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)

Parvovirus B19 infection leads to transient aplastic crises in individuals with chronic hemolytic anemias or immunodeficiency states. An additional unexplained sequela of B19 infection is thrombocytopenia. Because B19 is known to have a remarkable tropism for human erythropoietic elements, and is not known to replicate in nonerythroid cells, the etiology of this thrombocytopenia is uncertain. We sought to define the pathobiology of B19-associated thrombocytopenia by examining the role of B19 on in vitro megakaryocytopoiesis. B19 infection of normal human bone marrow cells significantly suppressed megakaryocyte (MK) colony formation compared with mock-infected cells. No such inhibition was observed with a nonpathogenic human parvovirus, the adeno-associated virus 2 (AAV). The B19-MK cell interaction was also studied at the molecular level. Whereas low-density bone marrow cells containing erythroid precursor cells supported B19 DNA replication, no viral DNA replication was observed in B19-infected MK-enriched fractions as determined by the presence of viral DNA replicative intermediates on Southern blots. However, analysis of total cytoplasmic RNA isolated from B19-infected MK fractions showed a low-level expression of the B19 genome as detected by quantitative RNA dot blots as well as by Northern analysis. Furthermore, a frame-shift mutation in a recombinant AAV-B19 hybrid genome segment that encodes the viral nonstructural (NS1) protein significantly reduced the observed inhibition of MK colony formation. These studies indicate tissue-tropism of B19 beyond the erythroid progenitor cell, and lend support to the hypothesis that B19 genome expression may be toxic to cell populations that are nonpermissive for viral DNA replication.
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PMID:Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro. 214 78

Prevalence and clinical features of human immunodeficiency virus (HIV)-related thrombocytopenia have been investigated among a random population of 657 anti-HIV-positive individuals. A platelet count below 100 X 10(9)/liter was detected in 72 patients (10.9%). Compared with anti-HIV-positive controls with normal platelets, a significantly higher prevalence of males (p less than 0.02) and of intravenous drug abusers (p less than 0.02) as well as a higher frequency of patients with advanced HIV-related disease (p less than 0.001) were detected among thrombocytopenic patients. Those patients whose thrombocytopenia was associated with neutropenia and/or anemia (14 cases, 2.1%) clearly differed from patients with isolated thrombocytopenia (IT) (58 cases, 8.8%) since they belonged to the more advanced groups of the CDC classification of HIV-related disorders, had lower CD4-positive lymphocyte counts, a higher frequency of cutaneous anergy, and less persistent thrombocytopenia. In the cohort of patients with persistent IT (47 cases), no single epidemiological or clinical data proved to correlate with the severity of thrombocytopenia. They did not differ significantly from anti-HIV-positive controls in their distribution among CDC groups, but the total lymphocyte and the CD4-positive lymphocyte counts were significantly lower in IT patients belonging to CDC group II (p less than 0.05 and p less than 0.02, respectively) and III (p less than 0.01 and p less than 0.005, respectively) compared with CDC group-matched controls; after a median followup of one year, the two cohorts showed similar rates of progression to CDC Group IV.
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PMID:Prevalence, clinical, and laboratory features of thrombocytopenia among HIV-infected individuals. 215 38

A retrospective study of 153 hemophiliacs infected with human immunodeficiency virus-1 (HIV-1) was performed to determine the clinical and immunological consequences of HIV-1 infection and the markers and cofactors associated with these changes. Nearly 80% of HIV-1-infected hemophiliacs have developed a significant reduction in their CD-4+ counts (less than 400 CD-4+ cells/mm3) with 40% having less than 200 CD-4+ cells/mm3 by the end of 1987. The rate of CD-4+ cell count decline was slightly greater in patients who have already developed the acquired immunodeficiency syndrome (AIDS) compared to those who have not (50 vs. 31 cells/mm3/6 months). Thrombocytopenia and older age were associated with a more rapid CD-4+ count deterioration, but the quantity of clotting factor utilized did not affect immunologic progression. In patients with less than 200 CD-4+ cells/mm3, the incidence of AIDS was significantly higher in adults (greater than 21 years old) compared to children/adolescents. Cytomegalovirus (CMV) seroprevalence increased with age but did not correlate with the amount of concentrated clotting factor used. Although there was no relationship between CMV status and progression to AIDS, CMV-seropositive patients were older and had a lower CD-4+ count. Thus the majority of HIV-1-infected hemophiliacs are developing progressive immune dysfunction measured by CD-4+ count decline. This drop in CD-4+ count significantly correlates with a risk for the development of AIDS in adults but not in children (less than 21 years old).
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PMID:Human immunodeficiency virus-1 disease progression in hemophiliacs. 216 86

