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Byun, Hayoung, Min-Kyun Oh, and Chang Han Lee. "Effects of Scrambler Therapy in Patients with Failed Back Surgery Syndromes and Factors Associated with Depression Affecting Pain before and after the Therapy." Pain Research and Management 2020 (July 6, 2020): 1–6. http://dx.doi.org/10.1155/2020/9342865.
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Objectives. To report the effects of scrambler therapy in patients diagnosed with failed back surgery syndromes and to analyze the factors affecting pain before and after the therapy. Methods. This study included 26 patients (12 males and 14 females). The Oswestry Disability Index (ODI) and Brief Pain Inventory (BPI) before and after scrambler therapy, Beck Depression Inventory (BDI) score before therapy, and residual pain after therapy were assessed. The changes in the ODI, BPI, and residual pain before and after the therapy were analyzed using the Wilcoxon signed rank test. Spearman correlation analysis and Fisher’s exact test were used to confirm the correlation between BDI and other factors. Multiple regression analysis was used to identify independent factors predicting residual pain, posttherapy ODI, and posttherapy BPI. Results. The ODI changed from 25.69 ± 7.98 to 21.80 ± 9.41 (p<0.05), and the BPI changed from 68.96 ± 18.00 to 61.62 ± 20.27 after scrambler therapy (p<0.05). In addition, residual pain changed from 100 to 76.15 (p<0.05). The BDI was negatively correlated with the duration of scrambler therapy and positively correlated with the initial OPD and BPI. In multiple regression analysis, residual pain was significantly correlated with the BDI (p<0.05). Conclusion. Scrambler therapy can be used to change the total scores of the ODI and BPI after 5 sessions of treatment. Also, residual pain was significantly related to the BDI. Clinical significance of depression severity on pain should be further investigated via prospective studies.
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Batinic, B., J. Nesvanulica, and I. Stankovic. "The presence of chronic pain in patients with major depressive disorder and its inter-correlation." European Psychiatry 33, S1 (March 2016): S406—S407. http://dx.doi.org/10.1016/j.eurpsy.2016.01.1468.
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IntroductionChronic pain is a common experienced symptom among patients diagnosed with major depressive disorder (MDD). The intensity of depression and chronic pain inter-correlated, having negative impact on the daily functioning of the patients.ObjectivesOur aim was to explore the presence of chronic pain in patients diagnosed with MDD (single episode or recurrent), correlation between intensity of depression and chronic pain, its interference on daily functioning, as well as sex differences regarding the explored variables.MethodsThe study sample consisted of 51 (62.2%) female and 31 (37.8%) male patients diagnosed with MDD (n = 82), aged between 18 and 65 years old (mean age of 46.21). Assessment instruments included The Beck Depression Inventory-II (BDI-II), The Brief Pain Inventory-Short Form (BPI) (consisting of BPI-I factor of pain intensity, and BPI-II-factor of pain interference with daily functioning), and semistructured questionnaire for sociodemographic characteristics.ResultsThe presence of chronic pain was found in the 51 (62, 2%) of patients with MDD. The mean score on the BDI-II for the whole sample was 22.5 (SD 12.8). There was a positive correlation between intensity of depression (BDI-II) and intensity of chronic pain (BPI-1), and its interference on the level of daily functioning (BPI-2) (P < 0.01). Women diagnosed with MDD experienced chronic pain of higher intensity and with greater interference on daily functioning.ConclusionOur research data show a high frequency of chronic pain among patients diagnosed with MDD and its positive inter-correlation which results in negative impact on daily functioning, especially in females.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Mapesi, Herry, James Okuma, Fabian Franzeck, Herieth Ismael Wilson, Elizabeth Senkoro, Theonestina Byakuzana, Robert Ndege, et al. "Prevalence, incidence and predictors of renal impairment in persons with HIV receiving protease-inhibitors in rural Tanzania." PLOS ONE 16, no. 12 (December 15, 2021): e0261367. http://dx.doi.org/10.1371/journal.pone.0261367.
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Objective Ritonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa. Methods Using data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate <60 mL/min/1.73m2) at the time of switch from first-line antiretroviral treatment (ART) to bPI-regimen and the incidence of renal impairment on bPI. We assessed risk factors for renal impairment using logistic and Cox regression models. Results Renal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6–5.1) years (incidence 22/1,000 person-years (95%CI 16.1–29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15–2.11), body mass index (BMI) <18.5 kg/m2 (aOR 2.80 versus ≥18kg/m2; 95%CI 1.28–6.14) and arterial hypertension (aOR 2.33; 95%CI 1.03–5.28). The risk of renal impairment was lower with increased duration of ART use (aOR 0.78 per one-year increase; 95%CI 0.67–0.91). The renal impairment incidence under bPI was associated with older age (adjusted hazard ratio 2.01 per 10 years; 95%CI 1.46–2.78). Conclusions In PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART.
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Dentener, M. A., E. J. Von Asmuth, G. J. Francot, M. N. Marra, and W. A. Buurman. "Antagonistic effects of lipopolysaccharide binding protein and bactericidal/permeability-increasing protein on lipopolysaccharide-induced cytokine release by mononuclear phagocytes. Competition for binding to lipopolysaccharide." Journal of Immunology 151, no. 8 (October 15, 1993): 4258–65. http://dx.doi.org/10.4049/jimmunol.151.8.4258.
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Abstract Serum proteins play an important role in LPS-induced cell activation. The LPS binding protein (LBP) enhances cellular responses to LPS, whereas the polymorphonuclear leukocyte product bactericidal/permeability-increasing protein (BPI) inhibits LPS-induced cell activation. In this study the influences of LBP and BPI, two proteins with opposite effects, but with considerable sequence homology, on LPS-induced mononuclear phagocytic cell cytokine release was studied. LBP was shown to enhance LPS-induced TNF-alpha, IL-6, and IL-8 release by mononuclear phagocytic cells, whereas BPI inhibited the release of these cytokines. Furthermore, the effects of LBP and BPI on LPS-induced cytokine release by mononuclear phagocytic cells were shown to be counteractive. BPI interfered with the enhancing effect of LBP on the LPS-induced cytokine release. At high LBP to BPI ratios, BPI could no longer inhibit LBP-induced enhancement. In accordance, increasing concentrations of BPI abrogated the LBP effect. Next, it was shown that LBP and BPI compete for binding to LPS by using an assay system that detects binding of free BPI to an anti-BPI mAb. LPS prevented binding of BPI to anti-BPI mAb, whereas preincubation of LPS with LBP prevented the LPS-induced inhibition. Also, it was observed that both BPI and LBP inhibited LPS activity in the chromogenic LAL assay. We conclude from this study that LBP and BPI have counteractive effects on LPS-induced mononuclear phagocytic cell cytokine release by competing for binding to LPS.
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Briot, Karine, Anthony A. Portale, Maria Luisa Brandi, Thomas O. Carpenter, Hae Ii Cheong, Martine Cohen-Solal, Rachel K. Crowley, et al. "Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension." RMD Open 7, no. 3 (September 2021): e001714. http://dx.doi.org/10.1136/rmdopen-2021-001714.
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ObjectivesTo report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks.MethodsAdults diagnosed with XLH were randomised 1:1 in a double-blinded trial to receive subcutaneous burosumab 1 mg/kg or placebo every 4 weeks for 24 weeks (NCT02526160). Thereafter, all subjects received burosumab every 4 weeks until week 96. PROs were measured using the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), and ambulatory function was measured with the 6 min walk test (6MWT).ResultsSubjects (N=134) were randomised to burosumab (n=68) or placebo (n=66) for 24 weeks. At baseline, subjects experienced pain, stiffness, and impaired physical and ambulatory function. At week 24, subjects receiving burosumab achieved statistically significant improvement in some BPI-SF scores, BFI worst fatigue (average and greatest) and WOMAC stiffness. At week 48, all WOMAC and BPI-SF scores achieved statistically significant improvement, with some WOMAC and BFI scores achieving meaningful and significant change from baseline. At week 96, all WOMAC, BPI-SF and BFI achieved statistically significant improvement, with selected scores in all measures also achieving meaningful change. Improvement in 6MWT distance and percent predicted were statistically significant at all time points from 24 weeks.ConclusionsAdults with XLH have substantial burden of disease as assessed by PROs and 6MWT. Burosumab treatment improved phosphate homoeostasis and was associated with a steady and consistent improvement in PROs and ambulatory function.Trial registration numberNCT02526160.
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Canny, Geraldine, Elke Cario, Andreas Lennartsson, Urban Gullberg, Ciara Brennan, Ofer Levy, and Sean P. Colgan. "Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein." American Journal of Physiology-Gastrointestinal and Liver Physiology 290, no. 3 (March 2006): G557—G567. http://dx.doi.org/10.1152/ajpgi.00347.2005.
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Epithelial cells of many mucosal organs have adapted to coexist with microbes and microbial products. In general, most studies suggest that epithelial cells benefit from interactions with commensal microorganisms present at the lumenal surface. However, potentially injurious molecules found in this microenvironment also have the capacity to elicit local inflammatory responses and even systemic disease. We have recently demonstrated that epithelia cells express the anti-infective molecule bactericidal/permeability-increasing protein (BPI). Here, we extend these findings to examine molecular mechanisms of intestinal epithelial cell (IEC) BPI expression and function. Initial experiments revealed a variance of BPI mRNA and protein expression among various IEC lines. Studies of BPI promoter expression in IECs identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. To assess the functional significance of this protein, we generated an IEC line stably transfected with full-length BPI. We demonstrated that, whereas epithelia express markedly less BPI protein than neutrophils, epithelial BPI contributes significantly to bacterial killing and attenuating bacterial-elicted proinflammatory signals. Additional studies in murine tissue ex vivo revealed that BPI is diffusely expressed along the crypt-villous axis and that epithelial BPI levels decrease along the length of the intestine. Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces.
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Senarath, Upul, Michael J. Dibley, and Kingsley E. Agho. "Breast-feeding Performance Index: a composite index to describe overall breast-feeding performance among infants under 6 months of age." Public Health Nutrition 10, no. 10 (October 2007): 996–1004. http://dx.doi.org/10.1017/s1368980007441428.
