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1
Rimawi, B. H., R. H. Rimawi, M. Micallef, L. Pinckney, S. L. Fowler, and T. C. Dixon. "Pediatric HIV Long-Term Nonprogressors." Case Reports in Infectious Diseases 2014 (2014): 1–3. http://dx.doi.org/10.1155/2014/752312.
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Patients infected with HIV are best categorized along a continuum from rapid progressors to HIV long-term nonprogressors. Long-term nonprogressors (LTNPs) are those in which AIDS develop many years after being infected with HIV, often beyond the 10-year mark, and represent 15–20% of the HIV infected patients. Many of these patients are able to control their infection and maintain undetectable viral loads for long periods of time without antiretroviral therapy. After a comprehensive literature search, we found extensive data related to HIV LTNPs in the adult population; however, very limited data was available related to LTNPs within the pediatric population. We present a case of pediatric HIV LTNPs, perinatally infected patient with undetectable viral loads, despite never receiving ART. Although there are not many instances of LTNPs among children, this child may be one, though she had intermittent viremia. She has continued to manifest serologic evidence of infection, with yearly ELISA and western blot positive tests. Based on the viral fitness studies that were performed, this case exemplifies an adolescent LTNP.
2
Pushker, Ravindra, Jean-Marc Jacqué, and Denis C. Shields. "Meta-Analysis To Test the Association of HIV-1 nef Amino Acid Differences and Deletions with Disease Progression." Journal of Virology 84, no. 7 (2010): 3644–53. http://dx.doi.org/10.1128/jvi.01959-09.
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ABSTRACT Previous relatively small studies have associated particular amino acid replacements and deletions in the HIV-1 nef gene with differences in the rate of HIV disease progression. We tested more rigorously whether particular nef amino acid differences and deletions are associated with HIV disease progression. Amino acid replacements and deletions in patients' consensus sequences were investigated for 153 progressor (P), 615 long-term nonprogressor (LTNP), and 2,311 unknown progressor sequences from 582 subtype B HIV-infected patients. LTNPs had more defective nefs (interrupted by frameshifts or stop codons), but on a per-patient basis there was no excess of LTNP patients with one or more defective nef sequences compared to the Ps (P = 0.47). The high frequency of amino acid replacement at residues S8, V10, I11, A15, V85, V133, N157, S163, V168, D174, R178, E182, and R188 in LTNPs was also seen in permuted datasets, implying that these are simply rapidly evolving residues. Permutation testing revealed that residues showing the greatest excess over expectation (A15, V85, N157, S163, V168, D174, R178, and R188) were not significant (P = 0.77). Exploratory analysis suggested a hypothetical excess of frameshifting in the regions 9SVIG and 118QGYF among LTNPs. The regions V10 and 152KVEEA of nef were commonly deleted in LTNPs. However, permutation testing indicated that none of the regions displayed significantly excessive deletion in LTNPs. In conclusion, meta-analysis of HIV-1 nef sequences provides no clear evidence of whether defective nef sequences or particular regions of the protein play a significant role in disease progression.
3
Huang, Lei, Jianning Deng, Ren Lang, Guoyang Liao, and Wei Jiang. "Enriched LPS Staining within the Germinal Center of a Lymph Node from an HIV-Infected Long-Term Nonprogressor but Not from Progressors." Journal of Immunology Research 2020 (May 6, 2020): 1–5. http://dx.doi.org/10.1155/2020/7471380.
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An increased level of microbial translocation has been observed in HIV-infected individuals. The host response to microbial translocation is compromised in HIV-infected progressors but remains unknown in HIV-infected long-term nonprogressors (LTNPs). To evaluate microbial translocation in HIV, we assessed lipopolysaccharide (LPS) immunohistochemistry staining in lymph nodes. We found enriched bacterial LPS immunohistochemistry staining in the germinal center of a lymph node from an HIV-infected LTNP, evenly distributed from three progressors with impaired germinal center structures and rarely detected from two HIV-negative individuals. The impaired germinal center structures were consistent with collagen deposition in lymph nodes using immunohistochemistry staining. These results suggest greater immune responses against bacterial LPS translocation in LTNPs, which may reveal an important mechanism in controlling microbial translocation and disease progression in HIV LTNPs.
4
Ogundeyi, MM, OO Oba-Daini, UP Adeniyi, and BI Adenuga. "A case report A Nigerian adolescent with Long term Non-progressive HIV-infection: A case report." Annals of Health Research 6, no. 2 (2020): 239–45. http://dx.doi.org/10.30442/ahr.0602-13-86.
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Children infected with the Human Immunodeficiency Virus (HIV) can be rapid progressors or be at the end of the spectrum of the illness as Long-term Non-progressors (LTNPs). Long term non-progressors are patients who never received Highly Active Anti-Retroviral Therapy (HAART) during the first decade of life and are maintaining good CD4+ count associated with declining HIV RNA values. The literature on paediatric patients with LTNP infection is sparse.
An adolescent with HIV LTNP and likely vertical transmission of HIV is presented in this report. She presented with chronic cough, severe anaemia and dyspnea. She was wasted with bodyweight less than the 5th centile for age. She was not sexually active and had no history of blood transfusion, scarification, incisions or sharing of sharp grooming objects.
The results of investigations suggested pulmonary tuberculosis and HIV infection. Her CD4 count was 42%. She was commenced on HAART and subsequently, anti-tuberculosis medications according to NTBLCP/DOTS Programme with improvement in symptoms and appreciable weight gain.
Therefore routine voluntary HIV testing is recommended for all paediatric admission after consent or assent is obtained bearing in mind that a small subset of patients may fall into the LTNPs population.
5
Mendoza, Daniel, Sarah A. Johnson, Bennett A. Peterson, et al. "Comprehensive analysis of unique cases with extraordinary control over HIV replication." Blood 119, no. 20 (2012): 4645–55. http://dx.doi.org/10.1182/blood-2011-10-381996.
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Abstract True long-term nonprogressors (LTNPs)/elite controllers (ECs) maintain durable control over HIV replication without antiretroviral therapy. Herein we describe 4 unique persons who were distinct from conventional LTNPs/ECs in that they had extraordinarily low HIV burdens and comparatively weak immune responses. As a group, typical LTNPs/ECs have unequivocally reactive HIV-1 Western blots, viral loads below the lower threshold of clinical assays, low levels of persistent viral reservoirs, an over-representation of protective HLA alleles, and robust HIV-specific CD8+ T-cell responses. The 4 unique cases were distinguished from typical LTNPs/ECs based on weakly reactive Western blots, undetectable plasma viremia by a single copy assay, extremely low to undetectable HIV DNA levels, and difficult to isolate replication-competent virus. All 4 had at least one protective HLA allele and CD8+ T-cell responses that were disproportionately high for the low antigen levels but comparatively lower than those of typical LTNPs/ECs. These unique persons exhibit extraordinary suppression over HIV replication, therefore, higher-level control than has been demonstrated in previous studies of LTNPs/ECs. Additional insight into the full spectrum of immune-mediated suppression over HIV replication may enhance our understanding of the associated mechanisms, which should inform the design of efficacious HIV vaccines and immunotherapies.
6
Michel, Katherine Gisella, Bing Ma, Kathleen Weber, et al. "4117 UNIQUE VAGINAL MICROBIOME POPULATIONS AND MICROBIAL GENE CONTENT AMONG WOMEN WHO NATURALLY CONTROL HIV PROGRESSION." Journal of Clinical and Translational Science 4, s1 (2020): 20–21. http://dx.doi.org/10.1017/cts.2020.102.