An infectious, virulence-attenuated molecular clone of simian immunodeficiency virus (SIV), SIVMAC-1A11, was derived from an SIV isolate that causes fatal immunodeficiency in rhesus macaques. When inoculated intravenously in rhesus macaques, SIVMAC-1A11 induced transient viremia (1 to 6 weeks) without clinical disease and a persistent humoral antibody response. The antibodies were directed mainly against the viral envelope glycoproteins, as determined by immunoblots and virus neutralization. The potential of this virulence-attenuated virus to protect against intravenous challenge with a pathogenic SIVMAC strain was assessed. Five rhesus macaques were each given two intravenous inoculations with SIVMAC-1A11 7 months apart. Three of the five immunized monkeys and four naive control animals were then challenged with 100 to 1,000 100% animal infectious doses of pathogenic SIVMAC. All seven animals became persistently viremic following the challenge. Four of four unimmunized animals developed severe clinical signs of simian acquired immunodeficiency syndrome by 38 to 227 days after challenge and were euthanatized 91 to 260 days postchallenge. However, no signs of illness were seen in immunized monkeys until 267 to 304 days postchallenge, when two of three immunized animals developed mild thrombocytopenia and lymphopenia; one of these animals died with clinical signs of simian immunodeficiency disease at 445 days after challenge. The two SIVMAC-1A11-immunized monkeys that were not challenged were healthy and antibody positive 22 months after the initial immunization. Thus, although live SIVMAC-1A11 was immunogenic and did not induce any disease, it failed to protect rhesus macaques against infection with a moderately high dose of pathogenic virus. However, immunization prevented severe, early disease and prolonged the lives of monkeys subsequently infected with pathogenic SIV.
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PMID:Immunization with a live, attenuated simian immunodeficiency virus (SIV) prevents early disease but not infection in rhesus macaques challenged with pathogenic SIV. 216 91

Factors contributing to the development of cytopenias in patients with advanced human immunodeficiency virus (HIV) disease include primary HIV-related suppression of blood cell production, opportunistic infections and neoplasms that directly involve the marrow cavity, and the toxicity of antiviral, antiinfective, and antineoplastic therapy. Indeed, bone marrow toxicity is often the complication limiting delivery of effective therapy in such patients. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to increase the leukocyte count in this patient population. Although there is concern that GM-CSF administration may increase HIV replication in myeloid cells, this effect has not been observed in clinical studies. In addition, the most appropriate use of hematopoietic growth factors would be in combination with effective antiretroviral agents, such as zidovudine. A pharmacologic basis for such combination is provided by the finding that inhibition of HIV by zidovudine may be augmented by GM-CSF. It recently has been shown that patients with severe leukopenia and intolerance to zidovudine can have reconstitution of effective myelopoiesis with low doses of subcutaneously self-administered GM-CSF and become hematologically tolerant of zidovudine 1,200 mg/d. The major adverse effects of this combination regimen were constitutional symptoms and thrombocytopenia. Further investigation of GM-CSF and other hematopoietic growth factors in this patient population is warranted.
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PMID:Granulocyte-macrophage colony-stimulating factor in human immunodeficiency virus disease. 219 62

Two different methods for evaluating platelet antibody were used to study 12 normal subjects and 24 patients consisting primarily of intravenous drug users (IVDUs) who were positive for human immunodeficiency virus (HIV). Total platelet-associated immunoglobulin G (IgG) and immunoglobulin M (IgM) were measured by enzyme-lined immunosorbent assay on platelet lysate, and platelet surface-associated IgG and IgM were measured by semiquantitative flow cytometry. IgG and IgM values showed significant correlations between the two measurement methods. Mean platelet surface IgG and total IgG were 3.6 and 4.3 times greater, respectively, in IVDUs than in controls, and platelet IgM was also significantly higher in IVDUs than in controls as measured by both techniques. Although mean platelet immunoglobulin levels were higher in the IVDUs with thrombocytopenia than in IVDUs with normal platelet counts, these differences did not achieve significance. These data show that platelet IgG and IgM levels are increased in IVDU-associated HIV infection and suggest that these increases are not confined to patients manifesting thrombocytopenia. The herein described platelet surface antibody and total platelet antibody measurements appear to be equally useful in studying this patient population. Specific details for generating platelet-associated immunofluorescence units are discussed.
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PMID:Assessment of platelet antibody by flow cytometric and ELISA techniques: a comparison study. 221 57

