Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A qualitative and quantitative assessment was made of the development of hepatic drug-metabolizing enzymes (DME) in sheep as part of a study of the ability of the food-producing species to metabolize drugs. The following DME and components were measured in this study: cytochromes P-450 and b5 and NADPH and NADPH-dependent reductases associated with each of these cytochromes; cytochrome P-450-mediated reactions, including aniline and coumarin hydroxylases, aminopyrine N-demethylase, and 7-ethoxycoumarin 0-deethylase; a uridine diphosphoglucuronic acid glucuronyl transferase with 4-methylumbelliferone as substrate; and glutathione-S-transferase with dinitrochlorobenzene and dichloronitrobenzene as substrates. Amounts or activities of most of these components and enzymes increased up to and beyond the time of weaning. Amount of cytochrome b5 and uridine diphosphoglucuronic acid transferase activity were not affected by age, whereas NADPH cytochrome c (P-450) reductase activity actually decreased after weaning. In some instances (eg, coumarin hydroxylase, cytochrome P-450, and dinitrochlorobenzene-glutathione-S-transferase), differences from preweaning DME values were observed only after sheep were greater than or equal to 6 months old. All other DME activities were definitely increased, compared with the values in lambs before weaning (0 to 12 weeks old). Approximately a third of the sheep studied had some type of clinical disease that might have affected the DME activities. Diseases were classified as sore mouth, pneumonia, foot rot, parasitism, and systemic bacterial infections. Except in a few instances, these diseases had minimal effect on DME activities measured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maturational development of drug-metabolizing enzymes in sheep. 224 Jul 98

The therapy of Pneumocystis carinii (PC) pneumonia is often unsuccessful, particularly in patients with acquired immune deficiency syndrome (AIDS). Because of difficulties in growing the organism in vitro or obtaining purified organisms, current treatment choices have been made with little information on the metabolic effects of therapeutic agents on PC. This report quantitates the effects of the commonly used antifolates as well as the classic antineoplastic antifolate methotrexate and a lipid-soluble analogue, trimetrexate, on the target enzyme, dihydrofolate reductase (DHFR), in the PC organisms. Trimethoprim and pyrimethamine were found to be weak inhibitors (ID50 = 39,600 and 2,800 nM, respectively), while methotrexate and trimetrexate were potent reductase inhibitors (ID50 = 1.4 and 26.1 nM, respectively). transport studies with radiolabeled compounds showed that compounds with the classic folate structure (methotrexate and leucovorin) were not taken up by the intact PC organisms. In contrast, trimetrexate exhibited rapid uptake. These results suggest a major therapeutic advantage may be gained by combining a potent, readily transported PC DHFR inhibitor such as trimetrexate with the reduced folate leucovorin to achieve a highly potent antiprotozoan effect while preventing toxicity to mammalian cells.
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PMID:Activity of antifolates against Pneumocystis carinii dihydrofolate reductase and identification of a potent new agent. 295 Feb

A 41-year-old man who had been taking pravastatin for two years developed hypersensitivity pneumonitis. The initial examination found intestinal pneumonitis and hypereosinophilia. The patient's syndromes gradually resolved with withdrawal of pravastatin. As HMG coenzyme A reductase inhibitors are commonly prescribed, any respiratory symptoms in this setting should be considered with special attention.
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PMID:[Hypersensitivity pneumonitis in a patient taking pravastatin]. 1154 51

An autopsied case of autosomal recessive hereditary spastic paraplegia with severe neurogenic muscular atrophy is described herein. This patient, a 16-year-old woman, presented with gait disturbance. She developed progressive spastic paralysis of the upper and lower limbs and mental deterioration. She became bedridden at approximately 40years of age. Dysarthria worsened at 45 years of age. She died of pneumonia at 50 years of age. Her younger sister has shown similar clinical symptoms and became bedridden at 37 years of age. Their parents were second cousins. Autopsy revealed a severely atrophic brain, weighing 720 g. The cerebral cortex was thin, and the white matter was extremely reduced in volume. Microscopically, neuronal loss and variable astrogliosis with diffuse spongy changes were evident at the cerebral cortex, thalamic nuclei, basal ganglia and hippocampus. The remaining neurons were atrophied with heavy deposition of lipofuscin. In the spinal cord, the pyramidal tracts as well as the dorsal spinocerebellar tracts were degenerated. In addition, marked loss of the anterior horn cells was seen. Severe neuronal loss of the nucleus gracilis was also detected. In contrast, only mild degeneration of the ventral spinocerebellar tracts and fasciulus cuneatus in the spinal cord were observed. In the frozen sections of skeletal muscle, severe neurogenic atrophy and fatty infiltration were evident. In addition, several rimmed vacuoles were observed in the atrophic fibers, and cytochrome coxidase-deficient fibers were present in part. Reduced nicotinamide adenine dinucleotide (NADH)-tetrazolium reductase reaction revealed abnormal accumulation of mitochondria around the center of the non-atrophic muscle fibers. It is suggested that an analysis of mitochondrial function of Japanese autosomal recessive hereditary spastic hemiplegia may provide additional information to clarify the pathogenesis.
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PMID:Autopsy case of autosomal recessive hereditary spastic paraplegia with reference to the muscular pathology. 1166 18