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OBJECTIVES/GOALS: The role of the vaginal microbiome (VM) in HIV disease progression is poorly understood. We examined VMs of HIV+ Elite Controllers (ECs) and HIV+ Long-Term Non-Progressors (LTNPs) compared to controls: HIV-positive antiretroviral (ARV) treated (HIV+ATs) and HIV-negative women in the Women’s Interagency HIV Study (DC/Chicago/Atlanta sites). METHODS/STUDY POPULATION: VMs were surveyed via both V3/V4 region of 16S rRNA gene amplicon sequencing and metagenomics sequencing in 67 women across 4 study groups: 1) LTNPs (CD4 >500 cells/mL for 5+ years without ARVs) (n = 7) and 2) ECs (HIV RNA <80 copies/mL for 2+ years without ARVs) (n = 8), matched with 3) HIV+ ATs (on ARVs for ≥1 year with CD4 increase ≥100 cells/mm3) (n = 34), and 4) HIV- women (n = 18). Metagenomes were characterized from specimens collected at two time points: 1) vaginal swabs collected 2016-2017 (n = 62) and 2) cervicovaginal lavage collected 2002-2016 (n = 35; DC/Chicago only). We used VIRGO (human vaginal non-redundant gene catalog), a newly developed referencing framework to comprehensively catalog VM gene content, taxonomy and functions. RESULTS/ANTICIPATED RESULTS: Women were 89% African American with a mean age of 46 years (SD 8.8). The most prevalent species were Gardnerella vaginalis (predominant in 34%), Lactobacillus iners (predominant in 21%), and L. crispatus (predominant in 14%). 90% of LTNP and 45% of EC samples were Lactobacillus-dominant vs. 28% of HIV- and 30% of HIV+ATs. L. crispatus and L. iners in ECs/LTNPs had significantly different gene content and greater gene richness vs. controls. G. vaginalis-predominant communities were found in 66% of HIV- and 68% of HIV+ATs, compared to 46% of EC and 0% of LTNP. The G. vaginalis strains present in EC/LTNP also showed significantly lower gene richness and different gene content vs. controls. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest unique VM communities among EC/LTNP, and led us to hypothesize that differential regulation of vaginal immunity drives the observed differences. The similarity between VMs of HIV- and HIV+ATs warrants further study. Larger longitudinal VM studies are needed to assess associated functional pathways and understand the etiology of VM association with HIV progression. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest to disclose.
7
Tobiume, Minoru, Mikako Takahoko, Takeshi Yamada, Masashi Tatsumi, Aikichi Iwamoto, and Michiyuki Matsuda. "Inefficient Enhancement of Viral Infectivity and CD4 Downregulation by Human Immunodeficiency Virus Type 1 Nef from Japanese Long-Term Nonprogressors." Journal of Virology 76, no. 12 (2002): 5959–65. http://dx.doi.org/10.1128/jvi.76.12.5959-5965.2002.
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ABSTRACT It has been reported that patients infected with nef-defective human immunodeficiency virus type 1 (HIV-1) do not progress to AIDS; however, mutations that abrogate Nef expression are not common in long-term nonprogressors (LTNPs). We postulated that Nef function might be impaired in LTNPs, irrespective of the presence or absence of detectable amino acid sequence anomalies. To challenge this hypothesis we compared in vitro function of nef alleles that were derived from three groups of Japanese patients: LTNPs, progressors, and asymptomatic carriers (ACs). The patient-derived nef alleles were subcloned into a nef-defective infectious HIV-1 molecular clone and an expression vector. We first examined Nef-dependent enhancement of infection in a single-round infectivity assay by the use of MAGNEF cells, in which Nef is required more strictly for the infection than in the parent MAGI cells. All nef alleles from LTNPs showed reduced enhancement in the infectivity of nef-defective HIV-1 mutants compared to the nef alleles of progressors or ACs. Second, we found that nef alleles from LTNPs were less efficient in CD4 downregulation than those of progressors or ACs. Third, all nef alleles from LTNPs, progressors, and ACs reduced the cell surface expression of major histocompatibility complex class I to a similar level. Last, there was no correlation between Hck-binding activity of Nef and clinical grouping. In conclusion, we detected inefficient enhancement of HIV-1 infectivity and CD4 downregulation by HIV-1 nef alleles of LTNPs. It awaits further study to conclude that these characteristics of nef alleles are the cause or the consequence of the long-term nonprogression after HIV-1 infection.
8
Jiang, Yongjun, Xiaojian Cui, Chen Cui, et al. "The Function of CD3+CD56+NKT-Like Cells in HIV-Infected Individuals." BioMed Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/863625.
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CD3+CD56+NKT-like cells are one of the critical effectors in the immune response to viral infection and tumors, but the functional features of NKT-like cells in HIV infection have been rarely reported. In this study, we observed and described the state of NKT-like cell functions in primary HIV-infected individuals (PHIs), chronic HIV-infected individuals (CHIs), long-term nonprogressors (LTNPs), and HIV-negative controls (NCs). The results showed that the percentage of IFN-γ+CD3+CD56+NKT-like cells was notably higher in LTNPs compared with CHIs, and the proportion of CD3+CD56+NKT-like cells with dual function (IFN-γ+CD107a+NKT-like cells) in LTNPs was also much higher than in CHIs. Additionally, the percentages of IFN-γ+CD107a+NKT-like cells negatively correlated with viral load. Taken together, our data demonstrated that good functions of CD3+CD56+NKT-like cells in LTNPs likely occurred as a protective mechanism that slows down HIV disease progression.
9
Zhang, Ji-Yuan, Zheng Zhang, Xicheng Wang, et al. "PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors." Blood 109, no. 11 (2007): 4671–78. http://dx.doi.org/10.1182/blood-2006-09-044826.
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Abstract The immunoreceptor PD-1 is significantly up-regulated on exhausted CD8+ T cells during chronic viral infections such as HIV-1. However, it remains unknown whether PD-1 expression on CD8+ T cells differs between typical progressors (TPs) and long-term nonprogressors (LTNPs). In this report, we examined PD-1 expression on HIV-specific CD8+ T cells from 63 adults with chronic HIV infection. We found that LTNPs exhibited functional HIV-specific memory CD8+ T cells with markedly lower PD-1 expression. TPs, in contrast, showed significantly up-regulated PD-1 expression that was closely correlated with a reduction in CD4 T-cell number and an elevation in plasma viral load. Importantly, PD-1 up-regulation was also associated with reduced perforin and IFN-γ production, as well as decreased HIV-specific effector memory CD8+ T-cell proliferation in TPs but not LTNPs. Blocking PD-1/PD-L1 interactions efficiently restored HIV-specific CD8+ T-cell effector function and proliferation. Taken together, these findings confirm the hypothesis that high PD-1 up-regulation mediates HIV-specific CD8+ T-cell exhaustion. Blocking the PD-1/PD-L1 pathway may represent a new therapeutic option for this disease and provide more insight into immune pathogenesis in LTNPs.
10
de Quiros, Juan Carlos Lopez Bernaldo, W. Lesley Shupert, Andrew C. McNeil, et al. "Resistance to Replication of Human Immunodeficiency Virus Challenge in SCID-Hu Mice Engrafted with Peripheral Blood Mononuclear Cells of Nonprogressors Is Mediated by CD8+T Cells and Associated with a Proliferative Response to p24 Antigen." Journal of Virology 74, no. 4 (2000): 2023–28. http://dx.doi.org/10.1128/jvi.74.4.2023-2028.2000.
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ABSTRACT High levels of resistance to challenge with human immunodeficiency virus type 1 SF162 were observed in animals engrafted with peripheral blood mononuclear cells of four long-term nonprogressors (LTNPs). Resistance was abrogated by depletion of CD8+ T cells in vivo and was observed only in LTNPs with proliferative responses to p24. In a subgroup of nonprogressors, CD8+ T cells mediated restriction of challenge viruses, and this response was associated with strong proliferative responses to p24 antigen.
11
Lefrère, Jean-Jacques, Laurence Morand-Joubert, Martine Mariotti, et al. "Even Individuals Considered as Long-Term Nonprogressors Show Biological Signs of Progression After 10 Years of Human Immunodeficiency Virus Infection." Blood 90, no. 3 (1997): 1133–40. http://dx.doi.org/10.1182/blood.v90.3.1133.
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Abstract Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T-cell count for a period of time. The aim of this study was to establish, through the sequential determination of all known predictors of HIV disease, the proportion of such patients having stringent criteria of true long-term nonprogression. Among 249 individuals who were HIV-infected and prospectively followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count greater than 500/μL (LTNP I group) and 9 having a CD4+ T-cell count less than 500 but stable over time (LTNP II group) after at least 10 years of infection without intervention of antiviral therapy, were studied over the entire follow-up period. The plasma HIV RNA copy number and the serum concentrations of p24 antigen, each anti-HIV antibody, neopterin, β-2-microglobulin, Immunoglobulin (Ig) G and IgA were determined every 18 months over the study period. Cellular and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two patients had strictly no marker of progression over the follow-up period. They were the only ones who had, over the 10-year period, a viral copy number too low to be detected. The other patients had a viral copy number higher than 400/mL at at least one visit and increasing over the follow-up period, and they evidenced one or more markers of virological or immunological deterioration. Cellular viremia was positive in all patients but two, while plasma viremia was negative in all but one. The population of individuals termed as LTNPs is not virologically and immunologically homogeneous. The majority present biological signs of HIV disease progression. A new pattern of true LTNP can be drawn through stringent criteria based on the whole known predictors. This pattern appears to be rare in HIV-positive population.