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AbstractObjectivesTo develop a composite index to describe the overall breast-feeding performance of infants < 6 months of age; and, using this index, to identify the factors associated with poor breast-feeding practices and the association between breast-feeding and infant morbidity.Design, setting and subjectsThe 2003 Demographic and Health Survey was a multi-stage cluster sample survey of 4320 households in Timor-Leste which covered 573 infants aged < 6 months. Breast-feeding Performance Index (BPI) was constructed by allocating one point for each of seven infant feeding practices: first suckling within an hour of birth; absence of prelacteals; non-use of feeding bottles; current breast-feeding; not receiving liquids; not receiving formula or other milk; and not receiving solids in the last 24 hours. BPI was treated as the dependent variable in univariate and multivariate analyses to identify the factors associated with poor breast-feeding.ResultsExclusive breast-feeding rate was 29.9%. The BPI (mean 4.4, standard deviation 1.77) was categorised as low, average and high according to tertiles. Multivariate analysis indicated that infants from the richest households were 1.70 (95% confidence interval (CI) 1.04–2.77) times more likely to have ‘low BPI’ than the poorest. Maternal BMI < 18.5 kg m− 2 was predictive of poor breast-feeding (odds ratio = 1.79; 95% CI 1.27–2.52). In the ‘low’ BPI group, the incidence of diarrhoea (13.4%) and acute respiratory infections (20.7%) during the previous two weeks was significantly higher than in ‘average’ (4.3 and 9.3%) and ‘high’ BPI groups (4.6 and 5.5%).ConclusionsCreating a composite index to assess the overall breast-feeding performance among infants < 6 months of age is feasible. BPI can be effectively used to identify target groups for breast-feeding promotion interventions.
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Weiss, J., and I. Olsson. "Cellular and subcellular localization of the bactericidal/permeability- increasing protein of neutrophils." Blood 69, no. 2 (February 1, 1987): 652–59. http://dx.doi.org/10.1182/blood.v69.2.652.bloodjournal692652.
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Human and rabbit polymorphonuclear leukocytes contain a bactericidal/permeability-increasing protein (BPI), a potent cytotoxin active specifically against gram-negative bacteria. To identify the cell population(s) producing BPI, we have examined mature and immature human blood cells for BPI by immunofluorescence of intact cells and radioimmunoassay and bioassay of cell extracts. By immunofluorescence and radioimmunoassay of cells from peripheral blood, BPI was detected only in neutrophils; immunofluorescent staining was punctate, indicative of the granule localization of BPI. Nearly all (greater than 90%) BPI was recovered during the subcellular fractionation of neutrophils (N2 cavitation and discontinuous Percoll gradient) in fractions containing primary granules. Little BPI was released from intact cells during degranulation (cytochalasin B and f-Met-Leu-Phe) or could be extracted from isolated granules with salt or weak acid, which suggests that most granule-associated BPI is membrane bound. Double staining of bone marrow smears for BPI and lactoferrin revealed BPI only in neutrophil precursors including (pro)myelocytelike cells lacking lactoferrin, a marker of neutrophil secondary granules. Of several human cell lines tested, only the promyelocytelike HL-60 (and to a lesser extent, KG-1) cells contained BPI. BPI was present in a more mature subpopulation (less than 25%) of untreated HL-60 cells, recognized by surface marker analysis (rosetting with IgG-sensitized sheep RBC, the absence of proliferation-associated cell surface antigen). Induction of neutrophilic or monocytic differentiation caused, respectively, a small (approximately 50%) rise or fall in the BPI content. These findings indicate that BPI is a specific product of the neutrophil lineage and, hence, of the specialized cytotoxic apparatus of the neutrophil that plays an essential role in host defense v gram-negative bacteria.
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Sundjaja, Arta Moro. "Investment Cost Model in Business Process Intelligence in Banking And Electricity Company." ComTech: Computer, Mathematics and Engineering Applications 7, no. 2 (June 1, 2016): 113. http://dx.doi.org/10.21512/comtech.v7i2.2248.
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Higher demand from the top management in measuring business process performance causes the incremental implementation of BPM and BI in the enterprise. The problem faced by top managements is how to integrate their data from all system used to support the business and process the data become information that able to support the decision-making processes. Our literature review elaborates several implementations of BPI on companies in Australia and Germany, challenges faced by organizations in developing BPI solution in their organizations and some cost model to calculate the investment of BPI solutions. This paper shows the success in BPI application of banks and assurance companies in German and electricity work in Australia aims to give a vision about the importance of BPI application. Many challenges in BPI application of companies in German and Australia, BPI solution, and data warehouse design development have been discussed to add insight in future BPI development. And the last is an explanation about how to analyze cost associated with BPI solution investment.
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Marra, M. N., C. G. Wilde, M. S. Collins, J. L. Snable, M. B. Thornton, and R. W. Scott. "The role of bactericidal/permeability-increasing protein as a natural inhibitor of bacterial endotoxin." Journal of Immunology 148, no. 2 (January 15, 1992): 532–37. http://dx.doi.org/10.4049/jimmunol.148.2.532.
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Abstract Systemic release of endotoxin (LPS) after Gram-negative infection initiates a cascade of host cytokines that are thought to be the direct cause of shock, multisystem organ failure, and death. Endogenous LPS-binding proteins may play a role in regulating LPS toxicity in vivo. The human neutrophil granule protein bactericidal/permeability-increasing protein (BPI) shares sequence homology and immunocrossreactivity with an acute phase lipopolysaccharide binding protein (LBP) which has been shown to bind to LPS and accelerate LPS activation of neutrophils and macrophages. Although structurally similar, LBP and BPI are apparently functionally antagonistic. We previously showed that BPI inhibits LPS-mediated neutrophil activation in vitro. Here we demonstrate that BPI binds to LPS near the lipid A domain, and formation of the LPS-BPI complex abrogates detrimental host responses to LPS. For example, BPI blocks LPS-stimulated TNF release in vitro and in vivo, and LPS complexed to BPI is not pyrogenic in rabbits. Results demonstrating that BPI is released by stimulated human neutrophils further support the idea that BPI functions extracellularly in vivo to neutralize endotoxin. Taken together, these data argue that BPI neutralizes the toxic effects of LPS in vivo, and that BPI may represent a new therapeutic approach to the treatment of endotoxic shock.
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Weiss, J., and I. Olsson. "Cellular and subcellular localization of the bactericidal/permeability- increasing protein of neutrophils." Blood 69, no. 2 (February 1, 1987): 652–59. http://dx.doi.org/10.1182/blood.v69.2.652.652.
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Abstract Human and rabbit polymorphonuclear leukocytes contain a bactericidal/permeability-increasing protein (BPI), a potent cytotoxin active specifically against gram-negative bacteria. To identify the cell population(s) producing BPI, we have examined mature and immature human blood cells for BPI by immunofluorescence of intact cells and radioimmunoassay and bioassay of cell extracts. By immunofluorescence and radioimmunoassay of cells from peripheral blood, BPI was detected only in neutrophils; immunofluorescent staining was punctate, indicative of the granule localization of BPI. Nearly all (greater than 90%) BPI was recovered during the subcellular fractionation of neutrophils (N2 cavitation and discontinuous Percoll gradient) in fractions containing primary granules. Little BPI was released from intact cells during degranulation (cytochalasin B and f-Met-Leu-Phe) or could be extracted from isolated granules with salt or weak acid, which suggests that most granule-associated BPI is membrane bound. Double staining of bone marrow smears for BPI and lactoferrin revealed BPI only in neutrophil precursors including (pro)myelocytelike cells lacking lactoferrin, a marker of neutrophil secondary granules. Of several human cell lines tested, only the promyelocytelike HL-60 (and to a lesser extent, KG-1) cells contained BPI. BPI was present in a more mature subpopulation (less than 25%) of untreated HL-60 cells, recognized by surface marker analysis (rosetting with IgG-sensitized sheep RBC, the absence of proliferation-associated cell surface antigen). Induction of neutrophilic or monocytic differentiation caused, respectively, a small (approximately 50%) rise or fall in the BPI content. These findings indicate that BPI is a specific product of the neutrophil lineage and, hence, of the specialized cytotoxic apparatus of the neutrophil that plays an essential role in host defense v gram-negative bacteria.
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Häggblom, J. O., A. B. Jokilammi-Siltanen, H. Peuravuori, and T. J. Nevalainen. "Time-resolved fluoroimmunoassay for bactericidal/permeability-increasing protein." Mediators of Inflammation 5, no. 1 (1996): 47–50. http://dx.doi.org/10.1155/s0962935196000087.
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Bactericidal/permeability-increasing protein (BPI) is a cationic antimicrobial protein produced by polymorphonuclear leukocytes, that specifically interacts with and kills Gram-negative bacteria. BPl competes with lipopolysaccharide-binding protein (LBP) secreted by liver cells into blood plasma for binding to lipopolysaccharide (LPS) and thus reduces the proinflammatory effects of LPS. We have developed a time-resolved fluoroimmunoassay for BPI and measured the concentration of BPI in human serum and plasma samples. The assay is based on a rabbit antibody against recombinant BPI. This antibody specifically adheres to polymorphonuclear leukocytes in immunostained human tissues. The difference in the serum concentration of BPI between unselected hospitalized patients with and without an infection was statistically significant. The mean concentration of BPI in serum samples was 28.3 μg/l (range 1.64–132, S.D. 26.8,n= 83). In contrast, there was no difference between the two groups in the BPI levels in plasma samples. For all individuals tested, BPI levels were consistently higher in plasma samples compared to the matched serum samples. The mean concentration of BPI in plasma samples was 52.3 μg/l (range 0.9–403, S.D. 60.6,n= 90). There was a positive correlation between the concentration of BPI and the white blood cell count as well as between the BPI concentration and C-reactive protein (CRP) in serum samples. In conclusion, the present study demonstrates that BPI can be quantified reliably by time-resolved fluoroimmunoassay in human serum samples.
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Mannion, B. A., E. S. Kalatzis, J. Weiss, and P. Elsbach. "Preferential binding of the neutrophil cytoplasmic granule-derived bactericidal/permeability increasing protein to target bacteria. Implications and use as a means of purification." Journal of Immunology 142, no. 8 (April 15, 1989): 2807–12. http://dx.doi.org/10.4049/jimmunol.142.8.2807.
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Abstract The specificity of the basic bactericidal/permeability increasing protein (BPI) of polymorphonuclear leukocytes (PMN) for gram-negative bacteria is attributable to its strong attraction for the negatively charged envelope LPS. The antibacterial activity of PMN homogenates or extracts toward Escherichia coli corresponds to their BPI content and is blocked by anti-BPI IgG, suggesting that BPI action is unaffected by the presence of other PMN proteins. To test if BPI is preferentially bound to E. coli when other antibacterial proteins are present, we have measured binding in buffered (pH 7.5) balanced salts solution of [125I] human BPI to E. coli J5 in the presence and absence of other human PMN granule proteins. BPI binding is saturable with an apparent K = 23 nM and 2.2 million binding sites/cell. While binding of [125I] human BPI is competitively inhibited by human or rabbit BPI, it is only weakly inhibited by myeloperoxidase, lysozyme, or cathepsin G. In contrast, myeloperoxidase binding to E. coli is strongly inhibited by BPI. Moreover, incubation of E. coli with crude extracts of PMN or CML spleen results in near quantitative binding of BPI, identified by silver staining and immunoblotting after SDS-PAGE of the washed E. coli pellet, without recognizable binding of other leukocyte proteins (greater than 98% of added total protein is recovered in supernatant). After addition of 200 mM MgCl2, approximately 80% of bound BPI is released as fully active and pure protein (as judged by SDS-PAGE and HPLC). Thus the selective and reversible binding of BPI in crude PMN extracts to target bacteria provides a one-step "affinity" purification procedure.
