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)

LIFE stress, mood, and other psychosocial factors may help to explain variability in HIV (human immunodeficiency virus) disease progression. Attempts to support this notion empirically have produced mixed findings; several studies report a positive relationship between psychosocial factors and various indicators of disease progression or immune function (e.g., Evans et al. 1992; Goodkin et. al. 1992), whereas others have failed to detect any association (e.g., Perry et. al. 1992).
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PMID:Stress and depressive symptoms prospectively predict immune change among HIV-seropositive men. HIV Neurobehavioral Research Center Group. 874 89

The woodchuck (Marmota monax) has proven to be a suitable animal model for studying hepatitis B virus (HBV) infection owing to similarities in the course of infection between woodchuck hepatitis virus (WHV) in woodchucks and HBV in humans. (-)-beta-L-2',3'-Dideoxy-3'-thiacytidine (3TC; lamivudine) is a nucleoside analog which has demonstrated antiviral activity against HBV as well as human immunodeficiency virus (HIV). The purpose of the present investigation was to characterize the pharmacokinetics of 3TC following intravenous and oral administration of 20 mg of 3TC per kg of body weight to woodchucks. Following intravenous administration, the concentrations of 3TC in plasma declined, with a terminal half-life of 2.84 +/- 0.85 h (mean +/- standard deviation). The systemic clearance and steady-state volume of distribution of 3TC were 0.22 +/- 0.078 liters/h/kg and 0.75 +/- 0.13 liters/kg, respectively. The renal clearance of the nucleoside analog was 0.063 +/- 0.016 liters/h/kg. The oral bioavailability of 3TC ranged from 18 to 54%. Allometric relationships between pharmacokinetic parameters and body weight developed by Hussey et al. (E.K. Hussey, K.H. Donn, M.J. Daniel, S.T. Hall, A.J. Harker, and G.L. Evans, J. Clin. Pharmacol. 34:975-977, 1994) were augmented by including data from woodchucks, monkeys (S.M. Blaney, M.J. Daniel, A.J. Harker, K. Godwin, and F.M. Balis, Antimicrob. Agents Chemother. 39:2779-2782, 1995), and additional data from rats (P. Rajagopalan, L. Moore, C.K. Chu, R.F. Schinazi, and F.D. Boudinot, submitted for publication). Interspecies scaling of the pharmacokinetic parameters of 3TC demonstrated a good correlation between clearance (0.74 . W0.76 [where W is body weight]; r = 0.93; P < 0.025), apparent volume of distribution (1.62 . W0.81; r = 0.98; P < 0.005), and steady-state volume of distribution (1.09 . W0.94; r = 0.99; P < 0.05) and species body weight. The allometric relationships for clearance and volume of distribution at steady state predicted the observed pharmacokinetic parameters in humans quite well; however, the apparent volume of distribution was underestimated in humans. Thus, the pharmacokinetic data obtained with the woodchuck HBV animal model should be useful for designing clinical trials.
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PMID:Pharmacokinetics of (-)-2'-3'-dideoxy-3'-thiacytidine in woodchucks. 885 86

The association of Epstein-Barr virus (EBV) with B-cell lymphoma was examined in 72 human immunodeficiency virus-negative Japanese patients using the polymerase chain reaction (PCR) on DNA obtained from formalin-fixed paraffin-embedded tissues and an in situ hybridization (ISH) technique. EBV-encoded RNA 1 (EBER-1) was detected in 12 of 72 cases (17%); five of 33 cases (15%) of nodal B-cell lymphomas and seven of 39 cases (18%) of extranodal B-cell lymphomas. Three cases of post-bone marrow transplantation and one case of autoimmune disease (Evans syndrome) were included among seven EBER-1 positive extranodal lymphomas. A combined study of immunohistochemistry and EBER-1 revealed that some L26 positive cells were EBER-1 positive. A DNA band was also observed in 13 of 70 examined cases (19%) (four of 33 cases of nodal B-cell lymphomas (12%) and nine of 37 cases of extranodal B-lymphomas (24%)) in the PCR study using primers to detect the Bam HI-W fragment of EBV. In the immunohistochemical study using a monoclonal antibody to the latent membrane protein 1 (LMP-1) of the EBV, one of the EBV-encoded latent gene products, LMP-1, was expressed in six of 34 cases (18%) of extranodal B-lymphomas, but none of the cases with nodal B-cell lymphomas were shown to be LMP-1 positive. Oncoprotein bcl-2 was examined by immunohistochemistry and found to be expressed in seven cases of nodal lymphomas and three cases of extranodal lymphomas, and two of these nodal cases were EBER ISH positive. In EBV serology, only two cases of nodal and one case of extranodal EBER positive B-cell lymphomas revealed a reactivation pattern. In the PCR study using primers to detect the lymphocyte-determined membrane antigen (LYDMA), the same sized monoclonal bands were observed in case 36 in the PCR products from the nose and skin, suggesting the monoclonal proliferation of the tumor. These findings suggested a low incidence of EBV association with B-cell lymphomas unless patients were in an immunologically impaired condition such as post-organ transplantation or autoimmune diseases.
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PMID:Determination of Epstein-Barr virus association with B-cell lymphomas in Japan: study of 72 cases--in situ hybridization, polymerase chain reaction, immunohistochemical studies. 963 83

