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)

Although Pneumocystis carinii is the most common opportunistic pathogen infecting individuals with AIDS, very little is known of the basic biology of the organism. We have examined the ribosomal RNA (rRNA) and the DNA encoding it (rDNA) in P. carinii in an attempt to clarify its taxonomic position and to begin to study its genetic processes. Electrophoretic analysis showed that the sizes of the P. carinii rRNAs are quite similar to the sizes of the corresponding rRNAs from Saccharomyces cerevisiae. Direct sequence analysis of approx. 60% of the 18S small subunit-rRNA (Ss-rRNA) confirmed that its sequence is similar to that of yeast-like fungi and that a putative group-I intron previously observed in the 18S rDNA is, in fact, excised from the mature rRNA. PCR analysis of the intron in P. carinii genomic DNA showed that each of the multiple rDNA genes bears the group-I intron and in vitro transcripts of the intron autocatalytically excise from the rRNA primary transcript in the presence of GTP. Finally, analogues of GTP inhibit the self-splicing reaction, indicating that the guanosine-binding site of the intron closely resembles that of other well-characterized group-I introns. Since no group-I introns have been found in higher eukaryotes, this self-splicing process represents a viable target for chemotherapy of P. carinii pneumonia (PCP).
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PMID:Characterization of the rRNA-encoding genes and transcripts, and a group-I self-splicing intron in Pneumocystis carinii. 139 96

An increase in total urinary neopterin was observed in 12 of 13 patients with acquired immunodeficiency syndrome (AIDS), seven of 13 patients with lymphadenopathy, one of six healthy homosexual males, seven of ten adult patients with staphylococcal pneumonia, 11 of 12 children with viral infections, four of seven children with bacterial infections, and 12 of 13 children with various immune defects. Extremely high values of total urinary neopterin and monapterin were observed in severely ill patients with AIDS and those with familial hemophagocytic lymphohistiocytosis. Neopterin excretion was normal in two AIDS patients with Kaposi's sarcoma, but without opportunistic infections at that time. On reexamination of one of these patients later on, elevated neopterin values were noted. Parallel increases in neopterin and monapterin were found, whereas biopterin was usually normal. The increase in total neopterin was mainly due to 7,8-dihydroneopterin and was accompanied by an increase in 3'-hydroxysepiapterin. Increased neopterin in urine is assumed to reflect the increase in GTP pool and GTP cyclohydrolase I activity as observed in stimulated monocytes. Thus, neopterin, as a measure of the activation of the nonspecific cellular immune system, may be used diagnostically to detect allograft rejection after transplantations and to follow-up HTLV-III positive patients.
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PMID:Neopterin in AIDs, other immunodeficiencies, and bacterial and viral infections. 301 91

Some studies were carried out on the use of 9,3"-diacetylmidecamycin (MOM) dry syrup, a new macrolide antibiotic preparation, in the treatment of children. The results are summarized below. 1) A single oral dose of 10 mg/kg of the MOM dry syrup was administered to 1 child at 2 hours after a meal. The peak concentration of the antibiotic in the blood was 0.88 micrograms/ml and occurred at 1 hour after administration. At 2 hours the concentration had fallen to 0.59 microgram/ml, and after 4 hours the blood level was already below the minimum detectable concentration (0.5 microgram/ml). During the first 6 hours after the administration, 6.7% of the MOM was recovered in the urine. 2) The MOM dry syrup was orally administered to 4 pneumonia patients (including 2 cases of mycoplasmal pneumonia) for 7 days at a daily dosage of 15.2--20.5 mg/kg (divided into 3 equal doses). The therapeutic results were excellent in 2 cases, good in 2 cases and poor in none. 3) No side effects such as exanthema were observed to occur. In 1 case only, there was a mild and temporary elevation in the laboratory test values for total bilirubin, GOT and GTP. 4) All 4 of the pneumonia patients found the MOM dry syrup to be easy to ingest. The taste and odor of this antibiotic preparation were judged to be sufficiently palatable to permit convenient use in the treatment of children.
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PMID:[Experience with the use of 9,3"-diacetylmidecamycin dry syrup in pediatrics]. 698 51