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Zarember, Kol, Peter Elsbach, Kwang Shin-Kim, and Jerrold Weiss. "p15s (15-kD Antimicrobial Proteins) Are Stored in the Secondary Granules of Rabbit Granulocytes: Implications for Antibacterial Synergy With the Bactericidal/Permeability-Increasing Protein in Inflammatory Fluids." Blood 89, no. 2 (January 15, 1997): 672–79. http://dx.doi.org/10.1182/blood.v89.2.672.
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Abstract The bactericidal potency toward complement-resistant Escherichia coli of bactericidal/permeability-increasing protein (BPI) released from polymorphonuclear leukocytes (PMNs) in glycogen-induced inflammatory peritoneal exudates of rabbits is dependent on synergy with extracellular p15s. This synergy depends on the high molar ratio of p15s to BPI in the extracellular fluid (∼50:1), which greatly exceeds the intracellular ratio (∼5:1). To explore the possible basis of the greater accumulation of p15s in inflammatory fluid, we examined the subcellular localization of BPI and p15 in PMNs. Immunogold electron microscopy confirmed the storage of BPI in primary granules and showed that p15s are stored in secondary granules. Reverse-transcription polymerase chain reaction of density-fractionated rabbit bone marrow cells verified that p15s are expressed later than BPI during myeloid differentiation. As the inflammatory response evolves, p15 mRNA appears earlier in blood and exudate cells than mRNA for BPI, consistent with release of progressively less mature precursors from bone marrow. Finally, Ca2+-ionophore–mediated exocytosis of p15s occurs more readily than release of BPI. We therefore propose that localization of a synergistic partner of BPI (p15s) in more readily released secondary granules allows the neutrophil to mobilize potent BPI-dependent antibacterial activity extracellularly without significant depletion of intracellular BPI stores.
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Lindberg, Ulrika, Malin Carlsson, Claes-Göran Löfdahl, and Mårten Segelmark. "BPI-ANCA and Long-Term Prognosis among 46 Adult CF Patients: A Prospective 10-Year Follow-Up Study." Clinical and Developmental Immunology 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/370107.
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Introduction. Anti-neutrophil cytoplasmic antibodies specific for bactericidal/permeability-increasing protein (BPI-ANCA) are frequent in CF patients and mainly develop in response to infection withPseudomonas aeruginosa. It is not known to what extent BPI-ANCA correlates to prognosis.Objectives. To evaluate the prognostic value of IgA-BPI-ANCA, measured at the beginning of the study, for transplantation-free survival.Methods. A cohort of 46 adult, nontransplanted CF patients was generated, 1995–1998, and characterized using Leeds criteria, lung function, and IgA-BPI-ANCA levels measured by ELISA. The cohort was followed until December 2009, using the combined endpoint of death or lung transplantation.Results. Lung function and IgA-BPI-ANCA, but not Leeds criteria, were significantly associated with adverse outcome. No patient with normal lung function at baseline reached endpoint. Within 10 years 8/11 with high BPI-ANCA reached an endpoint compared to 3/17 ANCA-negative patients. A similar result was seen within the Leeds I group where 7 out of 9 BPI-ANCA-positive patients reached endpoint, compared to none of the 5 patients without BPI-ANCA.Conclusions. IgA-BPI-ANCA is associated with adverse outcome amongPseudomonas aeruginosainfected CF patients, suggesting that BPI-ANCA is a biomarker of an unfavourable host-pathogen interaction.
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Prizment, Anna, Susan Halabi, Sean McSweeney, Amy Eisenberg, Arpit Rao, Shilpa Gupta, Alicia K. Morgans, and Charles J. Ryan. "Association of disease prognostic model (PM) with baseline quality of life (QOL) in metastatic castration resistant prostate cancer (mCRPC)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e16579-e16579. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e16579.
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e16579 Background: PM’s in mCRPC accurately predict survival, but little is known about their association with QOL. We hypothesize that pre-treatment QOL is inversely correlated with PM derived scores. Our study explored associations between baseline Halabi PM derived risk score (including metastatic site, opioid use, ECOG performance status (ECOG PS), Alk phos, albumin, hemoglobin, LDH, and PSA) and multiple QOL domains at treatment initiation with docetaxel and prednisone (DP). Methods: The DP arm of MAINSAIL, a multicenter, randomized Phase 3 study of DP +/- lenalidomide in mCRPC, was analyzed via ProjectDataSphere. Halabi PM score was computed as continuous with higher score reflecting worse survival and classified as low- ( < 140 points), intermediate- (140-194.96) or high-risk groups ( > 194.96 points). QOL tests included FACT-P (higher score = better QOL), BPI-SF Severity score (BPI-SFSS; higher score = higher pain severity); and BPI-SF Interference score (BPI-SFIS, higher score = worse pain). General linear regression model was used to calculate beta estimates and 95% confidence intervals. Results: The sample included 526 mCPRC pts (median 68 years, White: 91.9%, Black: 5.3%, median PSA 75.95 ng/ml). Median [range] for FACT-P, BPI-SFSS and BPI-SFIS were 111 [0-152], 1.8 [0-9.3], and 1.4 [0-10], respectively. PM score was correlated with BPI-SFIS and BPI-SFSS and inversely correlated with FACT-P with correlation of 0.36, 0.31 and -0.33, respectively (all p < 0.0001). For each unit increase in the PM score, BPI-SFIS increased by 2.1 points), BPI-SFSS increased by 1.5 points, and FACT-P decreased by 16.4 points. Using the three-risk groups, pts in the intermediate and high-risk groups had worse FACT-P QOL and higher BPI-SFIS and BPI-SFSS than pts in the low-risk group. In multivariate analysis, factors negatively impacting FACT-P QOL, BPI-SFSS and BPI-SFIS were higher ECOG PS, visceral metastases and opioid use. Declining hemoglobin levels were associated with increased BPI-SFSS and BPS-SFIS. Conclusions: Higher PM scores are associated with a lower baseline QOL overall, higher pain and higher pain interference. These results should be validated prospectively.
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Im, Dana D., Guruprasad D. Jambaulikar, Anna Kikut, Jasmine Gale, and Scott G. Weiner. "Brief Pain Inventory–Short Form: A New Method for Assessing Pain in the Emergency Department." Pain Medicine 21, no. 12 (September 11, 2020): 3263–69. http://dx.doi.org/10.1093/pm/pnaa269.
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Abstract Objective The numeric rating scale (NRS), which does not capture the multidimensional experience of pain, is commonly used to measure pain in the emergency department (ED). In this study, we assess the utility and feasibility of the Brief Pain Inventory–Short Form (BPI-SF) in the ED. Methods This was a cross-sectional, prospective, convenience sample study of adult patients presenting to the ED with chest, abdominal, or musculoskeletal pain. Using confirmatory factor analysis, we investigated the construct validity of the BPI-SF. We determined the association between NRS and BPI-SF scores. We assessed the feasibility and utility of administering the BPI-SF in the ED setting by evaluating 1) the time required to complete the BPI-SF and 2) how patients perceive the BPI-SF compared with the NRS. Results One hundred participants were included for analysis. The median NRS pain level on ED arrival (interquartile range [IQR]) was 7 (5–8). The median BPI-SF score (IQR) was 57 (43–73) on a 0–110 scale. Fit indices for the two-factor structure were statistically superior when compared with the one-factor model of the BPI-SF (comparative fit index 0.90 vs 0.64). Higher pain severity score, pain interference score, and total BPI-SF score were associated with higher NRS scores (P < 0.01). The mean time needed to complete the BPI-SF (SD) was 3 minutes 47 seconds (1 minute 35 seconds). Seventy-three percent of the patients preferred the BPI-SF to the NRS for pain assessment in the ED. Conclusions Our study demonstrates the validity, feasibility, and utility of the BPI-SF in the ED setting.
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Capodici, C., and J. Weiss. "Both N- and C-terminal regions of the bioactive N-terminal fragment of the neutrophil granule bactericidal/permeability-increasing protein are required for stability and function." Journal of Immunology 156, no. 12 (June 15, 1996): 4789–96. http://dx.doi.org/10.4049/jimmunol.156.12.4789.
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Abstract An N-terminal fragment (residues 1-199) of the 456-residue human bactericidal/permeability-increasing protein (BPI), isolated after limited proteolysis, exhibits antibacterial and LPS-neutralizing activities equal to or greater than those of holo-BPI. To assess minimal structural requirements for bioactivity, mutant species of BPI were expressed in vivo by transient transfection and in vitro by cellfree transcription/translation. BPI1-456 and BPI1-193 demonstrated the expected antibacterial and LPS-binding activities. Deletion of the N-terminal 12 residues did not diminish BPI function. However, further truncation either from the C-terminus to residue 169 (BPI1-169) or from the N-terminus (BPIdelta15-56) yielded in vitro products with little or no LPS-binding activity and in vivo products that could not be recovered from the culture medium or cellular acid extracts. The possible role of cysteine-175 (the three cysteines in human BPI are at residues 132, 135, and 175) in BPI stability/function was examined by substitution of Cys(175) with serine. Recovery of C175S BPI from extracellular medium was reduced 10-fold, and C175S BPI produced in vitro had little LPS-binding activity. Compared with wild-type holo-BPI and BPI1-193, BPI1-169, BPIdelta15-56, and C175S BPI showed increased susceptibility to cleavage by elastase in the region 1-193 (but not in the region 200-456), indicating conformational changes that may account for the loss of function. These findings suggest that the proteolytic N-terminal fragment of BPI corresponds closely to the minimum functional (antibacterial/anti-LPS) domain of BPI and that residues near both ends of this fragment are essential for structural stability and functional integrity.
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Inal, Ferda Yilmaz, Kursat Gul, Yadigar Yilmaz Camgoz, Hayrettin Daskaya, and Hasan Kocoglu. "Validation of the Turkish version of the Pain Sensitivity Questionnaire in patients with chronic pain." Journal of International Medical Research 49, no. 12 (December 2021): 030006052110601. http://dx.doi.org/10.1177/03000605211060158.
