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排序方式: 共有103条查询结果,搜索用时 15 毫秒
1.
Patrick J. Blair Lawrence H. Boise Stephen P. Perfetto Bruce L. Levine Gil McCrary Kenneth F. Wagner Daniel C. St. Louis Craig B. Thompson Jeffrey N. Siegel Carl H. June 《Journal of clinical immunology》1997,17(3):234-246
Progression to AIDS in asymptomatic HIV-infected individuals is characterized by a gradual but progressive loss of CD4+ T cells. While the mechanisms underlying this decline are currently unknown, recent evidence suggests that these cells are abnormally sensitive to apoptosis in response to activation signals. Recent work has implicated downregulation of Bcl-2 with the increased spontaneous apoptosis in lymphocytes from HIV-infected patients. We have evaluated the roles of the apoptosis-protective proteins Bcl-2 and Bcl-x in stimulated PBMC from asymptomatic HIV-infected and HIV-uninfected individuals. We found that Bcl-2 was constitutively expressed in PBMC from both HIV-infected and uninfected samples. However, Bcl-x induction was delayed and responses were decreased in stimulated HIV-infected samples. Additionally, single-cell intracellular staining of Bcl-x revealed a significant inverse correlation between PWM-induced Bcl-x expression and apoptosis (r = –0.695, P = 0.005). This was confirmed at the single-cell level in direct experiments when stimulated cells were sorted based on Bcl-x induction and then measured for apoptosis. Furthermore, low Bcl-x expression was not due to reduced lymphocyte activation following PWM stimulation. Our data indicate that the induction of Bcl-x is markedly impaired in asymptomatic HIV-infected patients and that stimuli which induce inadequate expression of Bcl-x are associated with increased levels of apoptosis in these cells. 相似文献
2.
Vaccination Decreases the Infectious Viral Load of Delta Variant SARS-CoV-2 in Asymptomatic Patients
Jessica A. Plante Rafael R. G. Machado Brooke M. Mitchell Divya P. Shinde Jordyn Walker Dionna Scharton Allan McConnell Nehad Saada Jianying Liu Bilal Khan Rafael K. Campos Bryan A. Johnson Vineet D. Menachery Corri B. Levine Ping Ren Susan L. F. McLellan Kenneth S. Plante Scott C. Weaver 《Viruses》2022,14(9)
The Delta variant of SARS-CoV-2 has caused many breakthrough infections in fully vaccinated individuals. While vaccine status did not generally impact the number of viral RNA genome copies in nasopharyngeal swabs of breakthrough patients, as measured by Ct values, it has been previously found to decrease the infectious viral load in symptomatic patients. We quantified the viral RNA, infectious virus, and anti-spike IgA in nasopharyngeal swabs collected from individuals asymptomatically infected with the Delta variant of SARS-CoV-2. Vaccination decreased the infectious viral load, but not the amount of viral RNA. Furthermore, vaccinees with asymptomatic infections had significantly higher levels of anti-spike IgA in their nasal secretions compared to unvaccinated individuals with asymptomatic infections. Thus, vaccination may decrease the transmission risk of Delta, and perhaps other variants, despite not affecting the amount of viral RNA measured in nasopharyngeal swabs. 相似文献
3.
Vikas A. Gupta Shannon M. Matulis Benjamin G. Barwick R. Devin Bog Conrad W. Shebelut Mala Shanmugam Paola Neri Nizar J. Bahlis Madhav V. Dhodapkar Leonard T. Heffner Craig C. Hofmeister Nisha S. Joseph Sagar Lonial Jonathan L. Kaufman David L. Jaye Ajay K. Nooka Lawrence H. Boise 《Blood cancer journal》2022,12(8)
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Boise L Neal MB Kaye J 《The journals of gerontology. Series A, Biological sciences and medical sciences》2004,59(6):M621-M626
BACKGROUND: Prior research has found that dementia is often undiagnosed in primary care, but there has been limited research on whether physicians respond to symptoms, behaviors, or other events that may be indicators of dementia. METHODS: A cross-sectional cohort study design was used to screen 553 patients aged 75 years or older for dementia in 3 managed health care systems in Portland, Oregon. For participants determined to be cognitively impaired, their medical charts were reviewed to determine if they had experienced adverse events, had been clinically evaluated for possible dementia, had received a diagnosis of dementia, or had been offered treatment. RESULTS: Nearly 43% of participants were identified as cognitively impaired: 29.7% were classified as mildly cognitively impaired (MI) and 13.7% as moderately to severely cognitively impaired (MSI). Eighteen percent of the MI group and 34.8% of the MSI group had evidence in their medical chart of having been clinically evaluated for dementia. None of the MI group and only 4.3% of the MSI group had been offered a cholinesterase inhibitor. Nearly two thirds (61.6%) of the MI and three fourths (75.4%) of the MSI participants had experienced 1 or more adverse events. Of those who had experienced adverse events, less than one quarter (23.7%) in the MI group and less than one half (44.2%) in the MSI group had received a clinical evaluation for dementia. CONCLUSIONS: These findings suggest the need for greater attention by primary care physicians to the cognitive functioning of older patients, especially patients who experience adverse events that may be indicators of dementia. 相似文献
7.