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Lefrère, Jean-Jacques, Laurence Morand-Joubert, Martine Mariotti, et al. "Even Individuals Considered as Long-Term Nonprogressors Show Biological Signs of Progression After 10 Years of Human Immunodeficiency Virus Infection." Blood 90, no. 3 (1997): 1133–40. http://dx.doi.org/10.1182/blood.v90.3.1133.1133_1133_1140.
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Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T-cell count for a period of time. The aim of this study was to establish, through the sequential determination of all known predictors of HIV disease, the proportion of such patients having stringent criteria of true long-term nonprogression. Among 249 individuals who were HIV-infected and prospectively followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count greater than 500/μL (LTNP I group) and 9 having a CD4+ T-cell count less than 500 but stable over time (LTNP II group) after at least 10 years of infection without intervention of antiviral therapy, were studied over the entire follow-up period. The plasma HIV RNA copy number and the serum concentrations of p24 antigen, each anti-HIV antibody, neopterin, β-2-microglobulin, Immunoglobulin (Ig) G and IgA were determined every 18 months over the study period. Cellular and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two patients had strictly no marker of progression over the follow-up period. They were the only ones who had, over the 10-year period, a viral copy number too low to be detected. The other patients had a viral copy number higher than 400/mL at at least one visit and increasing over the follow-up period, and they evidenced one or more markers of virological or immunological deterioration. Cellular viremia was positive in all patients but two, while plasma viremia was negative in all but one. The population of individuals termed as LTNPs is not virologically and immunologically homogeneous. The majority present biological signs of HIV disease progression. A new pattern of true LTNP can be drawn through stringent criteria based on the whole known predictors. This pattern appears to be rare in HIV-positive population.
13
Gaardbo, Julie C., Hans J. Hartling, Jan Gerstoft, and Susanne D. Nielsen. "Thirty Years with HIV Infection—Nonprogression Is Still Puzzling: Lessons to Be Learned from Controllers and Long-Term Nonprogressors." AIDS Research and Treatment 2012 (2012): 1–14. http://dx.doi.org/10.1155/2012/161584.
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In the early days of the HIV epidemic, it was observed that a minority of the infected patients did not progress to AIDS or death and maintained stable CD4+ cell counts. As the technique for measuring viral load became available it was evident that some of these nonprogressors in addition to preserved CD4+ cell counts had very low or even undetectable viral replication. They were therefore termed controllers, while those with viral replication were termed long-term nonprogressors (LTNPs). Genetics and virology play a role in nonprogression, but does not provide a full explanation. Therefore, host differences in the immunological response have been proposed. Moreover, the immunological response can be divided into an immune homeostasis resistant to HIV and an immune response leading to viral control. Thus, non-progression in LTNP and controllers may be due to different immunological mechanisms. Understanding the lack of disease progression and the different interactions between HIV and the immune system could ideally teach us how to develop a functional cure for HIV infection. Here we review immunological features of controllers and LTNP, highlighting differences and clinical implications.
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Pilotti, Elisabetta, Lisa Elviri, Elisa Vicenzi, et al. "Postgenomic up-regulation of CCL3L1 expression in HTLV-2–infected persons curtails HIV-1 replication." Blood 109, no. 5 (2006): 1850–56. http://dx.doi.org/10.1182/blood-2006-07-036046.
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Abstract Leukocytes of persons coinfected with HTLV-2 and HIV-1 secrete chemokines that prevent CCR5-dependent (R5) HIV-1 infection of CD4+ T cells and macrophages, with HTLV-2–induced MIP-1α as dominant HIV-1 inhibitory molecule. Two nonallelic genes code for CCL3 and CCL3L1 isoforms of MIP-1α, and the population-specific copy number of CCL3L1 exerts a profound effect on HIV-1 susceptibility and disease progression. Here, we demonstrate that CCL3L1 is secreted spontaneously by leukocytes of HTLV-2–infected persons and superinduced when cells of HTLV-2/HIV-1 multiply exposed-uninfected seronegative (MEU) persons were stimulated with HIV-1 Env peptides. The CCL3L1 median copy number in MEU, HTLV-2/HIV-1–coinfected long-term nonprogressors (LTNPs) and HIV-1–monoinfected LTNPs were 1, 2, and 3, respectively. An increased CCL3L1/CCL3 mRNA ratio versus PHA-activated healthy leukocytes was observed in both HIV-1–monoinfected LTNPs and in HTLV-2/HIV-1MEU subjects. An additional potential correlate of HTLV-2 infection was a rapid and persistent leukocyte secretion of GM-CSF and IFN-γ, 2 cytokines endowed with CCR5 down-regulation capacity. This study confirms a crucial protective role of CCL3L1 from both HIV infection and disease progression, highlighting a previously not described functional up-regulation of this chemokine variant in both HIV-positive and -negative persons infected with HTLV-2.
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Migueles, Stephen A., Alisha C. Laborico, Hiromi Imamichi, et al. "The Differential Ability of HLA B*5701+ Long-Term Nonprogressors and Progressors To Restrict Human Immunodeficiency Virus Replication Is Not Caused by Loss of Recognition of Autologous Viral gag Sequences." Journal of Virology 77, no. 12 (2003): 6889–98. http://dx.doi.org/10.1128/jvi.77.12.6889-6898.2003.
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ABSTRACT Although the HLA B*5701 class I allele is highly overrepresented among human immunodeficiency virus (HIV)-infected long-term nonprogressors (LTNPs), it is also present at the expected frequency (11%) in patients with progressive HIV infection. Whether B57+ progressors lack restriction of viral replication because of escape from recognition of highly immunodominant B57-restricted gag epitopes by CD8+ T cells remains unknown. In this report, we investigate the association between restriction of virus replication and recognition of autologous virus sequences in 27 B*57+ patients (10 LTNPs and 17 progressors). Amplification and direct sequencing of single molecules of viral cDNA or proviral DNA revealed low frequencies of genetic variations in these regions of gag. Furthermore, CD8+ T-cell recognition of autologous viral variants was preserved in most cases. In two patients, responses to autologous viral variants were not demonstrable at one epitope. By using a novel technique to isolate primary CD4+ T cells expressing autologous viral gene products, it was found that 1 to 13% of CD8+ T cells were able to respond to these cells by gamma interferon production. In conclusion, escape-conferring mutations occur infrequently within immunodominant B57-restricted gag epitopes and are not the primary mechanism of virus evasion from immune control in B*5701+ HIV-infected patients. Qualitative features of the virus-specific CD8+ T-cell response not measured by current assays remain the most likely determinants of the differential abilities of HLA B*5701+ LTNPs and progressors to restrict virus replication.
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Kramer, Ivan. "What TriggerstransientAIDS in the Acute Phase of HIV Infection andchronicAIDS at the End of the Incubation Period?" Computational and Mathematical Methods in Medicine 8, no. 2 (2007): 125–51. http://dx.doi.org/10.1080/17486700701395461.
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Novel dynamical models are introduced demonstrating that the T helper cell (THC) density drops in the acute infection phase of HIV infection, sometimes causingtransientAIDS, and at the end of the incubation period causingchronicAIDS have a common dynamical cause. The immune system's inability to produce enoughuninfectedTHCs to replace theinfectedones it is destroying causes a drop in the THC densityat any stage of HIV infection. Increases in viral infectivity, probably caused by random mutation of HIV, are shown to drive the progression of the infection. The minimum incubation period for the long term non-progressors (LTNPs) was calculated from a novel physical model: 0.3% of infecteds have incubation periods of 23.1 years or more, and there is no biomedical difference between LTNPs and progressors. Chronic AIDS is shown to result from three random transitions linking four clinically-distinct stages of HIV infection following seroconversion.
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Jin, Xia, Andy Brooks, Huiyuan Chen, Ryan Bennett, Richard Reichman, and Harold Smith. "APOBEC3G/CEM15 (hA3G) mRNA Levels Associate Inversely with Human Immunodeficiency Virus Viremia." Journal of Virology 79, no. 17 (2005): 11513–16. http://dx.doi.org/10.1128/jvi.79.17.11513-11516.2005.
