan. "Agonist and antagonist effects of interferon alpha and beta on activation of human macrophages. Two classes of interferon gamma receptors and blockade of the high-affinity sites by interferon alpha or beta." Journal of Experimental Medicine 167, no. 3 (March 1, 1988): 1171–85. http://dx.doi.org/10.1084/jem.167.3.1171.
Full textAbstract:
H2O2-releasing capacity and limited antitoxoplasma activity could be induced in human macrophages (derived from monocytes cultured greater than or equal to 5 d) but not in monocytes themselves (cells cultured less than or equal to 4 d) by a further 3-d incubation with pure natural or rIFN-alpha or -beta. More than 3 pM (10 U/ml) of these IFNs was required, with greatest effects at approximately 300 pM (10(3) U/ml). At 300 pM, H2O2-releasing capacity was enhanced 4.4 +/- 1.6-fold over medium control (mean +/- SD for natural INF-alpha, rIFN-alpha A, rIFN-alpha D, and rIFN-beta) compared to an 8.4 +/- 4.8-fold increase with rIFN-gamma (100 pM, 100 U/ml) in the same experiments. Unexpectedly, low concentrations of IFN-alpha or -beta (3 fM-300 pM) blocked induction of H2O2-releasing capacity by rIFN-gamma (10 pM), with a 50% inhibitory dose of approximately 80 fM. However, IFN-alpha or -beta (3 fM-300 pM) could not inhibit the effect of higher concentrations of rIFN-gamma (1 nM). In contrast to results with monocytes or young macrophages, Scatchard plots of binding of 125I-rIFN-gamma to mature macrophages (day 8 of culture) indicated two classes of binding sites: approximately 2,000 high-affinity sites (Kd approximately 0.43 nM) and approximately 23,000 low-affinity sites (Kd approximately 6.4 nM) per cell. Binding of 125I-rIFN-gamma to the high- but not the low-affinity sites was blocked by simultaneously added IFN-alpha or -beta, with a 50% inhibitory dose of approximately 2 U/0.25 ml (approximately 2 pM), or reversed by subsequently added IFN-alpha or -beta. Thus, differentiation of human mononuclear phagocytes in vitro is accompanied by the emergence of (a) an agonist response to submicromolar concentrations of IFN-alpha or -beta, (b) antagonism of the effect of picomolar IFN-gamma by femtomolar IFN-alpha or -beta, (c) two classes of IFN-gamma-Rs, and (d) nonstimulatory binding of IFN-alpha or -beta to the high- but not the low-affinity IFN-gamma-Rs, with higher affinity than rIFN-gamma itself. We speculate that traces of IFN-alpha or -beta derived from stromal cells, parenchymal cells, or resident macrophages may dampen the activation of mature tissue macrophages by the small amounts of IFN-gamma that diffuse from inflammatory sites into normal tissues. Such a mechanism could constrain the potentially destructive phenomenon of macrophage activation to areas where monocytes have recently immigrated and/or the concentration of IFNs is high.
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Rosidah, Rosidah, Ujang Subhan, Yuniar Mulyani, and Rifai Dermawan. "The effectiveness of honey supplementation in feed for improving goldfish fingerling Carassius auratus immune system against Aeromonas hydrophila bacteria attack." Jurnal Akuakultur Indonesia 18, no. 1 (January 31, 2019): 89–100. http://dx.doi.org/10.19027/jai.18.1.89-100.
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ABSTRACT The attack of Aeromonas hydrophila bacteria can cause mortality in goldfish approximately 100%. The controlling of this bacterial attack can be done through increased fish immunity. Honey is one of the natural ingredients that increases body immune system. This study aimed to determine the effective dose of honey supplemented in feed to increase goldfish fingerling resistance for disease prevention. Fish used in this study were goldfish fingerlings with 3.5 g average weight. This study was done using experimental complete randomized design method with five treatments and three replications. Treatments given were honey supplementation in feed with 0 ml/kg (A) as control treatment, 150 ml/kg (B), 200 ml/kg (C), 250 ml/kg (D), and 300 ml/kg (E). The result showed that honey supplementation in feed was effective to improve goldfish fingerlings resistance against Aeromonas hydrophila bacterial attack. The supplementation of honey in feed with 200 ml/kg was the best treatment for inducing goldfish fingerlings against A. hydrophila. This was proven by the increased white blood cells (leucocytes) (27.84 ± 5.07%) followed with no apparent clinical symptoms after attacked by A.hydrophila, such as hemorrhage, necrosis, exophthalmia or dropsy, besides showing the highest survival rate with 73.33 ± 11.5%. Keywords : Aeromonas hydophila, goldfish, honey, leucocyte, resistance ABSTRAK Serangan bakteri Aeromonas hydrophila dapat menyebabkan kematian ikan mas koki hingga mencapai 100%. Penanggulangan serangan bakteri tersebut dapat dilakukan dengan meningkatkan ketahanan tubuh (imun) ikan. Madu merupakan salah satu bahan alami yang dapat meningkatkan ketahanan tubuh. Penelitian ini bertujuan untuk menentukan dosis efektif penambahan madu pada pakan untuk meningkatkan daya tahan tubuh benih ikan mas koki dalam upaya pencegahan penyakit aeromonasis. Benih yang digunakan adalah benih ikan mas koki berukuran 3.5 gram. Metode penelitian yang digunakan adalah rancangan acak lengkap (RAL) dengan lima perlakuan dan tiga ulangan. Perlakuan yang digunakan adalah penambahan madu pada pakan dengan dosis 0 mL/kg (A) sebagai kontrol, 150 mL/kg (B), 200 mL/kg (C), 250 mL/kg (D), 300 mL/kg (E). Hasil penelitian menunjukkan bahwa penambahan madu ke dalam pakan efektif dalam meningkatkan ketahanan tubuh ikan mas koki terhadap serangan Aeromonas hydrophila. Dosis 200 ml/kg pakan memberikan hasil terbaik dalam meningkatkan ketahanan tubuh ikan mas koki terhadap serangan A. hydrophila terlihat dari peningkatan jumlah sel darah putih terbesar (27.84 ± 5.07%), tidak nampak adanya gejala klinis ikan terserang A. hydrophila seperti hemoragi, necrosis, exophthalmia maupun dropsy dan menghasilkan kelangsungan hidup benih ikan mas koki tertinggi yaitu sebesar 73.33 ± 11.5%. Kata kunci: Aeromonas hydrophila, ketahanan tubuh, ikan mas koki, madu, sel darah putih.
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Lücken, Anneke, Svenja Woudstra, Nicole Wente, Yanchao Zhang, and Volker Krömker. "Intramammary infections with Corynebacterium spp. in bovine lactating udder quarters." PLOS ONE 17, no. 7 (July 7, 2022): e0270867. http://dx.doi.org/10.1371/journal.pone.0270867.
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Corynebacterium spp. are frequently detected in bovine quarter milk samples, yet their impact on udder health has not been determined completely. In this longitudinal study, we collected quarter milk samples from a dairy herd of approximately 200 cows, ten times at 14 d intervals. Bacteriologically, Catalase-positive and Gram-positive rods were detected in 22.7% of the samples. For further species diagnosis, colonies were analyzed by MALDI-TOF MS. Corynebacterium bovis, C. amycolatum, C. xerosis and 10 other Corynebacterium spp. were detected. The three aforementioned species accounted for 88.4%, 8.65% and 0.94% of all cultured Corynebacterium spp., respectively. For further evaluation of infection dynamics, the following three infection definitions were applied: A (2/3 consecutive samples positive for the same species), B (≥1000 cfu/mL in one sample), C (isolated from a clinical mastitis case). Infections according to definition B occurred most frequently and clinical mastitis with Corynebacterium spp. occurred once during sampling. Life tables were used to determine the duration of infection. According to infection definition A, infection durations of 111 d and 98 d were obtained for C. bovis and C. amycolatum, respectively. Exemplarily, longer lasting infections were examined for their strain diversity by RAPD PCR. A low strain diversity was found in the individual quarters that indicates a longer colonization of the udder parenchyma by C. bovis and C. amycolatum.
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Patel, Drasti, Hamish Thomas Reid, Lara Rasha, Matilda Fransson, Ludovic Broche, and Paul R. Shearing. "In-Situ/Operando X-Ray CT Characterisation of Lithium-Ion Pouch Cells during Thermal Failure." ECS Meeting Abstracts MA2022-01, no. 2 (July 7, 2022): 349. http://dx.doi.org/10.1149/ma2022-012349mtgabs.
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The safety of concerns of lithium-ion batteries continues to be a prevalent obstacle toward their widespread application from vehicle electrification to space exploration. Aside from the highly oxidising and reducing electrode materials, their safety is compounded by an inherent drawback of poor heat dissipation [1]. High-speed imaging with in-situ/operando X-ray CT has been used extensively to study various lithium-ion battery safety features and failure mechanisms [2][3], including thermal failure [4]. However, these are exclusively using synchrotron X-ray sources which are limited in terms of both access and data recording capabilities: high frame rates require the data collection window to be restricted to a few seconds. During lithium-ion battery failure, there are several changes to a cell structure leading up to thermal runaway (TR) which can take minutes, and as a result are often missed. Here, we present an instrument that simulates thermal failure for lab-based radiography at slower imaging speeds and longer recording lengths, which has been validated by correlative synchrotron measurements. The failure mechanisms within a fully charged (100 % SOC, 4.2 V) commercially available LiCoO2 cathode and graphite anode pouch cell (651628-2C, AA Portable Power Corp) rated at 210 mAh are investigated. Three samples are studied using lab-based radiography at a frame rate of 3.75 fps with a 16.1 µm pixel resolution and, for comparison, an additional three samples are studied using synchrotron X-ray sources at a higher speed of 20,000 fps with a 13.3 µm pixel resolution. For the six samples investigated, the total time taken from a start temperature of 80 °C to TR is approximately 20 minutes and the onset temperatures for TR are recorded within the range of 196 °C to 210 °C. The beginning of the TR event (defined as a sample temperature increase greater than 15 °C s-1), where the effects to the electrode structure are the most catastrophic, lasts for approximately 1 s. Operando radiographic images during this event reveal that the structural displacement of electrode layers begins at the centre of the cell and propagates outwards in a wave-like motion. The electrode displacement, as a result, is quantified by cross-correlating Gabor signals and spatiotemporal mapping [5] in both types of datasets. For the lab-based radiography, data is recorded from the start temperature to TR (lasting approximately 20 minutes), and reactions such as the electrolyte decomposition, ca. 105 °C, and separator melting, ca.130 °C are characterised in the context of electrode deformation and gas evolution. Investigations of pre- and post-failure 3D X-ray CT images further verify the uniformity of the pristine (or pre-failure) cell assembly as well as the estimated post-failure behaviour between samples. Finally, by comparison with correlative synchrotron measurements, the instrument for inducing thermal failure for lab-based X-ray CT is proven to be a viable and more accessible method to investigate thermal failure within a 210 mAh pouch cell. While synchrotron data has a higher-speed imaging advantage, it is limited to only recording the short TR event at a high temporal resolution. Whereas continuous imaging in lab-based radiography has the benefit of measuring the slower architectural changes taking place up to TR, albeit at a marginally lower spatial resolution. References [1] D. H. Doughty and E. P. Roth, Interface Mag., 21, 37–44 (2012). [2] D. P. Finegan, M. Scheel, J. B. Robinson, B. Tjaden, M. Di Michiel, G. Hinds, D. J. L. Brett, and P. R. Shearing, Phys. Chem. Chem. Phys., 18, 30912–30919 (2016). [3] D. P. Finegan, M. Scheel, J. B. Robinson, B. Tjaden, I. Hunt, T. J. Mason, J. Millichamp, M. Di Michiel, G. J. Offer, G. Hinds, D. J. L. Brett, and P. R. Shearing, Nat. Commun., 6, 6924 (2015). [4] M. T. M. Pham, J. J. Darst, D. P. Finegan, J. B. Robinson, T. M. M. Heenan, M. D. R. Kok, F. Iacoviello, R. Owen, W. Q. Walker, O. V. Magdysyuk, T. Connolley, E. Darcy, G. Hinds, D. J. L. Brett, and P. R. Shearing, J. Power Sources, 470, 228039 (2020). [5] A. N. P. Radhakrishnan, M. Buckwell, M. Pham, D. P. Finegan, A. Rack, G. Hinds, D. J. L. Brett, and P. R. Shearing, ChemRxiv (2021).
