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

In 1987, under the aegis of the governmental campaign against AIDS, military hospitals in Moscow established a department for the diagnosis and treatment of HIV-infected and AIDS patients among the military and their families. Clinical and laboratory examinations showed that 96 people out of 130 examined either were positive for HIV or were suffering from symptoms of AIDS. 77 were military from African countries, 15 from Russia, and 4 were their family members. Out of these 15 patients from Russia, 8 had been infected via sexual intercourse: 1 via homosexual and 7 via heterosexual intercourse. In 10 patients, HIV infection had been diagnosed 1-2 years after being infected, in 3 patients 3-6 years later, and in 2 patients more than 10 years afterwards. Every other patient exhibited symptoms of the second stage of AIDS: persistent generalized lymphadenopathy. 4 patients had lost body weight, 8 patients had prolonged fever, 2 had diarrhea, 4 had various dermatological symptoms, 4 had opportunistic infections, 5 had other infections (viral hepatitis, acute pneumonia, and salmonella), and 3 patients had other ailments (paranephritis, salpingoophoritis, endometritis, purulent otitis). The cases of 3 patients are described in detail. 4 out of 5 patients who were transferred to this special department demonstrated severe inflammatory processes as a consequence of their HIV-infection: paranephritis, pneumonia, purulent cholangitis, and salmonella. All patients also evinced damage to their immune system: the reduction of T-lymphocyte count and T-helper cells and the reduction of the index of T-helper/T-suppressor cells (to 0.31 from the norm of 1.1-2.2). The treatment of AIDS patients consisted of the use of azidothimidine, which inhibits the activity of reverse transcriptase; the stimulation of the immune system by means of timalin (10 mg for 5 days im); and treating secondary fungal infections (up to 8 million IU of nystatin/day, up to 4 million IU of levorin, and up to 200 mg of diflucan).
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PMID:[HIV infection in servicemen (the work experience of a specialized hospital department)]. 757 95

The cpk mouse is the most extensively characterized model of autosomal recessive polycystic kidney disease (ARPKD). The major ARPKD-related renal and biliary phenotypes are modulated in F2 mutants by genetic background, suggesting that quantitative trait loci (QTL) modulate disease severity. In 461 F2 cpk mice, kidney length, weight, and volume were scored as quantitative traits (QT), and a semiquantitative method to assess biliary duct number, area (BDA), portal vein area, and total area of each portal field, as well as the severity of cholangitis, was developed. QTL mapping was performed with Pseudomarker v1.02. Candidate genes were identified within the QTL intervals on the basis of expression profiling, reverse transcriptase-PCR, haplotypes, and sequence analysis. The renal QT were normally distributed in the F2 cohort and strongly correlated (P < 0.001). Among the biliary QT, only BDA correlated with the renal QT (P < 0.01). Genome-wide scan identified a major effect QTL on chromosome (Chr) 4 for the renal traits, adjusted BDA, and cholangitis with logarithm of odds scores of 18, 8, and 5, respectively. Regression modeling refined the Chr 4 main effect into an approximately 50-cM region with three distinct QTL peaks at 16, 34, and 54 cM. Kif12, a gene encoding a novel kinesin, mapped beneath the 34 cM QTL peak and has expression level variants and strain-specific sequences that were associated with renal disease severity in affected mice. Therefore, the positional candidate gene, Kif12, fulfills the major criteria for QTL gene discovery established by the Complex Trait Consortium, and, thus, it is proposed that Kif12 is a cpk modifier gene.
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PMID:Kinesin family member 12 is a candidate polycystic kidney disease modifier in the cpk mouse. 1572 79

Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label extension study. Only a third of the PBC patients were able to tolerate the lopinavir but those maintained on tenofovir, emtricitabine and lopinavir experienced sustained and clinically meaningful reduction in hepatic biochemistry. While we await the histological and virological evaluation, it is clear that better tolerated regimens of antiretroviral treatment will be required in future clinical trials.
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PMID:Combination antiretroviral studies for patients with primary biliary cirrhosis. 2675 81