Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Group B streptococci (GBS) are the leading causes of neonatal sepsis and meningitis in the United States, with a high rate of fatality and serious morbidity despite appropriate therapy. The C-protein antigens of GBS appear to be important in immunity to experimental infection, yet these antigens remain incompletely characterized with respect to their number, structure, and function. None of these proteins has yet been purified to homogeneity. We have developed a novel method for extraction of surface proteins from the A909 (Ia/c) strain of GBS by using mutanolysin. Antibodies raised in rabbits against these partially purified proteins conferred passive protection to lethal GBS infection in mice challenged with a GBS strain expressing C proteins with a heterologous capsule type. In addition, mouse monoclonal antibodies were produced and identified by reactivity with the mutanolysin-extracted proteins. One of these monoclonal antibodies (4G8) identifies an epitope on the alpha-antigen of the GBS C proteins (identified by protease susceptibility and mouse protection). On sodium dodecyl sulfate-polyacrylamide gels, this epitope appears as a series of regularly spaced bands ranging in apparent molecular mass from 160,000 to 30,000 Da. The monoclonal antibody 4G8 induces opsonic killing of GBS and protects mice from lethal challenge with GBS. Thus, the 4G8 monoclonal antibody identifies a fully protective epitope on the C-protein alpha-antigen of GBS.
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PMID:A monoclonal antibody identifies a protective C-protein alpha-antigen epitope in group B streptococci. 170 59

Seventy-seven patients with drug refractory ventricular tachycardia (57) and ventricular fibrillation (20) received the implantable defibrillator. There were 55 men and 22 women with a mean age of 63 +/- 10 years. The anatomical diagnoses were coronary artery disease in 61 patients, cardiomyopathy in 15 patients, and aortic stenosis in one patient. The mean ejection fraction was 32 +/- 12%. Concurrent surgery at defibrillator implantation was coronary bypass in eight patients and aortic valve replacement in one patient. There were no intraoperative mortalities. The mean ventricular fibrillation termination threshold was 13 +/- 6 joules. During a follow-up period of 16 +/- 10 months (range 2-40 months) four patients died: electrical mechanical dissociation (two patients), respiratory failure, and sepsis. Thirty-eight patients (51%) continued receiving antiarrhythmic drug therapy, with quinidine sulfate and procainamide being the most frequently utilized agents. Fifty-four patients (72%) have received a mean of 9 +/- 10 shocks (range 1-44). Implantable defibrillators are often needed in patients seen in large community hospitals. This technology can be administered successfully in this setting with complications and results comparable to those reported from university hospitals. Implantable defibrillators are effective in preventing arrhythmic death and can be used with low risk to the patients.
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PMID:Long-term community hospital experience with the internal defibrillator. 170 35

Activation of the contact system has been documented in severe sepsis and hereditary angioedema, but a sensitive, specific, and quantitative assay for assessing the degree of involvement of this proteolytic enzyme cascade is not yet available. We have developed a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) for the alpha 2-macroglobulin-kallikrein (alpha 2M-Kal) complex using an F(ab')2 derivative of a monospecific polyclonal antibody against alpha 2 M as the capture antibody and a unique murine monoclonal antibody, 13G11, against the heavy chain of kallikrein as the detector antibody. The assay does not detect complexes in normal plasma but reacts with complexes generated by activating normal plasma with dextran sulfate at 4 degrees C in a range of 5 to 375 nmol/L. A close correlation of the ELISA with an amidolytic assay for alpha 2M-Kal was documented. Patients with sepsis syndrome but negative bacterial blood cultures did not show elevated plasma complexes, whereas a majority of those with positive blood cultures did show modest elevation and a single patient with septic shock showed a very high level of alpha 2M-Kal complex. Similarly, a patient with classic hereditary angioedema (HAE) showed increased concentration of complexes on three separate occasions during attacks but normal levels between attacks. Two other HAE patients did not show elevated levels at quiescent periods. The ELISA for alpha 2M-Kal appears to be sensitive, specific, and quantitative, and it can be used to reflect the degree of contact system activation in human sepsis and in HAE attacks.
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PMID:Alpha 2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis. 171 May 16

Group B streptococci (GBS) is the leading cause of neonatal sepsis and meningitis. C proteins are an immunologically important group of surface-associated antigens in GBS that remain incompletely characterized. Two C proteins have been designated alpha and beta on the basis of protease susceptibility. We recently used a monoclonal antibody to describe a protective epitope of the GBS alpha (or trypsin-resistant) C protein in the prototype Ia/c GBS strain. In the present study, we examined 51 GBS isolates for expression of C-protein alpha and beta antigens. The alpha antigen, as detected with monoclonal antibody in sodium dodecyl sulfate (SDS) extracts, appears as a heterogeneous series of proteins spaced 8 kDa apart on SDS-polyacrylamide gel electrophoresis, but has a maximum molecular mass that varies among strains from 62.5 to 167 kDa. By immunoblotting with human immunoglobulin A, polyclonal antiserum, or monoclonal antibody, the beta antigen, in contrast, appears as a single protein of molecular mass between 124 and 134 kDa. The amount of alpha antigen expressed by each strain was quantified by enzyme immunoassay inhibition and was found to vary markedly from strain to strain. The susceptibility of strains of GBS to opsonization and killing by human polymorphonuclear leukocytes in the presence of either complement alone or complement with alpha-specific monoclonal antibody was examined. Strains expressing the alpha antigen were less readily killed in the absence of specific antibody than were alpha-negative strains. Killing in the presence of alpha-specific monoclonal antibody was found to correlate directly with the maximum molecular mass of the alpha antigen and with the quantity of antigen on the bacterial cell surface. Isolates of GBS that express the alpha C protein vary widely in the quantity and molecular mass of the alpha antigen produced, and this heterogeneity appears to have biologic importance.
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PMID:Phenotypic diversity in the alpha C protein of group B streptococci. 185 84