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Aminatun, Rifqha Huriah, Dyah Hikmawati, Sofijan Hadi, Tahta Amrillah, and Che Azurahanim Che Abdullah. "Nanofiber Scaffold Based on Polylactic Acid-Polycaprolactone for Anterior Cruciate Ligament Injury." Polymers 14, no. 15 (July 23, 2022): 2983. http://dx.doi.org/10.3390/polym14152983.
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Anterior Cruciate Ligament (ACL) injuries are becoming more prevalent in athletes. Anterior Cruciatum Ligament Reconstruction (ACLR) surgery was used to treat ACL injuries and resulted in a recurrence rate of 94% due to the biomechanically repaired tissue being weaker than the original tissue. As a result, biodegradable artificial ligaments must be developed that can withstand mechanical stress during neoligament formation and stabilize the ACL. The purpose of this study is to determine the effect of composition variations in polylactic acid (PLA) and polycaprolactone (PCL) used as ACL nanofiber scaffolds on ultimate tensile strength (UTS) and modulus of elasticity, fiber diameter, cytotoxicity level, and degradation level, as well as the PLA-PCL concentration that provides the best value as an ACL scaffold. Electrospinning was used to fabricate the nanofiber scaffold with the following PLA-PCL compositions: A (100:0), B (85:15), C (80:20), D (70:30), and E (0:100) (wt%). The functional group test revealed no new peaks in any of the samples, and the ester group could be identified in the C-O bond at wave numbers 1300–1100 cm−1 and in the C=O bond at wave numbers 1750–1730 cm−1. The average fiber diameter, as determined by SEM morphology, is between 1000 and 2000 nm. The unbraided sample had a UTS range of 1.578–4.387 MPa and an elastic modulus range of 8.351–141.901 MPa, respectively, whereas the braided sample had a range of 0.879–1.863 MPa and 2.739–4.746 MPa. The higher the PCL composition, the lower the percentage of viable cells and the faster the sample degrades. All samples had a cell viability percentage greater than 60%, and samples C, D, and E had a complete degradation period greater than six months. The ideal scaffold, Sample C, was composed of PLA-PCL 80:20 (wt%), had an average fiber diameter of 827 ± 271 nm, a living cell percentage of 97.416 ± 5.079, and a degradation time of approximately 219 days.
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Maunder, Mark N., and Richard B. Deriso. "Estimation of recruitment in catch-at-age models." Canadian Journal of Fisheries and Aquatic Sciences 60, no. 10 (October 1, 2003): 1204–16. http://dx.doi.org/10.1139/f03-104.
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Management strategies must be designed to take into account the uncertainty inherent in fish populations and their assessments. Annual recruitment variation is an important component of uncertainty. Several methods that allow the estimation of annual recruitment in statistical catch-at-age models are described: (a) maximum likelihood estimation with no penalty on the annual recruitment residuals, (b) maximum likelihood estimation with a lognormal penalty on the annual recruitment residuals, (c) importance sampling to numerically approximate the marginal likelihood with a lognormal penalty on the annual recruitment residuals, and (d) full Bayesian integration using Markov Chain Monte Carlo with a lognormal prior on the annual recruitment residuals. Simulation analysis is used to test the performance of these methods. All four methods perform similarly at estimating quantities that are based on averaging or summing multiple estimates of annual recruitment; however the marginal likelihood method (c) and Bayesian integration (d) perform best at estimating annual recruitment and the standard deviation in annual recruitment residuals (σR) when catch-at-age data is missing for some years. The ability to estimate σR can be important for defining uncertainty when developing management strategies. The methods are applied to a New Zealand snapper (Pagrus auratus) stock and the estimate of σR is approximately 0.6.
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Matteson, D. R., and C. M. Armstrong. "Properties of two types of calcium channels in clonal pituitary cells." Journal of General Physiology 87, no. 1 (January 1, 1986): 161–82. http://dx.doi.org/10.1085/jgp.87.1.161.
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The calcium currents of GH3 cells have been studied using the whole cell variant of the patch-clamp technique. Under conditions that eliminate sodium and potassium currents, we observed inward currents that activated within a few milliseconds, and deactivated with two time constants, approximately 150 microseconds and 3 ms at -80 mV, 18-20 degrees C. The components are called FD and SD (fast deactivating and slow deactivating). Both components are calcium currents, and are greatly reduced when magnesium is substituted for most of the calcium in the bath. In addition to (a) their different rates of deactivation, the two components differ in a number of other properties. (b) The SD component inactivates almost completely, with a time constant of 23 ms at 20 mV, 19 degrees C. The FD component, on the other hand, shows little or no sign of inactivation, and is almost the same in amplitude from 10 to 100 ms. The components thus seem quite independent of each other, and must arise from two independent sets of channels. (c) The FD channels activate more rapidly than SD at 20 mV, by a factor of approximately 2 as is shown in several ways. (d) In 10 Ca or 10 Ba, the activation curve for SD channels is approximately 20 mV more negative than for FD or Na channels. (e) FD channels conduct barium ions more effectively than calcium by a ratio of approximately 2. (f) FD channels "wash out" within minutes after the patch electrode breaks into a cell, whereas SD channel current remains relatively stable. It is argued that SD channels, because of their negative activation threshold, are involved in electrical events near threshold, and that FD channels are best suited for calcium injection once a spike has been initiated.
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Romberg, M. K., R. L. Griffin, S. Murugan, B. D. Quinn, and B. J. R. Alexander. "First Report of Leaf Spot of Dracaena reflexa Caused by Burkholderia gladioli Worldwide." Plant Disease 94, no. 6 (June 2010): 781. http://dx.doi.org/10.1094/pdis-94-6-0781c.
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In December 2008 (austral summer), a new disease of Dracaena reflexa Lam. cv. Anita was observed in a postentry quarantine greenhouse near Auckland, New Zealand on plants imported from Costa Rica. Symptoms included rust-colored, water-soaked lesions with chlorotic margins approximately 5 by 10 mm. When the disease was first noticed, incidence approached 80%, but subsequent reduction in greenhouse temperature dramatically reduced symptom expression and lesions were only visible on some leaf tips. Bacteria consistently isolated from the lesions on King's medium B (KB) were cream-colored, shiny, and produced a yellow, diffusible, nonfluorescent pigment. All isolates were able to rot onion slices. On the basis of BIOLOG (Hayward, CA) carbon utilization profiles, isolates were initially identified as Burkholderia gladioli (Severini 1913) Yabuuchi et al. 1993 with a probability index of 100% and a similarity index of 0.85. For molecular identification, a near full-length sequence of the 16S rDNA gene was amplified from all isolates using primers fD2 and rP1 (1), obtaining a PCR product of approximately 1,500 bp. The nucleotide sequences were 100% identical to a number of B. gladioli GenBank entries, including Accession Nos. EF193645 and EF088209. To confirm pathogenicity, three isolates (two isolated prior to greenhouse temperature reduction and one after) were used. Three D. reflexa plants were inoculated per bacterial isolate by wounding three young fully expanded leaves on each plant (four wounds per leaf) and spraying the leaves with a bacterial suspension in sterile distilled water at 108 CFU/ml. At the same time, Gladiolus nanus plants were inoculated in a similar manner. Control plants (D. reflexa and G. nanus) were wounded and sprayed with sterile distilled water. All inoculated plants were covered with plastic bags to maintain humidity and placed in a growth chamber at 25°C. At 3 days, all inoculated plants began to show water soaking and reddish coloration around the inoculation sites, and by 7 days, the lesions had expanded to resemble natural infection. Bacteria isolated on KB from the leading edge of each lesion were morphologically identical to the initial isolates. No bacteria were recovered from the wound sites on the control plants. The 16S rDNA sequences of selected isolates from inoculated plants showed 100% identity to the sequences of the initial isolates, thereby fulfilling Koch's postulates. To our knowledge, this is the first report of B. gladioli causing leaf spot of D. reflexa in the world. Reference: (1) W. G. Weisburg et al. J. Bacteriol. 173:697, 1991.
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Cox, D. H., and K. Dunlap. "Inactivation of N-type calcium current in chick sensory neurons: calcium and voltage dependence." Journal of General Physiology 104, no. 2 (August 1, 1994): 311–36. http://dx.doi.org/10.1085/jgp.104.2.311.