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Objective The Pain Sensitivity Questionnaire (PSQ) is a clinically beneficial instrument that has been proven to be correlated with various experimental pain sensitivity assessments in healthy people and in patients with chronic pain. In this study, we aimed to translate the PSQ into Turkish (PSQ-T) and validate it for the measurement of pain sensitivity among Turkish people. Methods Seventy-three patients with chronic back pain who were planning to undergo an interventional procedure completed the Brief Pain Inventory-Short Form (BPI-SF), Beck Depression Inventory (BDI), Beck Anxiety Inventory, Pain Catastrophizing Scale, and PSQ prior to their procedure. Subcutaneous infiltration of lidocaine was used as a standardized experimental pain stimulus. Pain was evaluated using a visual analog scale (VAS 1: infiltration in the hand, and VAS 2: infiltration in the procedure area) Results Scores on the PSQ-T were significantly correlated with those on the BPI-SF. A significant positive relationship was observed between VAS 1 and VAS 2 values and the PSQ-T score, BPI pain score, and BPI interference score. Conclusions The PSQ-T can be used as a valid and reliable tool for the assessment of pain sensitivity in the Turkish population.
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Ren, Xi, Yan Zhang, Yuang Liu, Changxu Yang, Shengwei Dai, Xiaolei Wang, and Jingang Liu. "Preparation and Properties of Intrinsically Black Polyimide Films with CIE Lab Color Parameters Close to Zero and High Thermal Stability for Potential Applications in Flexible Printed Circuit Boards." Polymers 14, no. 18 (September 17, 2022): 3881. http://dx.doi.org/10.3390/polym14183881.
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Black polymer films with high thermal stability are highly desired in flexible electrical and electronic fields. Conventional black polymer films based on high-temperature resistant polymers and black inorganic dyes are usually suffered from the poor electrical and tensile properties. In the current work, a series of intrinsically black polyimide (BPI) films with International Commission on Illumination (CIE) Lab optical parameters close to zero and high thermal stability have been designed and prepared. For this purpose, an electron-rich aromatic diamine, 4,4′-iminodianiline (NDA), was copolymerized with 1,4-phenylenediamine (PDA) and 3,3′,4,4′-biphenyltetracarboxylic dianhydride (sBPDA) to afford a series of poly(amic acid) (PAA) solutions, which were then thermally dehydrated to provide the final BPI films at elevated temperatures up to 400 °C in air. The molar fraction of NDA in the total diamine monomers was 0 for BPI-0 (sBPDA-PDA), 10% for BPI-1, 20% for BPI-2, 30% for BPI-3, 40% for BPI-4, 50% for BPI-5, and 100% for BPI-6. For comparison, two referenced polyimide (PI) films, including PI-ref1 and PI-ref2, were prepared according to a similar procedure. The former was derived from pyromellitic dianhydride (PMDA) and 4,4′-oxydianiline (ODA) and the latter was from PMDA and NDA. The BPI films exhibited an increasing degree of blackness with the increasing contents of NDA units in the polymer films. For example, the BPI-6 (sBPDA-NDA) film exhibited the optical transmittance of 1.4% at a wavelength of 650 nm (T650), which was obviously lower than those of PI-ref1 (T650 = 74.6%) and PI-ref2 (T650 = 3.6%). In addition, the BPI-6 film showed the CIE Lab parameters of 0.39 for L*, 2.65 for a*, 0.66 for b*, and haze of 1.83, which was very close to the criterion of “pure blackness” for polymer films (L* = a* = b* = 0). At last, incorporation of the NDA units in the rigid-rod BPI-0 (BPDA-PDA) film slightly deteriorated the high-temperature dimensional stability of the derived BPI films. BPI-6 film showed a linear coefficient of thermal expansion (CTE) value of 34.8 × 10−6/K in the temperature range of 50 to 250 °C, which was higher than those of the BPI-0 (CTE = 12.3 × 10−6/K), PI-ref1 (CTE = 29.5 × 10−6/K), and PI-ref2 (CTE = 18.8 × 10−6/K) films. Nevertheless, the BPI films maintained good thermal stability with the 5% weight loss temperatures (T5%) higher than 590 °C, and the glass transition temperatures (Tg) higher than 340 °C.
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Hu, Jianrao, Mingfu Cao, and Jiong Chen. "Characterization of the cDNA encoding a BPI/LBP homologue in venom gland of the hundred-pace snake Deinagkistrodon acutus." Current Zoology 55, no. 5 (October 1, 2009): 376–82. http://dx.doi.org/10.1093/czoolo/55.5.376.
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Abstract Bactericidal/permeability-increasing protein (BPI) and LPS-binding protein (LBP) play an important role in host defence. Current evidence shows that BPI/ LBP may be widely existed in different cells and tissue types of animals. A full-length cDNA clone encoding a BPI/LBP homologue (dBPI), 1757 bp in size, was characterized in venom gland of the hundred-pace snake Deinagkistrodon acutus. Its deduced amino acid sequence of 417 residues had 13.8% - 21.5% identity to BPI like 1 (BPILl) and BPI like 3 (BPIL3) of other animals. Conserved cysteine residues which are involved in disulfide bond formation between the final strand of the N-terminal beta sheet and the long alpha helix of BPI are identified as Cysl46-Cysl83 of dBPI. Phylogenetic tree analysis showed that the BPI/LBP homologues formed five large clusters and dBPI was in a large cluster including BPILl and BPIL3. dBPI mRNA shows a tissue specific expression in venom gland. This is the first study to identify the cDNA encoding BPI/LBP homologues from reptiles.
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Levy, O., G. Canny, C. N. Serhan, and S. P. Colgan. "Expression of BPI (bactericidal/permeability-increasing protein) in human mucosal epithelia." Biochemical Society Transactions 31, no. 4 (August 1, 2003): 795–800. http://dx.doi.org/10.1042/bst0310795.
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Among the antimicrobial proteins and peptides of humans is the cationic 55 kDa bactericidal/permeability-increasing protein (BPI), which possesses antibacterial, endotoxin-neutalizing and opsonic activity against Gram-negative bacteria. Although identified originally as an abundant constituent of neutrophil granules, we have recently identified functional expression of BPI by human mucosal epithelia. BPI expression was markedly up-regulated by exposure of epithelia to lipoxins, endogenous anti-inflammatory eicosanoids that are generated in vivo in the context of aspirin treatment (aspirin-triggered lipoxins). Epithelial BPI was found to be surface expressed and fully functional, as measured by antibacterial activity against Salmonella typhimurium as well as lipopolysaccharide (LPS; endotoxin)-neutralizing activity. These results suggest a role for BPI as an effector of epithelial antibacterial activity and as a modulator of epithelial responses to LPS. Both BPI and the lipoxins are currently the subject of intensive biopharmaceutical development, raising the possibility that therapeutic use of BPI or modulation of epithelial BPI expression may be a useful adjunctive therapy for conditions in which epithelial inflammation is associated with Gram-negative infections and/or endotoxin.
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Calafat, Jero, Hans Janssen, Anton Tool, Mieke A. Dentener, Edward F. Knol, Helene F. Rosenberg, and Arne Egesten. "The Bactericidal/Permeability-Increasing Protein (BPI) Is Present in Specific Granules of Human Eosinophils." Blood 91, no. 12 (June 15, 1998): 4770–75. http://dx.doi.org/10.1182/blood.v91.12.4770.
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Abstract Eosinophils participate in the inflammatory response seen in allergy and parasitic infestation, but a role in host defense against bacterial infection is not settled. The bactericidal/permeability-increasing protein (BPI) has been demonstrated in neutrophils and it exerts bacteriostatic and bactericidal effects against a wide variety of Gram-negative bacterial species. Using the Western blot technique, a 55-kD band, corresponding to BPI, was detected in lysates from both neutrophils and eosinophils. The localization of BPI in immature and mature eosinophils was investigated using immunoelectron microscopy. BPI was found in immature and mature specific granules of eosinophils and was detected in phagosomes as well, indicating release of the protein from the granules into the phagosomes. Using a specific enzyme-linked immunosorbent assay, eosinophils were shown to contain 179 ng of BPI/5 × 106 eosinophils compared with 710 ng BPI/5 × 106 neutrophils. The presence of BPI in eosinophils suggests a role for these cells in host defense against Gram-negative bacterial invasion or may suggest a role for BPI against parasitic infestation.
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Calafat, Jero, Hans Janssen, Anton Tool, Mieke A. Dentener, Edward F. Knol, Helene F. Rosenberg, and Arne Egesten. "The Bactericidal/Permeability-Increasing Protein (BPI) Is Present in Specific Granules of Human Eosinophils." Blood 91, no. 12 (June 15, 1998): 4770–75. http://dx.doi.org/10.1182/blood.v91.12.4770.412k33_4770_4775.
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Eosinophils participate in the inflammatory response seen in allergy and parasitic infestation, but a role in host defense against bacterial infection is not settled. The bactericidal/permeability-increasing protein (BPI) has been demonstrated in neutrophils and it exerts bacteriostatic and bactericidal effects against a wide variety of Gram-negative bacterial species. Using the Western blot technique, a 55-kD band, corresponding to BPI, was detected in lysates from both neutrophils and eosinophils. The localization of BPI in immature and mature eosinophils was investigated using immunoelectron microscopy. BPI was found in immature and mature specific granules of eosinophils and was detected in phagosomes as well, indicating release of the protein from the granules into the phagosomes. Using a specific enzyme-linked immunosorbent assay, eosinophils were shown to contain 179 ng of BPI/5 × 106 eosinophils compared with 710 ng BPI/5 × 106 neutrophils. The presence of BPI in eosinophils suggests a role for these cells in host defense against Gram-negative bacterial invasion or may suggest a role for BPI against parasitic infestation.
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Aichele, Diana, Markus Schnare, Marc Saake, Martin Röllinghoff, and Andre Gessner. "Expression and Antimicrobial Function of Bactericidal Permeability-Increasing Protein in Cystic Fibrosis Patients." Infection and Immunity 74, no. 8 (August 2006): 4708–14. http://dx.doi.org/10.1128/iai.02066-05.
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ABSTRACT In cystic fibrosis (CF), the condition limiting the prognosis of affected children is the chronic obstructive lung disease accompanied by chronic and persistent infection with mostly mucoid strains of Pseudomonas aeruginosa. The majority of CF patients have antineutrophil cytoplasmic antibodies (ANCA) primarily directed against the bactericidal permeability-increasing protein (BPI) potentially interfering with antimicrobial effects of BPI. We analyzed the expression of BPI in the airways of patients with CF. In their sputum samples or bronchoalveolar lavage specimens, nearly all patients expressed BPI mRNA and protein, which were mainly products of neutrophil granulocytes as revealed by intracellular staining and subsequent flow cytometry. Repeated measurements revealed consistent individual BPI expression levels during several months quantitatively correlating with interleukin-8. In vitro, P. aeruginosa isolates from CF patients initiated the rapid release of BPI occurring independently of protein de novo syntheses. Furthermore, purified natural BPI as well as a 27-mer BPI-derived peptide displayed antimicrobial activity against even patient-derived mucoid P. aeruginosa strains and bacteria resistant against all antibiotics tested. Thus, BPI that is functionally active against mucoid P. aeruginosa strains is expressed in the airways of CF patients but may be hampered by autoantibodies, resulting in chronic infection.
