Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two enantiomers of carbovir, a carbocyclic analog of 2',3'-dideoxyguanosine, were compared with respect to their phosphorylation and the phosphorylation of their nucleotides by mammalian enzymes. 5'-Nucleotidase catalyzed the phosphorylation of (-)-carbovir, which is active against HIV (human immunodeficiency virus), but did not phosphorylate (+)-carbovir. (-)-Carbovir monophosphate was 7,000 times more efficient as a substrate for GMP kinase than was (+)-carbovir monophosphate. Pyruvate kinase, phosphoglycerate kinase, and creatine kinase phosphorylated both enantiomers of carbovir diphosphate at similar rates. Nucleoside-diphosphate kinase preferentially phosphorylated the (-)-enantiomer. Both enantiomers of carbovir triphosphate were substrates and alternative substrate inhibitors of HIV reverse transcriptase. Thus, the contrasting HIV-inhibitory activities of carbovir enantiomers were due to differential phosphorylation by cellular enzymes and not due to enantioselectivity of HIV reverse transcriptase.
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PMID:Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity. 138 19

There have been few cases of polymyositis in patients with AIDS, and polymyositis is rarely a cause of myoglobinuria. We studied a 20-year-old homosexual man with recurrent myoglobinuria. He was asymptomatic between episodes. Each episode was accompanied by muscle pain, limb weakness, high serum levels of creatine kinase, and pigmenturia. Muscle biopsy showed active necrosis without inflammation or abnormalities of glycolytic or other energy-generating enzymes. Antibodies to HIV were present in serum. Clinical evidence of AIDS has not developed in 2 years. Recurrent myoglobinuria may be another consequence of HIV infection.
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PMID:Recurrent myoglobinuria and HIV seropositivity: incidental or pathogenic association? 260 81

Neuromuscular disorders reported in association with human immunodeficiency virus (HIV) infection include several forms of peripheral neuropathy and polymyositis. We report 11 patients with HIV-associated myopathy. Five patients with acquired immunodeficiency syndrome (AIDS), 2 with AIDS-related complex, and 4 otherwise asymptomatic HIV-infected patients developed progressive proximal muscle weakness. Serum creatine phosphokinase levels were elevated and electromyography revealed abnormal spontaneous activity and myopathy in most patients. All 8 muscle biopsy specimens showed fiber necrosis. Four had inflammatory infiltrates, and nemaline rod bodies were prominent in 3. Immunosuppressant therapy in 5 patients resulted in improvement. Attempts at viral localization in 4 muscle biopsy specimens were unsuccessful. These findings suggest a distinct association between HIV infection and myopathy with features atypical for polymyositis.
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PMID:Human immunodeficiency virus-associated myopathy: analysis of 11 patients. 284 80

Zidovudine-induced myopathy is characterized by reversible muscle weakness, wasting, myalgia, fatigue, and elevated creatine kinase (CK). Some zidovudine-treated patients with normal muscle strength experience excessive fatigue, myalgia, or transient mild CK elevations that improve when zidovudine is stopped. To determine the cause of these symptoms, we studied 13 physically fit, HIV-infected men who developed fatigue, myalgia, and reduced endurance, while taking zidovudine for a mean period of 20 months (2-39 months), with neurological evaluation and muscle biopsy processed for enzyme histochemistry and electron microscopy (EM). All subjects had normal muscle strength. In 6 of the 13 patients, muscle biopsies were normal by enzyme histochemistry. EM, however, demonstrated proliferation of normal or abnormal mitochondria, and increased amounts of lipid, glycogen, and lipofuscin. Electromyographic (EMG) studies (5/5) and serum CK (6/6) were normal. The other 7 individuals had signs of moderate to severe mitochondrial abnormalities shown by both light microscopy and EM, characterized by severe destruction, vacuolization, and rare paracrystalline inclusions. Most had elevated CK (4 out of 7) and normal EMG (5 out of 7). The severity of morphological abnormalities did not correlate with duration of HIV infection, zidovudine therapy, or zidovudine dosage. We conclude that in zidovudine-treated patients, symptoms of fatigue, myalgia, reduced endurance, and exercise intolerance represent early signs of zidovudine-induced mitochondriotoxicity, which causes an energy shortage within the muscle fibers even when muscle strength is still normal. Zidovudine, a DNA chain terminator, results in overt myopathy when a critical threshold of molecular, histological, and biochemical dysfunction of mitochondria is crossed, which seems to vary between individuals.
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PMID:Early features of zidovudine-associated myopathy: histopathological findings and clinical correlations. 757 71