In 1985 a mixture of red cells collected in citrate anticoagulant with plasma derived from heparinized blood was introduced in Amsterdam to perform exchange transfusions in newborns. This heparin mixture has physiological levels of electrolytes, calcium and glucose, can be delivered on short notice and carries a minimal risk of transmission of infectious diseases because all blood components are tested for hepatitis B antigen and antibodies against syphilis and the human immunodeficiency virus. Retrospectively we evaluated 54 children treated in 1986 and 1987 with exchange transfusions using this heparin mixture. An adequate decrease in bilirubin values when necessary was observed while neither changes in sodium, potassium, calcium or glucose values nor adverse effects on the pH value were recorded. However, a remarkable transient thrombocytopenia was found following exchange transfusion with a decrease of the platelet count to an average of 39% of the initial value.
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PMID:[The use of a mixture of citrated erythrocytes and heparin plasma for exchange transfusions]. 221 59

Wiskott-Aldrich Syndrome (WAS) is a sex-linked disease characterized by immunodeficiency and thrombocytopenia. Supportive treatment of this disease is inadequate and bone marrow transplantation has been reported to result in excellent survival. The long-term follow-up of 8 male patients who received bone marrow transplantation for the WAS is reported here. All of these patients received ablative preparative treatment consisting of ATS (antithymocyte serum), cytoxan and either busulfan or TBI (total body irradiation). Bone marrow was transplanted from an HLA-matched donor. Seven of eight of these male patients have had excellent engraftment of their transplant and now have adequate lymphocyte and platelet function. In addition, they have had good growth and development. This suggests that ablative preparative treatment followed by early bone marrow transplantation from an HLA-matched donor is a highly successful therapy for this congenital disease.
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PMID:Bone marrow transplantation for the Wiskott-Aldrich syndrome. Long-term follow-up. 221 85

The CD4 antigen, which serves as the receptor for human immunodeficiency virus type 1 (HIV-1) on T cells, has been detected on human megakaryocytes. Recent evidence of impaired thrombopoiesis in HIV-1-related thrombocytopenia suggested that these cells could be directly infected by the virus and prompted a search for a receptor on megakaryocytes of normal subjects that could permit entry of HIV-1. Bone marrow specimens from uninfected normal control subjects were centrifuged over Ficoll-Hypaque (1.077 g/ml) and analyzed by three-color analysis with a flow cytometer utilizing monoclonal antibodies against CD4 and a glycoprotein present on the surface of megakaryocytes and platelets (GPIIb/IIIa; CD41), as well as 7-aminoactinomycin D, a stain for DNA. Cells presumed to be megakaryocytes were identified by having a DNA content greater than tetraploid and staining brightly with anti-CD41. Approximately 0.4% of the nucleated cells of the marrow met these criteria. Twenty-five percent of these megakaryocytes stained as brightly as CD4+ T cells. Several clones of antibody recognizing different epitopes of the CD4 molecule gave similar results. Platelets were CD4-. Staining of megakaryocytes with anti-CD4 was confirmed by direct microscopic examination of Percoll-gradient-enriched megakaryocytes employing two-color (CD4-phycoerythrin and CD41-fluorescein) immunofluorescence analysis and phase-contrast microscopy. The proportion of double-labeled cells among 112 phase-contrast-identifiable megakaryocytes from five bone marrow specimens varied between 20% and 26% with a mean and SD of 22% +/- 2.5%. Thus some human megakaryocytes express CD4 on their surface that should be capable of binding the HIV-1 gp120 envelope protein. This could serve as a portal of entry for HIV-1.
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PMID:Expression of CD4 by human megakaryocytes. 223 21

In a 4 1/2-year period, 4 of 68 children in a longitudinal study of neurological complications of human immunodeficiency virus (HIV) infection had clinical and/or neuroradiological evidence of stroke, yielding a clinical incidence of stroke in this population of 1.3% per year. During this period, 32 subjects died, and permission for autopsy was granted in 18 of the patients, including 3 of 4 who had clinical evidence of stroke. The prevalence of cerebrovascular pathological features in our consecutive autopsy series was higher than the clinical incidence. At autopsy cerebrovascular disease was documented in 6 (24%) of 25 children with HIV infection, including all 3 children who had clinical evidence of stroke. Four patients had intracerebral hemorrhages, 6 patients had nonhemorrhagic infarcts, and 3 had both. Hemorrhage was catastrophic in 1 child and clinically silent in 3 children, all of whom had immune thrombocytopenia. One child had an arteriopathy that affected meningocerebral arteries. In another child, the arteries of the circle of Willis were aneurysmally dilated. Two children had coexisting cardiomyopathy and subacute necrotizing encephalomyelopathy with vascular proliferation. These results suggest that stroke should be considered when children with HIV infection develop focal neurological signs.
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PMID:Stroke in pediatric acquired immunodeficiency syndrome. 224 Nov 13


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