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Scanu, Anna, Roberto Luisetto, Francesca Oliviero, Francesca Galuppini, Vanni Lazzarin, Gianmaria Pennelli, Stefano Masiero, and Leonardo Punzi. "Bactericidal/Permeability-Increasing Protein Downregulates the Inflammatory Response in In Vivo Models of Arthritis." International Journal of Molecular Sciences 23, no. 21 (October 28, 2022): 13066. http://dx.doi.org/10.3390/ijms232113066.
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We investigated the effects of bactericidal/permeability-increasing protein (BPI) alone or in combination with hyaluronic acid (HA) in two animal models: collagen-induced arthritis (CIA) and crystal-induced inflammation. In CIA, mice were intraperitoneally injected with PBS, HA, or BPI plus or minus HA, twice a week for 2 months, and then euthanized to collect paw and blood. Arthritis was assessed in ankle joints by clinical and histological evaluation. Pathogenic crystals were intraperitoneally injected in mice plus or minus BPI, or with a composition of BPI and HA. After sacrifice, total and differential leukocyte counts were determined. Cytokine levels were measured in serum and peritoneal fluids. In CIA mice, BPI improved clinical and histological outcomes (histological scores ≥2-fold), and downregulated inflammatory mediators (47–93%). In crystal-induced inflammation, BPI reduced leukocyte infiltration (total count: ≥60%; polymorphonuclear cells: ≥36%) and inhibited cytokine production (35–74%). In both models, when mice were co-treated with BPI and HA, the improvement of all parameters was greater than that observed after administration of the two substances alone. Results show that BPI attenuates CIA and inflammation in mice, and this effect is enhanced by HA co-administration. Combined use of BPI and HA represents an interesting perspective for new potential treatments in arthritis.
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Mao, Mao, Xiao-Lin Zhang, and Guo-Hua Wu. "Novel Imidazole Substituted Bodipy-Based Organic Sensitizers in Dye-Sensitized Solar Cells." International Journal of Photoenergy 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/2061472.
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A comparative study on the photophysical, electrochemical properties and photovoltaic performances of pure imidazole dyes containing varying linker groups is done. Two new organic dyes containing 4,5-bis(4-methoxyphenyl)-1H-imidazole (BPI) unit as an electron donor, boron dipyrromethene (Bodipy) chromophore as a conjugate bridge, cyanoacetic acid as an electron acceptor, and phenylene (BPI-P) or thienyl (BPI-T) as a additional linker have been synthesized for fabricating dye-sensitized solar cells (DSSCs). A reference dye (DPI-T) with 6,9-dimethoxy-1H-phenanthro[9,10-d]imidazole as the donor has also been synthesized for comparison. The overall conversion efficiencies of 0.18%, 0.32%, and 1.28% were obtained for DSSCs based on BPI-P, BPI-T, and DPI-T, respectively. DPI-T was found to be more efficient than BPI-P and BPI-T because of its enhanced light harvesting efficiency and better coplanar geometry of the electronic structure.
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Small, Eric Jay, Kim N. Chi, Simon Chowdhury, Katherine B. Bevans, Amitabha Bhaumik, Fred Saad, Byung Chung, et al. "Association between patient-reported outcomes (PROs) and changes in prostate-specific antigen (PSA) in patients (pts) with advanced prostate cancer treated with apalutamide (APA) in the SPARTAN and TITAN studies." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): 73. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.073.
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73 Background: In phase 3 placebo (PBO)-controlled studies, addition of APA to androgen deprivation therapy (ADT) improved overall survival, resulted in rapid and deep PSA declines, and reduced risk of disease progression while preserving health-related quality of life (HRQoL) in nonmetastatic castration-resistant prostate cancer (nmCRPC; SPARTAN) and metastatic castration-sensitive prostate cancer (mCSPC; TITAN). This post hoc analysis evaluated the association of a deep PSA decline with PROs in these studies. Methods: Pts on ADT were randomized to APA (240 mg QD) or PBO: SPARTAN 2:1 (N = 1,207; APA n = 806), TITAN 1:1 (N = 1,052; APA n = 525). Each cycle was 28 d. PROs were assessed using Functional Assessment of Cancer Therapy-Prostate (FACT-P), Brief Pain Inventory-Short Form (BPI-SF; TITAN only), and Brief Fatigue Inventory (BFI; TITAN only) at baseline, specific cycles during study treatment, and post progression up to 1 yr. A landmark analysis at Month 3 evaluated association between deep PSA decline (≤ 0.2 ng/mL) and time to subsequent deterioration in PROs (defined as decrease ≥ 10 points FACT-P total, ≥ 3 points Physical Wellbeing, ≥ 30% baseline for BPI-SF worst pain, or ≥ 2 points for BFI worst fatigue). At time of the landmark analysis, only pts continuing treatment were included; all deep PSA responses after, and all PRO deterioration events before, were ignored. Time-to-event end points were analyzed by Kaplan-Meier method and Cox proportional hazards model. Results: Median treatment durations were 32.9 mo (SPARTAN) and 39.3 mo (TITAN). Per assessment, > 90% (SPARTAN, cycles 1-81) and > 50% (TITAN, cycles 1-33) of eligible pts completed FACT-P; BPI-SF and BFI, both > 62% (TITAN, cycles 1-33). Pts in either study who achieved PSA ≤ 0.2 ng/mL at Month 3 had a lower risk of deterioration in FACT-P total or Physical Wellbeing (Table). Pts in TITAN with PSA ≤ 0.2 ng/mL at Month 3 had a lower risk of BPI-SF worst pain intensity or BFI worst fatigue intensity progression (Table). Conclusions: Deep and rapid PSA responses with APA were associated with prolonged time to deterioration in HRQoL, FACT-P Physical Wellbeing, BPI-SF worst pain intensity, and BFI worst fatigue intensity in pts with advanced PC. Clinical trial information: NCT02489318 (TITAN); NCT01946204 (SPARTAN). [Table: see text]
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Bowring, Darren L., Vasiliki Totsika, Richard P. Hastings, and Sandy Toogood. "Toward data-based clinical decision making for adults with challenging behavior using the Behavior Problems Inventory-Short Form (BPI-S)." Tizard Learning Disability Review 23, no. 2 (April 3, 2018): 103–10. http://dx.doi.org/10.1108/tldr-06-2017-0025.
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Purpose The Behavior Problems Inventory-Short Form (BPI-S) is a shorter version of the Behavior Problems Inventory-01. In this paper, BPI-S population norms are reported from a total administrative population of adults with intellectual disability (ID). To facilitate the use of the BPI-S in clinical services to assess behavior change, the purpose of this paper is to describe how to use BPI-S clinically significant and reliable change (RC) scores. Design/methodology/approach Data were gathered on 265 adults with ID known to services. Proxy informants completed the BPI-S on challenging behaviors over the previous six months. Clinically significant cut-off values and RC scores were calculated using the Jacobson and Truax’s (1991) method. Findings BPI-S clinical reference data are presented to provide benchmarks for individual and group comparisons regarding challenging behavior. Examples demonstrate how to use clinical norms to determine change. Practical implications Behavior change is a major goal of researchers and practitioners. Data from the present study can make the BPI-S a valuable tool for determining change in challenging behavior following service input or intervention. Originality/value Whilst well used in research, the BPI-S may be less extensively used in practice. This present study provides data to enable researchers and practitioners to use the BPI-S more widely in assessing clinical outcomes, such as intervention research and service evaluation.
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Zhu, Eric, Liz Rolf, Emma T. Smolev, David M. Brogan, and Christopher J. Dy. "“This New Chapter of Life”: Content Analysis of Facebook Posts After Traumatic Brachial Plexus Injury." HSS Journal®: The Musculoskeletal Journal of Hospital for Special Surgery 17, no. 2 (February 17, 2021): 174–79. http://dx.doi.org/10.1177/1556331621992336.
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Background: After traumatic brachial plexus injuries (BPI), the sudden loss of physical function is often accompanied by psychological distress. Given the complex nature and relative infrequency of the injury, BPI patients will often use online resources for information about their injury as well as emotional support. Questions/Purpose: Recognizing the influence of social media, we sought to search a popular social media platform to identify challenges faced by BPI patients and strategies used to overcome these challenges. Methods: We searched “traumatic brachial plexus injury” on Facebook and selected the 2 most popular BPI support groups. We collected posts regarding traumatic BPI from November 1, 2018 through November 1, 2019. We performed inductive and deductive thematic analysis of the posts to identify recurring topics, knowledge gaps, and peer interaction dynamics. Results: We analyzed 7694 posts from the 2 Facebook support groups. The following themes emerged: (1) BPI patients express discontent regarding the inability to use their arm and the slow or stagnant pace of recovery; (2) BPI patients are frustrated over their inability to retain their preinjury livelihood; and (3) BPI patients emphasize that acceptance and moving on are key components of adjustment to their condition. Some patients described the role of limb amputation in achieving these goals. Conclusions: Our analysis demonstrates the areas in which BPI patients are in need of emotional support. Adjustment to BPI might be facilitated through multidisciplinary care that addresses emotional aspects of recovery and emphasizes self-management skills, in addition to the traditional focus on physical function.
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Hegarty, Dominic A., Ger Batt, and Jonathan Brackett. "Relationship between Body Mass Index and the Sub-Dimensions of the Brief Pain Inventory in Chronic Pain Patients." Journal of Psychology & Behavior Research 1, no. 2 (October 18, 2019): p77. http://dx.doi.org/10.22158/jpbr.v1n2p77.
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Individuals with chronic pain find it hard to exercise which often results in an elevated Body Mass Index (BMI). Often these individuals only have mild to moderate structural or biomechanical reasons to explain their pain yet their fear of pain seems to influence their functional capacity before any biomechanical mechanism actually prevents them doing so.A retrospective analysis of 25 individuals with a diagnosis of chronic pain (>3 months duration) to establish anthropometric measures, pain severity and Brief Pain Inventory (BPI) questionnaire including the affective sub-dimension score (REM: relations with others, enjoyment of life, and mood) and the activity subdimension score (WAW: walking, general activity, and work) were assessed.BMI was shown to have a significant effect on the overall daily functional BPI score as assessed using ANOVA, F (4,110) = 29.4, p<0.05, with an effect size w = 0.5. Turkey HSD tests to compare all groups identified a significant relationship between BMI and (i) pain (p<0.05), (ii) REM (p<0.05), and (iii) sleep (p<0.05).These results would suggest that individuals who are overweight and who show higher REM scores on the BPI assessment may benefit from early psychological counselling rather than physical therapy.
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Zhu, Xiaoguan, Yuan Lu, Jing Guo, Dan Yan, Boyan Li, Xiaoping Chen, Haibo Chen, et al. "Abstract 5443: BPI-421286: A highly potent small molecule inhibitor targeting KRASG12C mutation." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5443. http://dx.doi.org/10.1158/1538-7445.am2022-5443.
