Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated an ADP-ribosylation factor (ARF) gene from the human malarial parasite, Plasmodium falciparum. The gene (P. falciparum arf1) has four introns and the exons encode a protein of 181 amino acids with high similarity to the mammalian class I ARF proteins 1-3 (> or = 74% amino acid identity). Southern hybridization suggests there is at least one additional arf in the P. falciparum genome. Northern analysis identified a single P. falciparum arf1 mRNA of 1.8 kb in the asexual blood stage form of the parasite. The P. falciparum arf1 mRNA levels are developmentally regulated, reaching a maximum during nuclear division towards the end of the intraerythrocytic cycle. P. falciparum arf1 cDNA was isolated by reverse-transcriptase polymerase chain reaction and used to express a recombinant protein in Escherichia coli. Recombinant P. falciparum ARF1 protein was purified with stoichiometric amounts of bound GDP, although intrinsic guanose triphosphatase activity of the protein could not be detected. The protein stimulated cholera-toxin-catalyzed ADP-ribosyltransferase activity in a reaction that was dependent upon the addition of both dimyristoylglycerophosphocholine and cholate. The protein bound GTP with first-order kinetics with an apparent rate constant, k', of 0.0145 (+/- 0.0019) min-1. These results suggest that P. falciparum ARF1 is a member of the class 1 ARF family and provide additional evidence for the existence of a classical secretory pathway in P. falciparum.
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PMID:Isolation, expression and characterization of the gene for an ADP-ribosylation factor from the human malaria parasite, Plasmodium falciparum. 895 60

A 37-year-old Belgian patient presented with acute nephropathia epidemica (NE) shortly after a camping holiday in southern France. Unusual symptoms were initial noncardiogenic lung involvement, followed by severe acute renal failure, acute acalculous cholecystitis, presence of immunoblasts in the bone marrow, and hemolytic anemia, presenting as hemolytic uremic syndrome. Positive immunoglobulin (Ig) A and rising IgG titers against Puumala hantavirus (PUUV) were detected, but IgM remained negative on days 8 and 20. The results of reverse-transcriptase-polymerase chain reaction performed on day 8 were positive for PUUV. This is the first report of an iatrogenically IgM-negative hantavirus case due to the selective removal of heavy-weight molecules during plasma exchange via the centrifugation technique. This is also the first report of proven NE from the Mediterranean part of France.
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PMID:Plasma exchange-associated immunoglobulin m-negative hantavirus disease after a camping holiday in southern france. 1515 69

Tenofovir disoproxil fumarate, a prodrug of tenofovir, is a potent nucleotide analogue reverse-transcriptase inhibitor with activity against human immunodeficiency virus (HIV). Although initially thought to be relatively safe with regards to nephrotoxic effects compared to its class drugs-adefovir and cidofovir, several cases of acute renal failure and proximal tubule dysfunction have been described in the last few months. We report another patient who developed Fanconi syndrome while on tenofovir. Her condition improved on discontinuation of the drug. We also review the literature of all patients who have developed Fanconi syndrome on tenofovir.
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PMID:Acute renal failure and Fanconi syndrome in an AIDS patient on tenofovir treatment--case report and review of literature. 1603 54

Hantaviruses are rodent-borne viruses capable of causing human disease. The Seoul virus is a hantavirus that causes hemorrhagic fever with renal syndrome in East Asia. To our knowledge, we report the first domestically acquired case of hemorrhagic fever with renal syndrome caused by the Seoul virus, confirmed by serology testing, reverse-transcriptase polymerase chain reaction, and nucleotide sequence analysis. The patient presented with myalgias and fever, and developed acute renal failure.
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PMID:Domestically acquired seoul virus causing hemorrhagic fever with renal syndrome-Maryland, 2008. 1984

Background: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications. Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted.
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PMID:Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study. 3314 42