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We have studied the inactivation of high-voltage-activated (HVA), omega-conotoxin-sensitive, N-type Ca2+ current in embryonic chick dorsal root ganglion (DRG) neurons. Voltage steps from -80 to 0 mV produced inward Ca2+ currents that inactivated in a biphasic manner and were fit well with the sum of two exponentials (with time constants of approximately 100 ms and > 1 s). As reported previously, upon depolarization of the holding potential to -40 mV, N current amplitude was significantly reduced and the rapid phase of inactivation all but eliminated (Nowycky, M. C., A. P. Fox, and R. W. Tsien. 1985. Nature. 316:440-443; Fox, A. P., M. C. Nowycky, and R. W. Tsien. 1987a. Journal of Physiology. 394:149-172; Swandulla, D., and C. M. Armstrong. 1988. Journal of General Physiology. 92:197-218; Plummer, M. R., D. E. Logothetis, and P. Hess. 1989. Neuron. 2:1453-1463; Regan, L. J., D. W. Sah, and B. P. Bean. 1991. Neuron. 6:269-280; Cox, D. H., and K. Dunlap. 1992. Journal of Neuroscience. 12:906-914). Such kinetic properties might be explained by a model in which N channels inactivate by both fast and slow voltage-dependent processes. Alternatively, kinetic models of Ca-dependent inactivation suggest that the biphasic kinetics and holding-potential-dependence of N current inactivation could be due to a combination of Ca-dependent and slow voltage-dependent inactivation mechanisms. To distinguish between these possibilities we have performed several experiments to test for the presence of Ca-dependent inactivation. Three lines of evidence suggest that N channels inactivate in a Ca-dependent manner. (a) The total extent of inactivation increased 50%, and the ratio of rapid to slow inactivation increased approximately twofold when the concentration of the Ca2+ buffer, EGTA, in the patch pipette was reduced from 10 to 0.1 mM. (b) With low intracellular EGTA concentrations (0.1 mM), the ratio of rapid to slow inactivation was additionally increased when the extracellular Ca2+ concentration was raised from 0.5 to 5 mM. (c) Substituting Na+ for Ca2+ as the permeant ion eliminated the rapid phase of inactivation. Other results do not support the notion of current-dependent inactivation, however. Although high intracellular EGTA (10 mM) or BAPTA (5 mM) concentrations suppressed the rapid phase inactivation, they did not eliminate it. Increasing the extracellular Ca2+ from 0.5 to 5 mM had little effect on this residual fast inactivation, indicating that it is not appreciably sensitive to Ca2+ influx under these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)
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Kracke, G. R., G. G. Preston, and T. H. Stanley. "Identification of a sorbitol permease in human erythrocytes." American Journal of Physiology-Cell Physiology 266, no. 2 (February 1, 1994): C343—C350. http://dx.doi.org/10.1152/ajpcell.1994.266.2.c343.
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Sorbitol, a polyol derived from glucose by the enzyme, aldose reductase, is a common organic solute in many cells. It plays a role in the osmotic regulation of epithelial cells and in the pathology of uncontrolled diabetes. To learn more about sorbitol transport, we measured D-[14C]sorbitol influx in human erythrocytes. Sorbitol influx at 37 degrees C was a linear function of sorbitol concentration over the range of 0.05-100 mM. The activation energy for sorbitol influx was 10.0 kcal/mol, and the Q10 over the range 10-50 degrees C was 1.8, higher than predicted for diffusion through an aqueous pore. Glucose transport inhibitors either had no effect (1 mM phloridzin) or minimally inhibited (approximately 35% inhibition by 10 microM cytochalasin B or 250 microM phloretin) sorbitol influx. Influx was stimulated twofold by 0.5 mM p-chloromercuribenzoic acid, an inhibitor of glucose transport, and this was reversed by 2 mM dithiothreitol. Sorbitol influx was neither Na dependent nor sensitive to changes in cell volume. Glucose, fructose, mannitol, myo-inositol, and gluconate, at four- to fivefold molar excesses over sorbitol, did not inhibit its influx. We conclude that there is a specific sorbitol transport pathway in human erythrocytes similar to the sorbitol permease in renal epithelial cells.
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Lynch, Gavin, and Maureen McKeurtan. "Supporting Low Ability Learners in a Tertiary Level Compulsory English Programme using CEFR Based Online Language Software." EuroCALL Review 20, no. 1 (March 22, 2012): 118. http://dx.doi.org/10.4995/eurocall.2012.16201.
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This report describes the processes, methods and results of using language software based on the Common European Framework of Reference for Languages (CEFR) in a tertiary level institute in Japan in order to facilitate the learning of low ability learners of English. None of the learners were English majors, all were between the ages of 18 and 20, and the classes were compulsory. Approximately 100 learners were divided into four classes, A, B, C and D, in order of decreasing ability, according to their performance on a placement test. This research focuses on Classes C and D. Students in these classes were all at or below the CEFR’s A1 level in their English ability. Online language software was first used in order to tackle factors which were considered by Lynch (2011) to be the cause of lower performance in students in Classes C and D, namely the lack of four factors: motivation, achievable goals, concentration ability and proper classroom management. In the first year, the lowest ability class, Class D, used online software designed to teach vocabulary at level A1 of the CEFR for 25 minutes out of a 90 minute session for a total of 15 sessions, while the higher level classes were taught using traditional methods. The software was used in such a way as to tackle the four factors for lower performance, mentioned above. It was found that Class D eventually performed as well as Class C (in terms of ability shown in a CEFR-based examination) after the 15 sessions. In the second year of the study (with new participants), Classes C and D both used the computer program yet Class D performed better in terms of the quantity and knowledge of vocabulary covered. The reasons for this are discussed in this paper with particular attention paid to difficult to control classroom circumstances. One significant difference between the classes was the achievement targets set by teachers, with the lowest ability class, Class D, having a target being only half of that set for the next higher class up, Class C. Despite this, the Class D average performance was significantly higher than that of Class C. We present our hypotheses for the above results in this paper, and it is hoped that it will be useful for other teachers of low ability language learners using CALL in the classroom.
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Bloy, C., D. Blanchard, P. Lambin, D. Goossens, P. Rouger, C. Salmon, and JP Cartron. "Human monoclonal antibody against Rh(D) antigen: partial characterization of the Rh(D) polypeptide from human erythrocytes." Blood 69, no. 5 (May 1, 1987): 1491–97. http://dx.doi.org/10.1182/blood.v69.5.1491.1491.
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Abstract A human monoclonal anti-Rh(D) antibody produced by an Epstein-Barr virus (EBV)-transformed B-cell line (IgG1(lambda), clone H2D5D2) has been purified on protein A-Sepharose column and used for binding studies and immune precipitation of the blood group rhesus (Rh) antigens. Scatchard plot analyses show that the 125I-labeled antibody (iodo-gen procedure), binds to 1.09 X 10(5), 0.43 X 10(5), and 0.32 X 10(5) antigen sites on each D--/D--, R2R2 and R1R1 RBC, respectively, with an association constant of approximately 0.6 X 10(8) mol/L-1. Immune precipitation studies indicate also that the Rh(D) antigen of the Rh(D)-positive RBCs is carried by a 29 kd polypeptide as deduced from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS- PAGE). No material could be precipitated from Rh(D)-negative or Rhnull RBCs. These results indicate that the monoclonal and the polyclonal human anti-Rh(D) behave similarly. A sample (Blo., presumed genotype R2r or R0R2) showing an increased number of antigen sites (0.76 X 10(5)/cell) and a high binding constant (5.7 X 10(8) mol/L-1) was used, as well as D--/D-- RBCs, for further purification of the 29-kd component. Extraction by Triton X-100 (0.1% to 5%) of the immune complexes formed between the membrane-bound Rh(D) antigens and the monoclonal antibody as well as a direct quantitative estimate of the 29- kd component, suggest that the Rh(D) polypeptide is loosely bound to the skeleton, since less than or equal to 80% can be solubilized from the membrane. In similar conditions, glycophorin A showed a slight association with the Triton-insoluble residue, whereas glycophorin B was easily and completely extracted. In contrast, both the minor RBC sialoglycoproteins, glycophorin C and glycoprotein gamma, remained predominantly bound to the membrane skeleton. The purified Rh(D) polypeptide obtained from Blo. and D--/D-- RBCs by immunoprecipitation and preparative gel electrophoresis was homogenous as judged by SDS- PAGE. Amino acid composition indicated that the Rh(D) protein contained sulfhydryl groups which are essential for biological activity.
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Bloy, C., D. Blanchard, P. Lambin, D. Goossens, P. Rouger, C. Salmon, and JP Cartron. "Human monoclonal antibody against Rh(D) antigen: partial characterization of the Rh(D) polypeptide from human erythrocytes." Blood 69, no. 5 (May 1, 1987): 1491–97. http://dx.doi.org/10.1182/blood.v69.5.1491.bloodjournal6951491.
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A human monoclonal anti-Rh(D) antibody produced by an Epstein-Barr virus (EBV)-transformed B-cell line (IgG1(lambda), clone H2D5D2) has been purified on protein A-Sepharose column and used for binding studies and immune precipitation of the blood group rhesus (Rh) antigens. Scatchard plot analyses show that the 125I-labeled antibody (iodo-gen procedure), binds to 1.09 X 10(5), 0.43 X 10(5), and 0.32 X 10(5) antigen sites on each D--/D--, R2R2 and R1R1 RBC, respectively, with an association constant of approximately 0.6 X 10(8) mol/L-1. Immune precipitation studies indicate also that the Rh(D) antigen of the Rh(D)-positive RBCs is carried by a 29 kd polypeptide as deduced from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS- PAGE). No material could be precipitated from Rh(D)-negative or Rhnull RBCs. These results indicate that the monoclonal and the polyclonal human anti-Rh(D) behave similarly. A sample (Blo., presumed genotype R2r or R0R2) showing an increased number of antigen sites (0.76 X 10(5)/cell) and a high binding constant (5.7 X 10(8) mol/L-1) was used, as well as D--/D-- RBCs, for further purification of the 29-kd component. Extraction by Triton X-100 (0.1% to 5%) of the immune complexes formed between the membrane-bound Rh(D) antigens and the monoclonal antibody as well as a direct quantitative estimate of the 29- kd component, suggest that the Rh(D) polypeptide is loosely bound to the skeleton, since less than or equal to 80% can be solubilized from the membrane. In similar conditions, glycophorin A showed a slight association with the Triton-insoluble residue, whereas glycophorin B was easily and completely extracted. In contrast, both the minor RBC sialoglycoproteins, glycophorin C and glycoprotein gamma, remained predominantly bound to the membrane skeleton. The purified Rh(D) polypeptide obtained from Blo. and D--/D-- RBCs by immunoprecipitation and preparative gel electrophoresis was homogenous as judged by SDS- PAGE. Amino acid composition indicated that the Rh(D) protein contained sulfhydryl groups which are essential for biological activity.
