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)

There are three major surface-localized protein antigens of group B streptococci: c, R, and X. Their precise role in human immunity to group B streptococci has not been defined. Studies of the c protein suggested that type II strains possessing both trypsin-resistant and trypsin-sensitive components of the c protein were less easily killed in vitro and were more virulent in an infant rat model of infection as compared with type II strains that do not bear these proteins. The c protein components were immunogenic in mice and rabbits. Polyclonal rabbit antisera were protective in the infant rat model of bacteremia/sepsis and facilitated killing of type II strains bearing the c protein in an in vitro opsonophagocytic bacterial killing assay. The role of the IgA-binding capacity of the c protein in altering the interaction of group B streptococcal strains with host defenses remains undefined at this time.
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PMID:Surface-localized protein antigens of group B streptococci. 305 5

Better methods are needed to assess mast-cell activation in vivo and to distinguish the activation of mast cells from that of basophils. Tryptase, a neutral protease selectively concentrated in the secretory granules of human mast cells (but not basophils), is released by mast cells together with histamine and serves as a marker of mast-cell activation. In 17 patients with systemic mastocytosis, concentrations of tryptase in plasma were linearly related to those of histamine (P less than 0.01). Eleven of the 17 patients had tryptase levels of 4 to 88 ng per milliliter, indicating ongoing mast-cell activation. In each of six patients who experienced corresponding anaphylactic reactions after penicillin, aspirin, or melon ingestion, a wasp sting, exercise, or antilymphocyte globulin injection, tryptase levels in serum ranged from 9 to 75 ng per milliliter, indicating mast-cell activation during each of these events. In contrast, serum tryptase levels were less than 5 ng per milliliter in all patients presenting with myocardial disease (n = 8, 6 with hypotension) or sepsis (n = 6, 3 with hypotension) and in the controls (n = 20). One patient had a myocardial infarction after anaphylaxis in response to a wasp sting and an elevated tryptase level of 25 ng per milliliter. Thus, the plasma or serum tryptase level is a diagnostic correlate of mast-cell-related events.
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PMID:Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. 329 49

Complement fragments (C3, C3d, C5a), thromboxane B2 (TxB2), 6-keto-PGF1 alpha and immunoreactive trypsin (IRT) were measured in 98 patients at risk of developing the adult respiratory distress syndrome (ARDS): 53 multiple trauma, 28 abdominal surgery and 17 acute pancreatitis. Sixty-five of these patients developed ARDS: 30 multiple trauma, 19 abdominal surgery and 16 acute pancreatitis patients. Forty of the 65 ARDS patients and 9 out of the 33 non-ARDS patients died. Mean value of the C3d to C3 ratio was abnormal in both ARDS and non-ARDS patients. C5a-like activity was detected in 70 out of the 98 patients (49 ARDS and 22 non-ARDS patients). TxB2 abnormal values (greater than 100 pg . ml-1) were found in 70% of the patients, especially when sepsis occurred. No correlation could be made between abnormal 6-keto PGF1 alpha values and ARDS or sepsis. The mean peak IRT value was 675 micrograms . 1(-1) for ARDS patients and 274 micrograms . 1(-1) for non-ARDS patients (p less than 0.05). A firm correlation was also measured between IRT and sepsis (p less than 0.01). C5a-like activity was regularly detected soon after injury, while TxB2 and IRT tend to appear later in patients developing ARDS. Neither C3d/C3, nor C5a-like activity, nor TxB2, nor IRT are specific markers of ARDS, since they also appeared in severely ill patients who did not develop ARDS.
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PMID:Biochemical pathways of acute lung injury. 387 73

Thrombocytopenia without other hemostatic changes is the most common coagulopathy associated with sepsis. We studied pneumococcus (PNC)-induced hemostatic changes, including thrombocytopenia, in rabbits. Nonviable PNC or saline solution was injected into rabbits preinfused with chromium 51-labeled platelets or iodine 125-fibrinogen. Blood was serially obtained for determination of platelet counts, 51Cr activity or 125I activity, and fibrinogen and fibrin degradation products. Lung, liver, and spleen tissues were counted for 51Cr or 125I activities per gram of wet tissue. PNC-challenged animals displayed profound thrombocytopenia from 0.5 to 48 hours with the mean nadir (-80% relative to the baseline) at 3 hours and a significantly (P less than 0.025) shortened 51Cr-platelet survival of 1.45 +/- 0.71 days vs. 2.72 +/- 1.09 days for saline-injected controls. Circulating fibrinogen level increased, whereas 125I-fibrinogen survival was unchanged (2.6 +/- 0.5 days in PNC-challenged vs. 2.8 +/- 1.0 days in saline-injected). No increased tissue deposition of either 51Cr-labeled platelets or 125I-fibrinogen was found. Rabbits infused with either serum, plasma, or saline solution after each was incubated with PNC all developed significant thrombocytopenia of less than 1 hour duration with maximal mean decreases relative to the baseline of -76% (P less than 0.001), -65% (P less than 0.0005), and -84% (P less than 0.0005), respectively. Inactivation of serum or plasma complement before PNC incubation or heat treatment after PNC incubation in serum or saline solution did not alter the thrombocytopenia. The thrombocytopenia-promoting activity was also trypsin resistant, did not require the presence of serum, plasma, or PNC capsular polysaccharide for its in vitro generation, and had a mol wt of 100,000 to 300,000. Therefore, PNC-induced thrombocytopenia, in the absence of other hemostatic changes, may be explained on the basis of the direct action of a PNC-derived substance(s) on circulating platelets.
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PMID:Pneumococcus-induced thrombocytopenia in rabbits. 403 31

