Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported 3 fatal cases of primary Epstein-Barr virus (EBV) infection resembling histiocytic medullary reticulosis (HMR) in young children in Taiwan, where an HMR-like illness has been previously found to be prevalent. The disease ran a fulminant course, manifesting as fever, anemia, jaundice, skin rash, pulmonary infiltration, and/or hepatosplenomegaly lasting for only 1-3 weeks. Laboratory tests revealed no hemolytic anemia and Coombs test was negative. Sepsis or HMR was the main clinical differential. At autopsy, the spleen, liver, lymph node, lung, and bone marrow showed infiltration of atypical "histiocytes" or blasts, lymphocytes, and mature histiocytes with hemophagocytosis. Immunophenotype and gene rearrangement studies of the lymphoid tissues revealed that these atypical "histiocytes" were actually polyclonal B immunoblasts in one case and transformed T lymphocytes in the remaining 2 cases, representing two different types of virus-host interaction. Southern blot and in situ hybridization studies on frozen lymphoid tissues demonstrated the presence of EBV DNA in all 3 patients; the study for cytomegalovirus was negative. The young age of these patients, closely correlated with the prevalent age of primary EBV infection in the general populations in Taiwan, strongly suggest that these childhood cases of previously diagnosed HMR-like disease may actually represent a lethal form of primary EBV infection or fatal infectious mononucleosis.
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PMID:Fatal primary Epstein-Barr virus infection masquerading as histiocytic medullary reticulosis in young children in Taiwan. 196 24

Fimbrial adhesins and hemolysins contribute to pathogenicity of extraintestinal Escherichia coli isolates causing urinary tract infections (UTI), sepsis and new born meningitis (NBM). Using gene cloning techniques and pulse field electrophoresis in combination with Southern hybridizations it was demonstrated that the genetic determinants coding for P and 'P-related' fimbrial adhesins and hemolysins are closely linked on the chromosomes of different pathogenic E. coli wild-type isolates. For two UTI strains, 536 (O6:K15) and J96 (O4:K6), a co-deletion of the linked gene clusters coding for hemolysin and fimbriae was observed. The deleted DNA regions which also comprise flanking DNA sequences were termed 'pathogenicity DNA islands'. Such 'pathogenicity DNA islands' were also detected in the genome of O18:K1 isolates of OMP type 6 but were absent on the chromosomes of O18:K1 strains of OMP type 9. A mutant strain, 536-22 was selected from rat kidneys after intraurethral infection of animals with the wild-type parental strain 536. This particular isolate also shows deletions of 'pathogenicity islands' leading to a non-pathogenic phenotype. It is therefore concluded that excisions of 'pathogenicity islands' from chromosomes of pathogenic E. coli strains are not restricted to the laboratory but also occur in vivo. The generation of deletions may represent a general mechanism of bacterial virulence modulation.
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PMID:Deletions of chromosomal regions coding for fimbriae and hemolysins occur in vitro and in vivo in various extraintestinal Escherichia coli isolates. 197 20

Certain DNA probes derived from accessory genes of cloned K88 and F41 determinants hybridize with Escherichia coli strains that express K88 or F41 and with certain other E. coli strains that do not express these antigens. We found that these probes hybridized with human enteroinvasive E. coli, and with bovine E. coli isolates which produced a fatal septicemia in experimentally infected piglets. These strains did not hybridize with probes derived from the structural subunit genes encoding the K88 and F41 antigens. E. coli strains isolated from turkeys with septicemia, Shigella and Salmonella strains did not hybridize to the K88 and F41 accessory gene probes. The K88 and F41 accessory genes probes hybridized with a 200 kb plasmid which is required for invasion by human enteroinvasive E. coli. The K88 and F41 accessory gene homology in the bovine isolates was located on a 150 kb transmissible plasmid but was unrelated to plasmids encoding aerobactin, Vir, or colicin V, which are suspected virulence factors in septicemic E. coli. A common plasmid-encoded antigen was associated with bovine isolates that hybridized with the K88 and F41 accessory gene probes. This included strains which express CS31A, a surface antigen associated with bovine septicemic E. coli, which also hybridized with the K88 and F4 accessory gene probes. The results suggest that the K88 and F41 accessory gene probes hybridized with sequences that may be associated with a common mechanism of pilus expression in distinct groups of E. coli pathogens.
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PMID:Characterization of bovine septicemic, bovine diarrheal, and human enteroinvasive Escherichia coli that hybridize with K88 and F41 accessory gene probes but do not express these adhesins. 198 1

