Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

To study the effects of bite opening on the fibre phenotypes of rat masseter, the mRNAs of four predominant myosin heavy-chain isoforms (MHC I, IIa, IId/x and IIb) and two alkali light-chain isoforms (LC1f and 3f) as well as those of two metabolic enzymes, carbonic anhydrase III (CAIII, oxidative enzyme) and glucose-phosphate isomerase (GPI, glycolytic enzyme), were measured in relation to the total RNA of masseter muscle by competitive, reverse transcriptase-polymerase chain reaction in control and bite-opened rats. Bite opening (2.8 mm increase in the vertical dimension for 1 week) significantly (P<0.05) increased the amount of MHC IIa mRNA but decreased (P<0.001) the amount of MHC IIb mRNA without changing the amount of MHC IId/x mRNA. No MHC I mRNA was found in any masseter studied. A significant (P<0.01) increase in the mRNA of LC1f associated with a decrease (P<0.05) in that of LC3f was observed after the bite opening. The CAIII mRNA increased significantly (P<0.001), while the GPI mRNA decreased (P<0.05) in association with the bite opening. These results strongly suggest that in 1 week of bite opening changes the rat masseter muscle from a glycolytic, MHC IIb-LC3f-dominant fibre to an oxidative, MHC IIa-LC1f-dominant fibre.
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PMID:Quantitative changes in the mRNA for contractile proteins and metabolic enzymes in masseter muscle of bite-opened rats. 1108 41

The use of reduced doses of Ritonavir (RIT) and Saquinavir (SQV) is considered a potent alternative in treating patients infected by HIV-1. We tested a combination of 300mg of RIT plus 600mg of SQV, twice daily, in association with two reverse transcriptase inhibitors to treat AIDS patients for a period of 6 months. Evaluation of HIV-1 RNA plasma levels, CD4+/CD8+ cell count and biochemical/hematological parameters (liver enzymes, serum electrolytes, creatinin, blood glucose, uric acid, white blood cell count, platelet count, and hemoglobin level) were performed after 30, 90 and 180 days of therapy. Clinical failure and adverse reactions were also recorded in order to assess safety and efficacy of the treatment. A total of 30 AIDS patients (25 male; 5 female) were enrolled in the study. Eight patients discontinued the therapy due to intolerance, 2 patients presented clinical failure (onset of AIDS-defining events during the study period), 2 patients werc excluded due to protocol violation. Five patients tolerated only a lower dose of RIT (400mg/day). Patients who completed 6 months of therapy had a drop in viral load from 4.8+/-.7 log(10) median 4.9 log) to 3.4 +/- 1.0 log(10) (median 2.6 log), and an increase in CD4+ count from 109 +/- 86cells/ml (median 84cells/ml) to 249+/- 114 cells/ml (median 265 cells/ml), compared to baseline values. However, patients who used a lower dose of RIT (400mg/day) had a less impressive drop in viral load values (mean 0.6 log(10) NA copies/ml) when compared with those using the 600mg/day of the drug (mean 2.4 log(10)). The percentage of patients presenting undetectable levels of HIV-1 RNA in plasma was quite different for the 2 groups: 92% of patients with a viral load <400 RNA copies/ ml were using 600mg of RIT. The combination of reduced doses of RIT and SQV reduced viral load >1.0 log(10) after 6 months in 83% of study patients. The dose of 600mg/day of RIT was morc effective in reducing viral load than 400mg/day, but was less well-tolerated. CD4+ cell counts increased in all patients regardless of the RIT dose used.
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PMID:Safety and Efficacy of Reduced Doses of Ritonavir (RTV) Plus Saquinavir (SQV) in the Treatment of AIDS Patients in Brazil. 1109 12