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ABSTRACT APOBEC3G/CEM15 (hA3G) is a novel host factor that confers resistance to lentiviral infection under experimental conditions. Human immunodeficiency virus (HIV) type 1, however, produces viral infectivity factor (Vif) that targets hA3G for proteolysis, thereby escaping this defense system. To examine hA3G's contribution to the protection against HIV disease progression in humans, we quantified hA3G mRNA levels in peripheral blood mononuclear cells from 6 HIV-uninfected and 25 HIV-infected subjects; the latter group included 8 long-term nonprogressors (LTNPs) and 17 progressors. None of the HIV-infected subjects were receiving antiretroviral therapy. We found a striking inverse correlation between hA3G mRNA levels and HIV viral loads (P ≤ 0.00009) and a highly significant positive correlation between hA3G mRNA levels and CD4 cell counts (P ≤ 0.00012) in these patients. Furthermore, we discovered that the order of hA3G mRNA levels is LTNPs > HIV-uninfected subjects > progressors.
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Oh, Myoung-Don, Sung Soon Kim, Eun Young Kim, et al. "The frequency of mutation in CCR5 gene among Koreans." International Journal of STD & AIDS 11, no. 4 (2000): 266–67. http://dx.doi.org/10.1258/0956462001915688.
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To better understand a role of the Delta32 allele of the CCR5 gene in HIV-1 transmission and disease progression, we determined the CCR5 genotypes within several groups of Koreans. Amplification of DNA from each subject was achieved with polymerase chain reaction, using the CCR5 specific primer pair, which flanks the 32 bp deletion. The 1.2 kb coding sequences of CCR5 were examined to see the possible effects of CCR5 polymorphism. All of the 339 healthy, HIV-uninfected individuals had no mutation in the CCR5 gene. All of the 115 HIV-1-infected patients including 11 long-term non-progressors (LTNPs) and 18 discordant spouses were also wild homozygotes. No variation in the 1.2 kb CCR5 coding sequence was found in 5 LTNPs and 5 discordant spouses. In conclusion, the 32 bp deletion mutant is rarely present in Koreans. Our data suggest that factors other than the CCR5 coding sequences may also play a role in the resistance to HIV infection.
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Bello, Gonzalo, Concepción Casado, Virginia Sandonis, et al. "A subset of human immunodeficiency virus type 1 long-term non-progressors is characterized by the unique presence of ancestral sequences in the viral population." Journal of General Virology 86, no. 2 (2005): 355–64. http://dx.doi.org/10.1099/vir.0.80410-0.
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Within human immunodeficiency virus type 1 (HIV-1)-infected patients, there are those who have been infected for more than 10 years with a CD4+ cell count of >500 cells μl−1 and who remain asymptomatic without antiretroviral therapy; these patients are designated long-term non-progressors (LTNPs). In a set of 16 LTNPs, viral dating, DNA viral load, quasispecies heterogeneity and antibody (Ab) titres against gp160 and β 2 microglobulin (β 2m) were determined. Plasma viral RNA and CD4+ and CD8+ T-cell numbers were estimated in more than three samples per patient. Host genetic characteristics, such as Δ32-CCR5 genotype and human leukocyte antigen (HLA) genotype and supertypes, and clinical–epidemiological factors were evaluated. Dating of global populations and of DNA and RNA viral quasispecies identified two subsets of patients: one displaying only ancestral sequences and the other displaying predominantly modern sequences. The ancestral patients displayed a significant reduction in RNA and DNA viral loads, quasispecies heterogeneity, CD8+ cell number, anti-gp160 Ab titres and β 2m level, and they were also associated with better use of safe-sex practices and higher presence of the HLA sB58 supertype than the modern subset. Viral dating has therefore permitted the segregation of LTNPs into two subsets that show very different virological, immunological, host and clinical–epidemiological characteristics. Moreover, whereas the modern subset displayed low levels of virus replication, the ancestral group displayed not only a very limited virus replication, often to undetectable levels, but also very slow or arrested viral evolution, maintaining the close relationship of the viral population to the transmitted virus.
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Jiménez-Sousa, María, José Jiménez, Amanda Fernández-Rodríguez, et al. "VDR rs2228570 Polymorphism Is Related to Non-Progression to AIDS in Antiretroviral Therapy Naïve HIV-Infected Patients." Journal of Clinical Medicine 8, no. 3 (2019): 311. http://dx.doi.org/10.3390/jcm8030311.
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Background: Vitamin D is a fundamental regulator of host defenses by activating genes related to innate and adaptive immunity. In this study, we analyzed the association among single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene, with clinical patterns of AIDS progression in antiretroviral treatment (ART)-naïve HIV-infected patients. Methods: We conducted a retrospective study in 667 HIV-infected patients, who were classified within three groups according to their AIDS progression pattern (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)). Five VDR SNPs (rs11568820, rs4516035, rs2228570, rs1544410, and rs7975232) were genotyped using Agena Bioscience’s MassARRAY platform. Results: Significant association results were found for rs2228570. Within all HIV patients, the presence of T allele at VDR rs2228570 SNP was protective against AIDS progression (ordinal outcome) under additive (adjusted odds ratio (aOR) = 0.75; p = 0.009), dominant (aOR = 0.69; p = 0.015), and codominant (aOR = 0.56; p = 0.017) inheritance models. In addition, the same allele was protective under additive and codominant inheritance models when we compared with LTNPs vs. RPs [aOR = 0.64 (p = 0.019) and aOR = 0.37 (p = 0.018), respectively] and when we compared MPs vs. RPs [aOR = 0.72 (p = 0.035) and aOR = 0.45 (p = 0.028), respectively]. Conclusions: The VDR rs2228570 T allele was related to a lower AIDS progression pattern in ART-naïve HIV-infected patients. These findings expand upon the knowledge about HIV pathogenesis in untreated HIV-infected patients with different clinical outcomes.
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Pantaleo, Giuseppe, Mauro Vaccarezza, Cecilia Graziosi, Oren J. Cohen, and Anthony S. Fauci. "Antiviral immunity in HIV-1 infected long-term non-progressors (LTNPs)." Seminars in Virology 7, no. 2 (1996): 131–38. http://dx.doi.org/10.1006/smvy.1996.0017.
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Bagaglio, S., S. Ghezzi, S. Lodrini, et al. "Hepatitis C virus infection in HIV-infected long term non progressors (LTNPS)." Journal of Hepatology 38 (April 2003): 125. http://dx.doi.org/10.1016/s0168-8278(03)80694-3.
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Patel, P., M. Brooks, G. Anabwani, and M. A. Tolle. "Control and non-progression of HIV-1 infection in sub-Saharan Africa: A case and review." Southern African Journal of HIV Medicine 13, no. 3 (2012): 152–55. http://dx.doi.org/10.4102/sajhivmed.v13i3.130.
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Elite and viraemic controllers represent unique subsets of HIV-infected patients who may also be long-term non-progressors (LTNPs). LNTPs constitute an estimated 1 - 15% of the total HIV-positive population in the USA and Europe, but less is known about their epidemiology in sub-Saharan Africa. Though the exact mechanisms for long-term non-progression appear to be numerous and are still under investigation, research on elite controllers may hold the key to new therapeutics and vaccine development. The clinical management of such patients can be challenging, as there are no standard guidelines for treatment, particularly in resource-limited settings. We describe the case of an HIV-infected Botswanan man who is likely an elite or viraemic controller.
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Jiang, Yongjun, Fangyuan Zhou, Yao Tian та ін. "Higher NK Cell IFN-γ Production is Associated with Delayed HIV Disease Progression in LTNPs". Journal of Clinical Immunology 33, № 8 (2013): 1376–85. http://dx.doi.org/10.1007/s10875-013-9930-1.
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EVANS-MOLINA, CARMELLA, ZEB I. SAEED, JAY SOSENKO, et al. "348-OR: Metabolic Phenotype of Autoantibody Positive (AbPos) Long-Term Nonprogressors (LTNPs) to Type 1 Diabetes (T1D)." Diabetes 69, Supplement 1 (2020): 348—OR. http://dx.doi.org/10.2337/db20-348-or.
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Wang, Zheng, Tian-yi Li, Jing-yun Li, et al. "Similar neutralizing activity in the HIV-1 infected long term non-progressors(LTNPs) and typical progressors(TPs)." Virologica Sinica 27, no. 3 (2012): 165–71. http://dx.doi.org/10.1007/s12250-012-3239-8.
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Juang, Feng Renn, Yean Kuen Fang, and Yong Jie Zhong. "In situ indium-induced crystallisation of low temperature nano-poly silicon (LTNPS) thin film on ITO glass substrate." International Journal of Nanotechnology 11, no. 12 (2014): 1056. http://dx.doi.org/10.1504/ijnt.2014.065131.