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Jaiswal, Anand Kumar, Rajesh Kumar Rai, and Abhishek Chandra. "Prospective study of accuracy of C-reactive protein and leucocyte count in diagnosis of acute appendicitis in comparison with histopathology." International Surgery Journal 7, no. 8 (July 23, 2020): 2662. http://dx.doi.org/10.18203/2349-2902.isj20203252.
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Background: Acute appendicitis is one of the most common surgical emergencies. Approximately 7.0% of the population will have appendicitis in their lifetime with the peak incidence occurring between the age of 10 and 30 years. The classical history of peri umbilical pain at beginning and later shifting to right iliac fossa is present in only 50% cases. C-reactive protein is an acute phase reactant synthesized by liver in response to tissue injury. Serial measurement of CRP can improve the accuracy of diagnosing acute appendicitis.Methods: A prospective study of 70 cases with clinical diagnosis of acute appendicitis admitted in the department of surgery, B. R. D. Medical College Gorakhpur during a period of one year.Results: There was young age predominance (54.2%) and commonest presenting symptom was RIF pain (100%) followed by nausea/vomiting (66%) and fever (60%). Among 48 cases of histopathology proven appendicitis, CRP was raised in 44 cases (91.6%).Conclusions: Serial measurement of CRP is more sensitive and specific than TLC count and the raised value of CRP is directly related to the severity of inflammation. Combining the TLC and CRP increases the diagnostic accuracy and therefore may reduce rate of negative appendectomy.
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Sahoo, Satya S., Shiqiang Tao, Andrew Parchman, Zhihui Luo, Licong Cui, Patrick Mergler, Robert Lanese, Jill S. Barnholtz-Sloan, Neal J. Meropol, and Guo-Qiang Zhang. "Trial Prospector: Matching Patients with Cancer Research Studies Using an Automated and Scalable Approach." Cancer Informatics 13 (January 2014): CIN.S19454. http://dx.doi.org/10.4137/cin.s19454.
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Cancer is responsible for approximately 7.6 million deaths per year worldwide. A 2012 survey in the United Kingdom found dramatic improvement in survival rates for childhood cancer because of increased participation in clinical trials. Unfortunately, overall patient participation in cancer clinical studies is low. A key logistical barrier to patient and physician participation is the time required for identification of appropriate clinical trials for individual patients. We introduce the Trial Prospector tool that supports end-to-end management of cancer clinical trial recruitment workflow with (a) structured entry of trial eligibility criteria, (b) automated extraction of patient data from multiple sources, (c) a scalable matching algorithm, and (d) interactive user interface (UI) for physicians with both matching results and a detailed explanation of causes for ineligibility of available trials. We report the results from deployment of Trial Prospector at the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center (Case CCC) with 1,367 clinical trial eligibility evaluations performed with 100% accuracy.
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Paar, W. H., Kurt Mereiter, R. S. W. Braithwaite, Paul Keller, and P. J. Dunn. "Chenite, Pb4Cu(SO4)2(OH)6, a new mineral, from Leadhills, Scotland." Mineralogical Magazine 50, no. 355 (March 1986): 129–35. http://dx.doi.org/10.1180/minmag.1986.050.355.17.
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AbstractChenite, a new lead-copper secondary mineral, has been found on specimens from the Leadhills area, Scotland. It is associated with caledonite, linarite, leadhillite, susannite, and other species, on oxidized galena with chalcopyrite. Electron microprobe analysis yielded PbO 74.5, CuO 7.8, SO3 13.3, H2O 4.4 (by difference), sum = 100 wt. %. The empirical formula (based on 14 oxygens) is Pb3.98Cu1.17S1.98O14H5.82; the ideal formula is Pb4Cu(SO4)2(OH)6, which requires PbO 75.2, CuO 6.7, SO3 13.5, H2O 4.6, sum = 100 wt. %.Infra-red spectroscopy showed the presence of only and OH− ions, with no H2O.Chenite is triclinic, P1 or P̄, with a = 5.791(1), b = 7.940(1), c = 7.976(1) Å, α = 112.02(1), β = 97.73(1), γ = 100.45(1)°, V = 326.0 Å3, Z = 1. The strongest lines in the X-ray powder diffraction pattern (d, I/Io, hkl) are: 5.55, 7, 100; 4.32, 6, 11; 3.60, 10 002; 3.41, 9, 10; 3.30, 5, 02; 3.00, 5, 111; 2.80, 7, 12; 2.07, 6, 211/21/13; 1.778, 5, 3/23.Chenite forms minute, singly terminated, transparent to translucent sky-blue crystals from 0.1 to over 1 mm long, elongated approximately [032]. Twenty different forms (pinacoids) have been identified on the four crystals studied. A good cleavage on {100}, and traces of a second on {001}, can be observed. Optically, chenite is biaxial negative, 2 V(measured) = 67±1°, 2 V(calc.) = 68° (Na). The refractive indices are α 1.871±0.005, β 1.909±0.005, γ 1.927±0.005 (Na). Dispersion is strong, r≫v. The mineral is weakly pleochroic. H (Mohs) ∼ 2½. D = 5.98, and calculated Dx = 6.044 g cm−3.
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CLARK, WILLIAM R., JOHN K. LEYPOLDT, LEE W. HENDERSON, BRUCE A. MUELLER, MERI KAY SCOTT, and EDWARD F. VONESH. "Quantifying the Effect of Changes in the Hemodialysis Prescription on Effective Solute Removal with a Mathematical Model." Journal of the American Society of Nephrology 10, no. 3 (March 1999): 601–9. http://dx.doi.org/10.1681/asn.v103601.
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Abstract. One potential benefit of chronic hemodialysis (HD) regimens of longer duration or greater frequency than typical three-times-weekly schedules is enhanced solute removal over a relatively wide molecular weight spectrum of uremic toxins. This study assesses the effect of variations in HD frequency (F: per week), duration (T: min per treatment), and blood/dialysate flow rates (QB/QD: ml/min) on steady-state concentration profiles of five surrogates: urea (U), creatinine (Cr), vancomycin (V), inulin (I), and β2-microglobulin (β2M). The regimens assessed for an anephric 70-kg patient were: A (standard):F= 3,T= 240,QB= 350,QD= 600; B (daily/short-time):F= 7,T= 100,QB= 350,QD= 600; C/D/E (low-flow/long-time):F= 3/5/7,T= 480,QB= 300,QD= 100. HD was simulated with a variable-volume double-pool model, which was solved by numerical integration (Runge-Kutta method). Endogenous generation rates (G) for U, Cr, and β2M were 6.25, 1.0, and 0.17 mg/min, respectively; constant infusion rates for V and I of 0.2 and 0.3 mg/min, respectively, were used to simulate middle molecule (MM)Gvalues. Intercompartment clearances of 600, 275, 125, 90, and 40 ml/min were used for U, Cr, V, I, and β2M, respectively, For each solute/regimen combination, the equivalent renal clearance (EKR: ml/min) was calculated as a dimensionless value normalized to the regimen A EKR, which was 13.4, 10.8, 6.6, 3.7, and 4.8 ml/min for U, Cr, V, I, and β2M, respectively. For regimens B, C, D, and E, respectively, these normalized EKR values were U: 1.04, 0.96, 1.58, and 2.22; Cr: 1.03, 1.08, 1.80, and 2.55; V: 1.06, 1.32, 2.21, and 3.12; I: 1.05, 1.54, 2.57, and 3.62; β2M: 1.00, 1.27, 1.73, and 2.19. The extent of post-HD rebound (%) was highest for regimens A and B, ranging from 16% (urea) to 50% (inulin), and lowest for regimen E, ranging from 6% (urea) to 28% (β2M). The following conclusions can be made: (1) Relative to a standard three-times-weekly HD regimen of approximately the same total (weekly) treatment duration, a daily/short-time regimen results in modest (3 to 6%) increases in effective small solute and MM removal. (2) Relative to a standard three-times-weekly HD regimen, a three-times-weekly low-flow/long-time regimen results in comparable effective small solute removal and progressive increases in MM and β2M removal. A daily low-flow/long-time regimen substantially increases the effective removal of all solutes.
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Somlo, G., I. Sniecinski, T. Odom-Maryon, B. Nowicki, W. Chow, V. Hamasaki, L. Leong, et al. "Effect of CD34+ Selection and Various Schedules of Stem Cell Reinfusion and Granulocyte Colony-Stimulating Factor Priming on Hematopoietic Recovery After High-Dose Chemotherapy for Breast Cancer." Blood 89, no. 5 (March 1, 1997): 1521–28. http://dx.doi.org/10.1182/blood.v89.5.1521.
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Abstract We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF ) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (≥7.5 × 108 nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day −2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 μg/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 μg/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 × higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day −2 (median, 2.26 × 108/kg nucleated cells [range, 1.7 to 3.3 × 108/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to ≥500/μL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34+-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34+-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P ≤ .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of ≈ 2.26 × 108/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34+-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier “sacrificial” reinfusion of approximately 2 × 108/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.
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Somlo, G., I. Sniecinski, T. Odom-Maryon, B. Nowicki, W. Chow, V. Hamasaki, L. Leong, et al. "Effect of CD34+ Selection and Various Schedules of Stem Cell Reinfusion and Granulocyte Colony-Stimulating Factor Priming on Hematopoietic Recovery After High-Dose Chemotherapy for Breast Cancer." Blood 89, no. 5 (March 1, 1997): 1521–28. http://dx.doi.org/10.1182/blood.v89.5.1521.1521_1521_1528.
Full textAbstract:
We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF ) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (≥7.5 × 108 nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day −2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 μg/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 μg/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 × higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day −2 (median, 2.26 × 108/kg nucleated cells [range, 1.7 to 3.3 × 108/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to ≥500/μL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34+-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34+-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P ≤ .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of ≈ 2.26 × 108/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34+-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier “sacrificial” reinfusion of approximately 2 × 108/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.
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Hosokawa, Y., and T. Miki-Noumura. "Bending motion of Chlamydomonas axonemes after extrusion of central-pair microtubules." Journal of Cell Biology 105, no. 3 (September 1, 1987): 1297–301. http://dx.doi.org/10.1083/jcb.105.3.1297.