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Abstract KRAS is a GTP-binding protein that links receptor tyrosine kinase activation to intracellular signaling. Mutation of KRAS favors the GTP-bound active state and constitutive activation of downstream effects. KRASG12C mutation has been identified as an oncogenic driver of tumorigenesis, which is found in approximately 14% of lung cancer, 4% of colorectal (CRC), and 1-3% of other solid tumors. Herein, we report BPI-421286, a highly potent and selective covalent small molecular KRASG12C inhibitor. In vitro, BPI-421286 showed a high Kinact/Ki value (256,000 M-1 s-1), and inhibited KRAS-GTP/GDP exchange with a lower IC50 (55 nM). In cell-based assays, BPI-421286 suppressed proliferation of KRASG12C mutant cell lines with sub-nanomolar potency, but did not affect cell lines with wide type or non-G12C KRAS mutations. BPI-421286 also inhibited phospho-ERK in MIA PaCa-2 cell with a low IC50 value (2.9 nM). In vivo, daily oral administration of 3-100 mg/kg BPI-421286 led to tumor growth suppression or regression in multiple KRASG12C mutant xenograft or PDX models of NSCLC, CRC and PDAC. The in vivo PKPD in MIA PaCa-2 xenograft model showed that durable pERK inhibition can be achieved without continuous drug exposure, featuring BPI-421286 as a covalent, non-reversible KRAS inhibitor. Combining BPI-421286 with several targeted agents, including a SHP2 inhibitor BPI-442096 and a CDK4/6 inhibitor BPI-16350, demonstrated enhanced tumor growth inhibition compared to either agent alone. Notably, for the acquired resistance mutations that are clinically observed after KRASG12C inhibitor treatment, such as G12C/H95D, G12C/H95Q, G12C/R68S and G12C/Y96C, BPI-421286 also exhibited strong inhibitory activities, suggesting that BPI-421286 could overcome the acquired resistance of currently approved KRASG12C inhibitors. Taken together, BPI-421286 is a highly potent and selective KRASG12C inhibitor, with favorable ADME properties and wide therapeutic index in pre-clinical toxicology studies. BPI-421286 is currently in Phase 1 clinical study. Citation Format: Xiaoguan Zhu, Yuan Lu, Jing Guo, Dan Yan, Boyan Li, Xiaoping Chen, Haibo Chen, Hong Lan, Hao Wu, Lieming Ding, Jiabing Wang. BPI-421286: A highly potent small molecule inhibitor targeting KRASG12C mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5443.
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Antun, Ana, Leandro Cerchietti, Santiago Aparo, Rita Shaknovich, and Ari Melnick. "BCL6 Inhibitor Peptide Have Powerful Anti-Lymphoma Activity in Animal Models of Diffuse Large B-Cell Lymphoma and Synergize with Other Anti-Lymphoma Drugs." Blood 108, no. 11 (November 16, 2006): 827. http://dx.doi.org/10.1182/blood.v108.11.827.827.
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Abstract The BCL6 oncogenic transcriptional repressor is constitutively expressed in about 60% of Diffuse Large B-cell Lymphomas (DLBCLs). We previously developed a recombinant inhibitor peptide that specifically blocks the ability of BCL6 to mediate transcriptional repression. Based on this peptide, we developed a novel retro-Inverso peptidomimetic inhibitor called BPI (BCL6 Peptidomimetic Inhibitor) that is far more potent and stable than its prototype. We have treated a large panel of DLBCL cell lines with BPI to determine the spectrum and mechanisms of sensitivity and resistance to this agent. BPI (1 to 20 μM) caused dose dependent killing of 6 of 10 DLBCL cell lines in vitro. Sensitive DLBCL cell lines display a high percentage of necrotic and apoptotic cells as shown by 7-ADD and Annexin-V staining. Additionally, by BrdU incorporation plus PI staining, we demonstrated that cells undergo cell cycle arrest before the death pathway is initiated. Since BCL6 represses genes involved in DNA repair checkpoints, cell cycle and protein ubiquitylation and degradation, we predicted that combination therapy with cytotoxic drugs or drugs that alter cellular protein metabolism might synergize with BPI to kill DLBCL cells. We performed combinatorial therapy studies where additional drugs were administered 24 hours after BPI and cells were evaluated for viability in several different assays. We found an additive to synergistic effect of BPI with several cytotoxic drugs commonly used in lymphoma therapy (such as doxorubicin, alkylating agents, etoposide and dexamethasone), as well as bortezomib (a proteasome inhibitor). In vivo xenotransplantation studies with the BPI sensitive cell lines Ly1, Ly7, SUDHL4 and SUDHL6 showed a marked decrease in tumor size and weight (p=0.03 for control vs BPI, T-test), as well as serum β2-microglobulin (BPI: 6.5 ± 2 μg/ml vs control: 14.3 ± 2.5 μg/ml, p=0.02), even when BPI was administered at very low doses (150 μg per day). The tumor remnants from BPI treated animals showed extensive induction of apoptosis (determined by TUNEL), a lower mitotic index (2 ± 0.8/100 cells vs 4.8 ± 0.9/100 cells, for BPI vs. control respectively, p<0.01), and upregulation of BCL6 target genes such as p53 and p21. Finally, we tested BPI in a series of 30 tissue samples obtained from patients with clinical suspicion of lymphoma. Of these, the 11 patients with BCL6 positive B-cell tumors were highly sensitive to BPI while none of the remaining 19 patients responded (of these 19 = 10 were reactive lymph node, 2 Hodgkin’s disease, 2 T-cell lymphomas and the rest were other non-lymphoid tumors), underlining the specificity of BPI for BCL6 positive tumors. Our data indicates that BPI alone has powerful anti-lymphoma activity and warrants clinical evaluation in patients with DLBCLs. BPI can synergize with other drugs suggesting that combination therapy might provide more potent and less toxic therapeutic regimens for these patients.
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Johannsen, Florian, Gregor Zellner, and Philipp Griesberger. "Creating a Functional Interdependency Map for Supporting the “Act of Improvement” in Business Process Improvement Projects." International Journal of Service Science, Management, Engineering, and Technology 13, no. 1 (January 2022): 1–23. http://dx.doi.org/10.4018/ijssmet.295557.
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Business process improvement (BPI) is of high priority for practitioners. But especially the most value-adding phase in a BPI project, namely the “act of improvement”, is insufficiently supported despite the many existing methods and techniques. Until now, it is largely unclear as to what degree existing BPI techniques support each other and are interrelated with one another. Thus, the purpose of this paper is to investigate the functional interdependencies between BPI techniques to get a better understanding for the beneficial synergies between the BPI techniques and to provide a basis for purposefully combining them within projects. Based on the functional interdependencies, a graphical “Functional Interdependency Map” is developed and its usability demonstrated in an experiment. The paper is valuable for academics and practitioners alike because the impact of BPI on organizational performance is high.
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Dy, Christopher J., David M. Brogan, Liz Rolf, Wilson Z. Ray, Scott W. Wolfe, and Aimee S. James. "A qualitative study of life satisfaction after surgery for adult traumatic brachial plexus injury." Bone & Joint Open 2, no. 1 (January 1, 2021): 9–15. http://dx.doi.org/10.1302/2633-1462.21.bjo-2020-0175.r1.
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Aims Brachial plexus injury (BPI) is an often devastating injury that affects patients physically and emotionally. The vast majority of the published literature is based on surgeon-graded assessment of motor outcomes, but the patient experience after BPI is not well understood. Our aim was to better understand overall life satisfaction after BPI, with the goal of identifying areas that can be addressed in future delivery of care. Methods We conducted semi-structured interviews with 15 BPI patients after initial nerve reconstruction. The interview guide was focused on the patient’s experience after BPI, beginning with the injury itself and extending beyond surgical reconstruction. Inductive and deductive thematic analysis was used according to standard qualitative methodology to better understand overall life satisfaction after BPI, contributors to life satisfaction, and opportunities for improvement. Results Among the 15 patients interviewed, the following themes emerged: 1) happiness and life satisfaction were noted despite limitations in physical function; 2) quality of social support influences life satisfaction during recovery from BPI; and 3) social participation and having a sense of purpose impact life satisfaction during recovery from BPI. Conclusion How patients perceive their BPI treatment and recovery varies widely, and is not directly linked to their self-reported functional outcome. Patients with stronger social circles and activities that give them a sense of fulfillment were more likely to be satisfied with their current status. Evaluating a patient’s social network, goals, and potential supportive adaptations early in the treatment timeline through coordinated multidisciplinary care may improve overall satisfaction during recovery from BPI. Cite this article: Bone Joint Open 2020;2(1):9–15.
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Monahan, P. O., T. Stump, W. H. Coryell, J. Harezlak, G. A. Marcoulides, H. Liu, C. M. Steeger, et al. "Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity." Psychological Medicine 45, no. 10 (March 31, 2015): 2181–96. http://dx.doi.org/10.1017/s0033291715000185.
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BackgroundThe first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders.MethodA cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998–2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA.ResultsThe two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives.ConclusionsThe BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.
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Macarulla, Teresa Mercade, Jens T. Siveke, Andrew Peter Dean, Richard Hubner, Jean-Frédéric Blanc, David Cunningham, Li-Tzong Chen, et al. "Subgroup analysis by baseline pain intensity (BPI) and analgesic use (BAU) in NAPOLI-1: A phase III study of liposomal irinotecan (nal IRI)±5-fluorouracil/ leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 379. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.379.
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379 Background: We report an exploratory, post hoc subgroup analysis in pts with BPI and BAU data receiving nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1 (NCT01494506). In this pivotal trial, nal-IRI+5-FU/LV improved median OS (mOS) vs. 5-FU/LV (6.1 vs. 4.2 mo [HR=0.67; p=0.012]). Methods: BPI/BAU included an average of 3-7 days pt-recorded data before randomisation. Greater values indicated greater pain for BPI using a 100 mm visual analogue scale. BAU was converted to morphine equivalent mg/day. Results: Of 417 ITT pts, 295 had BPI and 299 had BAU data. Mean and median BPI were 28.6 and 25.0, respectively, and BAU were 33.3 and 8.1 mg/day, respectively. The percentage of pts with KPS ≥ 80 was higher in ≤ mean/≤ median (n=159/148) BPI groups vs. > mean/> median (n=136/147) BPI groups (96-97 vs. 83%) and in ≤mean/≤median (n=207/150) BAU groups vs. > mean/> median (n=92/149) BAU groups (95-97 vs. 82-85%). mOS and median PFS (mPFS) were higher for nal-IRI+5-FU/LV vs 5-FU/LV in all groups, with ≤ mean/≤ median BPI or BAU showing better outcomes vs. > mean/> median BPI or BAU (Table). Conclusions: BPI and BAU appear to have a prognostic effect on outcomes in mPDAC pts in the NAPOLI-1 study. No predictive effect was observed, with nal-IRI+5-FU/LV showing higher mOS vs. 5-FU/LV in all groups. Clinical trial information: NCT01494506. [Table: see text]
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Grigoroiu-Serbanescu, M., C. C. Diaconu, S. Herms, J. Vollmer, C. Bleotu, M. M. Noethen, and S. Cichon. "Tryptophan Hydroxylase 2 (TPH2) Gene in Bipolar I Disorder in the Romanian Population." European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70813-2.