It has been well established that statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, reduce mortality from cardiovascular diseases. Statins, a class of cholesterol-lowering drug, may also affect mortality from various diseases by their pleiotropic effects of anti-inflammatory and anti-oxidative activities. However, there are only few reports concerning the effects of statins on diseases other than cardiovascular diseases. We therefore designed a population-based analysis, using the data from marketing surveys on statin sales and government reports on mortalities. We compared the statin use as expressed by statin sales per capita in the aged (> or = 65-year-old) population with mortality from major causes of death among 47 prefectures in Japan. As expected, there were significant negative correlations between statin sales per capita and mortality from cardiovascular diseases (p < 0.05). In addition, we found that there was a correlation between statin sales and the decrease in mortality from chronic obstructive pulmonary disease (COPD) (p < 0.0001), senility (p < 0.01), pneumonia (p < 0.05), accidents (p < 0.05), or all death causes (p < 0.05). However, statin sales were not associated with mortalities from renal failure, liver diseases, suicide, and malignant diseases. These results suggest a broad spectrum of beneficial effects of statins, including reduction of mortality rate of COPD as well as cardiovascular diseases. It will be worthy to confirm the protective effect of statins on COPD by prospective randomized clinical trials.
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PMID:Decrease in mortality rate of chronic obstructive pulmonary disease (COPD) with statin use: a population-based analysis in Japan. 1759 14

Actinobacillus pleuropneumoniae is the causative agent of severe necrotizing pneumonia in swine. Previously, we identified the ohr gene encoding organic hydroperoxide reductase as specifically induced during infection of pigs, induced in vitro by organic peroxides but not other oxygen radicals, and present in A. pleuropneumoniae serotypes 1, 9 and 11 but not in other serotypes (Shea & Mulks, 2002). Through analysis of flanking genomic sequence, we identify a homologue of gst, which encodes glutathione-S-transferase, immediately downstream of ohr and demonstrate that ohr-gst confers low but uninducible Ohr activity to serotype 5. We further identify a genomic island of 9.3 kb, flanked by lysR and araC homologues, in serotypes 1, 9 and 11, which contains ohr and gst. In serotypes 2-8, 10 and 12, this region of the genome contains a 1.1-kb islet with a putative transposase flanked by lysR and araC.
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PMID:Ohr, an in vivo-induced gene in Actinobacillus pleuropneumoniae, is located on a genomic island and requires glutathione-S-transferase for activity. 1965 90

Despite medical advances, pneumonia remains a leading cause of morbidity and mortality among patients in developed countries. It is therefore not surprising that much research has been devoted to improving outcomes associated with this condition. Traditionally thought of as lipid-lowering agents, the 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors (hereafter referred to as statins) have "pleiotropic" effects of clinical relevance. Several studies have reported an association between statin use and improved health outcomes, including those associated with pneumonia. While many of these are limited by their retrospective or observational methodology, the finding that statin use may improve pneumonia outcomes is tantalizing and worthy of further exploration. Our review of the literature found several potential mechanisms by which statins could influence the course of bacterial pneumonia. For instance, statins directly attenuate inflammation and inflammatory markers, are antioxidative and immunomodulatory, and exert in vitro antibacterial effects on microbial pathogens. On the other hand, statin use is also thought to be a surrogate marker for better health and may simply be a confounding variable when it comes to pneumonia. This article explores some of the potential mechanisms by which statin therapy may impact the course of pneumonia. In addition, we review the clinical studies both supporting and arguing against such an effect.
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PMID:Does statin use improve pneumonia outcomes? 2044 31

The capsular polysaccharide (CPS) of the important oral streptococcus Streptococcus anginosus, which causes endocarditis, and the genes for its synthesis have not been clarified. In this study, we investigated the gene locus required for CPS synthesis in S. anginosus. Southern hybridization using the cpsE gene of the well-characterized bacterium S. agalactiae revealed that there is a similar gene in the genome of S. anginosus. By using the colony hybridization technique and inverse PCR, we isolated the CPS synthesis (cps) genes of S. anginosus. This gene cluster consisted of genes containing typical regulatory genes, cpsA-D, and glycosyltransferase genes coding for glucose, rhamnose, N-acetylgalactosamine, and galactofuranose transferases. Furthermore, we confirmed that the cps locus is required for CPS synthesis using a mutant strain with a defective cpsE gene. The cps cluster was found to be located downstream the nrdG gene, which encodes ribonucleoside triphosphate reductase activator, as is the case in other oral streptococci such as S. gordonii and S. sanguinis. However, the location of the gene cluster was different from those of S. pneumonia and S. agalactiae.
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PMID:Organization of the capsule biosynthesis gene locus of the oral streptococcus Streptococcus anginosus. 2210 Aug 98

Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community-acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS-stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti-inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti-inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.
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PMID:Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells. 2247 Dec 85

Statins have dramatically improved the treatment of hyperlipidemia and cardiovascular disease through its inhibition of hydroxymethylglutaryl-coenzyme A reductase. Although its main effect has long been known, much is yet to be understood about the wide and varied pleiotropic properties of statins. Some studies have demonstrated that statins contain antiplatelet, antithrombotic, antiinflammatory, cardioprotective, and neuroprotective properties independent of their ability to lower plasma low-density lipoprotein cholesterol. More recently, statins have been used in novel ways in the treatment of Alzheimer disease, sepsis, pneumonia, and bacteremia. In 2000, it was first suggested that statins could decrease the incidence of venous thromboembolisms (VTEs). A recent publication showed that not only do statins lower the incidence of deep vein thrombosis and pulmonary embolism, but they do so in a dose-dependent manner. Although there is certainly strong evidence demonstrating that statins do indeed lower VTEs, the mechanism is not understood. Possible hypotheses include their antiinflammatory and antithrombotic properties. With only one randomized clinical trial available, further studies must be conducted before routinely recommending statins for prophylaxis of VTEs.
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PMID:Statins and venous thromboembolic disease prophylaxis. 2370 92


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