The inositol 1,4,5-trisphosphate receptors (IP3Rs) are ligand-gated Ca2+ channels that regulate intracellular Ca2+ mobilization. Among the IP3R mRNA isoforms I, II, and III, IP3R-I mRNA was expressed in mouse islets and the beta-cell line betaTC3, and was quantitatively the most abundant isoform as determined by reverse transcriptase-polymerase chain reaction. IP3R-II and -III mRNAs were expressed at similar levels in mouse islets, but neither isoform was detected in betaTC3 cells. Culture of mouse islets for 30 min and 2 hr at 20 mM glucose, or for 7 days at 11 mM glucose did not affect IP3R-I mRNA expression compared with islets cultured in 5.5 mM glucose. Culture of islets or betaTC3 cells with carbachol (0.5 mM) reduced IP3R-I mRNA expression levels below control. Mouse islet alpha- and beta-cells expressed IP3R-I and -III proteins, but IP3R-II protein was not detected by immunoblot or double-label immunohistochemistry. Culture of islets for up to 6 hr with carbachol reduced IP3R-I and -III protein expression in a time-dependent manner with a half-maximal effect on type I at 1 hr. Glucose (20 mM) stimulation for 2 hr did not affect IP3R-1 levels. The carbachol-induced decrease in IP3R-I and -III protein expression was reversed by carbobenzoxyl-leucinyl-leucinyl-leucinyl-H (MG-132), a proteasome inhibitor. Thus, glucose failed to regulate mouse islet IP3R mRNA expression, whereas carbachol stimulation down-regulated IP3R mRNA and protein. A proteasomal protein degradative pathway appeared to mediate the muscarinic receptor-induced effects on IP3R-I and -III.
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PMID:Inositol 1,4,5-trisphosphate receptor isoform expression in mouse pancreatic islets: effects of carbachol. 1117 37

Long-term therapy with protease inhibitors (PIs) can induce hypertriglyceridemia and development of a lipodystrophy. To better understand these metabolic alterations, the apoprotein and lipoparticle profile was investigated in male HIV patients under antiretroviral therapy: 49 received PIs, and 14 were given only two reverse transcriptase inhibitors. As controls, 63 male subjects were selected from a population study carried out in the Toulouse, France, area. Fasting glucose, insulin, and C-peptide were also determined. All patients under PIs displayed low levels of plasma glucose and increased insulin. PI administration was associated with moderate hypertriglyceridemia, low high-density cholesterol and apolipoprotein (apo) A-I levels. The most striking changes were a 2- to 3-fold increase in apo E and apo C-III, essentially recovered as associated to apo B-containing lipoparticles. Levels of those lipoparticles were two to eight times above control values. About 50% of PI-treated patients had developed a patent lipodystrophy. Multivariate analysis revealed that, among the investigated parameters, apo C-III was the only one found strongly associated with the occurrence of lipodystrophy (odds ratio, 5.5; P: < 0.015). Finally, 13 PI-receiving subjects with patent hypertriglyceridemia were given fenofibrate and were reevaluated 2 months later. Triglycerides, apo E, apo C-III, and the corresponding lipoparticles had returned to nearly normal levels. These results document the accumulation of potentially atherogenic lipoparticles under PIs. Apo C-III may play a pivotal role in the development of hypertriglyceridemia and lipodystrophy.
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PMID:Apoprotein c-III and E-containing lipoparticles are markedly increased in HIV-infected patients treated with protease inhibitors: association with the development of lipodystrophy. 1123 15

The preferential channeling of different fuels to fat and changes in the transcription profile of adipose tissue and skeletal muscle are poorly understood processes involved in the pathogenesis of obesity and insulin resistance. Carbohydrate and lipid metabolism may play relevant roles in this context. Freely moving lean Zucker rats received 3- and 24-h infusions of Intralipid (Pharmacia and Upjohn, Milan, Italy) plus heparin, or saline plus heparin, to evaluate how an increase in free fatty acids (nonesterified fatty acid [NEFA]) modulates fat tissue and skeletal muscle gene expression and thus influences fuel partitioning. Glucose uptake was determined in various tissues at the end of the infusion period by means of the 2-deoxy-[1-3H]-D-glucose technique after a euglycemic-hyperinsulinemic clamp: high NEFA levels markedly decreased insulin-mediated glucose uptake in red fiber-type muscles but enhanced glucose utilization in visceral fat. Using reverse transcriptase-polymerase chain reaction and Northern blotting analyses, the mRNA expression of fatty acid translocase (FAT)/CD36, GLUT4, tumor necrosis factor (TNF)-alpha, peroxisome proliferator-activated receptor (PPAR)-gamma, leptin, uncoupling protein (UCP)-2, and UCP-3 was investigated in different fat depots and skeletal muscles before and after the study infusions. GLUT4 mRNA levels significantly decreased (by approximately 25%) in red fiber-type muscle (soleus) and increased (by approximately 45%) in visceral adipose tissue. Furthermore, there were marked increases in FAT/CD36, TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 mRNA levels in the visceral fat and muscle of the treated animals in comparison with those measured in the saline-treated animals. These data suggest that the in vivo gene expression of FAT/CD36, GLUT4, TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 in visceral fat and red fiber-type muscle are differently regulated by circulating lipids and that selective insulin resistance seems to favor, at least in part, a prevention of fat accumulation in tissues not primarily destined for fat storage, thus contributing to increased adiposity and the development of a prediabetic syndrome.
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PMID:Preferential channeling of energy fuels toward fat rather than muscle during high free fatty acid availability in rats. 1124 80

Granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion from epithelial cells lining the female reproductive tract is induced during early pregnancy by ovarian steroid hormones and constituents of seminal plasma. In this study we have investigated the influence of GM-CSF on development of preimplantation mouse embryos. Blastocyst-stage embryos were found to specifically bind (125)I-GM-CSF and analysis of GM-CSF mRNA receptor expression by reverse transcriptase-polymerase chain reaction indicated expression of the low-affinity alpha subunit of the GM-CSF receptor, but not the affinity-converting beta subunit (beta(c)), or GM-CSF ligand. GM-CSF receptor mRNA was present in the fertilized oocyte and all subsequent stages of development, and in blastocysts it was expressed in both inner cell mass and trophectoderm cells. In vitro culture of eight-cell embryos in recombinant GM-CSF accelerated development of blastocysts to hatching and implantation stages, with a maximum response at a concentration of 2 ng/ml (77 pM). Blastocysts recovered from GM-CSF-null mutant (GM-/-) mice on Day 4 of natural pregnancy or after superovulation showed retarded development, with the total cell number reduced by 14% and 18%, respectively, compared with GM+/+ embryos. Blastocysts generated in vitro from two-cell GM-/- and GM+/+ embryos were larger when recombinant GM-CSF was added to the culture medium (20% and 24% increases in total cell numbers in GM+/+ and GM-/- blastocysts, respectively). Incubation of blastocysts with recombinant GM-CSF elicited a 50% increase in the uptake of the nonmetabolizable glucose analogue, 3-O-methyl glucose. In conclusion, these data indicate that GM-CSF signaling through the low-affinity GM-CSF receptor in blastocysts is associated with increased glucose uptake and enhanced proliferation and/or viability of blastomeres. Together, the findings implicate a physiological role for maternal tract-derived GM-CSF in targeting the preimplantation embryo, and suggest that defective blastocyst development contributes to compromised pregnancy outcome in GM-CSF-null mutant mice.
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PMID:Granulocyte-macrophage colony-stimulating factor promotes glucose transport and blastomere viability in murine preimplantation embryos. 1125 69

The lipoxygenase (LO) pathway has been implicated as an important mediator of chronic glucose and platelet-derived growth factor (PDGF)-induced effects in the vascular system. Endothelial cells treated with 12LO products or cultured in high glucose showed enhanced monocyte adhesion, an important step in atherogenesis. We have previously reported that PDGF increased HETE levels in porcine aortic smooth muscle cells. Although several pharmacological inhibitors to the LO pathway are available, most lack specificity and may harbor undesirable side effects. Therefore, we developed a recombinant adenovirus expressing a hammerhead ribozyme (AdRZ) targeted against the porcine leukocyte-type 12LO mRNA to investigate the involvement of LO in glucose- and PDGF-mediated effects in vascular cells. Infection of porcine aortic endothelial cells with AdRZ reduced the level of glucose-enhanced 12LO mRNA expression as determined by quantitative, real-time reverse transcriptase-polymerase chain reaction. Reverse-phase HPLC and RIA analysis also revealed a corresponding decrease in glucose-stimulated 12HETE production in both the cellular and supernatant fractions. In the ribozyme-treated porcine aortic endothelial cells, there was marked inhibition of high glucose-stimulated monocyte adhesion. Infection with AdRZ also reduced PDGF-induced porcine aortic smooth muscle cell migration by approximately 50%. These studies demonstrate the efficacy of recombinant adenovirus expressing 12LO ribozyme in studying the effects of 12LO in vascular wall cells. They document an important role for the 12LO pathway in regulating inflammatory changes in endothelial cells and smooth muscle cells.
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PMID:Adenoviral delivery of a leukocyte-type 12 lipoxygenase ribozyme inhibits effects of glucose and platelet-derived growth factor in vascular endothelial and smooth muscle cells. 1130 87

