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 three-dimensional structure of integrase, one of the enzymes that is necessary for HIV to reproduce, has been discovered at the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK). The discovery has implications for rational drug design and clinical treatment. Scientists will now be able to target all three enzymes: reverse transcriptase, protease, and integrase. An on-going strategy has been to block the reproduction of the HIV virus at several points in its life cycle. The discovery of integrase makes it possible to develop combinations of drugs that target different enzymes aimed at inhibiting the spread of HIV in the body.
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PMID:Integrase: third crucial enzyme discovered. 1136 58

Renal failure is a known complication of HIV infection. The most common form is HIV-associated nephropathy, or HIVAN. It is characterized by high-grade proteinuria with rapid progression to end-stage renal disease. The kidneys of affected patients appear enlarged on ultrasonography. Histopathologically, there is focal segmental glomerulosclerosis with glomerular collapse. Before the era of HAART, patients with HIVAN had limited survival, although in some cases this was prolonged if dialysis was instituted. Over the past few years, isolated case reports have shown that patients with HIVAN will recover renal function following initiation of HAART. We report 3 patients believed to have HIVAN who exhibited marked improvement in renal function after treatment with a regimen comprising 2 nucleoside reverse transcriptase inhibitors and a protease inhibitor.
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PMID:Resolution of renal failure after initiation of HAART: 3 cases and a discussion of the literature. 1196 39

Transforming growth factor (TGF)-beta1 is important in fibrogenesis and has been involved in the pathogenesis of chronic allograft nephropathy (CAN). The angiotensinogen (AGT) gene encodes the only glycoprotein known to be a precursor of the vasopressor angiotensin II. Angiotensin II is also a growth factor and a profibrogenic cytokine. It mediates the induction of TGF-beta1. We studied the relationship among the intragraft expression of AGT, TGF-beta1, and CAN in stable renal transplant patients (RTP). We used a competitive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)-ELISA assay to identify intragraft amounts of AGT expression in RTP and correlated it with TGF-beta1 mRNA expression. We studied and performed kidney biopsies on 12 RTP with long-functioning grafts and 6 RTP in the immediate posttransplantation period (7 days) who had acute tubular necrosis as control. Histology was based on Banff working classification criteria. Total RNA was isolated from biopsy specimens. For RT-PCR-ELISA, we created heterologous RNA competitors that coamplified with the same primers as AGT and TGF-beta1. Six of 12 long RTP had proteinuria >1000 mg/24 hr and 6 had proteinuria <1000 mg/24 hr. The differences between Banff grades (P =0.03), AGT, and TGF-beta1 levels by RT-PCR-ELISA were statistically significant between both groups (106.2+/-60.7 vs. 34.1+/-11.9 pg/microg total RNA [P =0.01] and 5954+/-5612 vs. 436+/-517 transcripts/microg total RNA [P =0.01], respectively). The control group showed AGT levels of 25+/-12.2 pg/microg total RNA and TGF-beta1 levels of 228+/-111 transcripts/microg total RNA, significant only for the higher proteinuria group (P=0.01 and P=0.04, respectively). There was a correlation between AGT and TGF-beta1 in both groups (r=0.96, P=0.001). We showed a relationship between mRNA expression of AGT and TGF-beta1 in kidney transplant patients with different grades of CAN and proteinuria.
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PMID:Intragraft messenger RNA expression of angiotensinogen: relationship with transforming growth factor beta-1 and chronic allograft nephropathy in kidney transplant patients. 1235 92

This report describes a 47-year-old woman with human immunodeficiency virus (HIV) and end-stage renal disease on hemodialysis, treated with combination antiretroviral drug therapy, who developed an acute, severe type B lactic acidosis 24 hours after homograft root replacement for endocarditis. She fully recovered after HIV medication was discontinued, along with administration of riboflavin and supportive measures including hemodialysis. The timing of this complication and previous reports suggest that open heart surgery may be a risk factor for nonischemic (type B) lactic acidosis in patients taking nucleoside analogue reverse transcriptase inhibitors.
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PMID:Type B lactic acidosis: a rare complication of antiretroviral therapy after cardiac surgery. 1240 Jul 87

