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221.
Robert M. Paris Constantinos Petrovas Sara Ferrando-Martinez Eirini Moysi Kristin L. Boswell Eva Archer Takuya Yamamoto David Ambrozak Joseph P. Casazza Richard Haubrich Mark Connors Julie Ake Jerome H. Kim Richard A. Koup 《PloS one》2015,10(12)
The role of PD-1 expression on CD4 T cells during HIV infection is not well
understood. Here, we describe the differential expression of PD-1 in
CD127high CD4 T cells within the early/intermediate differentiated (EI)
(CD27highCD45RAlow) T cell population among uninfected and
HIV-infected subjects, with higher expression associated with decreased viral
replication (HIV-1 viral load). A significant loss of circulating
PD-1highCTLA-4low CD4 T cells was found specifically in the
CD127highCD27highCD45RAlow compartment, while
initiation of antiretroviral treatment, particularly in subjects with advanced
disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in
PD-1high compared to PD-1low ED CD4 T cells. In line with an
increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset
was associated with increased activation and expression of the HIV co-receptor, CCR5.
Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and
IL-17a compared to PD-1low EI CD4 T cells. In line with our previous
findings, PD-1high EI CD4 T cells were also characterized by a high
expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in
vitro B cell help. Our data show that expression of PD-1 on
early-differentiated CD4 T cells may represent a population that is highly
functional, more susceptible to HIV infection and selectively lost in chronic HIV
infection. 相似文献
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The purpose of this study was to determine whether a change in respiratory sensation accompanies an increase in CO2 partial pressure (PCO2) in the absence of any changes in the level and pattern of thoracic displacement and respiratory muscle force. Eleven normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator. In separate trials the tidal volume (VT) was set at 10 and 18 ml/kg and the frequency of ventilation (f) was adjusted to maintain the base-line end-tidal PCO2 at approximately 30 Torr. Thereafter, at a constant controlled VT and f, the PCO2 was progressively increased by raising the inspired CO2 concentration. There were no changes in respiratory motor activity as determined from the peak inspiratory airway pressure (Paw) until the PCO2 reached 40.8 +/- 1.0 and 40.1 +/- 1.0 (SE) Torr in the large and small VT trials, respectively. Initially there was no conscious awareness of the change in respiratory activity. Subjects first signaled that ventilatory needs were not being satisfied only after a further increase in PCO2 to 44.7 +/- 1.3 and 42.3 +/- 1.0 (SE) Torr in the large and small VT trials and after the Paw had fallen to 55-60% of the base-line value. The results suggest that changes in respiratory sensation produced by increasing chemical drive are a consequence of increases in respiratory efferent activity, but a direct effect of changes in PCO2 on respiratory sensation cannot be excluded. 相似文献
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J Wally G Kica Y Zhang T Ericsson L H Connors M D Benson J J Liepnieks J Murray M Skinner R L Comenzo 《Biochimica et biophysica acta》1999,1454(1):49-56
Current concepts regarding the association between immunoglobulin (Ig) light chain structure and AL amyloidosis (AL) emphasize Ig variable region amino acid substitutions because the majority of light chain amyloid fibrils that have been sequenced contain amino termini of the variable region with only small amounts of the constant region. In this report, we describe a patient with rapidly progressive AL whose amyloid deposits contained primarily monoclonal kappa light chain constant region fragments. We sequenced and analyzed this AL protein, determining that it was an O18-O8 kappa1 variant and that the constant region possessed an unusual Ser-->Asn substitution at position 177. Using pre-mortem bone marrow cells, we cloned and sequenced the cDNA for this AL protein (HCAK1) and, using DNA from post-mortem somatic tissue, we cloned and sequenced the patient's kappa germline O18-O8 donor and kappa constant region (Ckappa) gene segments. The cDNA that coded for HCAK1 contained a variable region that was derived from O18-O8, showing 96.1% homology to germline, and a Ckappa that had a nucleotide substitution (AGC to AAC), resulting in the 177Ser-->Asn replacement. Two Ckappa genes were cloned from somatic tissue DNA, one identical to a known Ckappa sequence and another containing this substitution which likely is a new Ckappa allotype. Our findings indicate that further investigation is warranted into the contributions genetic polymorphisms and light chain constant regions may make to amyloidogenesis. 相似文献
228.
G Dispersyn R Nuydens R Connors M Borgers H Geerts 《Biochimica et biophysica acta》1999,1428(2-3):357-371
This report addresses the relation between Bcl-2 and mitochondrial membrane potential (DeltaPsi(m)) in apoptotic cell death. Rat pheochromocytoma (PC12) cells are differentiated into neuron-like cells with nerve growth factor (NGF). It is known that Bcl-2 can attenuate apoptosis induced by deprivation of neurotrophic factor. The protective effect of Bcl-2 has been correlated with preservation of DeltaPsi(m). Protonophores, such as carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), collapse the proton gradient across the mitochondrial inner membrane, resulting in a complete abolition of the mitochondrial membrane potential. Based on the analysis of morphology, of phosphatidylserine exposure and of nuclear fragmentation we conclude that FCCP induces apoptosis in PC12 cells, which can be prevented by overexpression of Bcl-2. To determine whether the cytoprotective effect of Bcl-2 is due to stabilization of DeltaPsi(m), we investigated the effect of Bcl-2 on changes in DeltaPsi(m), induced by FCCP in PC12 cells. We showed that treatment with FCCP induced a reduction in DeltaPsi(m), as assessed with the lipophilic cationic membrane potential-sensitive dye JC-1, and that Bcl-2 protects against FCCP-induced changes in NGF differentiated PC12 cells. Our data indicate that Bcl-2 protects against FCCP-induced cell death by stabilizing DeltaPsi(m). 相似文献
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John Connors 《Science activities》2013,50(2):13-17
A professional school and university collaboration enables elementary students and their teachers to explore hydrology concepts and realize the beneficial functions of wetlands. Hands-on experiences involve young students in determining water quality at field sites after laying the groundwork with activities related to the hydrologic cycle, cleaning up polluted water, and the nature of wetlands themselves. 相似文献