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Sandonís, Virginia, Concepción Casado, Tamara Alvaro, et al. "A combination of defective DNA and protective host factors are found in a set of HIV-1 ancestral LTNPs." Virology 391, no. 1 (2009): 73–82. http://dx.doi.org/10.1016/j.virol.2009.05.022.
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De La Torre, Erick. "PONENCIA: ESTRATEGIAS PARA LOGRAR UNA CURA FUNCIONAL DEL VIH." Revista Médica Panacea 7, no. 3 (2019): 116. http://dx.doi.org/10.35563/rmp.v7i3.259.
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Hace 35 años que conocemos a este virus y aún no hemos conseguido doblegarlo por completo. Sin embargo hay mucha investigación en este campo cuyo objetivo es contribuir a encontrar una cura funcional para la infección, que consiste en limitar el tamaño del reservorio viral y controlar la carga viral a través de una respuesta inmunológica adecuada (1). Entre un 2 – 5 % de los pacientes que están infectados por el VIH, son denominados LTNPs (long term non-progressors o progresores lentos), los cuales son capaces de mantener niveles altos de células T CD4 y/o baja carga viral sin estar en tratamiento antirretroviral, los cuales constituyen un modelo natural de cura funcional y que hay diversos factores genéticos o inmunológicos que están involucrados en este control de la infección (2,3).
La dinámica y los mecanismos involucrados en la latencia viral y en la persistencia de reservorios virales son muy complejos, y constituyen el mayor obstáculo para lograr una cura funcional de la infección (4).
Las diversas estrategias para que se han evaluado, y que algunas siguen en curso, durante estos últimos años para disminuir o limitar la expansión de los reservorios, así como mejorar los parámetro inmunológicos, dentro del contexto de conseguir una cura funcional
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Ayala-Suárez, Rubén, Francisco Díez-Fuertes, Esther Calonge, et al. "Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection." Journal of Clinical Medicine 9, no. 8 (2020): 2452. http://dx.doi.org/10.3390/jcm9082452.
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Long-term non-progressors (LTNP) and elite controllers (EC) represent spontaneous natural models of efficient HIV-1 response in the absence of treatment. The main purposes of this work are to describe the miRNome of HIV-1 infected patients with different extreme phenotypes and identify potentially altered pathways regulated by differentially expressed (DE) miRNAs. The miRNomes from peripheral blood mononuclear cells (PBMCs) of dual phenotype EC-LTNP or LTNP with detectable viremia and HIV-infected patients with typical progression before and after treatment, were obtained through miRNA-Seq and compared among them. The administration of treatment produces 18 DE miRNAs in typical progressors. LTNP condition shows 14 DE miRNA when compared to typical progressors, allowing LTNP phenotype differentiation. A set of four miRNAs: miR-144-3p, miR-18a-5p, miR-451a, and miR-324 is strongly downregulated in LTNP and related to protein regulation as AKT, mTOR, ERK or IKK, involved in immune response pathways. Deregulation of 28 miRNA is observed between EC-LTNP and viremic-LTNP, including previously described anti-HIV miRNAs: miR-29a, associated with LTNP phenotype, and miR-155, targeting different pre-integration complexes such as ADAM10 and TNPO3. A holistic perspective of the changes observed in the miRNome of patients with different phenotypes of HIV-control and non-progression is provided.
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Sauer, Steffen, Robert English, and Mark Clatworthy. "The Ratio of Tibial Slope and Meniscal Bone Angle for the Prediction of ACL Reconstruction Failure Risk." Surgery Journal 04, no. 03 (2018): e152-e159. http://dx.doi.org/10.1055/s-0038-1668111.
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Background A growing body of research is indicating that the tibial slope and the geometry of the tibiofemoral meniscal–cartilage interface may affect the risk of anterior cruciate ligament reconstruction (ACLR) failure. Increased lateral tibial posterior slope (LTPS) and reduced meniscal bone angle (MBA) are associated with increased risk of anterior cruciate ligament (ACL) injury. The significance of a LTPS–MBA ratio regarding the prediction of ACL failure risk remains unknown. As LTPS and MBA may eventually potentiate or neutralize each other, it is expected that a low LTPS–MBA ratio is associated with high chance of ACL graft survival while a high LTPS–MBA ratio is associated with high risk of ACL failure. Material and Methods Out of 1,487 consecutive patients who underwent hamstring ACLR between August 2000 and May 2013, 54 ACLR failures with intact lateral menisci were included in this study and matched one-to-one with 54 control participants by age, sex, graft, surgical technique, and graft fixation method. Control participants had undergone ACLR without signs of lateral meniscal injury, graft failure, or insufficiency. MBA and LTPS were assessed on magnetic resonance imaging. Logistic regression was used to identify LTPS/MBA key cut-off ratios. Results In this cohort, a LTPS–MBA ratio under 0.27 was associated with a 28% risk of ACLR failure (36% of patients), while a ratio exceeding 0.42 was associated with an 82% risk of ACLR failure (31% of patients). The odds of ACL failure increased by 22.3% per reduction of 1 degree in MBA (odds ratio [OR], 1.22; 95% limits, 1.1–1.34). No significant association was found between LTPS and the risk of ACL graft failure in transtibial ACLR, while the odds of ACL failure increased by 34.9% per degree of increasing LTPS in transportal ACLR (OR, 1.34; 95% limits, 1.01–1.79). No significant correlation was found between MBA and LTPS (p = 0.5). Conclusion Reduced MBA was associated with significantly increased risk of ACL graft failure. A ratio of LTPS and MBA was found to be useful for the prediction of ACLR failure risk and may preoperatively help to identify patients at high risk of ACLR failure. This may have implications for patient counseling and the indication of additional extra-articular stabilizing procedures.
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Mishra, Ankita, and Ashok Kumar. "Mapping B-Cell Epitopes for Nonspecific Lipid Transfer Proteins of Legumes Consumed in India and Identification of Critical Residues Responsible for IgE Binding." Foods 10, no. 6 (2021): 1269. http://dx.doi.org/10.3390/foods10061269.
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Nonspecific lipid transfer proteins (nsLTPs) have been categorized as panallergens and display widespread occurrence across plant-kingdom. Present study, investigated B-cell epitopes for LTPs from chickpea, mung-bean, cowpea, pigeon-pea, and soybean via in silico methods. In-silico predicted regions were evaluated for epitope-conservancy and property-based peptide similarity search by different allergen databases. Additionally, the in-silico predicted regions were compared with the experimentally validated epitopes of peach-LTP. Sequence-homology studies showed that chickpea and mung-bean LTPs shared significant homology, i.e., >70% and >60%, respectively, with other LTP allergens from lentil, garden-pea, peanut, etc. Phylogenetic-analysis also showed chickpea and mung-bean LTPs to be closely related to allergenic LTPs from lentil and peanut, respectively. Epitope-conservation analysis showed that two of the predicted B-cell epitopic regions in chickpea and mung-bean LTPs were also conserved in other allergenic LTPs from peach, peanut, garden-pea, lentil, and green-bean, and might serve as conserved B-cell epitopes of the LTP protein family. Property-distance index values for chickpea and mung-bean LTPs also showed that most of the epitopes shared similarity with the reported allergens like-lentil, peanut, apple, plum, tomato, etc. Present findings, may be explored for identification of probable allergenicity of novel LTPs, on the basis of the reported conserved B-cell epitopes, responsible for potential cross-reactivity.
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Akhiyarova, Guzel R., Ekaterina I. Finkina, Tatiana V. Ovchinnikova, Dmitry S. Veselov, and Guzel R. Kudoyarova. "Role of Pea LTPs and Abscisic Acid in Salt-Stressed Roots." Biomolecules 10, no. 1 (2019): 15. http://dx.doi.org/10.3390/biom10010015.
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Lipid transfer proteins (LTPs) are a class of small, cationic proteins that bind and transfer lipids and play an important role in plant defense. However, their precise biological role in plants under adverse conditions including salinity and possible regulation by stress hormone abscisic acid (ABA) remains unknown. In this work, we studied the localization of LTPs and ABA in the roots of pea plants using specific antibodies. Presence of LTPs was detected on the periphery of the cells mainly located in the phloem. Mild salt stress (50 mM NaCI) led to slowing plant growth and higher immunostaining for LTPs in the phloem. The deposition of suberin in Casparian bands located in the endoderma revealed with Sudan III was shown to be more intensive under salt stress and coincided with the increased LTP staining. All obtained data suggest possible functions of LTPs in pea roots. We assume that these proteins can participate in stress-induced pea root suberization or in transport of phloem lipid molecules. Salt stress increased ABA immunostaining in pea root cells but its localization was different from that of the LTPs. Thus, we failed to confirm the hypothesis regarding the direct influence of ABA on the level of LTPs in the salt-stressed root cells.
