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V Gross

Publications and source records attributed to V Gross.

At least 145 records · Page 8Linked to original sources

Elevation of serum interleukin-6 concentration precedes acute-phase response and reflects severity in acute pancreatitis.

Experimental studies have shown that interleukin-6 induces all major acute-phase proteins in the liver, including C-reactive protein. In 50 patients with acute pancreatitis, the serum concentrations of interleukin-6 and C-reactive protein were determined daily during the first week of hospitalization. Patients were divided into three groups according to clinical criteria: mild pancreatitis (less than or equal to 1 complication; n = 25), severe pancreatitis (greater than or equal to 2 complications; n = 15), and lethal outcome (n = 10). Patients with mild disease showed initially slightly elevated levels of interleukin-6 (22.0 +/- 9.8 U/mL) that decreased to low levels within 4 days (5.0 +/- 1.0 U/mL). In patients with severe pancreatitis, serum concentrations of interleukin-6 were initially clearly elevated (35.0 +/- 7.5 U/mL) and remained slightly elevated until day 7 (13.0 +/- 2.0 U/mL). Patients with lethal outcome had markedly elevated initial interleukin-6 concentrations (61.0 +/- 15.0 U/mL) that decreased but were still elevated at day 7 (26.0 +/- 2.5 U/mL). In all three groups, C-reactive protein concentrations followed the course of interleukin-6 concentrations by 1 day. There was a positive correlation between maximal interleukin 6 concentrations and maximal increases in the serum concentrations of C-reactive protein (r = 0.66). At days 1 and 2, increased (greater than 15 U/mL) interleukin-6 concentrations (positive predictive value, 91%; negative predictive value, 82%) predicted a severe or lethal course of the disease more accurately than elevated [greater than 0.10 g/L (greater than 10 mg/dL)] C-reactive protein concentrations (positive predictive value, 67%; negative predictive value, 79%). In conclusion, elevated serum concentrations of interleukin-6 followed by increased levels of C-reactive protein reflect the severity of acute pancreatitis.

Acute Disease↗

Activation of monocytes during inflammatory bowel disease.

Inflammatory bowel diseases lead to a systemic acute-phase response. Monocyte activation plays a central role during systemic acute-phase response via secretion of inflammatory cytokines. We determined the activation of peripheral-blood monocytes in patients with inflammatory bowel diseases by measuring their interleukin-6 (IL-6) secretion. Blood was obtained from patients with active Crohn's disease before treatment [mean Crohn's disease activity index (CDAI) = 332 +/- 34] and from patients after treatment with prednisolone (mean CDAI index = 139 +/- 20). The mean serum IL-6 levels measured by a hybridoma growth assay (B9) were 23 +/- 4 U/ml before therapy and fell to 16 +/- 3 U/ml after treatment with prednisolone. Healthy persons and patients with inactive Crohn's disease usually had serum IL-6 levels below the detection limit of 4 U/ml. An ex vivo whole-blood system was used to measure IL-6 secretion by peripheral-blood monocytes with and without stimulation. Spontaneous IL-6 secretion in this system was about 9 U/ml in patients with Crohn's disease and below the detection limit of 4 U/ml in healthy controls. Moderate stimulation of blood cells [100 pg/ml lipopolysaccharide (LPS)] from patients with active Crohn's disease before and after treatment led to mean IL-6 concentrations of 1,160 +/- 514 and 131 +/- 54 U/ml, respectively. Maximal stimulation of peripheral blood before and after therapy by LPS (100 ng/ml) led to mean IL-6 concentrations of 5,570 +/- 1,660 and 6,220 +/- 1,630 U/ml, respectively. Thus, administration of glucocorticoids led to a rapid down-regulation of IL-6 synthesis by peripheral-blood monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗

Hepatocyte specific long lasting inhibition of protein N-glycosylation by D-galactosamine.

