Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus. All patients had a CD4+ T-lymphocyte count of less than 100 cells/microl at study entry. Efficacy in this single-arm open-label prospective study was analyzed on an as-treated basis. No patient received highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. PCP developed in four patients, one of whom had been noncompliant. No PCP episode occurred in the first year. Probabilities of freedom from PCP were 0.97 (95%CI, 0.92-1) after 24 months and 0.93 (95%CI, 0.84-1) after 36 months. Of 74 (69.8%) patients positive for anti-toxoplasma IgG antibodies, one noncompliant patient developed toxoplasmic encephalitis after 24 months. Allergic reactions were observed in 18 (17%) patients and resulted in permanent discontinuation in 7 (6.6%) patients. One (0.9%) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction (Stevens-Johnson syndrome). The median survival of study participants was 29 months, with relentless progression of AIDS accounting for most deaths. The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance. Efficacy and safety compare favorably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens.
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PMID:Effectiveness of twice-weekly pyrimethamine-sulfadoxine as primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in patients with advanced HIV infection. 1207 19

The human immunodeficiency virus type 1 (HIV-1) enters the central nervous system (CNS) during the acute phase of infection and causes AIDS-related encephalitis and dementia in 30% of individuals. Previous studies show that HIV-1 sequences derived from the CNS of infected patients, including the sequence encoding reverse transcriptase (RT), are genetically distinct from sequences in other tissues. The hypothesis of the current study is that the RT sequence of HIV-1 is under positive selection within the CNS. Multiple alignments of non-CNS-derived and CNS-derived HIV-1 RT sequences were constructed using the ClustalW 1.8 program. The multiple alignments were analyzed with the Synonymous/Nonsynonymous Analysis Program. Codon positions 122-125, 135-149, and 166-212 of the CNS-derived RT sequences underwent a greater accumulation of nonsynonymous than synonymous substitutions, which was markedly different from the analysis results of the non-CNS-derived RT sequences. These residues are located in the finger and palm subdomains of the RT protein structure, which encodes the polymerase active site. The analysis of CNS-derived partial-length RT sequences that encompass these regions yielded similar results. A comparison of CNS-derived RT sequences to a non-CNS-derived RT consensus sequence revealed that a majority of the nonsynonymous substitutions resulted in a specific amino acid replacement. These results indicate that reverse transcriptase is under positive selection within the CNS. The amino acid replacements were visualized on a three-dimensional structure of HIV-1 RT using the Sybyl software suite. The protein structure analysis revealed that the amino acid replacements observed among the CNS-derived sequences occurred in areas of known structural and functional significance.
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PMID:The reverse transcriptase sequence of human immunodeficiency virus type 1 is under positive evolutionary selection within the central nervous system. 1216 13

A 3-month-old girl who developed severe measles encephalitis after neonatal measles is reported. Her mother had measles when she was ten days old and she was admitted to our hospital with low grade fever, Koplik spot, and mild exanthema seventeen days after birth, and she recovered in 7 days without any complication. At three months of age, she was readmitted because of intractable seizures. The levels of IgM and IgG antibodies against measles in the cerebrospinal fluid were elevated. The measles virus genome, amplifying the region encoding the nucleocapsid protein, was detected from the brain specimen by reverse transcriptase-polymerase chain reaction. Magnetic resonance imaging showed a focal destructive lesion and diffuse cerebral atrophy. The electroencephalogram did not show periodic synchronous discharges. Although the neonatal measles was believed to be relatively mild in severity, the possible development of measles encephalitis should be carefully monitored in an infant who had neonatal measles.
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PMID:Severe infantile measles encephalitis occurred three months after neonatal measles. 1253 72

Necropsy of an older dog submitted for evaluation of renal and central nervous system disease revealed histologic lesions compatible with West Nile viral encephalitis and myocarditis, as seen in other species. Using reverse transcriptase-polymerase chain reaction detection of envelope sequences, viral RNA was detected in most organs, and quantitative polymerase chain reaction revealed that at least 1,000 times more RNA was present in kidney than in brain, heart, spleen, or lung. Immunohistochemical evaluation of the kidney revealed intense staining of West Nile viral antigens in renal tubular epithelium and casts located within multifocal granulomatous interstitial inflammation. A canine immunoglobulin M (IgM)-capture enzyme-linked immunosorbent assay was developed, and patient serum was strongly positive for viral antibody. Retrospective and ongoing evaluation of sera from dogs with neurological disease and of those submitted for heartworm testing detected 4 dogs that were subclinically infected but without additional sickness. Judged by this experience, the kidney of West Nile virus-infected dogs may be an important target organ, one that might be suitable for antemortem biopsy. The presence of virus-specific IgM was demonstrated in the serum of this dog, and finding 4 positives among 169 additional canine sera received since late July 2002 suggests that seroconversion appears to be relatively uncommon in dogs during the outbreak in Missouri.
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PMID:Serological, reverse transcriptase-polymerase chain reaction, and immunohistochemical detection of West Nile virus in a clinically affected dog. 1291 12