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Relatively little is known about the functions of central-pair microtubules (Tamm, S. L., and G. A. Horridge, 1970, Proc. Roy. Soc. Lond. B, 175: 219-233; Omoto, C. K., and C. Kung, 1979, Nature (Lond.). 279:532-534) and radial spokes (Warner, F. D., and P. Satir, 1974, J. Cell Biol., 63:35-63), although a sliding microtubule mechanism has been established for the flagellar movement (Summers, K. E., and I. R. Gibbons, 1971, Proc. Natl. Acad. Sci. USA., 68:3092-3096). In the present report, an attempt was made to determine the functions of central-pair microtubules in flagellar motility. Central-pair microtubules were found to extrude from the tips of elastase-digested axonemes of demembranated Chlamydomonas flagella after the addition of ATP. The length of the extruded central-pair microtubules was approximately 70-100% that of the axoneme. After extrusion, axonemes continued to swim slowly backwards in the reactivation medium, with a trailing central pair attached like a tail to the flagellar tip. During bending movement of the axonemes, partially extruded central pairs rotated counterclockwise about the axoneme axis, as viewed from the distal end (Kamiya, R., 1982, Cell Motil. [Suppl.]:169-173). Axonemes swam backwards with a symmetric waveform and a beat frequency of approximately 10 Hz in the reactivation medium containing 10(-9)-10(-4) M Ca ions. Even at a lower Ca++ concentration, no ciliary-type swimming was noted on the axonemes.
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Tijssen, Marloes R., Paula B. Van Hennik, Franca Di Summa, Peter L. Hordijk, Jaap Jan Zwaginga, C. Ellen Van der Schoot, and Carlijn Voermans. "Transplantation of Human Peripheral Blood CD34-Positive Cells in Combination with Ex Vivo Expanded Megakaryocytes Results in Fast Platelet Formation in NOD/SCID Mice." Blood 108, no. 11 (November 16, 2006): 3203. http://dx.doi.org/10.1182/blood.v108.11.3203.3203.
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Abstract The period of severe thrombocytopenia after high dose chemotherapy may be shortened by the addition of ex vivo expanded megakaryocytes (MKs, CD41+ cells) to the graft. This has been shown for expanded cord blood stem cells in mouse models, but hardly any effect has been observed in clinical trials in PBSC transplantation. The aim of the present study is to show the fate, engraftment ability and platelet production capacity of ex vivo expanded megakaryocytes from human mobilized peripheral blood (MPB) in NOD/SCID mice. MPB CD34+ cells were cultured for 7 days in the presence of Tpo (100 ng/ml) and IL-1 (10 ng/ml). Cell numbers increased approximately 6-fold after 7 days of culture. Over 50% of the expanded cells expressed CD41, and only a limited number of cells still expressed CD34. After sublethal irradiation (3.5 Gy), NOD/SCID mice were transplanted with unmanipulated CD34+ cells (group A), expanded MKs (Group E) or a combination (group B, C, D) [Table 1]. As a control, the mice of group F did not receive any cells after irradiation. Blood was collected at day 3, 7, 10, 14, 21, 28, and 35 after transplantation. After three days, human platelets could be detected in the blood of the mice from groups C and E. After 7 days, human platelets were detected in the blood of the mice from all groups that received a transplant, except for group A. In the mice of the groups A, B, C and D platelet numbers increased till day 14 (to an average of 6.9 × 10^6/ml blood) with a small decrease toward day 35 (1.3 × 10^6/ml). The mice of group E reached a maximum of 3.4 × 10^5 human platelets per ml blood at day 10 and numbers declined from thereon to be below threshold at day 21. At day 35, mice were sacrificed and the presence of human cells in the blood, lung, spleen and BM was determined. In the BM, the chimerism (CD45+ cells) correlated with the number of unmanipulated CD34+ cells transplanted per group. This was also observed for all other lineages tested in the BM and a similar pattern was found in the spleen and blood. However, the percentages of CD45+ cells in spleen and blood were lower than in BM. No human cells were detected in the lung. In summary, IL-1- and Tpo-expanded MKs can significantly contribute to thrombocytopoiesis during the first days after transplantation. This indicates that the period of thrombocytopenia after intensive chemotherapy can be overcome by the co-transplantation of ex vivo generated human MPB-derived MKs. It may therefore be interesting to extend our culture protocol to a clinical setting. Group Cells Cells transplanted Mice (n) A MPB CD34-positive 4.5×106 NC/mouse 100% 4 B MPB CD34-positive + expanded CD34-positive 4.05×106 NC + 0.45×106 NC input culture/mouse 90% + 10% 4 C MPB CD34-positive + expanded CD34-positive 4.5×106 NC + 4.5×106 NC input culture/mouse 100% + 100% 4 D MPB CD34-positive + expanded CD34-positive 2.25×106 NC + 2.25×106 NC input culture/mouse 50% + 50% 4 E Expanded CD34-positive 4.5×106 NC input culture/mouse 100% 4 F Control - 3
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Yee, Helen S., and Nancy T. Fong. "Atorvastatin in the Treatment of Primary Hypercholesterolemia and Mixed Dyslipidemias." Annals of Pharmacotherapy 32, no. 10 (October 1998): 1030–43. http://dx.doi.org/10.1345/aph.17231.
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OBJECTIVE: To review the efficacy and safety of atorvastatin in the treatment of dyslipidemias. DATA SOURCES: A MEDLINE search (January 1960–April 1998), Current Contents search, additional references listed in articles, and unpublished data obtained from the manufacturer were used to identify data from scientific literature. Studies evaluating atorvastatin (i.e., abstracts, clinical trials, proceedings, data on file with the manufacturer) were considered for inclusion. STUDY SELECTION: English-language literature was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of atorvastatin. Additional relevant citations were used in the introductory material and discussion. DATA EXTRACTION: Open and controlled animal and human clinical studies published in the English-language literature were reviewed and evaluated. Clinical trials selected for inclusion were limited to those in human subjects and included data from animals if human data were not available. DATA SYNTHESIS: Atorvastatin is a recent hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia, mixed dyslipidemias, and homozygous familial hypercholesterolemia. In patients who have not met the low-density lipoprotein cholesterol (LDL-C) goal as recommended by the National Cholesterol Education Program Adult Treatment Panel II guidelines, atorvastatin 10–80 mg/d may be used as monotherapy or as an adjunct to other lipid-lowering agents and dietary modifications. In placebo-controlled clinical trials, atorvastatin 10–80 mg/d lowered LDL-C by 35–61% and triglyceride (TG) concentrations by 14–45%. In comparative trials, atorvastatin 10–80 mg/d showed a greater reduction of serum total cholesterol (TC), LDL-C, TG concentrations, and apolipoprotein B-100 (apo B) compared with pravastatin, simvastatin, or lovastatin. In comparison, currently available HMG-CoA reductase inhibitors (lovastatin, simvastatin, pravastatin, fluvastatin, cerivastatin) lower LDL-C concentrations by approximately 20–40% and TG concentrations by approximately 10–30%. In pooled placebo-controlled clinical trials of up to a duration of 52 weeks, atorvastatin in dosages up to 80 mg/d appeared to be well tolerated. The most common adverse effect of atorvastatin was gastrointestinal upset. The incidence of elevated serum hepatic transaminases may be greater at higher dosages of atorvastatin. The risk of myopathy and/or rhabdomyolysis is increased when an HMG-CoA reductase inhibitor is taken concomitantly with cyclosporine, gemfibrozil, niacin, erythromycin, or azole antifungals. CONCLUSIONS: Atorvastatin appears to reduce TC, LDL-C, TG concentrations, and apo B to a greater extent than do currently available HMG-CoA reductase inhibitors. Atorvastatin may be preferred in patients requiring greater than a 30% reduction in LDL-C or in patients with both elevated LDL-C and TG concentrations, which may obviate the need for combination lipid-lowering therapy. Adverse effects of atorvastatin appear to be similar to those of other HMG-CoA reductase inhibitors and should be routinely monitored. Long-term safety data (>1 y) on atorvastatin compared with other HMG-CoA reductase inhibitors are still needed. Cost-effectiveness studies comparing atorvastatin with other HMG-CoA reductase inhibitors remain a subject for further investigation. Published clinical studies evaluating the impact of atorvastatin on cardiovascular morbidity and mortality are still needed. Additionally, clinical studies evaluating the impact of lipid-lowering therapy in a larger number of women, the elderly (>70 y), and patients with diabetes for treatment of primary and secondary prevention of coronary heart disease are needed.
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Berthiaume, R., C. Lafrenière, C. Girard, C. P. Campbell, L. M. Pivotto, and I. B. Mandell. "Effects of forage silage species on yearling growth performance, carcass and meat quality, and nutrient composition in a forage based beef production system." Canadian Journal of Animal Science 95, no. 2 (June 2015): 173–87. http://dx.doi.org/10.4141/cjas-2014-107.
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Berthiaume, R., Lafrenière, C., Girard, C., Campbell, C. P., Pivotto, L. M. and Mandell, I. B. 2015. Effects of forage silage species on yearling growth performance, carcass and meat quality, and nutrient composition in a forage based beef production system. Can. J. Anim. Sci. 95: 173–187. Forty weaned, crossbred beef calves (predominantly Angus and Simmental) were forage-finished using all-silage diets (red clover–timothy versus tall fescue) to examine forage species’ effects on growth performance, carcass traits, meat quality, and nutrient composition. Weaned calves (257 d of age) were forage-finished using red clover–timothy or tall fescue silage and harvested at approximately 1 yr of age. During carcass processing, one side from each carcass was covered with a polyliner to examine if reducing rates of chilling could compensate for limited fat cover expected from low dietary energy contents fed, and limited time on feed. Longissimus thoracis, semimembranosus, and semitendinosus steaks were aged 10, 14, and 21 d to examine effects on Warner–Bratzler shear force values while fatty acid and vitamin B12 composition were determined on 10-d-aged steaks. Average daily gain, feed efficiency, hot carcass weights, and longissimus muscle area were greater (P<0.03) when cattle were fed red clover–timothy versus tall fescue silage, most likely due to the higher protein content of red clover–timothy silage. Shear force was greater (P<0.002) in steaks from all muscles evaluated from cattle fed tall fescue versus red clover–timothy silage. In comparison to 10-d-aged steaks, 14 d of ageing were needed to reduce (P<0.001) shear force for longissimus steaks, while 21 d of ageing were needed to reduce (P<0.001) shear force for semitendinosus steaks. Use of a polyliner decreased (P=0.0001) the rate of temperature decline at selected carcass sites, but did not reduce shear force values. The percent of n-3 fatty acids and polyunsaturated fatty acid/saturated fatty acid ratio were greater (P<0.04) in longissimus from cattle fed red clover–timothy versus feeding tall fescue silage. Feeding red clover–timothy silage improved growth performance, carcass, shear force, and fatty acid composition traits versus feeding tall fescue silage.
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Dousa, Khalid M., Sebastian G. Kurz, Christopher Bethel, Alita Miller, and Robert A. Bonomo. "1642. A Novel β-lactamase Inhibitor (Durlobactam, DUR) and β-Lactams Enhance Susceptibility Against Multidrug-Resistant (MDR) Mycobacterium abscessus (Mab)." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S810—S811. http://dx.doi.org/10.1093/ofid/ofaa439.1822.