Between June 1986 and October 1992, disseminated toxoplasmosis was diagnosed in 16 AIDS patients. 13 cases were diagnosed at autopsy where multiple organ involvement was documented in all 13. Three patients were diagnosed intra vitam. All 3 survived with appropriate treatment. Clinical features indicative of disseminated toxoplasmosis were: fever of unknown origin between 39 degrees and 40 degrees C in 16 cases, clinical signs suggestive of sepsis or septic shock in 15, with progression to multiorgan failure in 10, disseminated intravascular coagulopathy in 6, confusion, disorientation or apathy in 13 and lack of a systemic pneumocystis carinii prophylaxis in all 16. Typical laboratory markers were: CD4 cell counts below 100 x 10(6)/l in 16 cases, elevation of serum lactic dehydrogenase in 16 and creatine phosphokinase (in 4/6), normal or only slightly elevated C-reactive protein (in 9/11), positive Toxoplasma gondii IgG antibodies in 15/16 and negative IgM antibodies in all 16. Lesions indicative of cerebral toxoplasmosis were visualized on cranial computerized tomography in only 3/10 evaluated patients. In patients with advanced HIV infection presenting with a systemic illness, including the clinical and laboratory features described above, systemic Toxoplasma gondii infection must be included in the differential diagnosis. In these patients, specific and if warranted, invasive diagnostic procedures followed by early vigorous therapeutic intervention should be considered.
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PMID:Disseminated toxoplasmosis in AIDS patients--report of 16 cases. 778 18

Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.
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PMID:Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine. 826 54

To investigate potential mechanisms for HIV-1 proviral latency, we generated a set of chronically HIV-1 infected and stably long terminal repeat-chloramphenicol acetyl transferase (LTR-CAT)-transfected TE671/RD cells, and studied both their virus production and LTR-driven reporter gene expression. Established tissue culture models of retroviral latency in lymphoid and monocytoid cell lines have demonstrated that the induction of virus production is associated with a shift in HIV-1-specific mRNA from a predominance of singly and multiply spliced mRNA's to the production of full-length HIV-1 RNA. We found a similar pattern in TE671/RD cells, but in contrast to U1 and ACH2 cells, could not induce viral replication by exposure to phorbol myristate acetate (PMA) alone. We demonstrated instead that production of full-length viral RNA, viral replication, and LTR-driven CAT expression could be induced by exposure to sodium butyrate. The most proximate effect of sodium butyrate is inhibition of cellular histone deacetylase(s) which results in disruption of nucleosomes relieving one level of restriction to gene expression. Consistent with this mechanism of action, we further found that sodium butyrate's effects: (i) act synergistically with PMA and TNF-alpha; (ii) are independent of protein synthesis; (iii) do not affect the constitutively expressed creatine phosphokinase gene; (iv) do not map to a discrete sequence motif in the viral LTR; and (v) are not blocked by N-acetyl cysteine but (vi) are blocked by novobiocin, an inhibitor of cellular topoisomerase II. These data show that a similar pattern of restricted viral RNA expression exists in this nonlymphoid cellular model of HIV-1 latency. In contrast however, these results suggest that in these cells there is an additional block to viral gene expression, which is overcome with sodium butyrate. These results are discussed in the context of histone-mediated repression of HIV-1 gene expression.
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PMID:Sodium butyrate treatment of cells latently infected with HIV-1 results in the expression of unspliced viral RNA. 837 31