Adefovir dipivoxil (Preveon), a nucleotide analog and a prodrug of PMEA, has been approved for a limited expanded access program for patients who have failed approved treatments. Earlier results from phase I/II trials reveal Preveon has modest anti-HIV activity. Preveon is active against virus that has developed resistance to AZT, 3TC, and other approved nucleoside analogs. To be eligible, patients must be at least 13 years old, failed at least two nucleoside analog reverse transcriptase inhibitors and one protease inhibitor, and within the last 2 months have had a CD4 count of 50 or less and a viral load of at least 30,000 by PCR or at least 15,000 by bDNA. The program will supply only Preveon and the L-carnitine. The AIDS community has expressed concerns about the drug's potential kidney toxicity with long-term use, a condition that becomes clinically evident usually after the first 4 months, possibly leading physicians into complacency in performing regular laboratory tests after that time. The study requires monthly urine testing, including serum creatinine, urine protein, and urine glucose. Another concern is the study's CD4 and viral load restrictions; AIDS advocates believe the restrictions do not allow physicians flexibility in their drug treatment decision-making.
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PMID:Adefovir dipivoxil (Preveon) expanded access begins. 1136 18

Type 2 diabetes is characterized by insulin resistance and inadequate insulin secretion. In the advanced stages of the disease, beta-cell dysfunction worsens and insulin therapy may be necessary to achieve satisfactory metabolic control. Studies in autopsies found decreased beta-cell mass in pancreas of people with type 2 diabetes. Apoptosis, a constitutive program of cell death modulated by the Bcl family genes, has been implicated in loss of beta-cells in animal models of type 2 diabetes. In this study, we compared the effect of 5 days' culture in high glucose concentration (16.7 mmol/l) versus normal glucose levels (5.5 mmol/l) or hyperosmolar control (mannitol 11 mmol/l plus glucose 5 mmol/l) on the survival of human pancreatic islets. Apoptosis, analyzed by flow cytometry and electron and immunofluorescence microscopy, was increased in islets cultured in high glucose (HG5) as compared with normal glucose (NG5) or hyperosmolar control (NG5+MAN5). We also analyzed by reverse transcriptase-polymerase chain reaction and Western blotting the expression of the Bcl family genes in human islets cultured in normal glucose or high glucose. The antiapoptotic gene Bcl-2 was unaffected by glucose change, whereas Bcl-xl was reduced upon treatment with HG5. On the other hand, proapoptotic genes Bad, Bid, and Bik were overexpressed in the islets maintained in HG5. To define the pancreatic localization of Bcl proteins, we performed confocal immunofluorescence analysis on human pancreas. Bad and Bid were specifically expressed in beta-cells, and Bid was also expressed, although at low levels, in the exocrine pancreas. Bik and Bcl-xl were expressed in other endocrine islet cells as well as in the exocrine pancreas. These data suggest that in human islets, high glucose may modulate the balance of proapoptotic and antiapoptotic Bcl proteins toward apoptosis, thus favoring beta-cell death.
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PMID:High glucose causes apoptosis in cultured human pancreatic islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program. 1137 29

To clarify the target phase of thiazolidinediones, which are ligands for peroxisome proliferator-activated receptor (PPAR)gamma, during adipocyte differentiation, the effects of a thiazolidinedione, pioglitazone, on every stage during the course of adipocyte differentiation were investigated. Pioglitazone did not affect the cellular protein content and [3H]thymidine incorporation into preconfluent 3T3-L1 preadipocytes. Induction of differentiation of confluent 3T3-L1 preadipocytes with insulin, dexamethasone and isomethylbutylxanthine for 48 h resulted in 30% inhibition of [3H]thymidine incorporation into the cells and 354% increase in cellular protein content. Pioglitazone at 1 microM accelerated the increase in cellular protein content by 33% and the inhibition in the [3H]thymidine incorporation by 12%. Pioglitazone, when added from the start of the induction stage, dose-dependently enhanced cellular triglyceride accumulation, and both basal and insulin-stimulated glucose transporting activity producing only a slight increase in the ratio of insulin stimulation to basal glucose transporting activity. In mature adipocytes, however, pioglitazone did not enhance either of the transporting activities. PPARgamma messenger RNA (mRNA) levels estimated by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) increased during the course of adipocyte differentiation. Although pioglitazone dose-dependently up-regulated PPARgamma mRNA levels in postconfluent preadipocytes without induction, it down-regulated them in mature adipocytes. Thus, a PPARgamma agonist, pioglitazone, arrested the growth, and increased protein content and PPARgamma mRNA levels in postconfluent preadipocytes, followed by commitment and hypertrophy of 3T3-L1 cells without changing insulin sensitivity, whereas it failed to stimulate glucose transporting activities and down-regulated PPARgamma mRNA expression in mature adipocytes.
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PMID:Stage-specific effects of a thiazolidinedione on proliferation, differentiation and PPARgamma mRNA expression in 3T3-L1 adipocytes. 1143 Sep 9


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