Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol may have significant effects on human immunodeficiency virus type I (HIV-1) pathogenesis in vivo. As such, the effects of ethanol treatment were studied on the proapoptotic potential of various HIV-1 proteins in primary isolated human brain microvascular endothelial cells (MVECs), a major cellular component of the blood-brain barrier. Low-passage primary brain MVECs were treated with recombinant HIV-1 proteins Nef, Vpr, Tat and gp120 proteins from X4, R5, and X4R5 viral strains, with and without ethanol at various relevant concentrations. The apoptotic potential of each HIV-1 protein with and without ethanol was compared with cells treated with ethanol alone or GST protein as a control, under similar conditions. Specific HIV-1 proteins induced apoptosis in primary isolated human brain MVECs, which was potentiated on treatment with 0.1 and 0.3% (v/v) ethanol. Cotreatment with ethanol and specific HIV-1 proteins showed enhanced lactate dehydrogenase release, compared with MVECs treated with ethanol alone. The presence of ethanol in in vitro culture medium also enhanced HIV-1 protein-mediated tumor necrosis factor-alpha production, compared with cells treated with ethanol alone or GST protein. Thus, these studies demonstrate ethanol's potential for inducing apoptosis of human MVECs with relevant HIV-1-specific proteins and suggest a potential synergistic effect in augmenting HIV-1 neuroinvasion and neuropathogenesis in vivo.
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PMID:Ethanol strongly potentiates apoptosis induced by HIV-1 proteins in primary human brain microvascular endothelial cells. 1250 64

We report the case of a 25-year-old male Japanese homosexual with primary human immunodeficiency virus (HIV)-1 infection and early stage syphilis. Approximately 60 days after HIV exposure by sex with another man, the patient abruptly had high fever, after which he experienced a variety of severe, prolonged symptoms such as painful oral mucosa ulcerations, rash, lymphadenopathy, splenomegaly, and a 5.5-kg weight loss. Serum lactate dehydrogenase and liver biochemical test values were elevated. Antibodies to HIV by both enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) test were negative at the time of symptom onset, but serum HIV-1 RNA level was 1 585 000 copies/ml. Antibody seroconversions were found on day 9 after the onset of symptoms by ELISA and on day 16 by WB test, suggesting primary HIV infection. Within 2 weeks of starting highly active antiretroviral therapy (HAART), all symptoms except lymphadenopathy were resolved, and the serum HIV-1 RNA level dramatically decreased to 5011 copies/ml, eventually becoming undetectable by the standard method. The patient has remained asymptomatic for the 18 months since symptom resolution after HAART, and HIV-1 RNA remains undetectable.
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PMID:A patient with primary human immunodeficiency virus infection for whom highly active antiretroviral therapy was successful. 1252