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Abstract Background Mab is a MDR nontuberculous mycobacterium that causes lung infections in patients with structural lung disease. Mab harbors a chromosomally encoded class A β-lactamase, BlaMab, able to hydrolyze penicillins, cephalosporins and carbapenems. L,D- and D,D-transpeptidases (L,D TP and D,D TP) shape peptidoglycan (PG) synthesis and contribute to cell wall structure. Select combinations of β-lactams that inhibit L,D TP and D,D TPs and BlaMab are desirable as they can potentially improve treatment outcomes. DUR is a novel DBO β-lactamase inhibitor (BLI) with broad-spectrum activity against Ambler class A, C, and D β-lactamases (Fig.). Here, we investigated the mechanism of action and efficacy of DUR alone and combined with select β-lactams in restoring susceptibility of Mab to β-lactam antibiotics Methods Minimum inhibitory concentrations (MICs) of cefuroxime (CEF), imipenem (IMI) and amoxicillin (Amox) with or without DUR were determined using microdilution. Approximately 5 x 105 colony-forming units per milliliter were inoculated into Middlebrook 7H9 Broth supplemented with 10% (vol/vol) oleic albumin dextrose catalase and 0.05% (vol/vol) Tween 80. When more than 2 drugs were combined, Amox was added at fixed concentration of 8 µg/ml to serial dilutions of CEF-DUR or IMI-DUR. Mab isolates were incubated with test agents at 30°C for 48 h, and MIC was defined as lowest antibiotic concentration that prevented visible bacterial growth. Reaction intermediates in the inactivation pathway of BlaMab, L,D-TP and D,D-TPs with DUR Results One hundred clinically derived and previously characterized isolates were tested in these assays. MIC50 and MIC90 of DUR alone was 4 and 8 µg/ml, demonstrating intrinsic activity. Combinations of DUR-IMI or DUR-CEF plus 8 µg/mL Amox lowered MIC50 to < 0.06 µg/ml in all 100 clinical isolates (Table). Mass spectrometry analyses of BlaMab, L,D-TP and D,D-TPs Mab (2,4) inactivated by DUR showed formation of stable adducts of DUR to BlaMab, L,D-TP and D,D-TPs (Fig.) Chemical composition of durlobactam (DUR) and mass spectrometry of BlaMab, L,D TP and D,D TPs incubated with DUR MIC50 and MIC90 of 100 Mab clinical strains against DUR alone and in combination with Amox, CEF and IMI Conclusion We demonstrate that a novel DBO BLI, DUR, is an active agent with potent intrinsic activity against BlaMab and Mab L,D-TPs and D,D-TPs. We hypothesize that DUR improves b-lactam activity by protecting against the hydrolytic activity of BlaMab and by targeting multiple steps in PG synthesis Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)
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Heymsfield, Andrew J., Aaron Bansemer, and Cynthia H. Twohy. "Refinements to Ice Particle Mass Dimensional and Terminal Velocity Relationships for Ice Clouds. Part I: Temperature Dependence." Journal of the Atmospheric Sciences 64, no. 4 (April 1, 2007): 1047–67. http://dx.doi.org/10.1175/jas3890.1.
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Abstract This two-part study attempts to find appropriate mass dimension and terminal velocity relationships that, when considered together with particle size distributions (PSD), agree with coincident measurements of ice water content (IWC), and with variables related to higher moments such as the mean mass-weighted fall speed. Reliable relationships are required for improving microphysical parameterizations for weather forecast models and developing methods for evaluating them, subjects addressed in detail in Part II of this study. Here, a range of values from 1.5 to 2.3 is assumed for the exponent b in the mass dimension relationship, m = aDb, where D is the maximum particle dimension, to bound its likely value for sizes above about 100 μm. Measured IWC and size spectra are used to find appropriate values for the coefficient a. It is demonstrated that all values of the exponent b, with appropriate a coefficients, can fit the IWC measurements. Coincident information on particle cross-sectional areas with the m(D) relationships is used to develop general fall velocity relationships of the form Vt = ADB. These assessments use five midlatitude, synoptically generated ice layers, and 10 low-latitude, convectively generated ice cloud layers, spanning the temperature range from −60° to 0°C. The coefficients a and A and exponent B are represented in terms of the exponent b and are shown to be temperature-dependent for the synoptic clouds and relatively independent of it in the convective clouds, a result of particle mixing through the cloud column. Consistency is found with earlier results and with analytic considerations. It is found that the fall velocity is inversely proportional to the air density to approximately the exponent 0.54, close to values assumed in earlier studies.
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Hovell, F. D. DeB, E. R. Ørskov, D. J. Kyle, and N. A. MacLeod. "Undernutrition in sheep. Nitrogen repletion by N-depleted sheep." British Journal of Nutrition 57, no. 1 (January 1987): 77–88. http://dx.doi.org/10.1079/bjn19870011.
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1. Wether lambs of 29–44 kg live-weight, totally nourished by the infusion of volatile fatty acids (VFA) into the rumen and casein into the abomasum, were given five treatments in consecutive periods. The treatments were (daily amounts per kg live weight (W)0.75): (a) high-protein for 7 d (2500 mg nitrogen, 650 kJ VFA); (b) low-protein for 7–15 d (525 mg N, 650 kJ VFA); (c) N-free for 7 d (no N, 450 kJ VFA); (d) very-low-protein for 24–28 d (300 mg N, 400 kJ VFA); (e) high-protein for 40 d (2500 mg N, 650 kJ VFA). Nine lambs were subjected to treatments (a), (b) and (c) (Expt 1) and four of the lambs additionally received treatments (d) and (e) (Expt 2).2. In Expt 1 all nine lambs had a positive N retention on treatment (a) but abrupt change to treatment (b) resulted in substantial negative N balances initially, and a period of approximately 5 d adaptation was required before N equilibrium was re-established. Animals again exhibited negative N balances when the N-free infusion (treatment c) was introduced and during that period there was no evidence of adaptation. Basal urinary N excretion was estimated to be 356 (SE 12) mg N/kg W0.75.3. In Expt 2 all four lambs were depleted of N when receiving the very-low-protein treatment (d). The progressively decreasing N losses recorded during days 1 to 12 of the treatment period were slightly greater than those recorded during days 13 to 28 but the difference between the means was not significant (P > 0.05). There was no evidence of an adaptation in N retention between days 13 and 28 of the treatment. As assessed during days 13 to 28 of the treatment the efficiency of utilization of infused casein N was 1.0; this compared with a value of 0.66 recorded during treatment (b) in Expt 1. Live weight loss during the period of N depletion was 101 (SE 27) g/d.4. When lambs were given treatment (e) during the last period of Expt 2, N repletion was rapid and complete within a few days. Ten days after the introduction of the treatment the rate of N retention was estimated to be 1019 (SE 38) mg/kg W0.75 per d and this value declined at a rate of 9.5 (SE 1.9) mg N/kg W0.76 per d for the following 30 d. In comparison, N retention determined for the high-protein treatment in Expt 1 was 724 (SE 66) mg N/kg W0.75 per d. Live-weight gains during N repletion were 292 (SE 26) g/d.5. It is concluded that N-depleted lambs can replete rapidly and that enhanced N accretion (compensatory growth) may persist for 4–5 weeks. If the improved efficiency of utilization of infused N observed during N depletion reflects a changed basal N requirement, the validity of simple factorial systems for estimating N requirement is called into question.
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Echevarria, M., G. Frindt, G. M. Preston, S. Milovanovic, P. Agre, J. Fischbarg, and E. E. Windhager. "Expression of multiple water channel activities in Xenopus oocytes injected with mRNA from rat kidney." Journal of General Physiology 101, no. 6 (June 1, 1993): 827–41. http://dx.doi.org/10.1085/jgp.101.6.827.
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To test the hypothesis that renal tissue contains multiple distinct water channels, mRNA prepared from either cortex, medulla, or papilla of rat kidney was injected into Xenopus oocytes. The osmotic water permeability (Pf) of oocytes injected with either 50 nl of water or 50 nl of renal mRNA (1 microgram/microliter) was measured 4 d after the injection. Pf was calculated from the rate of volume increase on exposure to hyposmotic medium. Injection of each renal mRNA preparation increased the oocyte Pf. This expressed water permeability was inhibited by p-chloromercuriphenylsulfonate and had a low energy of activation, consistent with the expression of water channels. The coinjection of an antisense oligonucleotide for CHIP28 protein, at an assumed > 100-fold molar excess, with either cortex, medulla, or papilla mRNA reduced the expression of the water permeability by approximately 70, 100, and 30%, respectively. Exposure of the oocyte to cAMP for 1 h resulted in a further increase in Pf only in oocytes injected with medulla mRNA. This cAMP activation was not altered by the CHIP28 antisense oligonucleotide. These results suggest that multiple distinct water channels were expressed in oocytes injected with mRNA obtained from sections of rat kidney: (a) CHIP28 water channels in cortex and medulla, (b) cAMP-activated water channels in medulla, and (c) cAMP-insensitive water channels in papilla.
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Chen, Jichun, Karen Lipovsky, Felicia M. Ellison, Rodrigo T. Calado, and Neal S. Young. "Bystander destruction of hematopoietic progenitor and stem cells in a mouse model of infusion-induced bone marrow failure." Blood 104, no. 6 (September 15, 2004): 1671–78. http://dx.doi.org/10.1182/blood-2004-03-1115.
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Abstract Infusion of parental lymph node (LN) cells into sublethally irradiated hybrid F1 recipients created a murine model for bone marrow (BM) failure. Affected animals developed fatal pancytopenia within 2 to 3 weeks, accompanied by BM oligoclonal T-cell infiltration and severe marrow hypoplasia indicated by approximately 10-fold declines in total BM cellularity, 15-fold declines in BM Lin-Sca1+c-Kit+ cells, 100-fold declines in spleen colony-forming units, and 100-fold declines in hematopoietic progenitor and stem cells as estimated by irradiation protection in vivo. LN cells of both H2b/b and H2d/d haplotypes were effectors. Serum interferon-γ (IFN-γ) concentration increased 2- to 3-fold. Marrow cells were severely apoptotic, with high proportions of Fas+ and annexin V+ cells. Cotransplantation of 5 × 105 BM cells from clinically affected donors and 106 BM cells from H2 identical healthy mice could not rescue lethally irradiated recipients. Recipients had significantly lower cellularity in peripheral blood and BM, and cell mixtures failed to produce a stromal feeder layer to support marrow cell growth in vitro. Pathogenic T cells from donors after BM failure appeared capable of destroying hematopoietic progenitor, stem, and stromal cells from fully compatible healthy donors as “innocent bystanders.” This effect can be partially abrogated by anti-IFN-γ antibody. (Blood. 2004;104:1671-1678)
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Ghanem, Hady, Hagop M. Kantarjian, Elias J. Jabbour, Jorge E. Cortes, and Alfonso Quintás-Cardama. "Rare Blast Phase (BP) Phenotypes of Chronic Myeloid Leukemia (CML)." Blood 120, no. 21 (November 16, 2012): 4434. http://dx.doi.org/10.1182/blood.v120.21.4434.4434.