Glucocorticoid receptor (GR) hormone-binding activity, its physical characteristics, and GR mRNA levels were studied in the liver, brain and muscle of normal (saline-injected) and hypermetabolic septic rats 24 h after the subcutaneous injections of E. coli. The GR levels (hormone-binding activity) declined by about 40%, 56%, and 40% in septic liver, brain, and muscle cytosol, respectively. The mechanism of the decrease in the GR levels in sepsis was studied in liver. The GR levels remained low (45% of control hormone-binding) even after 48 h of E. coli administration. The decrease in the liver GR occurred in the 9S untransformed GR. The 9S GR from septic liver transformed to the 4S form in proportions comparable to the control liver GR. In addition, the 4S GR from control and septic liver was capable of binding to DNA-cellulose to a similar extent. The GR mRNA level in septic liver declined by about 30%. Thus, a decrease in GR hormone-binding activity in sepsis appears to be due to a decline in the steady-state GR mRNA level and not from a change in the qualitative properties of the GR protein.
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PMID:Depletion of rat liver glucocorticoid receptor hormone-binding and its mRNA in sepsis. 199 Feb 34

It is currently hypothesized that the mechanisms of cancer cachexia involve the host's production of inflammatory cytokines, which in turn orchestrate a series of complex interrelated steps that ultimately lead to a chronic state of wasting, malnourishment, and death (see Fig. 1). The metabolic changes seen in the tumor-bearing host are similar, but not identical, to those seen in sepsis and inflammation and appear to result from a generalized response of the host to the stimulus of invasion--the tumor. Although there are likely to be several humoral factors, of either host or tumor origin (see Fig. 1), involved in cancer cachexia, recombinant DNA methodology has provided sufficient amounts of only a few cytokines to enable careful investigation of their cachectic potential. TNF/cachectin has been most extensively studied and appears to play a clear role, because administration of low-dose continuous or escalating doses simulates changes associated with cancer cachexia. In addition, these cachectic changes have been blocked by a specific antisera. IL-1, IL-6, and interferon-gamma all have potential as mediators of cancer cachexia and more work is clearly indicated. It is possible that, given our current understanding of the mechanisms of cancer cachexia, it can be theorized that TNF, which causes many of the manifestations of cancer cachexia, and IL-1 are released by macrophages in response to tumor (see Fig. 1). Interferon-gamma appears to potentiate these effects and may also be necessary for the complete syndrome of cancer cachexia. IL-6 probably is released as another mediator, principally mediating the acute phase response seen in cancer cachexia. Other factors are certain to be involved. Further study into the mechanisms and possible treatment of cancer cachexia is needed, because a large proportion of cancer patients who are incurable by current therapies continue to suffer from this lethal wasting diathesis. Furthermore, specific strategies to reverse the cachectic changes associated with cancer will likely improve antitumor treatment.
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PMID:Mechanisms of cancer cachexia. 202 66

Production of beta-lactamase is the most common mechanism of bacterial resistance to beta-lactam antibiotics. Virtually all bacteria have the capability of synthesizing the enzyme. Microorganisms may already possess the native genetic information necessary for beta-lactamase production (i.e., chromosomal), or may acquire the capacity by transfer of DNA from another organism (i.e., plasmid-mediated). The level of beta-lactamase production may be stable and noninducible (constitutive enzyme production), or may be stimulated on exposure to selected beta-lactam antibiotics (inducible enzyme production). Inhibitors such as clavulanic acid and sulbactam prevent antibiotic degradation by the beta-lactamases of many clinically significant pathogens. Therefore, currently available beta-lactam-beta-lactamase-inhibitor combinations exhibit broad spectra of in vitro activity. Ticarcillin-clavulanate possesses clinically significant activity against many bacteria, including streptococci, Staphylococcus aureus, Bacteroides fragilis, and numerous Enterobacteriaceae. Amoxicillin-clavulanate and ampicillin-sulbactam demonstrate clinically significant activity against streptococci (including enterococci), S. aureus, B. fragilis, and some Enterobacteriaceae. Ticarcillin-clavulanate is indicated for treatment of serious infections, including septicemia. Amoxicillin-clavulanate is useful in the treatment of upper respiratory, urinary tract, and skin and soft tissue infections. Ampicillin-sulbactam may be used for treatment of intraabdominal, gynecologic, urinary tract, and skin and soft tissue infections.
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PMID:Effects of beta-lactamase-mediated antimicrobial resistance: the role of beta-lactamase inhibitors. 204 31