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Objective:Since the discovery of the tryptophan hydroxylase 2 gene (TPH2) several studies reported association of TPH2 genetic variation with bipolar I disorder (BPI). Our objectives were to replicate in the Romanian population the recently described association of a rare functional SNP (rs17110563) and of a haplotype covering the 5′ region of TPH2 with BPI (Cichon et al., 2008) and to investigate the influence of the phenotypic traits age-of-onset, family history and parent-of-origin”, defined according to clinical criteria, on the degree of association between TPH2 and BPI.Method:Sixteen TPH2 SNPs were genotyped in a Romanian sample of 198 BPI patients and 180 controls screened for psychiatric disorders. Statistical analysis of the data was performed with Haploview3.32 and FAMHAP.Results:The functional SNP rs17110563 (encoding a Pro206Ser substitution) was present in Romanian BPI patients and absent in controls. SNPs located in the 5′-region (rs11178997, rs11178998, rs7954758), significantly associated with BPI in German patients were not associated with BPI in Romanian patients at single-marker level, but gave evidence for association at haplotypic level in a subgroup of patients with paternal transmission of BPI. Evidence for association was identified between haplotypes located in the 3′-region of TPH2 and BPI in the overall sample as well as in the subgroups of familial cases, the subgroup with paternal transmission, and the subgroup with AO≤25 years.Conclusion:Our data provide support for the involvement of TPH2 in the etiology of BPI.
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Jin, Jian, Yanjie Huang, Shouyong Sun, Zhengchang Wu, Shenglong Wu, Zongjun Yin, and Wenbin Bao. "The Impact of BPI Expression on Escherichia coli F18 Infection in Porcine Kidney Cells." Animals 10, no. 11 (November 15, 2020): 2118. http://dx.doi.org/10.3390/ani10112118.
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The efficacy and regulatory activity of bactericidal/permeability-increasing protein (BPI) as a mediator of Escherichia coli (E. coli) F18 resistance remains to be defined. In the present study, we evaluated lipopolysaccharide (LPS)-induced changes in BPI gene expression in porcine kidney (PK15) cells in response to E. coli F18 exposure. We additionally generated PK15 cells that overexpressed BPI to assess the impact of this gene on Toll-like receptor 4 (TLR4) signaling and glycosphingolipid biosynthesis-related genes. Through these analyses, we found that BPI expression rose significantly following LPS exposure in response to E. coli F18ac stimulation (p < 0.01). Colony count assays and qPCR analyses revealed that E. coli F18 adherence to PK15 cells was markedly suppressed following BPI overexpression (p < 0.01). BPI overexpression had no significant effect on the mRNA-level expression of genes associated with glycosphingolipid biosynthesis or TLR4 signaling. BPI overexpression suppressed the LPS-induced TLR4 signaling pathway-related expression of proinflammatory cytokines (IFN-α, IFN-β, MIP-1α, MIP-1β and IL-6). Overall, our study serves as an overview of the association between BPI and resistance to E. coli F18 at the cellular level, offering a framework for future investigations of the mechanisms whereby piglets are able to resist E. coli F18 infection.
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Fatahillah, Ahmad, and Ignatius Sonny Winardhi. "Perbandingan Inversi Reflektifitas Menggunakan Basis Pursuit Inversion dan Orthogonal Matching Pursuit pada Lapisan Tipis." Jurnal Geofisika 15, no. 2 (November 20, 2019): 1. http://dx.doi.org/10.36435/jgf.v15i2.401.
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Meningkatnya kebutuhan energi membuat diperlukannya eksplorasi migas untuk reservoar-reservoar tipis. Metode seismik memiliki peran penting dalam eksplorasi minyak dan gas bumi namun keterbatasan bandwith frekuensi menjadi salah satu permasalahan penampang seismik dalam meresolusi lapisan tipis. Terdapat beberapa metode yang dapat meresolusi lapisan tipis salah satunya basis pursuit inversion (BPI) namun proses BPI memerlukan waktu yang relatif lama. Terdapat metode orthogonal matching pursuit (OMP) yang juga dapat meresolusi lapisan tipis dengan waktu yang lebih singkat dari BPI. Penelitian ini mencoba menganalisis faktor-faktor yang berpengaruh dalam metode BPI dan OMP yaitu, regularization parameter (lambda), noise, ekstraksi wavelet, dan panjang matriks dictionary. Uji coba pada data sintetik membuktikan bahwa ekstraksi wavelet berpengaruh pada metode BPI dan diperoleh batasan kesalahan fasa dari −14◦ sampai 14◦ pada model odd dan −16◦ sampai 16◦ pada model even, batasan kesalahan frekuensi dari -3 Hz sampai 3 Hz untuk model odd dan batasan keberadaan konvolusional noise sebesar 40% pada model even.Hasil uji coba data sintetik pada metode OMP menunjukkan bahwa OMP tidak memiliki ketahanan terhadap perubahan faktor ekstraksi wavelet dikarenakan tidak memiliki faktor denoising sehingga metode OMP kurang optimal untuk diterapkan pada data riil. Validasi metode BPI pada data riil dilakukan dengan membandingkan korelasi antara hasil BPI dengan data sumur. Hasil validasi menunjukkan metode BPI mampu meresolusi lapisan tipis dengan baik.
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Li, Kun, Yue Liu, Xiaoyu Xia, Li Wang, Meige Lu, Yanqin Hu, and Chen Xu. "Bactericidal/permeability-increasing protein in the reproductive system of male mice may be involved in the sperm–oocyte fusion." REPRODUCTION 146, no. 2 (August 2013): 135–44. http://dx.doi.org/10.1530/rep-13-0127.
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Bactericidal/permeability-increasing protein (BPI) is a 455-residue (∼55 kDa) protein found mainly in the primary (azurophilic) granules of human neutrophils. BPI is an endogenous antibiotic protein that belongs to the family of mammalian lipopolysaccharide (LPS)-binding and lipid transport proteins. Its major function is to kill Gram-negative bacteria, thereby protecting the host from infection. In addition, BPI can inhibit angiogenesis, suppress LPS-mediated platelet activation, increase DNA synthesis, and activate ERK/Akt signaling. In this study, we found thatBpiwas expressed in the testis and epididymis but not in the seminal vesicles, prostate, and solidification glands. BPI expression in the epididymis increased upon upregulation of testosterone, caused by injection of GNRH. In orchidectomized mice, BPI expression was significantly reduced, but its expression was restored to 30% of control levels in orchidectomized mice that received supplementary testosterone. The number of sperm fused per egg significantly decreased after incubation with anti-BPI antiserum. These results suggest that BPI may take part in the process of sperm–oocyte fusion and play a unique and significant role in reproduction.
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Kang, Dae Gill, Li Hua Cao, Jun Kyoung Lee, Deok Ho Choi, Seung Ju Kim, Hyuck Lee, Jin Sook Kim, and Ho Sub Lee. "Endothelium-Dependent Induction of Vasorelaxation by the Butanol Extract of Phellinus igniarius in Isolated Rat Aorta." American Journal of Chinese Medicine 34, no. 04 (January 2006): 655–65. http://dx.doi.org/10.1142/s0192415x06004181.
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The butanol extract of Phellinus igniarius (BPI) induced relaxation of the phenylephrin e-precontracted rat aorta in a dose-dependent manner, and its effect was abolished by the removal of functional endothelium. Pretreatment of the aortic tissues with NG -nitro-L-arginine methyl ester (L-NAME), methylene blue, or 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin1-one (ODQ) inhibited the vascular relaxation induced by BPI. BPI-induced vascular relaxations were also markedly attenuated by the addition of verapamil or diltiazem, while the relaxant effect of BPI was not blocked by pretreatment with indomethacine, glibenclamide, tetraethylammonium (TEA), atropine, or propranolol. Incubation of endothelium-intact rat aorta with BPI increased the production of cGMP in a dose-dependent manner. These results suggest that BPI dilates vascular smooth muscle via endothelium-dependent nitric oxide-cGMP signaling pathway, with the possible involvement of L-type Ca 2+ channels.
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Palmer, Christine D., Eva C. Guinan, and Ofer Levy. "Deficient expression of bactericidal/permeability-increasing protein in immunocompromised hosts: translational potential of replacement therapy." Biochemical Society Transactions 39, no. 4 (July 20, 2011): 994–99. http://dx.doi.org/10.1042/bst0390994.
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BPI (bactericidal/permeability-increasing protein) is a 55 kDa anti-infective molecule expressed in neutrophil and eosinophil granules and on some epithelial cells. BPI's high affinity for the lipid A region of endotoxin targets its opsonizing, microbicidal and endotoxin-neutralizing activities towards Gram-negative bacteria. Several immunocompromised patient populations demonstrate BPI deficiency, including newborns, those with anti-neutrophil cytoplasmic antibodies (as in cystic fibrosis and HIV infection) and those exposed to radiochemotherapy. BPI may be replenished by administering agents that induce its expression or by administration of recombinant BPI congeners, potentially shielding BPI-deficient individuals against Gram-negative bacterial infection, endotoxemia and its toxic sequelae.
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Satghare, Pratika, Edimansyah Bin Abdin, Aditi Hombali, Wen Lin Teh, Ellaisha Samari, Boon Yiang Chua, Swapna Verma, Yee Ming Mok, Siow Ann Chong, and Mythily Subramaniam. "Chronic Pain: Among Tertiary Care Psychiatric Out-Patients in Singapore—Prevalence and Associations with Psychiatric Disorders." Pain Research and Management 2022 (April 15, 2022): 1–9. http://dx.doi.org/10.1155/2022/1825132.
