Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study has evaluated changes in RNA synthesis in livers under the distant influence of a malignant tumor. A transplantable-induced sarcoma (MCG 101), transplanted on inbred adult mice (C57BL/6J), was used. Activities of DNA-dependent RNA polymerase (EC 2.7.7.6) were measured in relation to RNA content and translational activity. Liver nuclei from freely fed sarcoma-bearing mice had increased RNA synthesis. As a consequence of this, RNA content per DNA was increased in liver tissue. This was independent of depressed food intake and malnutrition. Elevated RNA synthesis, proportional to the tumor burden was due to an increased proportion of chromatin-engaged RNA polymerase I and II activities. RNA polymerase III activity (template-engaged form) was unchanged when evaluated in isolated nuclei, but appeared to be increased in partially purified extracts of nuclei. RNA content in tumor-host liver was a composite of increased levels of rRNA and tRNA, whereas the levels of poly(A)+ mRNA could not be measured as increased. Overall translational activities in vitro of mRNA from liver tissue of tumor-bearing, pair-weighed, and freely fed tumor-free controls were qualitatively and quantitatively different. mRNA from tumor-bearing mice directed an increased synthesis, particularly of larger proteins (above 55,000 daltons) compared with control animals. The results support the conclusion that previous evidence of elevated net protein synthesis in tumor-host liver is accompanied by increased transcription of genes coding for RNA and also for some or several hepatic proteins.
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PMID:Nuclear RNA polymerase activity in tumor-host livers. 241 3

Elevated protein synthesis in mouse tumor-host liver is the net result of both stimulatory and inhibitory responses. This study compares the directional change in transcription and synthesis of liver and plasma proteins in tumor-host liver as compared with para-neoplastic conditions, such as malnutrition, inflammation, benign cell proliferation and protein deficiency. A methylcholanthrene-induced sarcoma was used in weight stable mice (C57BI/6J). Inflammation was induced by s.c. turpentine injection, and benign cell proliferation by injection of heat-killed Corynebacterium parvum. DNA-dependent RNA-polymerase activity (I, II and III) (EC2.7.7.6) was measured in isolated hepatic nuclei. Protein synthesis was measured by labelling of hepatic and plasma proteins following the injection of a "flooding dose" of the labelled amino acid. Benign hepatic cell proliferation and sterile inflammation caused increased rates of transcription, while malnourished and healthy control animals had lower hepatic transcription than animals bearing a malignant tumor. Inflammation was associated with increased activities of free (nonchromatin engaged) RNA polymerase, which was not found in any other para-neoplastic condition or in the tumor-host liver. A protein- and calorie-deficient state was associated with depressed hepatic and plasma protein synthesis compared with the tumor condition. Tumor-host livers had a nonsecretory protein synthesis rate equal to that of normal livers, but 45% higher plasma protein synthesis. Animals with inflammation and benign cell growth had liver protein synthesis rates which were approximately 50% higher than in tumor-bearing animals, but plasma protein synthesis in tumor-bearing animals was comparable with that of animals which had inflammation. Benign cell growth was not associated with an overall elevated plasma protein synthesis. The translation rate per transcription activity was highest in normal animals and decreased in animals suffering from either tumor, protein deficiency or benign cell proliferation. Hepatic protein synthesis in tumor-host livers is high considering the degree of anorexia and malnutrition, although not as high as in livers from animals with pronounced inflammation. This counter-regulation in tumor-host livers may indicate a compensatory state to maintain protein synthesis against attenuating factors such as the declining food intake. Protein metabolism in tumor-host livers represents an unusual combination of findings.
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PMID:RNA polymerase activity and protein synthesis in mouse tumor-host liver compared to benign para-neoplastic reactions. 341 72

Ornithine decarboxylase (ODC) and nucleolar DNA-dependent RNA polymerase (RNA polymerase I) activities increased in the liver of young adult male rats fed a 6% casein diet (malnourished) for 1 week when compared with rats fed a 25% casein diet (control). ODC activity increased progressively and reached a peak after 3 weeks of malnutrition and then decreased to control values by 5 weeks. RNA polymerase I reached peak activity 1 week after malnutrition was imposed, decreasing thereafter to control values by 3 weeks. At 4 and 5 weeks, RNA polymerase I activity in malnourished animals was lower than control. Nucleoplasmic DNA-dependent RNA polymerase activity remained unchanged in the first 2 weeks of malnutrition and decreased thereafter to values significantly lower than control. The data confirm our previous observations of cyclical changes during prolonged malnutrition and suggests a process of "biochemical adaptation" to malnutrition in which the organism enhances essential metabolic processes to maintain cellular homeostasis to the detriment of less essential functions like systemic growth.
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PMID:Ribonucleic acid metabolism in rat liver during long-term adaptation to malnutrition. 617