A 55-year-old bat conservationist was admitted to Ninewells Hospital, Dundee, Scotland, on November 11, 2002, with an acute haematemesis. He gave a 5-day history of pain and paraesthesia in the left arm, followed by increasing weakness of his limbs with evidence of an evolving encephalitis with cerebellar involvement. The patient had never been vaccinated against rabies and did not receive postexposure treatment. Using a hemi-nested reverse transcriptase-polymerase chain reaction (RT-PCR), saliva samples taken intravitam from different dates proved positive for rabies. A 400-bp region of the nucleoprotein gene was sequenced for confirmation and identified a strain of European bat lyssavirus (EBLV) type 2a. The diagnosis was confirmed using the fluorescent antibody test (FAT) and by RT-PCR on three brain samples (cerebellum, medulla, and hippocampus) taken at autopsy. In addition, a mouse inoculation test (MIT) was performed. Between 13 and 17 days postinfection, clinical signs of a rabies-like illness had developed in all five inoculated mice. Brain smears from each infected animal were positive by the FAT and viable virus was isolated. This fatal incident is only the second confirmed case of an EBLV type-2 infection in a human after exposure to bats.
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PMID:Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. 1293 4

We examined sera from goats that developed more rapid and severe clinical disease after vaccination with inactivated caprine arthritis encephalitis virus (CAEV) and virus challenge for CAEV infection-enhancing antibodies. Sera from one control and two vaccinated goats were examined for neutralization or enhancement of virus infection in caprine macrophages. Macrophage cultures were incubated with virus-serum mixtures, then washed and fed with fresh media and incubated. Culture fluid was collected at days 2,4 and 8 post-infection and assayed for reverse transcriptase (RT) activity. Serum from one of the vaccinated goats neutralized virus at 10(-2) and 10(-3) dilutions (p = 0.045 and p = 0.020, respectively). The neutralizing effect was lost at higher dilutions (10(-4) and 10(-5)) of the serum, but no enhancement of infection was seen. Serum from the other vaccinated goat did not show any significant neutralizing effect at either 10(-2) or 10(-3) dilutions and increased infection (40% or greater) at higher dilutions, but the increases were not statistically significant. Therefore, there was no evidence of virus infection-enhancing activity in these sera that would suggest that the severe disease experienced by the vaccinated animals was due to serum enhancement of infection. Alternately, the severe arthritis observed could have resulted from the pro-inflammatory activities of cytokines and chemokines produced by macrophages upon phagocytosis, or receptor-mediated uptake of CAEV-antibody complexes.
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PMID:Lack of enhancement of caprine arthritis encephalitis virus infection in monocyte-derived macrophage cultures by sera from goats that developed severe arthritis after vaccination and virus challenge. 1468 1

West Nile virus (WNV) is an important arthropod borne flavivirus; usually causes a mild infection called West Nile fever (WNF) in human and horses. Mosquitoes are the principal vectors of WNV. Various Culex species are found to act as vectors in different geographical regions. The virus is maintained in a bird-mosquito cycle in nature. In India, Culex mosquitoes are tentatively incriminated as vectors of WNV. Experimental studies have shown that Culex tritaeniorhynchus, Cx. vishnui, Cx. bitaeniorhynchus and Cx. univittatus, Culex pipiens fatigans and Aedes albopictus could act as potential vectors of WNV. Transovarial transmission of WNV has been experimentally demonstrated in Culex mosquitoes. Apart from mosquitoes, the role of other arthropods is also considered in the maintenance of WNV during inter-enzootic periods. The possible role of ardeid birds in the maintenance of WNV has been described in India. Though very few clinically overt cases of human encephalitis due to WNV are observed, Japanese encephalitis virus (JEV) is found to dominate in southern India. WNF in horses has not been documented in India. JEV immunized monkeys were protected from WNV challenge and the WNV immunization was found to reduce the disease severity due to JEV. Based on the limited genome sequence analysis, the Indian isolates are grouped together under the genetic lineage-I. WNV infection is diagnosed by IgM antibody capture enzyme linked immunosorbant assay, haemagglutination inhibition test, neutralization test and reverse transcriptase-polymerase chain reaction (RT-PCR). For the effective control of Culex mosquitoes, integrated vector control strategies are recommended. Specific methods are not available for the treatment of WNV infection. However, in patients with encephalitis supportive therapy is recommended. Though a few candidate vaccines are under laboratory trial, no vaccine has been available commercially for the control of WNV infection in human and animals. In view of the global interest on WNV, this paper describes the present status of WNV in India.
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PMID:West Nile virus: the Indian scenario. 1470 Mar 42