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Objective. The study aimed to determine the prevalence and severity of chronic pain and its associations amongst psychiatric out-patients in a tertiary care hospital in Singapore. Methodology. The cross-sectional study was conducted among 290 psychiatric out-patients aged 21–65 years. Sociodemographic and clinical information, as well as data from Brief Pain Inventory-Short Form (BPI-sf), Beck’s Depression Inventory II (BDI-II), and Beck’s Anxiety Inventory (BAI) were collected. Cut points (C.P.s) dividing the sample into mild, moderate, and severe groups were created for the ratings of average pain. Eight possible cut-off values for the C.P.s between 3 and 7, representing 8 different categorical variables, were created and their relationships were examined with BPI’s set of seven interference items using multivariate analysis of variance. Sociodemographic and clinical correlates of chronic pain were determined using multinomial logistic regression analysis. Analysis of covariance was used to determine the association of BPI with continuous scores of BAI and BDI. Results. Based on the C.P. pain severity classification, 38.5% of the sample had mild pain, 22.9% had moderate pain, and 11.8% had severe pain. Patients with severe pain were more likely to be associated with older age ( p ≤ 0.006 ) (versus young age), less likely to be married ( p ≤ 0.025 ) (versus single), and more likely to have high risk for obesity ( p ≤ 0.030 ) (versus low risk for obesity). Participants with mild pain were seen to be significantly associated with older age ( p ≤ 0.021 ), whereas moderate pain ( p ≤ 0.002 ) and severe pain ( p ≤ 0.001 ) (versus no pain) were seen to be significantly associated with higher BAI scores. Conclusion. The current study observed high prevalence of pain among patients with psychiatric illness that was determined by optimal C.P.s for mild, moderate, and severe pain. Patients diagnosed with anxiety disorders and those with higher BMI were seen to be associated with pain of moderate to severe intensity. Improving the knowledge of correlates and co-morbidities of physical pain would aid in early identification, use of prophylactic strategies, and the intervention techniques to formulate basic guidelines for pain management among psychiatric population.
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Zeng, Liang, Arjun Sahgal, Liying Zhang, Kaitlin Koo, Lori Holden, Florencia Jon, May Tsao, et al. "Patterns of Pain and Functional Improvement in Patients with Bone Metastases after Conventional External Beam Radiotherapy and a Telephone Validation Study." Pain Research and Treatment 2011 (January 17, 2011): 1–9. http://dx.doi.org/10.1155/2011/601720.
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Patients experiencing lower body pain resulting from bone metastases have greater levels of functional interference than those with upper body pain. The purpose of this study was to assess the levels of interference caused by pain after treatment with conventional radiotherapy using the Brief Pain Inventory (BPI) and to validate this tool for telephone use. After radiotherapy, a total of 159, 129, and 106 patients completed the BPI over the telephone at months 1, 2, and 3, respectively. Cronbach's alpha, confirmatory factor analysis, and discriminant validity tests were performed to assess the validity of the BPI. One-way ANOVA was used to compare BPI scores. There was no statistically significant difference in functional interference among patients after treatment. Internal consistency of the BPI was high. Functional interference may be inherently higher in patients with pain in the lower body. Telephone use of the BPI is reliable and recommended in this population.
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Skopelja, Sladjana, JoNell Hamilton, Jonathan D. Jones, Alix Ashare, Alex H. Gifford, and William F. C. Rigby. "The nature and role of autoimmunity in cystic fibrosis lung immunopathology." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 124.47. http://dx.doi.org/10.4049/jimmunol.196.supp.124.47.
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Abstract Cystic Fibrosis (CF) arises due to the altered activity of the CF transmembrane regulator (CFTR) protein. While the lung disease in CF is associated with chronic infection by Pseudomonas aeruginosa (PA), identical CFTR mutations exhibit considerable clinical variability. To elucidate this, we evaluated the autoantibody response to bactericidal permeability-increasing protein (BPI) and anti-citrullinated proteins (ACPA) in CF patients (n=38) and compared it with the autoantibody profile in sera from Rheumatoid Arthritis (RA) patients (n=50), given the association of airway inflammation with ACPA induction in RA. The presence of ACPA was restricted to RA patients; no antibodies to BPI were seen. In contrast, 42% of CF patients had anti-BPI IgG, but no ACPA. Contrary to ACPA, the autoantibodies to BPI did not bind to post-translationally modified epitopes but mapped to the protein C-terminus (CT-BPI). Patients with high levels of anti-BPI IgG exhibited worse lung function (lower FEV1), the presence of anti-Cif antibodies (CFTR inhibitory factor), and the absence of the homozygous F508del CFTR mutation. Neutrophil incubation with PA led to the cleavage of BPI into a ~32kDa fragment corresponding to CT-BPI, in an elastase dependent process. In addition, anti-BPI IgG levels were higher in patients harboring the more pathogenic (mucoid) PA strain infection. These findings prompt the model that autoantibody responses reflect greater impairment of PA clearance, which is the hallmark of this chronic inflammatory disorder. Alternatively, given that no clear association between bacterial colonization and CF disease severity exists, the model that autoantibodies independently exacerbate CF lung pathology merits consideration.
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Alexander, Scott, Jonathan Bramson, Ronan Foley, and Zhou Xing. "Protection from endotoxemia by adenoviral-mediated gene transfer of human bactericidal/permeability-increasing protein." Blood 103, no. 1 (January 1, 2004): 93–99. http://dx.doi.org/10.1182/blood-2003-02-0660.
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Abstract Sepsis represents a growing concern in high-risk patients and there has been a lack of effective preventives and therapies. Bacterial/permeability increasing protein (BPI) is a human neutrophil granule-associated defense molecule specific for Gram-negative bacteria and their products. To develop a BPI-transgene–based prophylactic or therapeutic modality, we have developed a recombinant, replication-deficient adenoviral vector expressing full-length human BPI protein (AdhBPI). The expression of BPI is under control of a murine cytomegalovirus (CMV) promoter. Using in vitro and in vivo systems, AdhBPI-mediated gene transfer led to extracellular secretion of BPI protein, which effectively neutralized endotoxin (lipopolysaccharide [LPS]) and markedly reduced the production of proinflammatory cytokines tumor necrosis factor α (TNF-α) and macrophage inflammatory protein 2 (MIP-2) by freshly isolated murine alveolar macrophages. By using a mouse model of nonlethal sepsis elicited with LPS, we demonstrated that in vivo gene transfer of BPI was able to markedly inhibit the effect of a large dose of LPS on cytokine responses when injected intraperitoneally. Furthermore, such in vivo BPI gene transfer also improved the survival of mice suffering from lethal septic shock elicited by intraperitoneal injection of d-galactosamine and LPS. Thus, our results suggest that human BPI gene transfer vector has the potential to be used as a therapeutic agent for septic conditions.
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Chuang, Huai-Chia, and Tse-Hua Tan. "T-cell-derived Exosomal Proteins ECP and BPI Induce Cytokines and Tissue Inflammation in Systemic Lupus Erythematosus." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 108.08. http://dx.doi.org/10.4049/jimmunol.208.supp.108.08.
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Abstract T cells play critical roles in the pathogenesis of systemic lupus erythematosus (SLE). Serum-derived exosomes are increased in human SLE patients and are correlated with disease severity; however, the property of T-cell-derived exosomes from SLE patients remains unclear. We characterized proteins of SLE T cell-derived exosomes by exosome MACSPlex analysis and proteomics using T-cell supernatants from human SLE patients and healthy controls. We identified two exosoaml proteins, eosinophil cationic protein (ECP, also named human RNase 3) and bactericidal/permeability-increasing protein (BPI), which were overexpressed in SLE T-cell-derived exosomes and T cells. Both T-cell-specific ECP transgenic (Lck-ECP Tg) and BPI transgenic (Lck-BPI Tg) mice displayed multi-tissue inflammation. Lck-ECP and Lck-BPI Tg mice displayed early induction of serum IFN-γ levels and IL-1β levels, respectively. Single-cell RNA sequencing (scRNA-seq) showed the induction of IFN-γ mRNA and inflammatory pathways in ECP Tg T cells. ScRNA-seq also showed the reduction of Treg population in BPI Tg T cells; conversely, Treg differentiation was enhanced by BPI knockout. Remarkably, adoptively transferred ECP-containing or BPI-containing exosomes stimulated serum autoantibodies levels and induced nephritis/nephritis/arthritis in the recipient mice. Collectively, ECP or BPI overexpression in T-cell-derived exosomes or T cells are novel biomarkers and pathogenic factors for human SLE nephritis, hepatitis, and arthritis.
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van der Schaft, Daisy W. J., Elly A. H. Toebes, Judith R. Haseman, Kevin H. Mayo, and Arjan W. Griffioen. "Bactericidal/permeability-increasing protein (BPI) inhibits angiogenesis via induction of apoptosis in vascular endothelial cells." Blood 96, no. 1 (July 1, 2000): 176–81. http://dx.doi.org/10.1182/blood.v96.1.176.
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Abstract Bactericidal/permeability-increasing protein (BPI) has been known for some time to function in killing bacteria and in neutralizing the effects of bacterial endotoxin lipopolysaccharide. In the present study, BPI is found to be a novel endogenous inhibitor of angiogenesis. Within the sub-μM range, BPI shows a concentration-dependent inhibition of endothelial cell (EC) proliferation that is mediated by cell detachment and subsequent induction of apoptosis. As measured by flow cytometric analysis of the percentage of subdiploid cells, apoptosis induction was half-maximal at about 250 nmol/L BPI. Apoptosis was confirmed by quantification of cells with nuclear fragmentation. Apoptosis was found to be EC specific. In an in vitro collagen gel-based angiogenesis assay, BPI at 1.8 μmol/L inhibited tube formation by 81% after only 24 hours. Evidence for in vivo inhibition of angiogenesis was obtained, using the chorioallantoic membrane assay in which BPI was seen to be significantly effective at concentrations as low as 180 nmol/L. This newly discovered function of BPI might provide a possible therapeutic modality for the treatment of various pathologic disorders that depend on angiogenesis.
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van der Schaft, Daisy W. J., Elly A. H. Toebes, Judith R. Haseman, Kevin H. Mayo, and Arjan W. Griffioen. "Bactericidal/permeability-increasing protein (BPI) inhibits angiogenesis via induction of apoptosis in vascular endothelial cells." Blood 96, no. 1 (July 1, 2000): 176–81. http://dx.doi.org/10.1182/blood.v96.1.176.013k32_176_181.
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Bactericidal/permeability-increasing protein (BPI) has been known for some time to function in killing bacteria and in neutralizing the effects of bacterial endotoxin lipopolysaccharide. In the present study, BPI is found to be a novel endogenous inhibitor of angiogenesis. Within the sub-μM range, BPI shows a concentration-dependent inhibition of endothelial cell (EC) proliferation that is mediated by cell detachment and subsequent induction of apoptosis. As measured by flow cytometric analysis of the percentage of subdiploid cells, apoptosis induction was half-maximal at about 250 nmol/L BPI. Apoptosis was confirmed by quantification of cells with nuclear fragmentation. Apoptosis was found to be EC specific. In an in vitro collagen gel-based angiogenesis assay, BPI at 1.8 μmol/L inhibited tube formation by 81% after only 24 hours. Evidence for in vivo inhibition of angiogenesis was obtained, using the chorioallantoic membrane assay in which BPI was seen to be significantly effective at concentrations as low as 180 nmol/L. This newly discovered function of BPI might provide a possible therapeutic modality for the treatment of various pathologic disorders that depend on angiogenesis.