During the past two decades, the essentiality of zinc for man has been established. Deficiency of zinc in man due to nutritional factors and several diseased states has been recognized. High phytate content of cereal proteins decreases availability of zinc; thus the prevalence of zinc deficiency is likely to be high in a population subsisting mainly on cereal proteins. Alcoholism is known to cause hyperzincuria and thus may play a role in producing zinc deficiency in man. Malabsorption, cirrhosis of the liver, chronic renal disease and other chronically debilitating diseases may similarly induce zinc deficiency in human subjects. A severe deficiency of zinc has recently been recognized to occur in patients with sickle cell anemia and a beneficial effect of zinc therapy in such patients has been reported. Growth retardation, male hypogonadism, skin changes, poor appetite, mental lethargy and delayed wound healing are some of the manifestations of chronically zinc-deficient human subjects. Taste abnormalities, correctable with zinc supplementation, have been observed in uremic subjects. Recently, abnormal dark adaptation related to zinc deficiency in patients with cirrhosis of the liver and sickle cell disease has been reported. In severely zinc-deficient patients, dermatological manifestations, diarrhea, alopecia, mental disturbances and intercurrent infections predominate and if untreated the condition becomes fatal. Zinc deficiency is known to affect testicular functions adversely in man and animals. This effect of zinc is at the end organ level and it appears that zinc is essential for spermatogenesis and testosterone steroidogenesis. Zinc is involved in many biochemical functions. Several zinc metalloenzymes have been recognized in the past decade. Zinc is required for each step of cell cycle in microorganisms and is essential for DNA synthesis. Thymidine kinase, RNA polymerase, DNA-polymerase from various sources and RNA-dependent DNA polymerase from viruses have been shown to be zinc-dependent enzymes. Zinc also regulates the activity of RNase; thus the catabolism of RNA appears to be zinc-dependent. The effect of zinc on protein synthesis may be attributable to its vital role in nucleic acid metabolism. The activities of many zinc-dependent enzymes have been shown to be affected adversely in zinc-deficient tissues. Three enzymes, alkaline phosphatase, carboxypeptidase and thymidine kinase, appear to be most sensitive to zinc restriction in that their activities are affected adversely within three to six days of institution of a zinc-deficient diet to experimental animals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Zinc deficiency in human subjects. 636 78

The human placenta is an organ with a long period of growth in cell number later succeeded by cessation of cell division but some continued growth in cell size. The RNA concentration and content per cell (RNA/DNA ratio) are reduced between the end of the first trimester and the end of pregnancy, and there is a change in availability of placental chromatin for transcription when incubated in vitro with RNA polymerase II. Synthesis and secretion of placental peptide hormones on membrane-bound polyribosomes also undergo changes during pregnancy. During early pregnancy, levels of human chorionic gonadotropin are maximal, declining in later pregnancy, levels of human chorionic gonadotropin are maximal, declining in later pregnancy. The messenger RNA for this hormone undergoes similar changes in relative amount in the placenta. In contrast, the plasma level of placenta lactogen increases progressively during pregnancy, and in parallel with this, the placenta content of mRNA for this hormone increases throughout later pregnancy. It is concluded that placental programing regulates the relative amounts of mRNA for each hormone, and this in turn determines the amounts secreted at any stage of pregnancy. Nutritional status of the mother can affect placental RNA content, most clearly established in studies on rats in which a diet low in protein or with added alcohol results in a reduced capacity to form and secrete placental lactogen. The extent of this depression parallels the reduction in placental RNA content. It is suggested that underproduction of placental lactogen may be a factor in reducing flow of nutrients from the maternal tissues to the fetus in later pregnancy, under conditions of malnutrition.
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PMID:Placental protein and peptide hormone synthesis: impact of maternal nutrition. 735 83

OprE is a channel-forming outer membrane protein of Pseudomonas aeruginosa, the expression of which is induced under anaerobic conditions. We constructed various mutants and observed the effects on oprE expression. Deficiency in RpoN, an alternative sigma factor for RNA polymerase, abolished oprE expression under aerobic conditions, but did not affect the expression under anaerobic conditions. One mutation on the putative RpoN recognition site also caused reduction of oprE expression. The region 500 nucleotides upstream of the mRNA start site was required for optimal oprE transcription, which contains an AT-rich region including a putative integration host factor binding site. These results indicate that OprE production is directly or indirectly controlled by RpoN but also require some other regulatory proteins bound to the upstream region.
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PMID:Involvement of the RpoN protein in the transcription of the oprE gene in Pseudomonas aeruginosa. 959 61