PRESENTING FEATURES: A 53-year-old man who had human immunodeficiency virus (HIV) presented to the Johns Hopkins Hospital with a 3-month history of increasing dysphagia, cough, dyspnea, chest pain, and an episode of syncope. His past medical history was notable for oral and presumptive esophageal candidiasis that was treated with fluconazole 6 months prior to presentation. Three months prior to presentation, he discontinued his medications, and his symptoms of dysphagia recurred. During that time he developed intermittent fevers and chills, progressively worsening dyspnea on exertion, and a cough productive of white sputum. He also reported a 40-lb weight loss over the past 3 months. On the day prior to presentation, he had chest pain and shortness of breath followed by weakness, dizziness, and a brief syncopal episode. He denied orthopnea, paroxysmal nocturnal dyspnea, lower extremity edema, jaundice, hemoptysis, hematemesis, melena, hematochezia, or diarrhea. There was no history of alcohol use, and he stopped smoking tobacco approximately 1 month previously. He smoked cocaine but denied injection drug use. The patient had never been on antiretroviral therapy and had never had his CD4 count or viral load measured. On physical examination, the patient was a thin, cachectic man who appeared older than his stated age. His vital signs were notable for blood pressure of 102/69 mm Hg, resting tachycardia of 102 beats per minute, resting oxygen saturation of 92% on room air, normal resting respiratory rate, and a temperature of 38.1 degrees C. His oropharynx was clear, with no signs of thrush or mucosal ulcers. His pulmonary examination was notable for diminished breath sounds in the lower lung fields bilaterally. Cardiac, abdominal, and neurologic examinations were normal. His skin was intact, with no visible petechiae, rashes, nodules, or ulcers. Laboratory studies showed a total white blood cell count of 3.2 x 10(3)/microL, with a total lymphocyte count of 330/microL, hematocrit of 30.2%, a serum sodium level of 129 mEq/L, and a serum lactate dehydrogenase level of 219 IU/L. The patient had an absolute CD4 count of 8 cells/mm3 and a HIV viral load of 86,457 copies/mL. His arterial blood gas on room air had a pH of 7.51, a PCO2 of 33 mm Hg, and a PO2 of 55 mm Hg. Electrocardiogram and serial serum cardiac enzymes were normal. A chest radiograph showed bilateral upper lobe patchy infiltrates with left upper lobe consolidation. Computed tomographic (CT) scan of the chest with contrast showed bilateral ground glass infiltrates with focal consolidation (Figure 1) and no evidence of pulmonary embolism. Induced sputum was negative for Pneumocystis carinii, fungi, or acid-fast bacilli. A bronchoalveolar lavage was performed. What is the diagnosis?
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PMID:Cases from the Osler Medical Service at Johns Hopkins University. Diagnosis: P. carinii pneumonia and primary pulmonary sporotrichosis. 1533 85

Coinfections with opportunistic and pathogenic bacteria induce human immunodeficiency virus (HIV) replication through microbial antigen activation of NF-kappaB. Here, we assessed whether HIV type 1 protease inhibitors (PI) block microbial antigen activation of NF-kappaB. Human microvessel endothelial cells were transiently transfected with either endothelial cell-leukocyte adhesion molecule NF-kappaB luciferase or interleukin 6 (IL-6) promoter luciferase constructs by using FuGENE 6, and they were treated with PI (nelfinavir, ritonavir, or saquinavir) prior to stimulation with the Toll-like receptor 4 (TLR4) and TLR2 ligands, with lipopolysaccharide (LPS), soluble Mycobacterium tuberculosis factor, or Staphylococcus epidermidis phenol-soluble modulin, respectively, or with tumor necrosis factor alpha (TNF-alpha). Luciferase activity was measured by using a Promega luciferase kit. TNF-alpha release from the supernatant was measured by enzyme-linked immunosorbent assay. Cell death was assessed by lactate dehydrogenase assay. We observed that PI pretreatment blocked the TLR2- and TLR4- as well as the TNF-alpha-mediated NF-kappaB activation, in a dose-dependent manner. PI pretreatment also blocked the LPS-induced IL-6 promoter transactivation and TNF-alpha secretion. These data suggest that PI block HIV replication not only by inhibiting the HIV protease but also by blocking the TLR- and TNF-alpha-mediated NF-kappaB activation and proinflammatory cytokine production. These findings may help explain the immunomodulatory effects of PI, and they suggest an advantage for PI-containing drug regimens in the treatment of HIV-infected patients who are coinfected with opportunistic and pathogenic bacteria.
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PMID:Human immunodeficiency virus type 1 protease inhibitors block toll-like receptor 2 (TLR2)- and TLR4-Induced NF-kappaB activation. 1538 51