High glucose (HG) is the underlying factor contributing to long term complications of diabetes mellitus. The molecular mechanisms transforming the glomerular mesangial cell phenotype to cause nephropathy including diacylglycerol-sensitive protein kinase C (PKC) are still being defined. Reactive oxygen species (ROS) have been postulated as a unifying mechanism for HG-induced complications. We hypothesized that in HG an interaction between ROS generation, from NADPH oxidase, and PKC suppresses mesangial Ca2+ signaling in response to endothelin-1 (ET-1). In primary rat mesangial cells, growth-arrested (48 h) in 5.6 mM (NG) or 30 mm (HG) glucose, the total cell peak [Ca2+]i response to ET-1 (50 nM) was 630 +/- 102 nM in NG and was reduced to 159 +/- 15 nM in HG, measured by confocal imaging. Inhibition of PKC with phorbol ester down-regulation in HG normalized the ET-1-stimulated [Ca2+]i response to 541 +/- 74 nM. Conversely, an inhibitory peptide specific for PKC-zeta did not alter Ca2+ signaling in HG. Furthermore, overexpression of conventional PKC-beta or novel PKC-delta in NG diminished the [Ca2+]i response to ET-1, reflecting the condition observed in HG. Likewise, catalase or p47phox antisense oligonucleotide normalized the [Ca2+]i response to ET-1 in HG to 521 +/- 58 nM and 514 +/- 48 nM, respectively. Pretreatment with carbonyl cyanide m-chlorophenylhydrazone or rotenone did not restore Ca2+ signaling in HG. Detection of increased intracellular ROS in HG by dichlorofluorescein was inhibited by catalase, diphenyleneiodonium, or p47phox antisense oligonucleotide. HG increased p47phox mRNA by 1.7 +/- 0.1-fold as measured by reverse transcriptase-PCR. In NG, H2O2 increased membrane-enriched PKC-beta and -delta, suggesting activation of these isozymes. HG-enhanced immunoreactivity of PKC-delta visualized by confocal imaging was attenuated by diphenyleneiodium chloride. Thus, mesangial cell [Ca2+]i signaling in response to ET-1 in HG is attenuated through an interaction mechanism between NADPH oxidase ROS production and diacylglycerol-sensitive PKC.
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PMID:High glucose-suppressed endothelin-1 Ca2+ signaling via NADPH oxidase and diacylglycerol-sensitive protein kinase C isozymes in mesangial cells. 1282 78

Aquaporins (AQPs), membrane-inserted water channel proteins, play a highly important role in the reabsorption of water from the renal tubular fluid. Experimentally, both in rats and mice, failure to insert functional AQP molecules into renal tubular membranes leads to nephrogenic diabetes insipidus. In humans, most forms of renal disease lead to a reduction in the water handling capacity of the kidney. AQP distribution in various forms of human renal disease has not been documented. Immunohistochemical studies of biopsy samples from a wide range of renal diseases revealed a substantial and striking upregulation of AQP-1 in the glomeruli of most diseased kidneys. AQP-1 expression remained prominent in proximal tubules in all lesions. In contrast, there was judged qualitatively to be a reduction in the amounts of AQP-2 and AQP-3 expression, especially in lesions with substantial interstitial fibrosis and nephron loss, as compared with a healthy region of normal kidneys. The results were quantitatively confirmed by real-time reverse transcriptase-PCR. This is the first documentation of altered AQP expression in human renal disease. The significance of the increased AQP-1 expression requires further studies.
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PMID:Aquaporin expression in normal human kidney and in renal disease. 1451 35

Oxidative stress plays an important role in the cardiovascular complications in end-stage renal disease (ESRD) patients on long-term hemodialysis (HD). Heme oxygenase-1 (HO-1) inhibits inflammatory events and protects against oxidative stress and endothelial injury. Therefore, we followed the effects of single HD sessions on HO-1 expression. A competitive reverse transcriptase PCR method was used to estimate HO-1 induction before and immediately after HD and 48 h later in 17 young uremic patients. We also measured the concentrations of plasma hemoglobin and bilirubin as indicators of hemolysis, the ferroxidase activity, and the erythrocyte-derived reduced and oxidized glutathione levels as oxidative stress markers, and the homocysteine levels as an independent risk factor. We found significant differences in HO-1 expression patterns in the patients, depending on the duration of HD treatment. Short-term HD [ n=7, median 19 months (9, 29 quartiles)] resulted in an elevated HO-1 expression, which was not further upregulated during HD. Long-term HD [ n=10, median 97 months (53, 150 quartiles)] led to downregulation of baseline HO-1 expression in ESRD patients. In these patients, a single HD session results in erythrocyte injury and a transient one- to five-fold elevation of HO-1 expression. The chronic downregulation of the baseline expression of HO-1 in long-term HD patients resulted in recurring oxidative stress during each HD session, which may contribute to accelerate the progression of atherosclerosis.
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PMID:Heme oxygenase 1 expression in young uremic patients on hemodialysis. 1498 81