Clinical and experimental findings in idiopathic amyothrophic lateral sclerosis (ALS) would be compatible with a retroviral involvement. In 35 adult patients with non-familial ALS we observed elevated circulating immune complexes, a decrease in IgG3 isotype and enzyme-linked sorbent assay (ELISA) serum antibodies against human spuma retrovirus (HSRV), confirmed by specific human foamy virus immunoblots. All 35 were negative for IgM or relevant IgG anti-ganglioside antibodies. We treated 12 HIV-negative, immune-complex-positive ALS patients with 500 mg d-1 zidovudine p.o. over 2-10 months and found reductions of serum creatine kinase and circulating immune complexes from two days to two weeks after the beginning of medication.
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PMID:Antiretroviral therapy in sporadic adult amyotrophic lateral sclerosis. 839 59

Zidovudine (ZDV), a nucleoside analogue which inhibits viral replication, is currently used in the treatment of type 1 human immunodeficiency virus (HIV-1) infection. It has been considered to be the cause of an acquired form of myopathy associated with a depletion of mitochondrial DNA (mtDNA) in muscle fibres, although the fact that the patients previously studied were clearly symptomatic, and the theoretical difficulty in differentiating on HIV-related myopathy from the effects of ZDV, led to a controversy on the possible deleterious effect of ZDV on muscle fibres. We studied the muscle biopsy taken from 42 HIV-1 infected patients, regardless of their medical complaints, and two series of controls: 12 HIV-negative patients suffering from diverse neuromuscular diseases and 10 normal patients who underwent orthopaedic surgery. Whole DNA was extracted following standard procedures and analysed by means of Southern blotting and polymerase chain reaction (PCR). We found that mtDNA was only depleted in HIV-1 infected patients treated with ZDV, but not in controls or patients untreated with this antiretroviral drug. Moreover, the depletion was more marked in patients who either presented weakness, myalgia, raised serum creatine kinase (CK), or ragged-red fibres. Mitochondrial DNA deletions were found in low proportion in all groups of patients, regardless of their HIV infection or ZDV status, but not in normal controls. We conclude that ZDV treatment in HIV-1 positive patients produces depletion of muscle mtDNA. The depletion can be demonstrated even in asymptotic patients, but is more marked in patients with clinical symptoms or abnormalities in their muscle biopsies. Other mtDNA abnormalities such as deletions seemed to be more related to other circumstances concurring in HIV-1 infected patients than to the effects of ZDV.
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PMID:The effect of zidovudine on skeletal muscle mtDNA in HIV-1 infected patients with mild or no muscle dysfunction. 881 97

Cryptococcosis is the commonest fungal infection of the CNS and it is an important cause of morbidity and mortality in immunodeficient patients [1]. It has been occasionally described in immunocompetent patients [2]. We report a patient with no predisposing factors who was treated with flucytosine and amphotericin B for cryptococcal meningitis. Following treatment, she developed a reversible acute cerebellar syndrome that was probably secondary to the administration of flucytosine, an adverse effect that has not previously been described [3, 4]. An 87-year old women with no relevant personal or family history was admitted to the hospital for headache, fever, and confusion over the past week. The vital signs, general and neurological examination were normal. In laboratory tests, the urine, urea nitrogen, glucose, bilirubin, electrolytes, aspartate aminotransferase, creatine kinase, alkaline phosphatase, haematocrit, white-cell count, and platelet were also normal. A lumbar puncture was performed which showed: 60 typical lymphocytes per ml, adenosine deaminase (ADA) activity 6 U.l-1 (normal under 4 U.l-1), proteins 75.7 mg.dl-1, and glucose 13 mg.dl-1 with a glycaemia of 120 mg.dl-1. The microbiology study showed staining and a positive culture for Cryptococcus neoformans, and an antigen titre of 1/2080. The serology for HIV infection was negative, and other predisposing factors for this fungal infection, such as immunological defects, a lymphoreticular malignancy and sarcoidosis were excluded. A CT scan of the cranial-thoracic-abdominal regions was normal and tumour markers were absent.
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PMID:Acute cerebellopathy as a probable toxic effect of flucytosine. 911 68


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