Despite its recognition as a distinct, extremely rare entity, no large studies of intravascular lymphoma (IVL) have been reported. The clinico-pathological characteristics of 38 human immunodeficiency virus-negative patients with IVL diagnosed in Western countries were reviewed to better delineate clinical presentation, clinical variants, natural history and optimal therapy. The IVL is an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of cases) that predominantly affects elderly patients (median age 70 years, range: 34-90; male:female ratio 0.9), resulting in poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS >1 in 61%), B symptoms (55%), anaemia (63%) and high serum lactate dehydrogenase level (86%). The brain and skin are the most common sites of disease. In contrast to previous reports, hepatosplenic involvement (26%) and bone marrow infiltration (32%) were found to be common features in IVL, while nodal disease was confirmed as rare (11% of cases). Patients with disease limited to the skin ('cutaneous variant'; 26% of cases) were invariably females with a normal platelet count, and exhibited a significantly better outcome than the remaining patients, which deserves further investigation. Overall survival was usually poor; however, the early use of intensive therapies could improve outcome in young patients with unfavourable features. ECOG-PS >1, 'cutaneous variant', stage I and chemotherapy use were independently associated with improved survival.
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PMID:Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the 'cutaneous variant'. 1546 23

We prospectively studied presentation biological differences and the response to therapy in patients with thrombotic thrombocytopenic purpura (TTP) associated with, or unrelated to human immunodeficiency virus (HIV) infection. TTP patients underwent standard evaluations and were treated with prednisone 1 mg/kg in addition to infusions of fresh frozen plasma (FFP; 30 ml/kg/d) until normalization of the platelet count. Unresponsive patients were referred for plasma exchange. Compared with HIV- TTP patients (n=23), in HIV+ subjects (n=21) microangiopathy was dominant among Black females, who had lower presentation Hb (median 5.8 g/dl; P=0.03), platelet count (13 x 10(9)/l; P=0.05) and a CD4 count of 0.096 x 10(9)/l. HIV+ individuals responded to FFP faster than HIV- patients and none of them required apheresis. Ten HIV- TTP patients required apheresis (P=0.03) and four died. Responses in the HIV+ and HIV- groups occurred after treatment with a median of 33 and 55 units (one unit=320 ml) of FFP (P=0.004) respectively. Response to this protocol was seen in 84% (95% response in HIV+ patients). Regression analysis showed that survival was associated with younger age (P=0.001), rapid platelet (P=0.001) and Hb (P=0.0009) recovery, and fewer FFP units to normal lactate dehydrogenase levels (P=0.006). We conclude that in HIV+ individuals, microangiopathy is highly responsive to plasma infusions. This observation is important particularly when apheresis is not available.
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PMID:Thrombotic thrombocytopenic purpura in patients with retroviral infection is highly responsive to plasma infusion therapy. 1566 40

The human immunodeficiency virus (HIV)-Tat protein has been implicated in the neuropathogenesis of HIV infection. However, its role in modulating astroglial function is poorly understood. Astrocyte infection with HIV has been associated with rapid progression of dementia. Intracellularly expressed Tat is not toxic to astrocytes. In fact, intracellularly expressed Tat offers protection against oxidative stress-related toxins such as the mitochondrial toxin 3-nitroproprionic acid (3-NP). In the current study, human astrocytes expressing Tat (SVGA-Tat) and vector controls (SVGA-pcDNA) were each treated with the irreversible mitochondrial complex II inhibitor 3-NP. Proteomics analysis was utilized to identify changes in protein expression levels. By coupling 2D fingerprinting and identification of proteins by mass spectrometry, actin, heat shock protein 90, and mitochondrial single-stranded DNA binding protein were identified as proteins with increased expression, while lactate dehydrogenase had decreased protein expression levels in SVGA-Tat cells treated with 3-NP compared to SVGA-pcDNA cells treated with 3-NP. Oxidative damage can lead to several events including loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, ultimately leading to neuronal death. Identification of specific proteins protected from oxidation is a crucial step in understanding the interaction of Tat with astrocytes. In the current study, proteomics also was used to identify proteins that were specifically oxidized in SVGA-pcDNA cells treated with 3-NP compared to SVGA-Tat cells treated with 3-NP. We found beta-actin, calreticulin precursor protein, and synovial sarcoma X breakpoint 5 isoform A to have increased oxidation in control SVGA-pcDNA cells treated with 3-NP compared to SVGA-Tat cells treated with 3-NP. These results are discussed with reference to potential involvement of these proteins in HIV dementia and protection of astrocytes against oxidative stress by the HIV virus, a prerequisite for survival of a viral host cell.
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PMID:Proteomic analysis of oxidatively modified proteins induced by the mitochondrial toxin 3-nitropropionic acid in human astrocytes expressing the HIV protein tat. 1571 Feb 47