Cytochemical staining of monocyte-specific esterase (MSE) is widely used for identification of the monocytic lineage in leukaemias. Deficiency of this enzymatic activity occurs as a familial trait and the deficiency has been shown to occur with greater frequency in patients with lymphoproliferative or gastrointestinal malignant neoplastic diseases than in normal blood donors. Reverse transcriptase polymerase chain reaction (RT-PCR), sequencing and quantification by Northern blot analysis was conducted on the MSE mRNA of 12 subjects with monocyte esterase deficiency (MED) and seven MSE-positive subjects to examine whether mutations were present or whether the defect was quantitative. Mutations were not found in the mRNA sequences. However, MED subjects had significantly less MSE mRNA than MSE-positive subjects (P = 0.001). These findings show that deficiency of monocyte esterase activity in MED is not as a result of the presence of inactive isoenzymes and may be owing to an abnormality in the regulation of mRNA production.
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PMID:Quantitative deficiency of monocyte-specific esterase (MSE) mRNA in monocyte esterase deficiency (MED). 1099 83

We present a group of 18 illegal immigrant stowaways who arrived in a shipboard cargo container suffering from gastroenteritis, dehydration, and malnutrition and showing evidence of viral myocarditis in 3 of 4 fatalities. Our investigation included an evaluation of the 2-week ocean voyage, analysis of medical records and laboratory results of the survivors, autopsies on the decedents, and viral studies on their heart tissue. Of 3 stowaways who died shipboard, 2 showed lymphocytic myocarditis and 1 could not be evaluated histologically due to decomposition. A fourth stowaway died 4 months after arrival with dilated cardiomyopathy and lymphocytic myocarditis. Reverse-transcriptase polymerase chain reaction and nucleotide sequencing of viral isolates from the decedents' heart tissues demonstrated Coxsackie virus B3 genome. We believe that these cases represent an outbreak of viral myocarditis, exacerbated by acute dehydration and malnutrition, due to confinement within the shipping container. Our evidence indicates that close confinement promoted the spread of the virus, and nutritional deprivation increased the stowaways' vulnerability. Furthermore, our observations support the conclusion, based on experimental studies, that nutritionally induced oxidative stress increased the virulence of the etiologic viral agent. In summary, these cases represent a potential infectious disease hazard of illegal immigration.
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PMID:Unexpected hazard of illegal immigration: Outbreak of viral myocarditis exacerbated by confinement and deprivation in a shipboard cargo container. 1516 61

Expansion of an unstable GAA.TTC repeat in the first intron of the FXN gene causes Friedreich ataxia by reducing frataxin expression. Deficiency of frataxin, an essential mitochondrial protein, leads to progressive neurodegeneration and cardiomyopathy. The degree of frataxin reduction correlates with GAA.TTC tract length, but the mechanism of reduction remains controversial. Here we show that transcription causes extensive RNA.DNA hybrid formation on GAA.TTC templates in bacteria as well as in defined transcription reactions using T7 RNA polymerase in vitro. RNA.DNA hybrids can also form to a lesser extent on smaller, so-called 'pre-mutation' size GAA.TTC repeats, that do not cause disease, but are prone to expansion. During in vitro transcription of longer repeats, T7 RNA polymerase arrests in the promoter distal end of the GAA.TTC tract and an extensive RNA.DNA hybrid is tightly linked to this arrest. RNA.DNA hybrid formation appears to be an intrinsic property of transcription through long GAA.TTC tracts. RNA.DNA hybrids have a potential role in GAA.TTC tract instability and in the mechanism underlying reduced frataxin mRNA levels in Friedreich Ataxia.
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PMID:A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro. 1769 31

Recent increases in access to highly active antiretroviral therapy (HAART) have made the management of drug toxicities an increasingly crucial component of human immunodeficiency virus (HIV) care in developing countries. The spectrum of adverse effects related to HAART in developing countries may differ from that in developed countries because of the high prevalence of conditions such as anemia, malnutrition, and tuberculosis and frequent initial presentation with advanced HIV disease. The severity of adverse effects may vary as a result of host genetics and diagnostic delays attributable to inadequate laboratory monitoring. This article reviews current knowledge about toxicities related to HAART in resource-limited regions, which are in the process of rapid treatment scale-up. We conclude that initiating HAART before advanced immunosuppression, titrating doses in single-pill drug combinations to differences in patients' body weights, providing more intensive laboratory monitoring during the initial months of therapy, and providing access to less-toxic nucleoside reverse-transcriptase inhibitors may decrease the incidence of toxicities related to HAART in resource-limited regions.
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PMID:Adverse effects of highly active antiretroviral therapy in developing countries. 1787 31


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