The North American West Nile virus (WNV) epizootic, which began in 1999, has caused significant morbidity and mortality in horses. Because experimental infection has failed to consistently produce encephalitis in inoculated horses, investigation of naturally occurring cases was used to optimize strategies for diagnosis of this disease. Although WNV RNA could be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) performed on whole blood collected from both clinically affected horses and unaffected herdmates, the diagnostic sensitivity of this approach was low compared with IgM-capture enzyme-linked immunosorbent assay. In addition, it was observed that 18.5% of herdmates of clinically ill horses seroconverted to WNV yet exhibited no overt clinical signs of WNV encephalitis. West Nile viral RNA was detected in neural tissue of 46 of 64 dead horses that were suspected of having WNV encephalitis. Some of these animals were IgM negative or had not been tested serologically. A primary cause of death other than WNV encephalitis was identified in 15 of the 64 cases, whereas the final diagnosis for 3 of these cases remains unresolved. Quantitative RT-PCR analysis of neural tissue from WNV RNA-positive horses demonstrated that the medulla contained the highest mean concentration of viral RNA and that WNV RNA could be detected in samples extracted from formalin-fixed neural tissue. A comparison of WNV RT-PCR amplification strategies found that nested RT-PCR improved diagnostic sensitivity only slightly over a single round of amplification and that a quantitative (TaqMan) assay had sensitivity and specificity that were equivalent to those of nested amplification.
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PMID:Diagnosis of West Nile virus infection in horses. 1497 40

Visna/maedi virus (VMV) causes severe encephalitis and a progressive demyelinating disease in sheep. Previous in vitro studies have demonstrated that VMV-infection leads to apoptosis in sheep choroid plexus cells (SCPC) via induction of both intrinsic and extrinsic pathways with subsequent activation of caspases. 3' azido-2',3'-deoxythymidine (AZT) is a potent and selective Human immunodeficiency virus 1 (HIV-1) reverse transcriptase inhibitor, widely used in antiretroviral therapy; however its effects on retrovirus-induced apoptosis are unknown. Using diverse strategies to detect apoptosis, we analysed the broad range effect of AZT treatment on inhibition of VMV-induced apoptosis. First, we found that AZT treatment inhibited the appearance of characteristic apoptotic morphologic changes documented by DAPI staining and oligonucleosomal DNA laddering. Secondly, AZT treatment inhibited caspase cascade and resulted in (i) diminished caspase-3, -8 and -9 activities and (ii) no fluorescein isothiocynate-[VAD]-fluoromethylketone (FITC-VAD-FMK) in situ labelling in VMV-infected cells treated with AZT. Finally, immunocytochemistry indicated that VMV-infection of SCPC induced the subsequent release of apoptosis inducing factor (AIF), whereas AZT treatment inhibited AIF leakage. Consequently, the anti-apoptotic effects of AZT are not restricted, since AZT treatment blocks all the apoptotic pathways induced during VMV-infection.
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PMID:AZT inhibits Visna/maedi virus-induced apoptosis. 1499 45

An aged Barbary ape (Macaca sylvanus) at the Toronto Zoo became infected with naturally acquired West Nile virus encephalitis that caused neurologic signs, which, associated with other medical problems, led to euthanasia. The diagnosis was based on immunohistochemical assay of brain lesions, reverse transcriptase-polymerase chain reaction, and virus isolation.
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PMID:West Nile virus encephalitis in a Barbary macaque (Macaca sylvanus). 1520 Aug 66


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