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)

Dithiocarbamates and iron chelators were recently considered for the treatment of AIDS and neurodegenerative diseases. In this study, we show that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes. Using cell cultures, the pyrrolidine derivative of dithiocarbamate (PDTC) was investigated in detail. Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit I kappa B from the latent cytoplasmic form of NF-kappa B in cells treated with phorbol ester, interleukin 1, and tumor necrosis factor alpha. Other DNA binding activities and the induction of AP-1 by phorbol ester were not affected. The antioxidant PDTC also blocked the activation of NF-kappa B by bacterial lipopolysaccharide (LPS), suggesting a role of oxygen radicals in the intracellular signaling of LPS. This idea was supported by demonstrating that treatment of pre-B and B cells with LPS induced the production of O2- and H2O2. PDTC prevented specifically the kappa B-dependent transactivation of reporter genes under the control of the HIV-1 long terminal repeat and simian virus 40 enhancer. The results from this study lend further support to the idea that oxygen radicals play an important role in the activation of NF-kappa B and HIV-1.
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PMID:Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. 131 83

Excessive hemosiderin-laden perivascular macrophages have been described in the brains of patients with the acquired immunodeficiency syndrome (AIDS) who underwent autopsy; its meaning remains unclear. In the brains of 53 patients with AIDS who consecutively underwent autopsy, we quantified the abnormality, elucidated its relationship to the pathologic features of AIDS, and asked if there was some relationship to endogenous iron storage and transport proteins in brain macrophages and microglia. The number of perivascular siderotic macrophages was significantly increased in patients with AIDS compared with age-matched control subjects. Macrophage siderosis was strongly correlated with the presence of disseminated mycobacterial infection and vacuolar myelopathy at autopsy; a generalized wasting (cachexia) also was related significantly. Many other pathologic abnormalities were not related, including putative human immunodeficiency virus-specific neuropathologic changes such as multinucleated cells and myelin pallor. Activated macrophages and microglial cells in the central nervous system had dense intracytoplasmic accumulation of ferritin (iron storage protein) in AIDS and non-AIDS patients. These results suggest that siderosis of cerebral macrophages is related to an ill-defined nonspecific systemic imbalance associated with the breakdown of abundant stores of endogenous intracellular ferritin. Understanding chronic "secondary" effects of human immunodeficiency virus type 1 infection will become increasingly important as improved survival in patients with AIDS is realized.
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PMID:Siderotic cerebral macrophages in the acquired immunodeficiency syndrome. 158 Jul 55

In the 6-year period 1984-1989, 101 liver biopsies or 'needle necropsies' from human immunodeficiency virus positive patients were examined histologically. Of these, only nine showed no abnormality whatsoever. The commonest histological findings were either fatty change or changes related to co-existent chronic viral hepatitis. Granulomas were seen in 15 cases, four of which were positive for acid-fast bacilli. A range of organisms were recorded: cytomegalovirus (4); Histoplasma capsulatum (1); Pneumocystis carinii (2); Cryptococcus neoformans (1); and Leishmania donovani (1). There were two cases of non-Hodgkin's lymphoma, but no cases of Kaposi's sarcoma. Marked iron deposition, which correlated with multiple blood transfusions was seen in nine biopsies. We were unable to identify any histological feature in the liver as being specific for HIV infection. The high incidence of liver abnormalities reflects: (i) the coincident exposure to hepatotropic viruses; (ii) the presence of opportunistic infections and neoplasms, usually part of a disseminated multi-organ process arising in the setting of profound immune depression; (iii) iatrogenic causes, in particular iron overload related to multiple blood transfusions received for treatment of zidovudine-induced anaemia; and (iv) non-specific changes associated with chronic debilitating disease.
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PMID:Surgical pathology of the liver in HIV infection. 165 81