The effect of D-galactosamine on protein N-glycosylation was studied in rat hepatocyte primary cultures for alpha 1-antitrypsin (three complex type oligosaccharide chains) and alpha 1-acid glycoprotein (six complex type oligosaccharide chains). D-Galactosamine at a concentration of 4 mM inhibited partially de novo N-glycosylation leading to the formation of alpha 1-antitrypsin lacking one to two and of alpha 1-acid glycoprotein lacking one to five of its carbohydrate side chains. In addition D-galactosamine interfered with oligosaccharide processing, leading to the formation of some carbohydrate side chains remaining in an endoglucosaminidase H sensitive, i.e., not completely processed, form. D-Galactosamine impaired the secretion of alpha 1-antitrypsin and of alpha 1-acid glycoprotein but did not inhibit the secretion of the unglycosylated albumin. The inhibitory effect of D-galactosamine on de novo glycosylation as well as on oligosaccharide processing lasted for at least 24 h after it had been removed from the cells. D-Galactosamine impaired the glycosylation of alpha 1-antitrypsin only in hepatocytes, but not in human monocytes. Furthermore, D-galactosamine did not impair the N- and O-glycosylation of interleukin-6 in human monocytes and in MRC 5 fibroblasts. The results indicate that the effect of D-galactosamine on protein glycosylation is restricted to D-galactosamine metabolizing hepatocytes and is not exerted by the drug itself but by its metabolites.

Acetylglucosaminidase↗

[Colonic carcinoma localized in the chest in enterothorax due to congenital diaphragmatic hernia].

A 51-year-old man with congenital diaphragmatic hernia and enterothorax was found to have persisting leucocytosis (25,000/microliters), diarrhoea and weight loss (20 kg). Computed tomography (CT) revealed intrahepatic space-occupying lesions. CT-directed needle biopsy demonstrated adenocarcinoma metastases. Colon contrast enema was ambiguous. Since no primary tumour had been found, ambulatory treatment with 5-fluorouracil was started. After initial improvement diarrhoea and obstipation alternated so that the patient finally gave permission for coloscopy to which he had not consented at first. It revealed a carcinoma of the colon located in the thorax about 10 cm oral to the left colonic flexure. Progressive ileus necessitated an ileodescendostomy for palliation. The patient died three months later while on symptomatic treatment.

Adenocarcinoma↗

Fate of interleukin-6 in the rat. Involvement of skin in its catabolism.

Iodinated recombinant human interleukin-6 (125I-rhIL-6) was intravenously injected into rats and its fate was studied during 24 h. Between 10-20 min after a single-dose injection, 125I-rhIL-6 accumulated in liver as previously reported [Castell et al. (1988) Eur. J. Biochem. 177, 357-361]. After 1 h, the radioactivity disappeared from the liver and accumulated in skin, reaching 35% of injected 125I-rhIL-6 5-8 h after injection. No comparable accumulation of radioactivity was found in skin when [125I]iodide or rat serum 125I-albumin was administered. Finally the radioactivity was detected as [125I]iodide in urine. Autoradiographic analysis of skin sections 5 h after 125I-rhIL-6 injection showed radioactivity in the interstitium. When the experiments were carried out with [35S]rhIL-6, essentially the same results were obtained: a decrease in radioactivity in the liver after 20 min, and a substantial increase in skin 7 h after injection. In vitro experiments showed that 125I-rhIL-6 is degraded by rat and human fibroblasts, whereas no degradation was observed with rat hepatoma cells (Fao) or human hepatocytes. These observations suggest the involvement of skin in the catabolism of IL-6.

Animals↗

[Clinical relevance of sonographic findings of the gastrointestinal system].

Each abnormal sonographic finding in the gastrointestinal tract requires further evaluation including other diagnostic means, since differentiation of abdominal diseases is not possible by sonography alone. The pathologic finding of a stomach-cocarde is suspicious for a malignoma. Sonographic control is useful in patients with chronic inflammatory diseases of the intestinal tract, since intestinal as well as extraintestinal complications determining further treatment can be anticipated.

Colorectal Neoplasms↗

Microheterogeneity of human interleukin 6 synthesized by transfected NIH/3T3 cells: comparison with human monocytes, fibroblasts and endothelial cells.