Atevirdine mesylate (U-87201E) is a highly specific nonnucleoside inhibitor of human immunodeficiency virus type 1 reverse transcriptase. The absorption, metabolism, and excretion of atevirdine were investigated in male and female Sprague-Dawley rats after oral administration of nonradiolabeled atevirdine mesylate at doses of 20 mg/kg/day or 200 mg/kg/day for 8 days, with [14C]atevirdine mesylate single doses of 10 mg/kg or 100 mg/kg on study days 1 and 10. The distribution of [14C]atevirdine mesylate was also evaluated by whole-body autoradiography in male and female Sprague-Dawley, pregnant Sprague-Dawley, and male Long-Evans rats after a single 10 mg/kg oral dose. Plasma levels of atevirdine and its N-desethyl and O-desmethyl metabolites were determined by high-performance liquid chromatography (HPLC) with ultraviolet detection, urine and feces were profiled for atevirdine and metabolites by HPLC with radiochemical detection, major metabolites in urine were isolated and identified by nuclear magnetic resonance and mass spectrometry, and minor urinary metabolites were identified by liquid chromatography/mass spectrometry. Atevirdine was rapidly absorbed. The pharmacokinetics of atevirdine were nonlinear. Gender differences in the pharmacokinetics and metabolism of atevirdine were observed, consistent with the involvement of cytochrome P450 3A. Atevirdine effectively crossed the blood-brain barrier and had a high rate of maternal-fetal transfer. At the low doses, <2% of the dose was excreted as unchanged parent drug, while atevirdine constituted 9%-25% of the dose at the high doses. The metabolism of atevirdine was extensive in the rat and involved N-deethylation, O-demethylation, hydroxylation at the C-6 position of the indole ring, and hydroxylation of the pyridine ring.
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PMID:Absorption, distribution, metabolism, and excretion of atevirdine in the rat. 976 7

A 53-year-old woman had asymptomatic multiple nodules on her gluteal region for 6 months. She had a history of systemic corticosteroid treatment for Evans' syndrome. Recently she had developed an immunodeficiency condition with CD4+ cell depletion without an HIV infection and a normal serum gamma globulin level. A smear from the purulent exudate of the nodules revealed many brown-coloured hyphae, spores and few large dark-brown cells. A short, hairy, dark-brown coloured colony was cultivated on Sabouraud glucose agar. Slide culturing revealed only a Phialophora-type conidia formation, and the fungus was diagnosed as Phialophora verrucosa. Severe immunosuppressive condition (non-HIV acquired immunodeficiency syndrome) of this patients after systemic corticosteroid treatment for Evans' syndrome predisposed an opportunistic cutaneous fungal infection due to P. verrucosa. Cases with cutaneous infection due to P. verrucosa reported in Japan are summarized and discussed.
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PMID:Case report. Phaeohyphomycosis caused by Phialophora verrucosa developed in a patient with non-HIV acquired immunodeficiency syndrome. 1185 38

We describe a case report of a patient who developed common variable immunodeficiency (CVID) after autologous haematopoietic stem cell transplantation (SCT) for recurrent Evans syndrome. The disease manifested as attacks of haemolytic anaemia, thrombocytopenia and neutropenia from the age of 12 years. Presence of autoantibodies to blood elements was confirmed together with C4 deficiency. The patient also suffered from dermatitis herpetiformis Duhring without signs of coeliac disease. Autologous T cell-depleted peripheral blood stem cell (PBSC) transplant following conditioning regimen was performed at the age of 20 years. Immunological reconstitution was incomplete and 2 years after SCT he fulfilled laboratory criteria for common variable immunodeficiency (CVID). The patient was found to be a carrier of a risk haplotype for development of CVID DRB1*03/DQB1*0201. We conclude that T cell-depleted SCT here performed for autoimmune manifestations can hasten development of CVID in genetically predisposed patients.
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PMID:Development of common variable immunodeficiency in a patient with Evans syndrome treated by autologous stem cell transplantation. 1291 16

A 26-year-old man with a history of common variable immunodeficiency and Evans syndrome (immunthrombocytopenia and immunhemolytic anemia) with sarcoid like lesions and lymph node enlargements in the previous history is described. The patient presented with symptoms resembling Guillain-Barre-Strohl as paraneoplastic syndrome just before the diagnosis of acute lymphoblastic leukemia of the L3 type. The patient was treated according to the B-ALL protocol of the German ALL study group and achieved a complete response after six cycles of chemotherapy together with a resolution of all neurologic symptoms.
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PMID:Guillain-Barre-Strohl syndrome unraveled as paraneoplastic syndrome of B-cell acute lymphoblastic leukemia in a patient with preceding common variable immunodeficiency syndrome with Evans syndrome. 1506 Dec 20