Erythropoietin (EPO) is a major regulatory factor controlling red blood cell (RBC) production in humans. Although other humoral factors can alter the proliferation of committed early erythroid progenitors in vitro, no factor other than EPO has been clearly shown to induce proliferation of these cells in vivo. In a clinical trail of recombinant granulocyte colony-stimulating factor (G-CSF) and recombinant EPO in patients with advanced human immunodeficiency virus (HIV) infection, we noted reticulocytosis and increases in hemoglobin when G-CSF was administered before the administration of EPO. Subsequent studies demonstrated a significant increase in circulating burst forming unit-erythron (BFU-E) during daily recombinant G-CSF therapy. This increase was both time- and dose-dependent. The magnitude of increase in BFU-E correlated with the magnitude of increase in neutrophils and was associated with a mean increase in reticulocytes of 32,363/microL and a significant increase in mean hemoglobin of 1.04 +/- 0.34 g/dL over an 18-day interval. There was a significant increase in iron binding capacity and decreases in iron saturation and ferritin levels. In patients who were not recently transfused, there was an associated fall in endogenous erythropoietin levels. The increase in RBC production was most marked in patients who were severely anemic, transfusion-dependent, and who had elevated pretreatment EPO levels. There was no correlation between the increase in BFU-E and endogenous EPO levels or the time since last dose of zidovudine. The addition of recombinant EPO therapy three times weekly to patients did not result in further significant increases in BFU-E but did significantly increase hemoglobin. Our data suggest that recombinant G-CSF may be one of the hematopoietic factors that influences production of BFU-E and RBCs in humans.
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PMID:Recombinant human granulocyte colony-stimulating factor increases circulating burst forming unit-erythron and red blood cell production in patients with severe human immunodeficiency virus infection. 169 97

To determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus (HIV) and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications, 216 bone marrow biopsies, aspirates, and/or imprint preparations from 178 patients who either were seropositive for HIV infection or met the Centers for Disease Control (CDC) criteria for acquired immunodeficiency syndrome (AIDS) were studied. Detailed morphologic review was performed in a blind fashion as to clinical status. Extensive clinical, therapeutic, and laboratory data were collected for each patient. Statistical analysis was performed to detect significant correlations between morphologic findings and clinical/therapeutic/laboratory features. Among the most common bone marrow findings were hypercellularity (53% of specimens), myelodysplasia (69%), evidence of reticuloendothelial (RE) iron blockade (65%), megaloblastic hematopoiesis (38%), fibrosis (20%), plasmacytosis (25%), lymphocytic aggregates (36%), and granulomas (13%). A number of statistically significant correlations between morphologic findings and clinical features were noted. No significant association was detected between any morphologic finding and therapy with a variety of drugs. In 7 of 14 (50%) patients found to have marrow involvement by malignant neoplasm, the bone marrow represented the initial site of diagnosis of the neoplasm. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. In certain clinical situations, bone marrow examination continues to be useful in the management of patients infected with HIV.
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PMID:The bone marrow in human immunodeficiency virus (HIV)-related disease. Morphology and clinical correlation. 170 27

Hemosiderin deposition and vascular inflammation were evaluated in muscle specimens from 50 human immunodeficiency virus (HIV)-infected individuals with neuromuscular symptoms. Iron deposits were detected in 25 of 50 cases, and were found more frequently in the distal muscles of lower limbs than in proximal muscles (22 of 30 cases v three of 20 cases; P less than .001). The incidence was higher than in controls (P less than .01). Polyarteritis nodosa was observed in three cases and microvascular inflammation was observed in 27. Direct immunofluorescence showed deposits of both immunoglobulins (mainly immunoglobulin M) and complement in small vessel walls of 19 of 34 patients. The p17 and p24 HIV antigens were detected in three of 27 cases. Both T8 lymphocytes and macrophages were significantly more numerous in patients with Perls'-positive material; these patients also showed vascular inflammation more frequently. Other findings included noninflammatory microangiopathy (18 cases), tubuloreticular inclusions in endothelial cells (one case), and free and intracytoplasmic eosinophilic globules likely representing digested erythrocytes (seven cases). The present study shows that iron pigment deposition in skeletal muscle is a nonspecific finding, frequently observed in the lower extremities of HIV-infected individuals, where it reflects immunopathologic alterations of the microcirculation. Erythrophagocytosis, which may be observed in the muscle of some HIV-infected individuals, may also be implicated.
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PMID:Iron pigment deposits, small vessel vasculitis, and erythrophagocytosis in the muscle of human immunodeficiency virus-infected patients. 174 26