Andrew D. Redd Aleisha Collinson-Streng Craig Martens Stacy Ricklefs Caroline E. Mullis Jordyn Manucci Aaron A. R. Tobian Ethan J. Selig Oliver Laeyendecker Nelson Sewankambo Ronald H. Gray David Serwadda Maria J. Wawer Stephen F. Porcella Thomas C. Quinn 《Journal of clinical microbiology》2013,51(8):2805
8.
Ricolinostat (ACY‐1215) induced inhibition of aggresome formation accelerates carfilzomib‐induced multiple myeloma cell death 下载免费PDF全文
Yuko Mishima Loredana Santo Homare Eda Diana Cirstea Neeharika Nemani Andrew J. Yee Elizabeth O'Donnell Martin Karl Selig Steven N. Quayle Shirin Arastu‐Kapur Christopher Kirk Lawrence H. Boise Simon S. Jones Noopur Raje 《British journal of haematology》2015,169(3):423-434
Proteasome inhibition induces the accumulation of aggregated misfolded/ubiquitinated proteins in the aggresome; conversely, histone deacetylase 6 (HDAC6) inhibition blocks aggresome formation. Although this rationale has been the basis of proteasome inhibitor (PI) and HDAC6 inhibitor combination studies, the role of disruption of aggresome formation by HDAC6 inhibition has not yet been studied in multiple myeloma (MM). The present study aimed to evaluate the impact of carfilzomib (CFZ) in combination with a selective HDAC6 inhibitor (ricolinostat) in MM cells with respect to the aggresome‐proteolysis pathway. We observed that combination treatment of CFZ with ricolinostat triggered synergistic anti‐MM effects, even in bortezomib‐resistant cells. Immunofluorescent staining showed that CFZ increased the accumulation of ubiquitinated proteins and protein aggregates in the cytoplasm, as well as the engulfment of aggregated ubiquitinated proteins by autophagosomes, which was blocked by ricolinostat. Electron microscopy imaging showed increased autophagy triggered by CFZ, which was inhibited by the addition of ACY‐1215. Finally, an in vivo mouse xenograft study confirmed a decrease in tumour volume, associated with apoptosis, following treatment with CFZ in combination with ricolinostat. Our results suggest that ricolinostat inhibits aggresome formation, caused by CFZ‐induced inhibition of the proteasome pathway, resulting in enhanced apoptosis in MM cells. 相似文献
9.
The chemistry and pharmacology of synthetic cannabinoid SDB‐006 and its regioisomeric fluorinated and methoxylated analogs 下载免费PDF全文
Samuel D. Banister Alexander Olson Matthew Winchester Jordyn Stuart Amelia R. Edington Richard C. Kevin Mitchell Longworth Marco Herrera Mark Connor Iain S. McGregor Roy R. Gerona Michael Kassiou 《Drug testing and analysis》2018,10(7):1099-1109
Synthetic cannabinoids are the largest and most structurally diverse class of new psychoactive substances, with manufacturers often using isomerism to evade detection and circumvent legal restriction. The regioisomeric methoxy‐ and fluorine‐substituted analogs of SDB‐006 (N‐benzyl‐1‐pentyl‐1H‐indole‐3‐carboxamide) were synthesized and could not be differentiated by gas chromatography–mass spectrometry (GC–MS), but were distinguishable by liquid chromatography–quadrupole time‐of‐flight–MS (LC–QTOF–MS). In a fluorescence‐based plate reader membrane potential assay, SDB‐006 acted as a potent agonist at human cannabinoid receptors (CB1 EC50 = 19 nM). All methoxy‐ and fluorine‐substituted analogs showed reduced potency compared to SDB‐006, although the 2‐fluorinated analog (EC50 = 166 nM) was comparable to known synthetic cannabinoid RCS‐4 (EC50 = 146 nM). Using biotelemetry in rats, SDB‐006 and RCS‐4 evoked comparable reduction in body temperature (~0.7°C at a dose of 10 mg/kg), suggesting lower potency than the recent synthetic cannabinoid AB‐CHMINACA (>2°C, 3 mg/kg). 相似文献
10.
Rebecca Dann Tarik Hadi Emilie Montenont Ludovic Boytard Dornaszadat Alebrahim Jordyn Feinstein Nicole Allen Russell Simon Krista Barone Kunihiro Uryu Yu Guo Caron Rockman Bhama Ramkhelawon Jeffrey S. Berger 《Journal of the American College of Cardiology》2018,71(1):53-65