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Abstract Abstract 4434 Approximately 65% of patients (pts) with CML BP exhibit a myeloid phenotype, 30% a lymphoid, and 5% of cases exhibit other phenotypes. The vast majority of lymphoid BP cases are of B-cell origin. Other phenotypes of CML BP are very infrequent and poorly characterized. To evaluate the incidence and outcome of unusual BP phenotypes, we reviewed 1143 pts with CML BP diagnosed and treated at M.D. Anderson Cancer Center between November 1973 and February 2012. Thirteen (1%) pts had non-B-cell/non-myeloid CML BP: 8 pts with T-cell differentiation (T-BP) (including 4 pts with biphenotypic T-cell/myeloid), 2 pts with basophilic (B-BP), and 3 pts with megakaryoblastic phenotype (M-BP) (Table 1). Five pts presented initially in BP, whereas 7 other cases evolved to BP from chronic phase (CP) and 1 pt from accelerated phase (AP). The median time from diagnosis to transformation was 15.2 months (mos) (range, 0–103). The median age was 50 years (range, 21–74), median WBC count at presentation 40.2×109/L (range, 2.6–236), hemoglobin 10.7 g/dL (range, 7.1–13.6), platelet count 171×109/L (range, 17–383), peripheral blood blasts 9% (range, 0–100), and bone marrow blasts 20% (range, 0–88). Nine (69%) pts developed extramedullary disease: 4 with lymphadenopathy (LAN), 1 with LAN and mediastinal mass, 1 with pericardial tamponade and mediastinal mass, 1 with central nervous system disease, 1 with facial muscle involvement and 1 with splenomegaly, LAN, and granulocytic sarcoma of the breast. Four pts expressed a b2a2 BCR-ABL1 transcript (p210), whereas 3 pts expressed b3a2 (p210), 3 expressed e1a2 (p190), 2 expressed b2a2+b3a2 (p210), and 1 expressed an e13b2+e14a2 (p210) transcript at transformation that switched to e1a2 (p190) during dasatinib (DAS) therapy. Median number of treatments received prior to BP was 2 (range, 1 to 12): 6 pts received interferon (IFN), 5 imatinib (IMA), 3 allogenetic stem cell transplant (ASCT), 3 Ara-C, 1 DAS and 1 hyper-CVAD (HCVAD). Initial therapy consisted of HCVAD (n=4, combined with IMA 600 mg/d in 1 pt and with DAS 70 mg/d in 1 pt), VAD (n=1), nilotinib 400 mg twice daily (n=1), DAS 50 mg twice daily (n=1), troxicitabine (n=1), gemtuzumab (n=1), idarubicin (IDA) and ara-C (n=3; 1 with IMA 600 mg/d and 1 with IMA 400 mg/d), and ara-C (n=1). Four pts responded: 3 with chemotherapy and IMA, achieving a complete cytogenetic response (CCyR) that lasted 22, 26 and 79 mos, respectively; 1 pt achieved a major molecular response (MMR) after receiving gemtuzumab followed by haploidenticial SCT, lasting for 24 mos. Median duration of response was 25 mos (range, 22–79). Subsequent therapy consisted of a tyrosine kinase inhibitor (TKI) in 6 out of 13 pts. Two pts treated with DAS at 140 mg/d and 70 mg twice daily achieved a CCyR and 1 pt achieved MMR on DAS 140 mg/d. Of the 7 pts treated with DAS, 2 had BCR-ABL1 mutations: 1 carried K271R, Y232C/K271R, and M343Y/K271R prior to DAS, then acquired V299L and F317I on DAS, while the other pt carried Y264S prior to DAS, then developed V299L on DAS. After a median follow up of 4.2 years (range, 0.2 to 14.4), 4/13 (30%) pts are alive: 1 in MMR on IMA 400 mg/d, 1 in complete molecular response (CMR) on DAS 100 mg/d, 1 not in remission (non-compliance to DAS 140 mg/d), and 1 currently receiving HCVAD and DAS. By phenotype, 5/8 pts with T-BP responded to TKIs: 1 CMR, 1 CCyR, 1 MMR, 1 partial cytogenetic response (PCyR) and 1 hematologic response (HR); 2/3 pts with M-BP responded: 1 CCyR and 1 CHR. None of the B-BP pts responded. In conclusion, non-B-cell/non-myeloid CML BP occurs in 1% of pts with CML, frequently infiltrates extramedullary sites, and exhibits high resistance to conventional chemotherapy. Long-term responses can be achieved with ABL1 TKIs (preferably in combination with chemotherapy), which can be used as a bridge to allogeneic SCT. Table 1. Summary of pts clinical and molecular characteristics, response to treatments and outcomes by BP Phenotype Disclosures: No relevant conflicts of interest to declare.
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Sztul, E. S., K. E. Howell, and G. E. Palade. "Biogenesis of the polymeric IgA receptor in rat hepatocytes. II. Localization of its intracellular forms by cell fractionation studies." Journal of Cell Biology 100, no. 4 (April 1, 1985): 1255–61. http://dx.doi.org/10.1083/jcb.100.4.1255.
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In the companion paper (Sztul, E. S., K. E. Howell, and G. E. Palade, J. Cell Biol., 100:1248-1254), we have shown that pulse labeling of hepatic proteins with [35S]cysteine can be obtained in vivo in intact rats. Soluble label clears the plasma in approximately 5 min, and incorporated label reaches peak values in the liver approximately 20 min after injection. In the present study, we show that the 105,000-mol-wt protein (105K), kinetically the earliest intracellular form of secretory component (SC), is the predominant form found, between 5 and 20 min postinjection, in homogeneous rough microsomal fractions. The second kinetically defined form, i.e., 116K, is the predominant species present in relatively homogeneous, light Golgi fractions in which it appears at approximately 15 min, and peaks at approximately 25 min, postinjection. The third kinetically defined form, 120K, is found 30 min after injection as the major SC species (albeit still accompanied by its immediate precursor, 116K), in a sinusoidal plasmalemmal fraction isolated by immunoadsorption to anti-SC-coated Sepharose beads. These findings lead to the following conclusions: (a) SC is synthesized on polysomes attached to the rough endoplasmic reticulum (ER) membrane; (b) it is partially translocated across the ER membrane and core glycosylated co-translationally to give a 105K peptide; (c) 105K moves from the ER to the Golgi complex where it is terminally glycosylated to give the 116K form; (d) the latter moves to the sinusoidal plasmalemma where it appears together with the final mature form, 120K. Kinetic evidence indicates that the vesicular carriers involved in the transport of SC from the Golgi complex to the sinusoidal plasmalemma, and from the latter to the biliary front of the hepatocytes, are present in a Golgi heavy fraction and a crude carrier vesicle fraction from which they remain to be isolated, purified, and characterized.
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Williams, P. E. V., L. Pagliani, G. M. Innes, K. Pennie, C. I. Harris, and P. Garthwaite. "Effects of a β-agonist (clenbuterol) on growth, carcass composition, protein and energy metabolism of veal calves." British Journal of Nutrition 57, no. 3 (May 1987): 417–28. http://dx.doi.org/10.1079/bjn19870049.
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1. Twenty-two British Friesian bull calves were used in a comparative slaughter experiment to determine the effects of a β-agonist (clenbuterol) on body composition and energy retention. Four calves were slaughtered at 18 d of age and constituted the initial slaughter group. Of the remaining calves, eight (group A, controls) were given milk replacer only, and ten calves (groups B and C, five calves per group) were given milk replacer plus clenbuterol(O.1 and 1.0 mg clenbuterol/kg milk replacer equivalent to approximately 2 and 20 μg/kg body-weight respectively over the 105±3 d of the experimental period). Calves were slaughtered over the weight range 146–177 kg.2. Clenbuterol had no significant effect on dry matter (DM) intake, daily live-weight gain or feed conversion ratio. DM digestibility of the milk replacer was not affected by treatment. Nitrogen balance was measured on three separate occasions starting when the calves weighed approximately 60, 110 and 130 kg. N retention was increased over the experimental period in clenbuterol-treated calves, although the effect only achieved significance in calves weighing approximately 110 kg live weight (P < 0.05).3. Clenbuterol (20 μg/kg body-weight) increased estimated mean daily N retention in the carcass of the calves from 22 to 25 g whilst N retention in the non-carcass components decreased from 10 to 8 g/d. Effects of clenbuterol on N retention occurred mainly in skeletal muscle. Fat in both carcass and non-carcass components was reduced by treatment with clenbuterol. The total energy content of live-weight gain was reduced from 1077 to 897 MJ in clenbuterol-treated calves and mean daily heat production was estimated to increase from 23.1 in controls to 25.9 MJ/d in calves in group C.4. In calves of mean live weight during balance of 120 and 136 kg, clenbuterol significantly increased daily urinary creatinine excretion and in 120 kg calves NT-methylhistidine was significantly decreased (P < 0.05). Based on estimates of muscle mass from urinary creatinine and protein degradation fromN7-methylhistidine NT-methylhistidine excretion, the fractional breakdown rate of muscle protein in clenbuterol-treated calves was only 0.66 of that in the controls when the calves weighed 120 kg.
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Ling, B. N., C. L. Webster, and D. C. Eaton. "Eicosanoids modulate apical Ca(2+)-dependent K+ channels in cultured rabbit principal cells." American Journal of Physiology-Renal Physiology 263, no. 1 (July 1, 1992): F116—F126. http://dx.doi.org/10.1152/ajprenal.1992.263.1.f116.