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Das, Koushik, Natsuki Watanabe, and Tomoyoshi Nozaki. "Two StAR-related lipid transfer proteins play specific roles in endocytosis, exocytosis, and motility in the parasitic protist Entamoeba histolytica." PLOS Pathogens 17, no. 4 (2021): e1009551. http://dx.doi.org/10.1371/journal.ppat.1009551.
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Lipid transfer proteins (LTPs) are the key contributor of organelle-specific lipid distribution and cellular lipid homeostasis. Here, we report a novel implication of LTPs in phagocytosis, trogocytosis, pinocytosis, biosynthetic secretion, recycling of pinosomes, and motility of the parasitic protist E. histolytica, the etiological agent of human amoebiasis. We show that two StAR-related lipid transfer (START) domain-containing LTPs (named as EhLTP1 and 3) are involved in these biological pathways in an LTP-specific manner. Our findings provide novel implications of LTPs, which are relevant to the elucidation of pathophysiology of the diseases caused by parasitic protists.
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Finkina, E. I., D. N. Melnikova, I. V. Bogdanov, and T. V. Ovchinnikova. "Lipid Transfer Proteins As Components of the Plant Innate Immune System: Structure, Functions, and Applications." Acta Naturae 8, no. 2 (2016): 47–61. http://dx.doi.org/10.32607/20758251-2016-8-2-47-61.
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Among a variety of molecular factors of the plant innate immune system, small proteins that transfer lipids and exhibit a broad spectrum of biological activities are of particular interest. These are lipid transfer proteins (LTPs). LTPs are interesting to researchers for three main features. The first feature is the ability of plant LTPs to bind and transfer lipids, whereby these proteins got their name and were combined into one class. The second feature is that LTPs are defense proteins that are components of plant innate immunity. The third feature is that LTPs constitute one of the most clinically important classes of plant allergens. In this review, we summarize the available data on the plant LTP structure, biological properties, diversity of functions, mechanisms of action, and practical applications, emphasizing their role in plant physiology and their significance in human life.
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Swathirajan, Chinnambedu Ravichandran, Ramachandran Vignesh, Greer Waldrop, et al. "HIV-specific T-cell Responses and Generalized Activation in HIV-1 Infected Long-term Non-progressors and Progressors from South India." Current HIV Research 16, no. 4 (2019): 302–14. http://dx.doi.org/10.2174/1570162x17666181212122607.
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Background:Anti-viral cytokine expressions by cytotoxic T-cells and lower activation rates have been reported to correlate with suppressed HIV replication in long-term non-progressors (LTNP). Immune mechanisms underlying disease non-progression in LTNP might vary with HIV-1 subtype and geographical locations.Objective:This study evaluates cytokine expression and T-cells activation in relation to disease non-progression in LTNP.Methods:HIV-1 Subtype C infected LTNP (n=20) and progressors (n=15) were enrolled and flowcytometry assays were performed to study HIV-specific CD8 T-cells expressing IL-2, IFN-γ, TNF-α and MIP-1β against gag and env peptides. CD4+ T-cell activation was evaluated by surface expression of HLADR and CD38.Results:Proportions of cytokines studied did not differ significantly between LTNP and progressors, while contrasting correlations with disease progression markers were observed in LTNP. CD4+ T-cell activation rates were significantly lower in LTNP compared to progressors which indicate the potential role of T-cell activation rates in disease non-progression in LTNP.Conclusion:LTNP and progressors showed similar CD8+ T-cell responses, but final conclusions can be drawn only by comparing multiple immune factors in larger LTNP cohort with HIV-1 infected individuals at various levels of disease progression. A possible role of HIV-1 subtype variation and ethnic differences in addition to host-genetic and viral factors cannot be ruled out.
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Koli, Katri, Juha Saharinen, Mira Kärkkäinen та Jorma Keski-Oja. "Novel non-TGF-β-binding splice variant of LTBP-4 in human cells and tissues provides means to decrease TGF-β deposition". Journal of Cell Science 114, № 15 (2001): 2869–78. http://dx.doi.org/10.1242/jcs.114.15.2869.
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Small latent TGF-β consists of latency associated peptide (LAP) bound to the 25 kDa TGF-β by noncovalent interactions. Small latent TGF-β is secreted from cells and deposited into the extracellular matrix as covalent complexes with its binding proteins, LTBPs. Four LTBPs have been molecularly cloned and their structures contain repetitive sequences. The 3rd 8-Cys repeats of LTBP-1, -3 and -4 are able to associate with small latent TGF-β. We analyzed by RT-PCR the expression of LTBPs 1-4 in a panel of cultured human cell lines including fibroblasts of different origin, endothelial cells and immortalized keratinocytes. LTBPs were expressed in an overlapping manner, but differences in their expression levels were detected. SV-40 transformed human embryonic lung fibroblasts contained less of the mRNAs for the LTBPs, suggesting that malignant transformation leads to decrease in LTBP expression. A novel alternatively spliced form of LTBP-4 lacking the 3rd 8-Cys repeat (LTBP-4Δ8-Cys3rd) was identified. LTBP-4Δ8-Cys3rd does not bind TGF-β and it was found to be expressed in the same tissues as the full length LTBP-4. The exon-intron structure of LTBP-4 around the 3rd 8-Cys repeat was similar to those of LTBP-2 and -3. LTBP-4Δ8-Cys3rd was produced by alternative splicing over two exons. In addition, HL-60 promyelocytic leukemia cells expressed a splice variant lacking only one exon of this region. The expression of the non-TGF-β-binding variant of LTBP-4 may be important for the regulation of TGF-β deposition in tissues. Since LTBPs are a part of the extracellular matrix microfibrils, the LTBP-4Δ8-Cys3rd protein may also be involved in various structural functions not related to TGF-β signaling.
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Panoutsakopoulou, Vily, Kathryn Hunter, Thomas G. Sieck, Elizabeth P. Blankenhorn, and Kenneth J. Blank. "Genetic Regulation of Long-Term Nonprogression in E-55+ Murine Leukemia Virus Infection in Mice." Journal of Virology 73, no. 11 (1999): 9232–36. http://dx.doi.org/10.1128/jvi.73.11.9232-9236.1999.
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ABSTRACT Certain inbred mouse strains display progression to lymphoma development after infection with E-55+ murine leukemia virus (E-55+ MuLV), while others demonstrate long-term nonprogression. This difference in disease progression occurs despite the fact that E-55+ MuLV causes persistent infection in both immunocompetent BALB/c–H-2k (BALB.K) progressor (P) and C57BL/10–H-2k (B10.BR) long-term nonprogressor (LTNP) mice. In contrast to immunocompetent mice, immunosuppressed mice from both P and LTNP strains develop lymphomas about 2 months after infection, indicating that the LTNP phenotype is determined by the immune response of the infected mouse. In this study, we used bone marrow chimeras to demonstrate that the LTNP phenotype is associated with the genotype of donor bone marrow and not the recipient microenvironment. In addition, we have mapped a genetic locus that may be responsible for the LTNP trait. Microsatellite-based linkage analysis demonstrated that a non-major histocompatibility complex gene on chromosome 15 regulates long-term survival and is located in the same region as the Rfv3 gene. Rfv3 is involved in recovery from Friend virus-induced leukemia and has been demonstrated to regulate neutralizing virus antibody titers. In our studies, however, both P and LTNP strains produce similar titers of neutralizing and cytotoxic anti-E-55+ MuLV. Therefore, while it is possible that Rfv3 influences the course of E-55+ MuLV infection, it is more likely that the LTNP phenotype in E-55+ MuLV-infected mice is regulated by a different, closely linked gene.
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Kang, Seok, Ha-Mok Jeong, Beom-Suk Kim, and Joon-Shik Yoon. "Risk Analysis of Needle Injury to the Long Thoracic Nerve during Ultrasound-Guided C7 Selective Nerve Root Block." Medicina 57, no. 6 (2021): 635. http://dx.doi.org/10.3390/medicina57060635.
