UMLS:C0519030 - FACTA Search

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Query: UMLS:C0519030 (Klebsiella)
21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW-2228, has some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. Recently, the application of G-CSF against infectious diseases has been considered, and some animal experiments have been carried out to support its clinical applications. In this paper, we investigated protective effects of KW-2228 against systemic infections caused by Klebsiella pneumoniae in mice with leukopenia induced by the administration of cyclophosphamide. KW-2228 (1 microgram/mouse) was administered (s.c.) once a day for 4 days following cyclophosphamide administration, then mice were challenged with K. pneumoniae (i.p.) 4 hours after the last administration of KW-2228. An antibiotic was administered (s.c., p.o.) 2 hours after the bacterial challenge. Combination effects of KW-2228 with cefazoline, cefmetazole, ceftazidime or cefaclor were evaluated in the systemic infection with K. pneumoniae. Each combination therapy using KW-2228 with each of the cephems exhibited an excellent protective effect in comparison to the therapy with a cephem alone. These results show the possibility that KW-2228 could be of use in treating obstinate infections not successfully treated with an antimicrobial agent alone.
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PMID:[Combination effect of KW-2228 and cephem antibiotics in a systemic infection model in neutropenic mice]. 137 49

Ethanol suppresses functions of the polymorphonuclear leukocyte (PMNL), seriously compromising normal host defenses against pneumonia. Because granulocyte colony-stimulating factor (G-CSF) augments the number and function of PMNL, the effect of G-CSF on the antibacterial defenses of the lung in normal and acutely intoxicated rats was studied. Animals received G-CSF or vehicle twice a day for 2 days, then ethanol or saline, followed by challenge with Klebsiella pneumoniae. K. pneumoniae elicited an intrapulmonary influx of PMNL in control rats that was markedly suppressed by prior ethanol administration. G-CSF augmented the recruitment of PMNL into the lungs of control rats and significantly attenuated the adverse effects of ethanol on PMNL entry into the lung. G-CSF enhanced intrapulmonary bactericidal activity against this pathogen in normal and ethanol-treated rats. All intoxicated rats pretreated with the vehicle died, while greater than 90% of rats pretreated with G-CSF survived. These findings suggest a potential role for G-CSF in mitigating the adverse effects of ethanol on PMNL delivery and pulmonary host defenses.
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PMID:Granulocyte colony-stimulating factor enhances pulmonary host defenses in normal and ethanol-treated rats. 171 3

Colony-stimulating factors are a family of glycoproteins instrumental in regulation of hematopoiesis and inflammation. Clinical effects of various colony-stimulating factors have been reported in murine and human hosts. This review summarizes findings from some clinical trial evaluations of macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin-1, interleukin-3, interleukin-4, interleukin-5, interleukin-6, and interleukin-7 administration to other species. These factors stimulate clonal expansion of progenitor cells in the bone marrow, induce differentiation of various cell lineages to a mature phenotype, and, in some cases, enhance the effector activities of immune cells. Each colony-stimulating factor has distinct lineages of bone marrow cells upon which they act, although there is some overlap in lineage activity and synergy between colony-stimulating factors. The close relationship in biological activity among different colony-stimulating factors is also reflected at the genomic level at which genes for some hematopoietic growth factors have been mapped to a region of human chromosome 5. Recently, colony-stimulating factor administration to cattle and its potential application to disease control in bovine preventive medicine programs has been investigated. Data from recent hematological, immunological, and intramammary bacterial (Staphylococcus aureus and Klebsiella pneumoniae) challenge studies in dairy cows are reviewed. These studies, with limited numbers of cows, found that rate of new infections, as well as duration and severity of infection, were reduced by pretreatment of cows with granulocyte-colony stimulating factor. The dose-dependent hematological and immunomodulatory effects of granulocyte colony-stimulating factor administration may explain reduced severity and incidence of mastitis in dairy cows given granulocyte colony-stimulating factor.
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PMID:Immunobiology of hematopoietic colony-stimulating factors: potential application to disease prevention in the bovine. 172 1

The preventive capability of interleukin 1 alpha (IL-1) against bacterial infections was estimated in normal and anticancer drug-treated BALB/c mice in comparison with OK432, granulocyte colony-stimulating factor, interferons alpha and gamma, and interleukin 2. Pretreatment with IL-1 (days -4 and -2) resulted in a significantly higher survival rate in normal mice inoculated i.p. with Klebsiella pneumoniae, Pseudomonas aeruginosa or Listeria monocytogenes (day 0). The i.p. and s.c. administrations of IL-1 were equally effective for the induction of antibacterial resistance. Pretreatment with OK432 showed an equal degree of resistance to i.p. infection but was effective only by i.p. administration. Enhanced antibacterial resistance by IL-1 and OK432 was also observed in cyclophosphamide- and aminomethylpyrimidinylmethylchloroethylnitrosourea hydrochloride-pretreated (day -5) normal hosts and in cyclophosphamide-treated tumor-bearing hosts. In the case of granulocyte colony-stimulating factor (i.p. or s.c.) (days -4 to -1), a statistical difference in survival rate between granulocyte colony-stimulating factor and its vehicle-treated groups was observed in cyclophosphamide-pretreated hosts, but not in normal hosts or aminomethylpyrimidinylmethylchloroethylnitrosourea hydrochloride-pretreated hosts. Viable bacteria in the peritoneal cavity and blood at 12 h after i.p. infection of K. pneumoniae correlated well with the survival rate. In IL-1-pretreated hosts, the earlier and increased accumulation of neutrophils into peritoneal cavity after the infection was observed and the number of inflammatory cells in peritoneal cavity correlated well with the survival rate. The enhanced resistance to bacterial infection by IL-1 was suggested to be in part due to the enhanced cellular defense mechanisms. The prophylactic administration of IL-1 would be beneficial for the management of serious infections in cancer patients.
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PMID:Prevention of fatal infections by recombinant human interleukin 1 alpha in normal and anticancer drug-treated mice. 231 99