Human immunodeficiency virus (HIV)-infected South African patients (n=468) received blinded lamivudine or emtricitabine, stavudine, and either nevirapine or efavirenz (based on screening viral load). Baseline characteristics were analyzed in univariate and multivariate regression, to identify risk factors for hepatotoxicity (grade 3 or greater increase in serum aminotransferase levels). The occurrence of early hepatotoxicity was 17% in the nevirapine group and 0% in the efavirenz group and was balanced between the lamivudine and emtricitabine arms. Two subjects died of hepatic failure. Independent risk factors were body-mass index (BMI) <18.5, female sex, serum albumin level <35 g/L, mean corpuscular volume >85 fL, plasma HIV-1 RNA load <20,000 copies/mL, aspartate aminotransferase level <75 IU/L, and lactate dehydrogenase level <164 IU/L. The use of nevirapine in female patients with a low BMI should be discouraged.
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PMID:Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects. 1599 71

We report an instructive case of diffuse large B-cell lymphoma presenting as acute heart failure. A 69-year-old human immunodeficiency virus-negative man was admitted to our hospital for general fatigue. A computed tomographic scan of the chest and abdomen showed pericardial effusion, but there was no evidence of tumor masses, lymph node enlargement, or hepatosplenomegaly. During the chemotherapy, increased lactate dehydrogenase and pleural effusion appeared. The tumor cells in the effusion showed positivity for CD5, CD19, CD20, kappa chain, and Bcl-2 and negativity for CD10 and CD23. The chromosomes showed t(8;14)(q24;q32) with c-myc/immunoglobulin (Ig)H rearrangement, and the MIB-1 index was not high (60%). Neither human herpes virus 8 nor Epstein-Barr virus DNA was detected in the cells by polymerase chain reaction. The response to chemotherapy was very poor, and the patient died 4 months after the diagnosis. A spectrum of the symptoms of CD5+ lymphoma encompasses pericardial effusion and also can accompany c-myc/IgH rearrangement.
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PMID:CD5+ diffuse large B-cell lymphoma with c-myc/IgH rearrangement presenting as primary effusion lymphoma. 1591 62

Induction of heat shock protein 70 (Hsp70) via sublethal stress protects neurons from subsequent lethal injuries. Here we show that specific and efficient intracellular transduction of Hsp70 can be achieved utilizing an 11 amino acid leading sequence from human immunodeficiency virus (TAT-Hsp70) in primary neuronal cultures. Western blot and immunohistochemistry demonstrated intracellular accumulation of Hsp70 in insoluble protein fractions and mitochondrial compartments. We then examined the effects of Hsp70 overexpression using TAT-Hsp70 in models of nitrosative and excitotoxic neuronal death in vitro. Neurons were pre-incubated with 300 nM TAT-Hsp 70 overnight, then exposed to either peroxynitrite (ONOO-) or glutamate. TAT-Hsp70 maintained cellular respiration, inhibited extracellular lactate dehydrogenase release, and/or reduced cell death assessed by flow cytometry vs. vehicle, wild-type Hsp70, and TAT-beta-galactosidase controls. Hsp70 transduction using a TAT fusion protein is an effective method to selectively increase Hsp70 in neurons and is sufficient to provide neuroprotection from nitrosative stress and excitotoxicity. Further study is needed to confirm whether TAT-Hsp70 is protective in in vivo models of brain injury.
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PMID:Selectively increasing inducible heat shock protein 70 via TAT-protein transduction protects neurons from nitrosative stress and excitotoxicity. 1599 87


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