Leukocytes can generate procoagulant (tissue factor) activity when incubated with endotoxin. These studies were undertaken to determine whether platelets could influence the procoagulant activity generated by leukocytes. Intact or disrupted platelets (rabbit or human) enhanced the clot-promoting properties of rabbit leukocytes. The enhancing effect of human platelets on human leukocytes required the presence of human serum (devoid of factor VII and X activities). When platelets were incubated with endotoxin in the absence of leukocytes, no increase in their clot-promoting properties was discernible. However, a mixture of platelets, leukocytes, and endotoxin generated procoagulant activity which appeared rapidly and was fivefold greater than that produced by leukocytes incubated with endotoxin alone. The enhancement produced by platelets was even more pronounced if homogenates were used. The platelet effect was examined in more detail by the substitution of membranes, granules, and the "soluble" fraction for whole platelets in the test system. The stimulating activity was localized to the particulate fractions, i.e., membranes and granules. Prior treatment of platelet membranes with phospholipase C or gangliosides or by extraction of lipid resulted in loss of enhancing activity, whereas no inhibition was observed after exposure to neuraminidase or trypsin. It is proposed that platelets contribute a membrane lipoprotein surface which enhances the procoagulant activity generated by leukocytes in the presence of endotoxin. This mechanism may be involved in some of the clinical and pathologic manifestations of gram-negative sepsis with disseminated intravascular coagulation.
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PMID:The stimulatory effect of platelets and platelet membranes on the procoagulant activity of leukocytes. 461 59

Pancreatic sepsis in acute pancreatitis is the most lethal complication of the disease. This study was done to create a rational basis for the choice of antibiotics used in the treatment of severe acute pancreatitis. We postulated that, unless the antibiotics were present in therapeutic concentrations in the pancreatic tissue during pancreatitis, their use was of no value. Six mongrel dogs were used to test each antibiotic, each dog acting as its own control. The doses were based on the weight of the dogs: 15.0 milligrams per kilogram of clindamycin; 50.0 milligrams per kilogram of chloramphenicol; 10.0 milligrams per kilogram of metronidazole; 5.0 milligrams per kilogram of gentamicin; 12.5 milligrams per kilogram of cefazolin, and 50.0 milligrams per kilogram of ampicillin. Baseline serum and pancreatic tissue levels were obtained after intravenous injection of the antibiotics. Bile-trypsin hemorrhagic pancreatitis was induced one week later, and the serum and pancreatic tissue level antibiotics were measured again. The results showed significant differences in bioactive levels of antibiotics between blood and the pancreas. Ampicillin, gentamicin and cefazolin reached therapeutic blood levels, but did not achieve a parallel therapeutic level in the normal pancreatic tissue or during pancreatitis. Only three of the antibiotics tested, clindamycin, metronidazole and chloramphenicol, achieved therapeutic tissue penetrance in the normal and inflamed pancreas. After 1982, based on these results, clindamycin became our prophylactic antibiotic of choice in instances of acute severe pancreatitis. This resulted in the eradication of Bacteroides as a cause of pancreatic sepsis between 1980 and 1985. In 1993, our recommendation is to use a broad-spectrum gram-negative and gram-positive antibiotic with good penetration of the pancreatic tissue, such as cefotaxime or imipenem.
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PMID:Antibiotics bioavailability in acute experimental pancreatitis. 816 85

Group B streptococci (GBS) are the major cause of neonatal pneumonia, sepsis, and meningitis. Steps considered to be important in the pathogenesis of this infection include colonization of the rectum and vagina of the mother, aspiration of GBS into the fetal lung during or just prior to delivery, and invasion of GBS into pulmonary epithelial cells. We have previously demonstrated that GBS can invade pulmonary epithelial cells both in vivo and in vitro. Adherence of GBS to epithelial cells may play an important role in colonization of the rectum and vagina and constitute a first step in invasion of pulmonary epithelial cells. Because GBS can both adhere to and invade epithelial cells, we have developed two assays for GBS adherence which measure cell surface and not intracellular bacteria. Using these assays, we were able to demonstrate specific adherence of GBS to pulmonary epithelial cells. Adherence levels were similar at 4 and 37 degrees C and for log- and stationary-phase bacteria. Physiologic conditions vary considerably between the rectum, vagina, and lung, and a range of conditions was therefore tested. Adherence was enhanced in hypotonic solutions, while magnesium and calcium had no effect on adherence at physiologic concentrations. In comparison with adherence at neutral pH, adherence was increased 6- to 20-fold at pH 4, which is the normal vaginal pH. Neither capsular polysaccharide nor lipoteichoic acid was important for adherence in these assays. Treatment of GBS with trypsin decreased their adherence by more than 75%, indicating that surface proteins play an important role.
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PMID:Adherence of group B streptococci to cultured epithelial cells: roles of environmental factors and bacterial surface components. 818 70