To 10 cases with respiratory infections, 200 mg, twice daily, of netilmicin was administered without other antibiotics and the following results were obtained. 1) Netilmicin was administered to 2 cases of pneumonia and 8 cases of bronchitis for 7 to 30 days, and 4 remarkably effective and 6 effective cases were observed, that is, netilmicin was effective in all cases. 2) Abnormal laboratory test values were found in 2 cases; 1 case showed slightly elevated creatinine value, and 1 case showed slightly increase GTP value, and these values were normalized rapidly without any treatment after discontinuation of netilmicin administration. Netilmicin 100 mg was intramuscularly injected to 15 patients with pleural effusion to see the time-course distribution of the drug to serum and to pleural fluid by determining the concentration of netilmicin. 1) Netilmicin concentrations in serum reached the peak at 30 minutes after the intramuscular injection and it gradually decreased, while in the pleural fluid, it reached the peak at 3 hours after the injection, and the peak value in the pleural fluid in average was 2.63 +/- 1.98 micrograms/ml, and it was still detectable at 24 hours after the injection. 2) The ratio of netilmicin concentrations in the serum and pleural fluid at the peak was 31.7 +/- 23.4%, and distribution of netilmicin into the pleural fluid was considered to be high enough.
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PMID:[Clinical trial of netilmicin in infections of respiratory organs and studies on its penetration into pleural fluid II. (author's transl)]. 708 85

Pathogenic Escherichia coli are responsible for a variety of diseases, including diarrhoea, haemolytic uraemic syndrome, kidney infection, septicaemia, pneumonia and meningitis. Toxins called cytotoxic necrotizing factors (CNFs) are among the virulence factors produced by uropathogenic (CNF1) or enteropathogenic (CNF2) E. coli strains that cause diseases in humans and animals, respectively. CNFs induce an increase in the content of actin stress fibres and focal contacts in cultured cells. Effects of CNFs on the actin cytoskeleton correlated with a decrease in the electrophoretic mobility of the GTP-binding protein Rho and indirect evidence indicates that CNF1 might constitutively activate Rho. Here we show that CNF1 catalyses the deamidation of a glutamine residue at position 63 of Rho, turning it into glutamic acid, which inhibits both intrinsic GTP hydrolysis and that stimulated by its GTPase-activating protein (GAP). Thus, this deamidation of glutamine 63 by CNF1 leads to the constitutive activation of Rho, and induces the reorganization of actin stress fibres. To our knowledge, CNF1 is the first example of a bacterial toxin acting by deamidation of a specific target protein.
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PMID:Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine. 919 1

The GTP-binding regulatory proteins (G proteins) in the membranes of the lung parenchyma from normal, uninfected ferrets were compared to those from immunosuppressed animals with and without Pneumocystis carinii pneumonitis. In lung membranes, pertussis toxin (PT) catalyzed ADP ribosylation of a 41-kDa protein; treatment with cholera toxin (CT) led to ribosylation of a 44-kDa polypeptide. Compared to that in the normal ferrets, the level of the 44-kDa protein was dramatically suppressed in the P. carinii-infected animals. Western blot analysis with specific antibodies to alpha s (which recognized CT substrates), alpha common (which reacted to PT substrates), the alpha q/11 epitope, and the beta subunit demonstrated that these proteins were decreased in animals with P. carinii pneumonitis (PCP). Western blotting of PCP-free membranes with a pan-Ras antibody revealed a 21-kDa polypeptide (corresponding to small G proteins). The level of the 21-kDa protein in membranes from PCP-affected animals was only 30% of that in membranes from PCP-free animals. Finally, analogous studies performed with rat lung membranes revealed similar findings. These data suggest that, independent of its exacerbation of immunosuppression, PCP leads to extensive changes in the GTP-binding proteins in the lung.
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PMID:Pneumocystis carinii infection alters GTP-binding proteins in the lung. 926 11

Severe acute respiratory syndrome coronavirus (SARS-CoV), a newly identified group 2 coronavirus, is the causative agent of severe acute respiratory syndrome, a life-threatening form of pneumonia in humans. Coronavirus replication and transcription are highly specialized processes of cytoplasmic RNA synthesis that localize to virus-induced membrane structures and were recently proposed to involve a complex enzymatic machinery that, besides RNA-dependent RNA polymerase, helicase, and protease activities, also involves a series of RNA-processing enzymes that are not found in most other RNA virus families. Here, we characterized the enzymatic activities of a recombinant form of the SARS-CoV helicase (nonstructural protein [nsp] 13), a superfamily 1 helicase with an N-terminal zinc-binding domain. We report that nsp13 has both RNA and DNA duplex-unwinding activities. SARS-CoV nsp13 unwinds its substrates in a 5'-to-3' direction and features a remarkable processivity, allowing efficient strand separation of extended regions of double-stranded RNA and DNA. Characterization of the nsp13-associated (deoxy)nucleoside triphosphatase ([dNTPase) activities revealed that all natural nucleotides and deoxynucleotides are substrates of nsp13, with ATP, dATP, and GTP being hydrolyzed slightly more efficiently than other nucleotides. Furthermore, we established an RNA 5'-triphosphatase activity for the SARS-CoV nsp13 helicase which may be involved in the formation of the 5' cap structure of viral RNAs. The data suggest that the (d)NTPase and RNA 5'-triphosphatase activities of nsp13 have a common active site. Finally, we established that, in SARS-CoV-infected Vero E6 cells, nsp13 localizes to membranes that appear to be derived from the endoplasmic reticulum and are the likely site of SARS-CoV RNA synthesis.
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PMID:Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. 1514 Sep 59