Septicemia in hematologic malignancies and infection of herpes zoster in cancer patients were studied, and trend in organisms in a cancer hospital was investigated. 1) Septicemia in hematologic malignancies. The success rate of antibiotic therapy for septicemia was 76% if the patients were not under antibiotic therapy when septicemia developed. But recovery from septicemia was only 25% if the patients were undergoing antibiotic therapy when septicemia developed. Some 90% of neutropenic patients under 500/microliters, who were not under antibiotic therapy when septicemia developed, recovered from septicemia if the neutrophil count increased in the following 5 days. Change in the neutrophil count was an important factor determining the success or failure of antibiotic therapy for septicemia. The use of granulocyte colony-stimulating factor may prevent chemotherapy-induced neutropenia. Shortening of the period of neutropenia or preventing its occurrence should reduce the incidence and the severity of infection. 2) Infection of herpes zoster in cancer patients. Thirty-four cancer patients were associated with herpes zoster. Eleven of them were patients with malignant lymphoma and ten of them were patients of breast cancer. Most patients were heavily pretreated by chemotherapy and/or radiotherapy before the development of herpes zoster. Marked lymphocytopenia was observed at the onset of herpes zoster. Absolute lymphocyte count was under 1000/microliters in 71% of these patients. Development of herpes zoster in cancer patients was considered to be due to the depression of cell-mediated immunity which was the result of repeated and continued anticancer therapy. Acyclovir was found to be effective to treat herpes zoster in these patients. 3) Trend of organisms detected in cancer hospital. The frequency of organisms isolated from clinical materials in the National Cancer Center Hospital was compared during the period from 1978 to 1982 and the period from 1983 to 1987. The most common organism detected in both periods was P. aeruginosa and no change in frequency was observed. But the frequency of gram-negative bacilli, E. coli, Klebsiella and Serratia, decreased significantly in the latter period while the frequency of gram-positive cocci, Enterococcus and Staphylococcus increased markedly in the latter period. The use of cephems of third generation in the latter period could be one reason for the recent change of organisms detected in the hospital. Appropriate therapy for infection based on the latest and accurate information should be used.
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PMID:[Infection and immunosuppression in cancer patients]. 273 15

In the 1960s, almost all patients who developed gram-negative bacteremia during granulocytopenia died; death occurred before blood culture results were available in about 50% of cases; many patients received antibiotics that were, at best, suboptimal and frequently inactive against the invading pathogen. In the early 1970s epidemiological studies demonstrated that more than 50% of gram-negative bacteremias were caused by hospital-acquired strains which colonized along the alimentary canal and caused infection in a limited number of locations, especially the pharynx, lungs, colon, and perianum. Surveillance culture studies have demonstrated that among acquired gram-negative bacilli, Pseudomonas aeruginosa will almost invariably proceed to bacteremia if the patient becomes profoundly neutropenic, with Escherichia coli and Klebsiella pneumoniae leading to bacteremia in only a moderate number of patients and other gram-negative bacilli rarely progressing to bacteremia despite colonization. Hence, the leading causes of bacteremia in the granulocytopenic patient are E. coli, K. pneumoniae and P. aeruginosa. Further investigations demonstrated that gram-negative bacilli were acquired from hands, food, and water, thus leading to approaches to infection prevention which included careful handwashing, low-microbial-content diet, and attention to water sources, including ice machines. Another basic approach to infection prevention has been to suppress gram-negative bacilli colonizing the alimentary canal with oral nonabsorbable antibiotics or, more recently and more effectively, with agents such as the fluoroquinolones which, unlike previous regimens, do not concurrently suppress the anaerobic flora, hence maintaining colonization resistance. The third basic approach to infection prevention is to improve the host defense factors, principally by a more rapid return of circulating granulocytes with the use of colony-stimulating factors such as granulocyte/macrophage colony-stimulating factor or granulocyte colony-stimulating factor. As to therapy, the fundamental approach with presumed gram-negative bacteremia is the prompt institution of empiric antibiotic therapy when fever first develops in the setting of granulocytopenia. There is a short "window of opportunity" after which no therapy will be effective. Combinations of antibiotics such as a beta-lactam and an aminoglycoside are used for multiple reasons: to afford coverage in the event the pathogen, proves resistant to one of the agents, to afford a synergistic activity thus improving and prolonging the serum bactericidal activity, and to reduce the development of resistance. However, patients can be divided into two risk groups: those with granulocytopenia and a regenerating bone marrow and those with an aplastic marrow who will have persistent, profound (< 100 microliters) granulocytopenia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gram-negative bacteremia. 814

Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. We studied the effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae, an important gram-negative bacillary pulmonary pathogen. Using a highly reproducible murine model, we here show the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Binding of 125I-G-CSF to K pneumoniae was displaced by an excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1alpha, did not compete with G-CSF binding to the bacteria. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes.
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PMID:Granulocyte colony-stimulating factor worsens the outcome of experimental Klebsiella pneumoniae pneumonia through direct interaction with the bacteria. 951 54

We have recently reported that endotoxin (lipopolysaccharide [LPS]) derived from Klebsiella pneumoniae dramatically decreased the biliary excretion of the beta-lactam antibiotic cefoperazone (CPZ), which is primarily excreted into the bile via the anion transport system, in rats. The present study was designed to investigate the effect of human recombinant granulocyte colony-stimulating factor (G-CSF), which is reported to be beneficial in experimental models of inflammation, on the pharmacokinetics and biliary excretion of CPZ in rats. CPZ (20 mg/kg of body weight) was administered intravenously 2 h after the intravenous injection of LPS (250 microgram/kg). G-CSF was injected subcutaneously at 12 microgram/kg for 3 days and was administered intravenously at a final dose of 50 microgram/kg 1 h before LPS injection. Peripheral blood cell numbers were also measured. LPS dramatically decreased the systemic and biliary clearances of CPZ and the bile flow rate. Pretreatment with G-CSF enhanced these decreases induced by LPS. The total leukocyte numbers were increased in rats pretreated with G-CSF compared to the numbers in the controls, while the total leukocyte numbers were decreased (about 3,000 cells/microliter) by treatment with LPS. Pretreatment with G-CSF produces a deleterious effect against the LPS-induced decrease in biliary secretion of CPZ, and leukocytes play an important role in that mechanism.
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PMID:Granulocyte colony-stimulating factor enhances endotoxin-induced decrease in biliary excretion of the antibiotic cefoperazone in rats. 973 31

The time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic cytochrome P450-dependent drug-metabolizing capacity (cytochrome P450 and b5 content, activity of aminopyrine N-demethylase, p-nitroanisole O-demethylase, aniline hydroxylase and benzphetamine N-demethylase) and on the pharmacokinetics of antipyrine have been determined in rats. Measurement of enzyme activity and antipyrine (after intravenous injection of 20 mg kg(-1)) were performed 2, 24 and 96 h after a single intraperitoneal injection of endotoxin (1 mg kg(-1)) and after repeated doses (once daily for 4 days). The contribution of tumour necrosis factor alpha (TNFalpha) to the endotoxin-induced changes was also examined in rats pretreated with granulocyte colony-stimulating factor (G-CSF). The systemic clearance of antipyrine and the activity of hepatic cytochrome P450-dependent drug-metabolizing enzymes were dramatically reduced 24 h after a single injection of endotoxin, but had returned to control levels by 96h. The magnitudes of these decreases in these measurements after repeated doses of endotoxin were similar to those seen 24h after the single dose. The systemic clearance of antipyrine correlated significantly with cytochrome P450 content and aminopyrine N-demethylase activity. In histopathological experiments, moderate hypertrophy of Kupffer cells was observed, with no evidence of severe liver-tissue damage. G-CSF pretreatment suppressed the increased plasma concentrations of TNFalpha produced 2 h after single endotoxin injection, but did not eliminate the endotoxin-induced decrease in the systemic clearance of antipyrine, suggesting that TNFalpha is not the sole component responsible for the reduction of cytochrome P450-mediated drug-metabolizing enzyme activity. These results provide evidence that a single intraperitoneal injection of 1.0 mgkg(-1)K. pneumoniae endotoxin in rats reduces hepatic P450 and b5 levels, and reduces the activity of various cytochrome P450-mediated drug-metabolizing enzymes without causing severe liver-tissue damage. This suggests that the effect of endotoxin on hepatic cytochrome P450-mediated drug-metabolizing isozymes is non-selective.
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PMID:Time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic drug-metabolizing enzyme activity in rats. 975 51

Bacterial pneumonia is an increasing complication of HIV infection and inversely correlates with the CD4(+) lymphocyte count. Interleukin (IL)-17 is a cytokine produced principally by CD4(+) T cells, which induces granulopoiesis via granulocyte colony-stimulating factor (G-CSF) production and induces CXC chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokine production and lung host defenses. To test this, we used a model of Klebsiella pneumoniae lung infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R-deficient mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO) mice displayed a significant delay in neutrophil recruitment into the alveolar space, and had greater dissemination of K. pneumoniae compared with control mice. This defect was associated with a significant reduction in steady-state levels of G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling is critical for optimal production of G-CSF and MIP-2 and local control of pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.
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PMID:Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. 1151 7

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