Neonatal infections caused by Group B streptococci (GBS) may lead to pneumonia, sepsis, or meningitis indicating that GBS are able to invade tissues and enter the bloodstream from infected sites. In this study, we showed that the tissue invasiveness of GBS may be related to their ability to invade epithelial cells in vitro by correlating the degree of GBS invasion of cultured human respiratory epithelial cells with the clinical source of isolation. Among 77 isolates tested, those from invasive infections of neonates and adults were significantly (P < 0.001) more invasive than those from vaginal carriers and colonised neonates without clinical symptoms. Furthermore, isolates from the blood were more invasive (P < 0.05) than those from other sites. GBS invasion seemed to be mediated by bacterial surface proteins since trypsin treatments of streptococci significantly reduced their invasion into epithelial cells and invasiveness was not limited to a certain capsular serotype. The two major GBS surface protein antigens c and R, however, were not involved in the invasion process. These results indicate that in vitro invasion of cultured human cells reflects the in vivo invasive property of GBS and involves bacterial surface components different from known virulence factors such as capsule or protein antigens c and R.
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PMID:Correlation of epithelial cell invasiveness of group B streptococci with clinical source of isolation. 857 38

To evaluate the effects of sepsis on the exocrine pancreas, we studied (1) serum amylase levels, pancreatic water and trypsin content; (2) pancreatic histological changes; (3) pancreatic subcellular distribution of lysosomal enzyme in the acinar cells; and (4) protective effects of a new synthetic protease inhibitor, FUT-187 against the pancreatic injuries in sepsis of rats induced by cecal ligation and puncture. Elevated serum amylase levels, increased pancreatic water and trypsin content, were observed in rats with fecal peritonitis induced by cecal ligation and puncture. Subcellular redistribution of lysosomal enzyme, cathepsin B, activity from the lysosomal fraction to the zymogen fraction was also observed. FUT-187 was found to significantly prevent these pancreatic injuries induced by fecal peritonitis. These results indicate that the exocrine pancreas is injured during sepsis, and that some unknown protease activities, which are present during sepsis and are susceptible to the inhibition of FUT-187, seem to play an important role in the pathogenesis of the pancreatic injuries induced by fecal peritonitis. These results also indicate the important pathological role of lysosomal enzymes in the pancreatic injuries induced by sepsis.
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PMID:Pancreatic injuries in rats with fecal peritonitis: protective effect of a new synthetic protease inhibitor, sepinostat mesilate (FUT-187). 865 99

alpha2-HS glycoprotein is a major protein of human plasma whose function is still obscure. A proteolytically processed form of alpha2-HS glycoprotein lacking a segment of 40 amino acid residues bridging its heavy and light chain portions ("connecting peptide") has been described suggesting that this peptide is released by post-translational processing to fulfill biological role(s) of alpha2-HS glycoprotein. To test this hypothesis we investigated how the connecting peptide is released from the parental molecule by limited proteolysis. We developed monoclonal antibodies to various portions of the connecting peptide and its NH2-terminal flanking region which cross-react with the native alpha2-HS glycoprotein. Purified alpha2-HS glycoprotein from human plasma was subjected to limited proteolysis by proteinases including trypsin, chymotrypsin, elastase plasmin, kallikrein, thrombin, and renin. Immunoprint analysis of the proteolytic digests indicated that alpha2-HS glycoprotein is readily cleaved in its connecting peptide region. NH2-terminal amino sequence analysis of the generated fragments demonstrated that a single proteinase, chymotrypsin, cleaves the critical Leu-Leu bond flanking the NH2-terminal portion of the connecting peptide region. Most but not all of the other proteinase cleavage sites map to a short stretch of 9 residues located in the center portion of the connecting peptide region. Immunoprint analysis of plasma samples from patients with sepsis demonstrate that the connecting peptide region is cleaved under pathological conditions. Our results indicate that the connecting peptide and/or fragments thereof are readily releasable from alpha2-HS glycoprotein in vitro and in vivo.
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PMID:Limited proteolysis of human alpha2-HS glycoprotein/fetuin. Evidence that a chymotryptic activity can release the connecting peptide. 894 Jan 98


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