Group B streptococci (GBS) are the principal causal agents of human neonatal pneumonia, sepsis and meningitis. We had previously described the existence of a eukaryotic-type serine/threonine kinase (Stk1) and phosphatase (Stp1) in GBS that regulate growth and virulence of the pathogen. Our previous results also demonstrated that these enzymes reversibly phosphorylated an inorganic pyrophosphatase. To understand the role of these eukaryotic-type enzymes on growth of GBS, we assessed the stk1-mutants for auxotrophic requirements. In this report, we describe that in the absence of the kinase (Stk1), GBS are attenuated for de novo purine biosynthesis and are consequently growth arrested. During growth in media lacking purines, the intracellular G nucleotide pools (GTP, GDP and GMP) are significantly reduced in the Stk1-deficient strains, while levels of A nucleotides (ATP, ADP and AMP) are marginally increased when compared with the isogenic wild-type strain. We provide evidence that the reduced pools of G nucleotides result from altered activity of the IMP utilizing enzymes, adenylosuccinate synthetase (PurA) and IMP dehydrogenase (GuaB) in these strains. We also demonstrate that Stk1 and Stp1 reversibly phosphorylate and consequently regulate PurA activity in GBS. Collectively, these data indicate the novel role of eukaryotic-type kinases in regulation of metabolic processes such as purine biosynthesis.
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PMID:Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae. 1588 24

Type IV pili (Tfp) are polar surface structures of Pseudomonas aeruginosa required for twitching motility, biofilm formation and adherence. One protein required for the assembly of tfp is FimX, which possesses both GGDEF and EAL domains characteristic of diguanylate cyclases and phosphodiesterases respectively. In this work we demonstrate that FimX has phosphodiesterase activity towards bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), but does not show diguanylate cyclase activity. Instead, the imperfect GGDEF domain of FimX likely serves to activate phosphodiesterase activity when bound to GTP, as has recently been described for the Caulobacter crescentus composite GGDEF-EAL protein, CC3396. Bacteria expressing FimX in which either the GGDEF or EAL domain is deleted or mutated have phenotypes indistinguishable from a DeltafimX strain, demonstrating the importance of both domains to function. Previous work has shown that FimX localizes to the bacterial pole. In this work we show that restriction of FimX to a single pole requires intact GGDEF and EAL domains. Deletion of the amino-terminal REC domain of FimX, which contains a putative polar localization signal, results in a protein that still supports intermediate levels of pilus assembly and function. RFP-FimXDeltaREC, unlike RFP-FimX, is no longer localized to the bacterial pole, while transmission electron microscopy shows that surface pili can originate from non-polar sites in this mutant. Although DeltafimX mutants show limited in vitro cytotoxicity, they are as virulent as the wild-type strain in a murine model of acute pneumonia.
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PMID:Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa. 1667 12

The authors review studies on 8-nitroguanine (8-NO(2)-G) formed by reactions of guanine, guanosine, and 2 - deoxyguanosine, either free or in DNA or RNAwith reactive nitrogen species (RNS) generated from peroxynitrite, the myeloperoxidase-H(2)O(2)-nitrite system, and others. Use of antibodies against 8-NO(2)-G has revealed increased formation of 8-NO(2)-G in various pathological conditions, including RNA virus-induced pneumonia in mice, intrahepatic bile ducts of hamsters infected with the liver fluke Opisthorchis viverrini, and gastric mucosa of patients with Helicobacter pylori-induced gastritis. Immunoreactivity has been found in the cytosol as well as in the nucleus of inflammatory cells and epithelial cells in inflamed tissues, but not in normal tissues. 8- NO(2)-G in DNA is potentially mutagenic, yielding G:C to T:A transversion, possibly through its rapid depurination to form an apurinic site and/or miscoding with adenine. 8-NO(2)-G in RNA may interfere with RNA functions and metabolism. Nitrated guanine nucleosides and nucleotides in the nucleotide pool may contribute to oxidative stress via production of superoxide mediated by various reductases and may disturb or modulate directly various important enzymes such as GTP-binding proteins and cGMP-dependent enzymes. Further studies are warranted to establish the roles of 8-NO(2)-G in various pathophysiological conditions and inflammation-associated cancer.
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PMID:8-nitroguanine, a product of nitrative DNA damage caused by reactive nitrogen species: formation, occurrence, and implications in inflammation and carcinogenesis. 1677 87


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