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Patch clamp technology was utilized to study the effects of apical phospholipase A2 (PLA2) metabolites on “maxi K” channels in the principal cell apical membrane of rabbit cortical collecting tubule (CCT) primary cultures (B. N. Ling, C. F. Hinton, and D. C. Eaton. Kidney Int. 40: 441–452, 1991). At resting membrane potential, this channel is quiescent in the cell-attached configuration. Apical application of the PLA2 agonist melittin (1 microgram/ml) for 10 min increased single-channel open probability (Po) from 0.0004 +/- 0.0010 to 0.11 +/- 0.05. Similarly, apical exposure to 50 microM arachidonic acid (AA) or 0.5 microM prostaglandin (PG) E2, but not 0.5 microM PGF2 alpha, also increased channel activity. Conversely, 10 microM of the PLA2 antagonist quinacrine applied apically decreased Po. Removal of apical bath Ca2+ did not prevent melittin-, AA-, or PGE2-induced channel activation. We then examined the role of maxi K channels and eicosanoids in principal cell volume regulation. Within seconds of reducing basolateral bath tonicity (285 to 214 mosmol/kgH2O), NPo (i.e., no. of channels x Po) initially increased approximately 200%, followed by a delayed but prolonged activation phase that was attenuated by removal of apical bath Ca2+. Pretreatment with 10 microM quinacrine, 100 microM indomethacin (cyclooxygenase inhibitor), or 0.25 microM thapsigargin (to deplete intracellular Ca2+ stores) abolished the initial phase of swelling-induced channel activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Goyal, Rakesh, Nicole Nasrah, Dan Johnson, and William Ho. "548 Phase 2 study of FLX475 in combination with ipilimumab in advanced melanoma." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A578. http://dx.doi.org/10.1136/jitc-2021-sitc2021.548.
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BackgroundRegulatory T cells (Treg) can dampen antitumor immune responses in the tumor microenvironment (TME) and have been shown to correlate with poor clinical outcome. Translational studies have demonstrated an accumulation of Treg in tumors after treatment with immunotherapies including CAR-T cells and anti-CTLA-4, which could potentially reflect a mechanism of adaptive immune resistance.1–2 CCR4, the receptor for the chemokines CCL17 and CCL22, is the predominant chemokine receptor on human Treg and is responsible for the migration and accumulation of Treg in the TME. Preclinical studies with orally available CCR4 antagonists have demonstrated potent inhibition of Treg migration into tumors, an increase in the intratumoral Teff/Treg ratio, and antitumor efficacy as a single agent and in combination with checkpoint inhibitors, including anti-CTLA-4.3 In a first-in-human trial conducted in healthy volunteers, the oral CCR4 antagonist FLX475 was demonstrated to be well tolerated with outstanding pharmacokinetic and pharmacodynamic properties.4 An ongoing Phase 1/2 clinical trial of FLX475 is examining the safety and preliminary antitumor activity of FLX475 as monotherapy and in combination with pembrolizumab in subjects with several types of advanced cancer.5 Given the preclinical data demonstrating a significant enhancement of the antitumor activity of anti-CTLA-4 when combined with FLX475, a Phase 2 study investigating the combination of FLX475 and ipilimumab is now being conducted in subjects with advanced melanoma.MethodsThis clinical trial is a Phase 2, multicenter, open-label, single-arm study to determine the antitumor activity of FLX475 in combination with ipilimumab in subjects with advanced melanoma previously treated with an anti-PD-1 or anti-PD-L1 agent. The primary objectives of the study are to evaluate objective response rate, and the safety and tolerability of this combination. The study will first examine the safety of the combination of the 100 mg PO QD recommended Phase 2 dose of FLX475 and the approved 3 mg/kg IV Q3W dose of ipilimumab as part of a safety run-in phase, prior to examining the degree of antitumor activity in approximately 20 subjects. Evidence of an overall response rate (ORR) notably greater than the expected ORR of ipilimumab monotherapy alone in such subjects, which has been shown to be approximately 14%,6 would provide preliminary clinical evidence in support of the clinical hypothesis that CCR4 blockade by FLX475 can significantly enhance the antitumor activity of an anti-CTLA-4 checkpoint inhibitor.Trial RegistrationClinicalTrials.gov Identifier: NCT04894994ReferencesO’Rourke D, Nasrallah M, Desai A, Melenhorst J, Mansfield K, Morrissette J, Martinez-Lage M, Brem S, Maloney E, Shen A, Isaacs R, Mohan S, Plesa G, Lacey S, Navenot J, Zheng Z, Levine B, Okada H, June C, Brogdon J, Maus M. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med 2017;9:eaaa0984. doi: 10.1126/scitranslmed.aaa0984.Sharma A, Subudhi S, Blando J, Vence L, Wargo J, Allison JP, Ribas A, Sharma P. Anti-CTLA-4 immunotherapy does not deplete FOXP3+ regulatory T cells (Tregs) in human cancers-Response. Clin Cancer Res 2019;25:1233–1238.Marshall L, Marubayashi S, Jorapur A, Jacobson S, Zibinsky M, Robles O, Hu D, Jackson J, Pookot D, Sanchez J, Brovarney M, Wadsworth A, Chian D, Wustrow D, Kassner P, Cutler G, Wong B, Brockstedt D, Talay O. Tumors establish resistance to immunotherapy by regulating Treg recruitment via CCR4. J Immunother Cancer 2020;8:e000764.van Marle S, van Hoogdalem E, Johnson D, Okal A, Kassner P, Wustrow D, Ho W, Smith S. Pharmacokinetics, pharmacodynamics, and safety of FLX475, an orally-available, potent, and selective small-molecule antagonist of CCR4, in healthy volunteers. J Immunother Cancer 2018; 6(Suppl 1):P484(SITC 2018).Powderly J, Chmielowski B, Brahmer J, Piha-Paul S, Bowyer S, LoRusso P, Catenacci D, Wu C, Barve M, Chisamore M, Nasrah N, Johnson D, Ho W. Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer. Journal of Clinical Oncology 2020;38(15_suppl): TPS3163 (ASCO 2020).Long G, Mortier L, Schachter J, Middleton M, Neyns B, Sznol M, Zhou H, Ebbinghaus S, Ibrahim N, Arance A, Ribas A, Blank C and Robert C. Society for Melanoma Research 2016 Congress. Pigment Cell & Melanoma Research 2017;30:76–156.Ethics ApprovalThis study has been approved by the Institutional Review Board at each investigational site.
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Zhao, Tong, Ping Zhao, Joe W. West, John K. Bernard, Heath G. Cross, and Michael P. Doyle. "Inactivation of Enterohemorrhagic Escherichia coli in Rumen Content- or Feces-Contaminated Drinking Water for Cattle." Applied and Environmental Microbiology 72, no. 5 (May 2006): 3268–73. http://dx.doi.org/10.1128/aem.72.5.3268-3273.2006.
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ABSTRACT Cattle drinking water is a source of on-farm Escherichia coli O157:H7 transmission. The antimicrobial activities of disinfectants to control E. coli O157:H7 in on-farm drinking water are frequently neutralized by the presence of rumen content and manure that generally contaminate the drinking water. Different chemical treatments, including lactic acid, acidic calcium sulfate, chlorine, chlorine dioxide, hydrogen peroxide, caprylic acid, ozone, butyric acid, sodium benzoate, and competing E. coli, were tested individually or in combination for inactivation of E. coli O157:H7 in the presence of rumen content. Chlorine (5 ppm), ozone (22 to 24 ppm at 5�C), and competing E. coli treatment of water had minimal effects (<1 log CFU/ml reduction) on killing E. coli O157:H7 in the presence of rumen content at water-to-rumen content ratios of 50:1 (vol/wt) and lower. Four chemical-treatment combinations, including (i) 0.1% lactic acid, 0.9% acidic calcium sulfate, and 0.05% caprylic acid (treatment A); (ii) 0.1% lactic acid, 0.9% acidic calcium sulfate, and 0.1% sodium benzoate (treatment B); (iii) 0.1% lactic acid, 0.9% acidic calcium sulfate, and 0.5% butyric acid (treatment C); and (iv) 0.1% lactic acid, 0.9% acidic calcium sulfate, and 100 ppm chlorine dioxide (treatment D); were highly effective (>3 log CFU/ml reduction) at 21�C in killing E. coli O157:H7, O26:H11, and O111:NM in water heavily contaminated with rumen content (10:1 water/rumen content ratio [vol/wt]) or feces (20:1 water/feces ratio [vol/wt]). Among them, treatments A, B, and C killed >5 log CFU E. coli O157:H7, O26:H11, and O111:NM/ml within 30 min in water containing rumen content or feces, whereas treatment D inactivated approximately 3 to 4 log CFU/ml under the same conditions. Cattle given water containing treatment A or C or untreated water (control) ad libitum for two 7-day periods drank 15.2, 13.8, and 30.3 liters/day, respectively, and cattle given water containing 0.1% lactic acid plus 0.9% acidic calcium sulfate (pH 2.1) drank 18.6 liters/day. The amounts of water consumed for all water treatments were significantly different from that for the control, but there were no significant differences among the water treatments. Such treatments may best be applied periodically to drinking water troughs and then flushed, rather than being added continuously, to avoid reduced water consumption by cattle.
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LOPES, ROGÉRIO BIAGGIONI, MARCO ANTONIO TAMAI, SÉRGIO BATISTA ALVES, SINVAL SILVEIRA NETO, and SÉRGIO DE SALVO. "Occurence of thrips on Niagara table grape and its control with the insecticides thiacloprid and methiocarb associated with Metarhizium anisopliae." Revista Brasileira de Fruticultura 24, no. 1 (April 2002): 269–72. http://dx.doi.org/10.1590/s0100-29452002000100060.
Full textAbstract:
Thrips are reported as important pests on table grapes in United States and several countries of Europe. Damage caused by thrips, particulary Frankliniella occidentalis, was observed on niagara table grape crop in Limeira-SP, Brazil. During the blooming period, high thrips densities were observed feeding on pollen and small berries. The symptoms left were more visible after the development of the berries and were characterized by dark scars and suberized surface on berries, sometimes causing the berry to crack, and the seed to prolapse. The effect of insecticides thiacloprid or methiocarb, associated or not with the entomopathogenic fungus Metarhizium anisopliae were evaluated during the blooming period. For evaluation of thrips damage on fruits, the treatments were applied three additional times, 7, 14 and 21 days after the first application. The treatments were: a) M. anisopliae (strain 1037) 1x10(7) conidia/mL; b) thiacloprid 20mL/100L; c-d) methiocarb 100 and 150mL/100L; e) methiocarb 100mL/100L + M. anisopliae 1x10(7) conidia/mL. Only methiocarb, associated or not with the fungus, was effective in reducing thrips infestation, and no phytotoxic damage was observed. The efficiency of methiocarb 150mL/100L and the insecticide associated with the fungus for the control of the thrips population was 84.2 and 95.5%, respectively. In both cases, there was a reduction of approximately 70% in the number of berries with scars symptoms. For control of thrips on table grapes, chemical insecticides associated or not with M. anisopliae should be applied during the blooming period of the crop.