Porphyria cutanea tarda (PCT) is a disorder of heme synthesis characterized by (a) a diminished activity of uroporphyrinogen decarboxylase biochemically and (b) cutaneous lesions secondary to a delayed type of photosensitivity clinically. A human immunodeficiency virus (HIV)-infected patient with PCT is reported and the world literature is reviewed. To date, 17 HIV-seropositive men with PCT have been described. The initial appearance of PCT occurred before or concurrent with the diagnosis of HIV infection in 71% of these individuals (12 men). The median age at onset of PCT was 36 years (range of 20 to 69 years); the median age for the detection of HIV infection was 35 years (range of less than 20 to 71 years). All of these patients had elevated levels of urine porphyrins and blisters on their dorsal hands. Abnormal liver function tests, erosions, hyperpigmentation, hypertrichosis, and skin fragility were also present in some of the men. Polycythemia, serologic evidence of increased iron stores, scarring, milia, and sclerodermoid changes were rarely observed. Successful therapeutic approaches for PCT in men with HIV infection included (a) elimination of PCT-precipitating agents, (b) avoidance of sun exposure, and (c) periodic phlebotomy. Multiple hypotheses for an etiologic role of the HIV and/or an HIV-associated infection, directly or indirectly, in the pathogenesis of PCT in HIV-seropositive men have been suggested.
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PMID:Porphyria cutanea tarda in human immunodeficiency virus-seropositive men: case report and literature review. 175 38

A new method, "laser magnet immunoassay" (LMIA), has been developed for sensitive detection of viral antigens. Target viruses captured on microbeads were made to react with antibodies labeled with magnetite particles. In a magnetic field, magnetically labeled antigens dispersed in water were attracted to and concentrated at one point on the surface, resulting in the lifting up of a small surface area. A laser beam which was incident on the point reflected, making an interference fringe. The intensity of the fringe indicates the amount of the magnetite conjugated with antigen. A very low concentration of antigens, such as 5 particles of influenza virus and 0.1 pg/ml of human immunodeficiency virus (HIV) p24 antigen in human serum, could be detected by this method. Application of this method to diagnoses of viral diseases in early stages is discussed.
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PMID:Sensitive detection of viral antigens with a new method, "laser magnet immunoassay". 180 69

A longitudinal (10-22 month) evaluation of intestinal symptoms and function was performed in five children with symptomatic human immunodeficiency virus (HIV) infection. All received cotrimoxazole, ketoconazole, and immunoglobulins. A search for enteric pathogens and intestinal function tests were repeatedly performed in all patients. Mild episodes of diarrhea were observed in two children. One had cow's milk protein intolerance. Giardia lamblia was found in an asymptomatic carrier. Evidence for impaired intestinal function was found in all patients. These consisted of positive D-xylose and iron oral loads, increased steatorrhea, increased fecal excretion of alpha 1-antitrypsin, abnormal intestinal permeability, and increased food antibody levels. Our results suggest that severe diarrhea may be uncommon in children with HIV infection receiving antimicrobial prophylaxis, but that the intestinal function is frequently, and often markedly, impaired.
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PMID:Impaired intestinal function in symptomatic HIV infection. 186 78

Iron-deficiency anemia (IDA) in rats is attended by secondary cellular immunodeficiency. The authors studied the importance of lymphocyte dysfunction in the pathogenesis of hematological disorders in rats with IDA. Transplantation of lymphocytes from intact donors subjected to hypoxia to syngeneic recipients led to stimulation of erythropoiesis in them. The effect of "iron deficiency' cells was less manifest. It was established that the hematological disorders in IDA are lymphocyte-determined. This was also demonstrated in experiments on rats with IDA and changed functional condition of the lymphoid tissue.
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PMID:[Disordered lymphoid regulation of hematopoiesis in iron-deficiency anemia]. 192 12


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