To describe the main characteristics and outcome of autoimmune thrombocytopenic purpura (AITP) in patients with common variable immunodeficiency (CVID), we analyzed data from 21 patients and reviewed additional cases from the literature. To be included in this study, patients had to have CVID and a previous history of AITP with a platelet count < or = 50 x 10(9)/L at onset. A complete response to treatment was defined by a platelet count > or = 150 x 10(9)/L, and a partial response by a platelet count >>50 x 10(9)/L with an increase of at least twofold the initial level. The median platelet count at AITP diagnosis was 20 x 10(9)/L (range, 2-50 x 10(9)/L). The median age at AITP diagnosis was 23 years (range, 1-51 yr), whereas the median age at CVID diagnosis was 27 years (range, 10-74 yr). CVID was diagnosed before the onset of AITP in only 4 patients (19%), 3 of whom were being treated with intravenous immunoglobulin (i.v.Ig) replacement therapy. CVID was diagnosed more than 6 months after AITP in 13 cases (62%), and the 2 conditions were diagnosed concomitantly in 4 cases. Eleven patients (52%) had at least 1 autoimmune manifestation other than AITP, among which autoimmune hemolytic anemia (7 cases) and autoimmune neutropenia (5 cases) were preeminent. Seventeen of the 21 patients (80%) received at least 1 treatment for AITP; 13 patients received corticosteroids alone and 7 (54%) achieved at least a partial response; 8 patients received i.v.Ig at 1-2 g/kg alone or in combination with steroids, leading to a short-term response rate of 50%. Four patients underwent a splenectomy (2 complete responses, 2 failures); 2 additional splenectomies were performed for associated autoimmune hemolytic anemia. With a mean follow-up of 5.6 years after the surgical procedure, none of the 6 splenectomized patients had a life-threatening infection. With a median follow-up after AITP onset of 12 years, 13/21 patients (62%) were in treatment-free remission (7 complete responses, 6 partial responses), 7 patients (23%) were in remission while on prednisone < or = 20 mg/day with or without azathioprine, and only 1 patient still had a platelet count <50 x 10(9)/L. Five patients had died at the time of the analysis; none of the deaths was related to a hemorrhage. Severe infections including 3 fatal bacterial infections and 2 opportunistic infections occurred in 6 patients during or after treatment of AITP. In conclusion, AITP, alone or in combination with autoimmune hemolytic anemia (Evans syndrome) and/or autoimmune neutropenia, is frequent in patients with CVID, and is not prevented by i.v.Ig substitutive therapy. Since AITP frequently precedes the diagnosis of CVID, testing for immunoglobulin levels should be performed in every patient diagnosed with AITP. Steroids and splenectomy seem to have the same efficacy as in idiopathic AITP, but the increased risk of severe infections must be taken into consideration.
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PMID:Autoimmune thrombocytopenic purpura and common variable immunodeficiency: analysis of 21 cases and review of the literature. 1523 13

The results of yeast and mammalian two-hybrid assays previously indicated complex formation between prenylated Rab acceptor 1 (PRA1) and the cytoplasmic domain of gp41 (gp41CD) for both the human and simian immunodeficiency viruses [Evans, D. T., Tilman, K. C. & Desrosiers, R. C. (2002). J Virol 76, 327-337]. The assembly and release of infectious virus particles was studied under conditions of PRA1 overexpression in a transient transfection assay or suppression by RNA interference. Although a clear pattern of co-localization of PRA1 and gp41 was observed, no changes in virion release, infectivity or envelope content were observed as a result of either PRA1 suppression or overexpression. These data show that PRA1 co-localizes with gp41 inside cells and they are consistent with a direct or indirect interaction between these proteins. However, variation in the levels of PRA1 expression did not influence virion production, infectivity or envelope incorporation under the conditions of these assays.
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PMID:PRA1 co-localizes with envelope but does not influence primate lentivirus production, infectivity or envelope incorporation. 1591 57

Common variable immunodeficiency (CVID) is associated with autoimmunity, most commonly immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA). In a retrospective chart review of 326 CVID patients, 35 (11%) patients had a history of autoimmune hematologic disease. Fifteen patients had ITP, 9 had AIHA, and 11 had Evans syndrome (both ITP and AIHA). The age at diagnosis for CVID ranged from 5 to 66 years and for autoimmunity, from 2 to 66 years. There were 16 males and 19 females. Nineteen patients (54%) had the first episode of thrombocytopenia or hemolytic anemia prior to the diagnosis of immunodeficiency, 11 (32%) were diagnosed concurrently, and 5 (14%) developed one or both of these autoimmune diseases following the diagnosis of CVID. Eight patients were known to have granulomatous changes in one or more organs. Treatments for autoimmunity included corticosteroids, anti-Rh immunoglobulin, and intravenous immunoglobulin; 11 patients underwent splenectomy. While 5 patients had recurrences of autoimmune hemolytic disease while receiving maintenance intravenous immunoglobulin, most episodes occurred for subjects not yet on this therapy (P < 0.0001). Most patients with frequent infections and hematologic autoimmunity should be evaluated for CVID.
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PMID:Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). 1599 61


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