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

Pro-inflammatory cytokines, in addition to their role in host defence, can be considered a disease mediator; therefore, a reduction in cytokine synthesis or its effects is becoming a target of many diseases. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that could play a role in several clinical problems related to dialysis treatment. Biological activities of IL-6 could be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R can enhance the inflammatory effects of IL-6 and; therefore, is an "agonistically" acting molecule. On the contrary, sgp130 efficiently binds the IL-6/sIL-6R complex with "antagonistic" effects. In this study we evaluated sgp130 release by peripheral blood mononuclear cells (PBMC) harvested from 10 healthy controls (CON) and 11 end-stage renal disease (ESRD) patients undergoing renal dialysis therapy RDT) with cellulosic hemophan membrane (HD). We also evaluated gp130 gene expression by reverse transcriptase polymerase chain reaction (RT-PCR). gp130 is the membrane bound receptor of IL-6 that could be proteolytically cleaved to generate soluble sgp130. Our results demonstrated that HD. at basal conditions, showed a higher release of sgp130 as compared with CON. We also demonstrated by RT-PCR at basal conditions a higher gene expression of gp130 in HD, as compared with CON. These results took place in the absence of any mitogenic stimulation and suggest that in HD patients an inflammatory subclinical status increases sgp130 release. The results obtained after lipopolysaccharide (LPS) stimulation confirm the role of inflammation on the increased release of sgp130 in HD patients.
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PMID:[The IL-6 soluble receptors in hemodialyzed patients]. 1574 93

In people infected with the human immunodeficiency virus (HIV) both the CD4 T-cell count and the viral load are used to monitor disease progression to acquired immunodeficiency syndrome (AIDS). CD4 counts of <500/mm(3) are associated with opportunistic infections and certain malignancies, so-called 'AIDS-defining' conditions. Highly active antiretroviral therapy, using combinations of reverse transcriptase inhibitors and/or protease inhibitors, can improve considerably the prognosis of people who are HIV-positive, but such therapy is not yet widely available in many developing countries. People with AIDS are predisposed to urinary tract infection (UTI) by uncommon bacteria and pathogens, e.g. fungi, parasites and viruses, which may affect any urogenital organ; treatment should be culture-specific and long-term, because there is a tendency to recurrence, infection with multiple organisms and resistant isolates. Voiding dysfunction in patients with AIDS is usually a result of neurological complications caused by opportunistic infections, and has a poor prognosis. Of patients with AIDS, 30-50% develop a cancer, especially Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL). KS may involve any urogenital organ, but is usually part of systemic disease. Small lesions on the external genitalia can be treated with laser, cryotherapy or surgical excision, larger lesions with radiotherapy, and disseminated or visceral KS with multidrug chemotherapy. NHL may involve the kidneys, testes and retroperitoneal lymph nodes, thus obstructing the ureters, which may require ureteric stenting or percutaneous nephrostomy. NHL can be treated with radiotherapy and combination chemotherapy. Urolithiasis in patients with AIDS may be caused by indinavir, a protease inhibitor, but the more common types of stones may also occur. Fluid-electrolyte and acid-base disturbances are common in patients with advanced AIDS, secondary to vomiting, diarrhoea, malnutrition or septicaemia. HIV-associated nephropathy occurs in 10-30% of patients, and often leads to renal failure. Testicular atrophy is common, leading to infertility, erectile dysfunction (ED) and decreased libido. Treatment for ED must include counselling about strategies to reduce the transmission of HIV. The risk of HIV transmission after parenteral exposure to blood from an HIV-positive patient is relatively low (0.2-0.4%); the urologist can reduce the risk of transmission during surgery by adopting certain precautions. After occupational exposure to HIV, chemoprophylaxis with antiretroviral medication can significantly reduce the probability of HIV transmission.
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PMID:The urological management of the patient with acquired immunodeficiency syndrome. 1692 74


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