Veterans Health Administration

About: Veterans Health Administration is a government organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Population & Veterans Affairs. The organization has 63820 authors who have published 98417 publications receiving 4835425 citations. The organization is also known as: VHA.

Early viral brain invasion in iatrogenic human immunodeficiency virus infection.

Abstract: We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood.

Mechanism of NLRP3 inflammasome activation

Abstract: Inflammasomes continue to generate interest in an increasing number of disciplines owing to their unique ability to integrate a myriad of signals from pathogen- and damage-associated molecular patterns into a proinflammatory response This potent caspase-1-dependent process is capable of activating the innate immune system, initiating pyroptosis (an inflammatory form of programmed cell death), and shaping adaptive immunity The NLRP3 inflammasome is the most thoroughly studied of the inflammasome complexes that have been described thus far, perhaps owing to its disparate assortment of agonists This review highlights our current understanding of the mechanisms of both priming and activation of the NLRP3 inflammasome

Decreased memory performance in healthy humans induced by stress-level cortisol treatment.

Abstract: Background Glucocorticoids (GCs) can regulate hippocampal metabolism, physiologic functions, and memory. Despite evidence of memory decreases during pharmacological GC treatment, and correlations between memory and cortisol levels in certain disease conditions, it remains unclear whether exposure to the endogenous GC cortisol at levels seen during physical and psychological stress in humans can inhibit memory performance in otherwise healthy individuals. Methods Randomized, double-blind, placebo-controlled comparison of 2 fixed oral doses of cortisol (40 mg/d and 160 mg/d using split doses to approximate circadian rhythm) given for 4 days to matched groups of healthy subjects (n=51). Lower-dose treatment approximated cortisol exposure during mild stress, whereas the higher dose approximated cortisol exposure during major stress. Cognitive testing and plasma sampling were done at baseline, after 1 and 4 days of treatment, and after a 6-day washout period, hypothesizing dose-dependent decreases in verbal declarative memory. Results Cortisol treatment at the higher dose produced reversible decreases in verbal declarative memory without effects on nonverbal memory, sustained or selective attention, or executive function. A significant interaction between time and treatment condition for paragraph recall was explained by treatment-induced differences in performance after 4 treatment days, with lower immediate and delayed recall performance during higher-dose cortisol treatment compared with lower-dose treatment and placebo. Conclusions Several days of exposure to cortisol at doses and plasma concentrations associated with physical and psychological stress in humans can—similar to pharmacological GC treatment—reversibly decrease specific elements of memory performance in otherwise healthy individuals.

Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis.

Abstract: Integrin alpha(V)beta(3) is a heterodimeric plasma membrane protein whose several extracellular matrix protein ligands contain an RGD recognition sequence. This study identifies integrin alpha(V)beta(3) as a cell surface receptor for thyroid hormone [L-T(4) (T(4))] and as the initiation site for T(4)-induced activation of intracellular signaling cascades. Integrin alpha(V)beta(3) dissociably binds radiolabeled T(4) with high affinity, and this binding is displaced by tetraiodothyroacetic acid, alpha(V)beta(3) antibodies, and an integrin RGD recognition site peptide. CV-1 cells lack nuclear thyroid hormone receptor, but express plasma membrane alpha(V)beta(3); treatment of these cells with physiological concentrations of T(4) activates the MAPK pathway, an effect inhibited by tetraiodothyroacetic acid, RGD peptide, and alpha(V)beta(3) antibodies. Inhibitors of T(4) binding to the integrin also block the MAPK-mediated proangiogenic action of T(4). T(4)-induced phosphorylation of MAPK is inhibited by small interfering RNA knockdown of alpha(V) and beta(3). These findings suggest that T(4) binds to alpha(V)beta(3) near the RGD recognition site and show that hormone-binding to alpha(V)beta(3) has physiological consequences.