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

The erythrocyte receptors for S-fimbriated Escherichia coli, which causes sepsis and meningitis in newborn infants, were investigated. Neuraminidase and trypsin treatments of erythrocytes abolished the hemagglutination ability of the bacteria. To identify the receptor glycoproteins, we separated erythrocyte membrane proteins by gel electrophoresis, blotted them to nitrocellulose, and incubated them with 125I-labeled bacteria. The only bacterium-binding bands identified corresponded to glycophorin A dimer and monomer, and the binding was abolished by neuraminidase treatment of the blot. Radiolabeled bacteria also bound to purified glycophorin A adsorbed to polyvinyl chloride microwells, and the binding was inhibited by other sialoglycoproteins and isolated sialyloligosaccharides containing the NeuAc alpha 2-3Gal sequence. Oligosaccharides which contain the NeuAc alpha 2-3Gal beta 1-3GalNAc and NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-6)GalNAc sequence and which are identical to the O-linked saccharides of glycophorin A were twofold more effective inhibitors of binding than were other oligosaccharides containing the NeuAc alpha 2-3Gal sequence. The replacement of sialic acid in asialoerythrocytes with a purified Gal beta 1-3GalNAc alpha 2-3 sialyltransferase, which forms the O-linked NeuAc alpha 2-3Gal beta 1-3GalNAc sequence in asialoglycophorins, restored bacterial hemagglutination. These results indicated that the major erythrocyte receptor for S-fimbriated E. coli is the NeuAc alpha 2-3Gal beta 1-3GalNAc sequence of the O-linked oligosaccharide chains of glycophorin A.
 ...
PMID:Identification of the O-linked sialyloligosaccharides of glycophorin A as the erythrocyte receptors for S-fimbriated Escherichia coli. 287 51

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.
 ...
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.
 ...
PMID:Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. 329 49

Staphylococcus aureus is known to produce three very active extracellular proteinases. One of these enzymes, a cysteine proteinase, after purification to homogeneity was found to degrade insoluble bovine lung elastin at a rate comparable to human neutrophil elastase. This enzyme had no detectable activity against a range of synthetic substrates normally utilized by elastase, chymotrypsin, or trypsin-like proteinases. However, it did hydrolyze the synthetic substrate carbobenzoxy-phenylalanyl-leucyl-glutamyl-p-nitroanilide (Km = 0.5 mM, kcat = 0.16 s-1). The proteolytic activity of the cysteine proteinase was rapidly and efficiently inhibited by alpha 2-macroglobulin and also by the cysteine-specific inhibitor rat T-kininogen (Ki = 5.2 X 10(-7) M). Human kininogens, however, did not inhibit. Human plasma apparently contains other inhibitors of this enzyme, since plasma depleted of alpha 2-macroglobulin retained significant inhibitory capacity. The elastolytic activity of this S. aureus proteinase and its lack of control by human kininogens or cystatin C may explain some of the connective tissue destruction seen in bacterial infections due to this and related organisms such as may occur in septicemia, septic arthritis, and otitis.
 ...
PMID:Degradation of elastin by a cysteine proteinase from Staphylococcus aureus. 342 37

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.
 ...
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.
 ...
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.
 ...
PMID:The stimulatory effect of platelets and platelet membranes on the procoagulant activity of leukocytes. 461 59

alpha 2-macroglobulin is probably the most important of the antiproteases in plasma. In this study, the relationships of plasma alpha 2-macroglobulin to the clinical features of acute pancreatitis as well as to plasma levels of other antiproteases, immunoglobulins, and immunoreactive trypsin, were investigated in 55 patients with acute pancreatitis. The mean level of alpha 2-macroglobulin in 395 plasma samples from the patients was 2.12 g/liter compared with 2.41 g/liter in 29 healthy subjects and 2.93 g/liter in 17 patients with septicemia. Plasma levels were lower in 12 patients with severe pancreatitis than in 43 with mild attacks, and the lowest levels in three fatal attacks were less than half the mean of the normal range. Lowest levels were recorded at a mean time of 3 days after admission in the patients with mild attacks, at 5 days after admission in the patients with severe attacks, and 9 days after admission in those with fatal attacks. In contrast, plasma levels of the alpha 1-proteinase inhibitor antichymotrypsin and C-reactive protein increased to above normal levels during the attack, significantly more so in severe compared with mild attacks. Plasma levels of IgA, IgG, and IgM remained within the normal range or were increased. In patients with severe pancreatitis, plasma levels of immunoreactive trypsin remained elevated for longer than in those with mild attacks although there was little initial difference in the levels. These data suggest that decreasing levels of alpha 2-macroglobulin during the course of acute pancreatitis are due to a specific mechanism and unrelated, for the most part, to any generalized effect of pancreatitis on protein synthesis. The formation of rapidly cleared complexes between alpha 2-macroglobulin and active proteases is the most tenable explanation for the depletion of plasma levels, but the clinical significance of the changes remains unclear.
 ...
PMID:Relation of alpha 2-macroglobulin and other antiproteases to the clinical features of acute pancreatitis. 619 93

A method was developed to study the adhesion of Streptococcus pneumoniae to human pharyngeal epithelial cells. Epithelial cells from healthy persons, pneumococcal strains from patients with otitis media, meningitis, or septicemia, and pneumococcal cells from the nasopharynx of healthy carriers were used. Adhesion was found to be influenced by changes in the bacterial incubation medium and growth phase, the concentration of bacteria and epithelial cells, the epithelial cell donor, the incubation time and temperature, and the pH and osmolarity of the incubation medium. Pretreatment of bacteria with heat, Formalin, or trypsin decreased adhesion. The highest adhesion was obtained when 10(9) bacteria cultivated for 18 h in streptococcus cultivation broth were added to 10(4) pharyngeal cells and incubated at 37 degrees C for 30 min. S. pneumoniae strains from patients with frequent episodes of otitis media and strains from healthy carriers had the highest adhesion values; septicemia and meningitis strains had the lowest. The capsular polysaccharide type did not determine the adhesive capacity of the strains, but otitis strains belonging to the capsular types often associated with otitis media adhered in high numbers. Adhesion may be important for pneumococci colonizing the nasopharynx or inducing otitis media.
 ...
PMID:Adhesion of Streptococcus pneumoniae to human pharyngeal epithelial cells in vitro: differences in adhesive capacity among strains isolated from subjects with otitis media, septicemia, or meningitis or from healthy carriers. 721 90

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.
 ...
PMID:Antibiotics bioavailability in acute experimental pancreatitis. 816 85


<< Previous 1 2 3 4 5 6 Next >>