Flow cytometric parameters of neutrophil function, such as phagocytosis and degradation of Escherichia coli, intracellular pH value, esterase activity, and cell volume, were evaluated as risk indicators for sepsis- and trauma-related pulmonary and cardiovascular organ failure in intensive care patients. Serial blood samples (n = 201) were obtained from 47 prospectively identified patients. Each patient's condition was classified daily within four categories: post-traumatic (n = 22) or septic (n = 28) organ failure, transition state (n = 119), and stable organ function after recovery (n = 27). Thirty-two parameters of neutrophil function were automatically calculated for each blood sample from several flow cytometric list mode measurements of cell samples vitally stained with acridine orange for intact and denatured DNA or with 1,4-diacetoxy-2,3-dicyanobenzene for intracellular pH and esterase activity. The DNA of dead cells was simultaneously counterstained with propidium iodide. The cell biochemical parameter pattern was significantly different among samples of patients from the four clinical categories (p less than 0.05). Hyperergic phagocytosis was observed after trauma, in contrast to hypoergic phagocytosis, increased neutrophil cell volume, and elevated intracellular pH during sepsis. The clinical categories were correctly identified in 82% of the samples by automated classification with the DIAGNOS1/SPSS program system from the flow cytometrically determined cell functions. The course of the disease was correctly predicted 3 days in advance to the clinical manifestation of pulmonary or cardiovascular organ failure in 92% of the samples. The multifunctional analysis of neutrophils by flow cytometry seems of interest for early medical intervention in preseptic and preshock patients.
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PMID:Flow cytometric parameters of neutrophil function as early indicators of sepsis- or trauma-related pulmonary or cardiovascular organ failure. 210 66

To understand the genomic changes contributing to the various metabolic derangements in sepsis and septic shock, we measured the activities of the following liver enzymes intimately associated with DNA function: (1) DNA topoisomerases I and II (topo I and topo II) controlling DNA conformation in mammalian nuclei, and (2) O6-methylguanine-DNA-methyltransferase (MT) capable of removing the methyl groups from the O6-position of guanine in DNA. We found that in septic rat livers the specific activities (units/mg protein) of topo II and MT were elevated by 1.4- and 1.6-fold, respectively, over the sham-operated controls (P less than 0.001). There was no significant difference in topo I activity. We believe that peritonitis sepsis alters topo II levels modulating the selective pretranscriptional changes in chromatin and that MT functions as a cellular stress protein.
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PMID:Alterations in the activities of DNA topoisomerase enzymes and O6-methylguanine-DNA-methyltransferase in septic rat liver. 217 49

Molecular biology has provided new technology for evaluating the traits of bacterial pathogens that are important in the pathogenesis of infections. The ability to derive isogenic strains that differ by a single trait provides a powerful tool for investigating the interaction of a putative virulence factor with the host at any of the various steps in pathogenesis. Recombinant DNA techniques afford the opportunity to clone the genes involved in the biosynthesis of a particular virulence factor. Once the gene(s) are cloned, a vast amount of information can be learned about their composition, structure, and regulation, and similarity with genes in other organisms. Understanding the molecular biology of a virulence factor also provides information about potential targets for future therapies and preventive modalities. The molecular analysis of two virulence factors from the type III group B streptococcus has been reviewed to provide specific examples of how these techniques can be used. The data has shown that the capsular polysaccharide is an essential factor in GBS virulence. The structural influence of sialic acid on the capsule plays a major role in its virulence properties. The importance of the capsule has been tested in several assays to identify its role in pathogenesis. Its primary role appears to be evading host phagocytic mechanisms, but it does not appear to be essential in the vascular response observed during GBS sepsis. Using the isogenic strains, we have also learned that the capsule does not mask a fibronectin receptor on GBS. In contrast to the capsule, the beta-hemolysin of GBS does not appear to be essential for systemic disease once the organism has invaded. Its role in the initial invasive steps in GBS pathogenesis has not been tested, but the availability of isogenic mutants in beta-hemolysin production will allow this question to be answered once the model systems are available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular analysis of two group B streptococcal virulence factors. 217 47

We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6-month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short-term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment.
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PMID:Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial. 221 80


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