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Background and Objectives: Ultrasound (US)-guided cervical selective nerve root block (SNRB) is a widely used treatment for upper limb radicular pain. The long thoracic nerve (LTN) passes through the middle scalene muscle (MSM) at the C7 level. The needle trajectory of US-guided C7 SNRB pierces the MSM, therefore indicating a high probability of injury to the LTN. We aimed to identify the LTN and to investigate the risk of needle injury to the nerve during US-guided C7 SNRB. Materials and Methods: This retrospective observational study included 30 patients who underwent US-guided SNRB at the C7 level in a university hospital. We measured the maximal cross-sectional diameter (MCSD) of the LTN and cross-sectional area (CSA) of the C7 nerve root and assessed the injury risk of LTN during US-guided C7 SNRB by simulating the trajectory of the needle in the ultrasound image. Results: The LTN was detectable in all the cases, located inside and outside the MSM in 19 (63.3%) and 11 (36.7%) of cases, respectively. The LTN’s mean MCSD was 2.10 mm (SD 0.13), and the C7 root’s CSA was 10.78 mm2 (SD 1.05). The LTN location was within the simulated risk zone in 86.7% (26/30) of cases. Conclusion: Our findings suggest a high potential for LTN injury during US-guided C7 SNRB. The clear visualization of LTNs in the US images implies that US guidance may help avoid nerve damage and make the procedure safer. When performing US-guided C7 SNRB, physicians should take into consideration the location of the LTN.
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Pii, Youry, Tiziana Pandolfini, and Massimo Crimi. "Signaling LTPs: A new plant LTPs sub-family?" Plant Signaling & Behavior 5, no. 5 (2010): 594–97. http://dx.doi.org/10.4161/psb.11499.
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Zhang, Qian, Wenchun Jiang, and Yanting Zhang. "Effect of geometrical parameters on the effective elastic modulus for an X-type lattice truss panel structure." Science and Engineering of Composite Materials 25, no. 6 (2018): 1135–44. http://dx.doi.org/10.1515/secm-2017-0257.
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AbstractThe lattice truss panel structure (LTPS), which is a high strength material with high efficiency of heat transfer, has a good potential to be used as compact heat exchanger. The core of LTPS is a periodic porous structure, and the effective elastic modulus (EEM) will be different from the base material. It is essential to calculate the EEM for the design of this type of heat exchanger. This paper presents a study on the EEM of X-type LTPS by homogenization method, which has been verified by finite element method (FEM). It reveals that the effects of seven geometrical parameters of the X-type LTPS on EEM are not identical, and the relationship between the seven parameters and EEM has been established. Results calculated by homogenization method and FEM show a good agreement. The EEM decreases with the increase of truss length, stamping angle, shearing angle and node length, while it increases with the increase of truss width, truss thickness and face sheet thickness. Unlike the conventional foam material, there is no clear correlation between the EEM and the relative density, and a formula has been fitted to calculate the EEM of LTPS.
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Broström, Christina, Anders Sönnerborg, Stefan Lindbäck, and Hans Gaines. "Low Relative Frequencies of CD26+CD4+ Cells in Long-Term Nonprogressing Human Immunodeficiency Virus Type 1-Infected Subjects." Clinical Diagnostic Laboratory Immunology 5, no. 5 (1998): 662–66. http://dx.doi.org/10.1128/cdli.5.5.662-666.1998.
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ABSTRACT A broad antibody panel was used for immunophenotyping of human immunodeficiency virus type 1 (HIV-1)-infected patients who were long-term nonprogressors (LTNP). The LTNP were compared with patients in the early phase of infection and patients who had progressed to advanced immunodeficiency. Changes in CD8+ subset distribution were observed mainly at acquisition of HIV-1 infection, whereas CD4+ subset changes appeared during progression of HIV-1 infection. The decreasing levels of CD4+ cells were characterized by an increasing frequency of cells expressing the activation markers HLA-Dr and CD45RO but not the CD28 surface antigen. The LTNP exhibited significant changes compared to HIV-negative patients in almost all markers. Compared to patients in the early phase of infection, the only difference was a relatively lower frequency of CD4+ cells expressing CD26 among the LTNP. The results show that HIV-1-infected persons who have no signs of immunodeficiency despite many years of infection have an immunophenotypic pattern that is substantially different from that of noninfected persons. Despite the long duration of infection, the LTNP exhibit a pattern similar to that of newly infected persons, with the exception of lower expression of CD26 on CD4+ cells.
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Jang, Kyungsoo, Youngkuk Kim, Pham Duy Phong, Younjung Lee, Joonghyun Park, and Junsin Yi. "Improvement of Electrical Performance in P-Channel LTPS Thin-Film Transistor with a-Si:H Surface Passivation." Materials 12, no. 1 (2019): 161. http://dx.doi.org/10.3390/ma12010161.
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We report the effects of surface passivation by depositing a hydrogenated amorphous silicon (a-Si:H) layer on the electrical characteristics of low temperature polycrystalline silicon thin film transistors (LTPS TFTs). The intrinsic a-Si:H layer was optimized by hydrogen dilution and its structural and electrical characteristics were investigated. The a-Si:H layer in the transition region between a-Si:H and µc-Si:H resulted in superior device characteristics. Using a-Si:H passivation layer, the field-effect mobility of the LTPS TFT was increased by 78.4% compared with conventional LTPS TFT. Moreover, the leakage current measured at VGS of 5 V was suppressed because the defect sites at the poly-Si grain boundaries were well passivated. Our passivation layer, which allows thorough control of the crystallinity and passivation-quality, should be considered as a candidate for high performance LTPS TFTs.
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Zhu, Kai, Peng Peng, Ning Wu, Xianrong Zhou, Jianfei Mu, and Xin Zhao. "Preventive Effect of Liupao Tea Polyphenols on HCl/Ethanol-Induced Gastric Injury in Mice." Journal of Food Quality 2020 (February 11, 2020): 1–10. http://dx.doi.org/10.1155/2020/5462836.
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Liupao tea is a traditional Chinese tea drink. The preventive effect of crude polyphenols in Liupao tea on HCl/ethanol-induced gastric injury was investigated in this study. After a model of gastric injury in mice was established, mouse serum and tissues were analyzed by biochemical and molecular biological methods. The results showed that Liupao tea polyphenols (LTPs) could effectively reduce the area of gastric mucosal lesions, decrease the volume of gastric juice, and increase the pH of gastric juice in mice with gastric injury. Observations of the pathology revealed that LTPs could alleviate cell necrosis and gastric mucosal injury in mice with gastric injury. The SOD activity and GSH level were decreased in mice after gastric injury, while the level of MDA was increased. LTPs could inhibit the changes caused by gastric injury and make the SOD activity, GSH, and MDA levels close to the normal levels. In addition, LTPs could upregulate the mRNA expression of Cu/Zn-SOD, Mn-SOD, CAT, nNOS, and eNOS and downregulate the expression of iNOS in the gastric tissue of mice with gastric injury. Therefore, LTPs can effectively prevent HCl/ethanol-induced gastric injury. HPLC analysis showed that LTP contains six bioactive substances of gallic acid, catechin, caffeine, epicatechin, epigallocatechin gallate, and epicatechin gallate, so the effect of LTP might mainly come from these six components. The effect of a high concentration of LTP is similar to that of ranitidine. LTPs represent a kind of active substance with a protective effect on gastric tissue.
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Li, Shaohua, Wenchun Jiang, Xiaolei Zhu, and Xuefang Xie. "Experimental and Analytical Analysis of Mechanical Properties for Large-Size Lattice Truss Panel Structure Including Role of Connected Structure." Materials 14, no. 17 (2021): 5099. http://dx.doi.org/10.3390/ma14175099.
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The large-size lattice truss panel structure (LTPS) is continually increasing for higher upsizing, but the roles of its connected structures on the mechanical properties are always ignored during the previous structural integrity assessment. Thus, in this paper, a series of mechanical tests, including the fabricating of panel-to-panel LTPSs, monotonous tensile, and three- and four-point bending tests, were performed to comprehensively understand the mechanical behavior. Furthermore, a theoretical model including the role of connected structures was developed to predict both the elastic and plastic deformation behavior of panel-to-panel LTPS. Results show that the connected structure has a very significant effect on the mechanical properties of panel-to-panel LTPS during the three-bending tests, and I-beam element depresses its carrying capacity. The developed theoretical model was proved to accurately predict the experimental results, and the maximum error was limited within 20%. Finally, the dimensional effects of the connection components on mechanical properties were also analyzed by the theoretical model, and indicated that the panel-to-panel LTPS will present better mechanical performance than the intact structure when the width of I-beam element exceeds 12.2 mm or the its length downgrades to 39.1 mm, which provide a comprehensive guidance for the engineering design of large-size LTPS.