When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S-TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with radiation injury.
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PMID:Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: a review of current work. 192 43

The potential deleterious effects of aerosolized fibrin on contaminated procedures were investigated in a rat model of peritonitis. One hundred forty rats were divided into two groups. In the control group, gelatin capsules containing feces (10(7) bacteria per milliliter) and barium sulfate at various dilutions were placed into the abdomen; in the second experimental group, a solution of cryoprecipitate, thrombin, and calcium was sprayed diffusely into the peritoneal cavity after similar fecal contamination. Fecal inocula with low bacterial concentrations (0.01, 0.1, and 0.15 mL) caused few deaths from peritonitis or abscess formation in either group. Heavy peritoneal contamination (0.25, 0.3, and 0.5 mL) caused early deaths from peritonitis in both groups, with 80% of the deaths due to sepsis in the first 48 hours. However, in the moderately contaminated rats (0.2 mL of fecal inoculate), fibrin aerosol reduced the 10-day mortality from 80% to 10%. In all survivors in the fibrin-treated group, intraperitoneal abscesses developed. With intraperitoneal bacterial concentrations of 2 x 10(6) organisms, early acute mortality from fibrinopurulent peritonitis is decreased at the expense of late, localized, nonlethal abscess formation. Aerosolized fibrin solution must be used with caution in contaminated surgery.
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PMID:Effect of aerosolized fibrin solution on intraperitoneal contamination. 198 38

Gut bacteria have been incriminated as causing or contributing to generalized sepsis with multiple organ failure in severely ill patients, and selective decontamination of the gastrointestinal tract of Enterobacteriaceae has been claimed to decrease septic complications in these patients. We studied the effects of selective decontamination of the gastrointestinal tract on survival and organ function in an experimental model of sepsis with multiple organ failure. Wistar rats were inoculated intraperitoneally with zymosan and randomized into control or treatment groups (trimethoprim or streptomycin sulfate). Selective decontamination effectively prevented bacterial translocation of Enterobacteriaceae. However, only early mortality was decreased, and only so in the streptomycin-treated rats. Selective decontamination did not result in a significantly better condition of the surviving animals on day 12.
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PMID:Does selective decontamination of the gastrointestinal tract prevent multiple organ failure? An experimental study. 202 35

In order to elucidate a possible role of hypercoagulability leading to disseminated intravascular coagulation (DIC) in the pathogenesis of multiple organ failure (MOF), unfractionated heparin and the related agents were administered to septic rabbits which manifest DIC and MOF. Administration of heparin resulted in prevention of thrombocytopenia, leukopenia and elevation of plasma bilirubin and creatinine. The morphological hepatic damage was also ameliorated by heparin. Similar favorable effects were obtained by the administration of low molecular weight heparin. Dextran sulfate prevented the hepatic damage to some extent without improvement on other parameters. No significant effect was observed by the administration of a synthetic thrombin inhibitor (MD805). These results indicate that the favorable effect of heparin is due to its anticoagulant property, especially anti-Xa activity. Thereby, it is concluded that the hypercoagulable state leading to DIC is a prerequisite for the occurrence of MOF in sepsis.
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PMID:The effect of heparin on multiple organ failure and disseminated intravascular coagulation in a sepsis model. 208 91

A case is presented of a 57-year-old male patient who underwent total gastrectomy due to gastric adenocarcinoma. During the postoperative period the patient required long-term parenteral nutrition due to a high-debit GI fistula (over 700 ml/day) and sepsis. Two months after parenteral nutrition was started, the patients presented irritability, mucocutaneous lesions and progressive bolding. Serum alkaline phosphatase and zinc levels were lower than normal, although a supplemental 0.03 mg/k/day of zinc was administered. Faced with this zinc deficiency picture, 10 mg zinc sulfate was administered parenterally on a daily basis. The deficiency picture improved markedly over a week's period, and serum zinc and alkaline phosphatase levels returned to normal. The importance of zinc balance control in patients under long-term parenteral nutrition and high fluid debit through GI fistulas is highlighted.
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PMID:[Zinc deficiency caused by postgastrectomy fistula with high flow in a patient undergoing prolonged parenteral nutrition]. 212 25

Secretion of tumor necrosis factor (TNF)/cachectin occurs during gram-negative bacterial sepsis in response to macrophage stimulation by lipopolysaccharide (endotoxin) and may play an early pivotal role in the subsequent host response. We sought to determine whether administration of: (1) murine monoclonal antibody directed against endotoxin, (2) steroids, or (3) antimicrobial agents would abrogate TNF production and whether the protective capacity would correlate with TNF levels in an experimental model of murine gram-negative bacterial sepsis. Mice were pretreated with anti-lipopolysaccharide monoclonal antibody, gentamicin sulfate, hydrocortisone, or saline and were then challenged with a lethal dose of intraperitoneal Salmonella minnesota. Murine serum TNF levels were measured by the L929 fibroblast cytotoxicity assay. Both gentamicin and anti-lipopolysaccharide monoclonal antibody significantly enhanced survival, and TNF activity at 1.5 and 3 hours was significantly suppressed in animals receiving these agents compared with animals that received either steroids or saline. We conclude that agents such as gentamicin, which inhibits bacterial replication, or monoclonal antibodies, which may neutralize lipopolysaccharide, indeed enhance survival, and survival was correlated with a significant reduction in circulating TNF during the early stages of infection.
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PMID:Decreased tumor necrosis factor production during the initial stages of infection correlates with survival during murine gram-negative sepsis. 229 80


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