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Uchikoga, Shuichi. "Low-Temperature Polycrystalline Silicon Thin-Film Transist or Technologies for System-on-Glass Displays." MRS Bulletin 27, no. 11 (2002): 881–86. http://dx.doi.org/10.1557/mrs2002.277.
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AbstractThe elimination of conventional peripheral LSI (large-scale integration) drivers is considered essential to the development of future low-cost, energy-efficient, lightweight, and thin displays. System-on-glass (SOG) displays are a type of display with various functional circuits integrated on a glass substrate. Low-temperature polycrystalline silicon (LTPS) thin-film transistors (TFTs) make the integration of circuits possible because they can be assembled into complex, high-current driver circuits. Furthermore, LTPS TFTs are attracting attention for driving organic light-emitting devices (OLEDs). This article introduces present and future LTPS TFT technologies for SOG displays.
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Crotti, Andrea, Francesca Neri, Davide Corti, et al. "Nef Alleles from Human Immunodeficiency Virus Type 1-InfectedLong-Term-Nonprogressor Hemophiliacs with or without Late Disease Progression Are Defective in Enhancing Virus Replication and CD4 Down-Regulation." Journal of Virology 80, no. 21 (2006): 10663–74. http://dx.doi.org/10.1128/jvi.02621-05.
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ABSTRACT Infection with human immunodeficiency virus (HIV)-encoding defective nef variants may contribute to a relatively benign course of disease in a minority of long-term nonprogressors (LTNP). We have examined the functions of nef alleles from six individuals belonging to the same cohort of hemophiliacs infected with HIV-1 prior to 1985 and classified as LTNP in 1995. Three out of six individuals have progressed to HIV disease (late progressors [LP]), whereas the three remainders have maintained their LTNP status at least up to 2003. The nef alleles were obtained from both plasma virus and peripheral blood mononuclear cells of all six individuals in 1995 and 1998. The proportion of sequences containing mutations not yielding Nef expression significantly diminished in 1998 versus that in 1995. Several previously defined functional regions of intact nef alleles were highly conserved. However, the major variant obtained in 1998 from plasma RNA of five out of six individuals significantly reduced HIV infectivity/replication and impaired Nef-mediated CD4 but not major histocompatibility complex class I antigen down-modulation from the cell surface. Thus, functional alterations of the nef gene are present in both LP and LTNP, suggesting that Nef defectiveness in vitro is not necessarily associated with the long-term maintenance of LTNP status. Of interest is the fact that isolates from three out of three LP showed a dual CCR5/CXCR4 coreceptor use (R5X4), in contrast to those from LTNP, which were exclusively R5. Thus, in vivo evolution of gp120 Env to CXCR4 use appears to be associated with HIV disease progression in individuals infected with nef-defective viruses.
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Jagannathan, Prasanna, Christine M. Osborne, Cassandra Royce, et al. "Comparisons of CD8+ T Cells Specific for Human Immunodeficiency Virus, Hepatitis C Virus, and Cytomegalovirus Reveal Differences in Frequency, Immunodominance, Phenotype, and Interleukin-2 Responsiveness." Journal of Virology 83, no. 6 (2009): 2728–42. http://dx.doi.org/10.1128/jvi.02128-08.
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ABSTRACT To better understand the components of an effective immune response to human immunodeficiency virus (HIV), the CD8+ T-cell responses to HIV, hepatitis C virus (HCV), and cytomegalovirus (CMV) were compared with regard to frequency, immunodominance, phenotype, and interleukin-2 (IL-2) responsiveness. Responses were examined in rare patients exhibiting durable immune-mediated control over HIV, termed long-term nonprogressors (LTNP) or elite controllers, and patients with progressive HIV infection (progressors). The magnitude of the virus-specific CD8+ T-cell response targeting HIV, CMV, and HCV was not significantly different between LTNP and progressors, even though their capacity to proliferate to HIV antigens was preserved only in LTNP. In contrast to HIV-specific CD8+ T-cell responses of LTNP, HLA B5701-restricted responses within CMV pp65 were rare and did not dominate the total CMV-specific response. Virus-specific CD8+ T cells were predominantly CD27+45RO+ for HIV and CD27−45RA+ for CMV; however, these phenotypes were highly variable and heavily influenced by the degree of viremia. Although IL-2 induced significant expansions of CMV-specific CD8+ T cells in LTNP and progressors by increasing both the numbers of cells entering the proliferating pool and the number of divisions, the proliferative capacity of a significant proportion of HIV-specific CD8+ T cells was not restored with exogenous IL-2. These results suggest that immunodominance by HLA B5701-restricted cells is specific to HIV infection in LTNP and is not a feature of responses to other chronic viral infections. They also suggest that poor responsiveness to IL-2 is a property of HIV-specific CD8+ T cells of progressors that is not shared with responses to other viruses over which immunologic control is maintained.
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ÖKLÜ, Rahmi, та Robin HESKETH. "The latent transforming growth factor β binding protein (LTBP) family". Biochemical Journal 352, № 3 (2000): 601–10. http://dx.doi.org/10.1042/bj3520601.
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The transforming growth factor β (TGFβ) cytokines are a multi-functional family that exert a wide variety of effects on both normal and transformed mammalian cells. The secretion and activation of TGFβs is regulated by their association with latency-associated proteins and latent TGFβ binding proteins (LTBPs). Over the past few years, three members of the LTBP family have been identified, in addition to the protoype LTBP1 first sequenced in 1990. Three of the LTBP family are expressed in a variety of isoforms as a consequence of alternative splicing. This review summarizes the differences between the isoforms in terms of the effects on domain structure and hence possible function. The close identity between LTBPs and members of the fibrillin family, mutations in which have been linked directly to Marfan's syndrome, suggests that anomalous expression of LTBPs may be associated with disease. Recent data indicating that differential expression of LTBP1 isoforms occurs during the development of coronary heart disease is considered, together with evidence that modulation of LTBP function, and hence of TGFβ activity, is associated with a variety of cancers.
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Cooper, Joseph D., Wei Wang, Heather A. Prentice, Tadashi T. Funahashi, and Gregory B. Maletis. "The Association Between Tibial Slope and Revision Anterior Cruciate Ligament Reconstruction in Patients ≤21 Years Old: A Matched Case-Control Study Including 317 Revisions." American Journal of Sports Medicine 47, no. 14 (2019): 3330–38. http://dx.doi.org/10.1177/0363546519878436.
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Background: There is evidence that tibial slope may play a role in revision risk after anterior cruciate ligament reconstruction (ACLR); however, prior studies are inconsistent. Purpose: To determine (1) whether there is a difference in lateral tibial posterior slope (LTPS) or medial tibial posterior slope (MTPS) between patients undergoing revised ACLR and those not requiring revision and (2) whether the medial-to-lateral slope difference is different between these 2 groups. Study Design: Case-control study; Level of evidence, 3. Methods: We conducted a matched case-control study (2006-2015). Cases were patients aged ≤21 years who underwent revision surgery after primary unilateral ACLR; controls were patients aged ≤21 years without revision who were identified from the same source population. Controls were matched to cases by age, sex, body mass index, race, graft type, femoral fixation device, and post-ACLR follow-up time. Tibial slope measurements were made by a single blinded reviewer using magnetic resonance imaging. The Wilcoxon signed rank test and McNemar test were used for continuous and categorical variables, respectively. Results: No difference was observed between revised and nonrevised ACLR groups for LTPS (median: 6° vs 6°, P = .973) or MTPS (median: 4° vs 5°, P = .281). Furthermore, no difference was found for medial-to-lateral slope difference (median: −1 vs −1, P = .289). A greater proportion of patients with revised ACLR had an LTPS ≥12° (7.6% vs 3.8%) and ≥13° (4.7% vs 1.3%); however, this was not statistically significant after accounting for multiple testing. Conclusion: We failed to observe an association between revision ACLR surgery and LTPS, MTPS, or medial-to-lateral slope difference. However, there was a greater proportion of patients in the revision ACLR group with an LTPS ≥12°, suggesting that a minority of patients who have more extreme values of LTPS have a higher revision risk after primary ACLR. A future cohort study evaluating the angle that best differentiates patients at highest risk for revision is needed.