A cDNA containing the entire coding region of human interleukin 6 (IL 6) was stably expressed in murine NIH/3T3 fibroblasts using a bovine papilloma virus-based expression vector with a metallothionein promoter. Expression of IL 6 in transfected cells was highly inducible by heavy metals like cadmium as measured at mRNA and protein levels. Cadmium-stimulated transfected NIH/3T3 cells synthesized and exported biologically active IL 6 (1.7 x 10(4) U/10(6) cells/24 h). IL 6 from the culture medium of transfected NIH/3T3 cells exhibited at least eight bands on Western blots after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that human IL 6 expressed in NIH/3T3 cells shows a complex glycosylation pattern. Using glycosidases and the N-glycosylation inhibitor tunicamycin it was possible to discriminate between five species carrying N-linked carbohydrate side chains and two species carrying only O-linked side chains. In addition, a substantial amount of unglycosylated IL 5 was observed. IL 6 from transfected NIH/3T3 cells differed markedly in its glycosylation pattern from those of stimulated human monocytes, fibroblasts and endothelial cells.

Animals↗

Granulocyte elastase in assessment of severity of acute pancreatitis. Comparison with acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and protease inhibitor alpha 2-macroglobulin.

Complexes of granulocyte elastase and alpha 1-antitrypsin are markers for granulocyte activation. In 75 patients with acute pancreatitis these complexes were immunologically determined daily in plasma during the first week of hospitalization. Patients were classified into three groups: mild pancreatitis (I, less than or equal to 1 complication, N = 34), severe pancreatitis (II, greater than or equal to 2 complications, N = 29), lethal outcome (III, N = 12). Initially, granulocyte elastase (mean +/- SEM) was lower in group I (348 +/- 39 micrograms/liter) as compared to groups II (897 +/- 183 micrograms/l) and III (799 +/- 244 micrograms/liter), P less than 0.001 for I vs II + III. Initial elastase concentrations greater than 400 micrograms/liter were consistent with a severe or fatal course of the disease but did not distinguish between severe and lethal pancreatitis. In patients with mild or severe disease, mean elastase concentrations decreased continuously during the following days (197 +/- 15 micrograms/liter in mild cases, 325 +/- 30 micrograms/liter in severe cases at day 7). In patients with lethal disease, however, mean elastase concentrations even increased at day 2 and remained higher than 700 micrograms/liter during the observation period. At days 1 and 2 the predictive value for severe or lethal disease of raised (greater than 400 micrograms/liter) elastase concentrations [positive predictive value (PPV) 82%, negative predictive value (NPV) 81%] was better than that of elevated (greater than 100 mg/liter) C-reactive protein (PPV 73%, NPV 73%), elevated (greater than 4.0 g/liter) alpha 1-antitrypsin (PPV 59%, NPV 50%), or decreased (less than 1.5 g/liter) alpha 2-macroglobulin (PPV 82%, NPV 67%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease.

Sera of 64 patients with chronic inflammatory bowel disease (IBD) were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) using an indirect immunofluorescence technique on ethanol-fixed human neutrophil granulocytes. 20 of 34 sera (59%) from patients with ulcerative colitis (UC) produced a fine-granular and perinuclear ANCA staining pattern (p-ANCA) clearly different from the typical diffuse and granular cytoplasmic ANCA fluorescence (c-ANCA, synonym ACPA) seen in active Wegener's granulomatosis (WG). The majority of the 20 p-ANCA positive UC patients had a high inflammatory disease activity. Among the 14 p-ANCA negative UC patients nine were without steroids; five of them had active disease, two were inactive and two had previously undergone colectomy. The remaining five patients still had active disease but received steroids for more than 4 weeks. Only 3 of the 30 sera from patients with Crohn's disease (CD) showed positive p-ANCA reactions. To narrow the specificity of the p-ANCA reaction all 64 sera were tested by ELISA for antibodies against anti-proteinase-3 (WG specific) and on HEp-2 cells for antinuclear (ANA) and anticytoplasmic antibodies. Ten p-ANCA positive UC sera were also tested in a myeloperoxidase ELISA. Only one UC serum reacted positively in the proteinase-3-ELISA and another one produced a weakly positive anti-nucleolar ANA fluorescence on HEp-2 cells. None of the tested sera reacted with myeloperoxidase suggesting that the p-ANCA staining pattern of granulocytes is not restricted to anti-myeloperoxidase antibodies as reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biosynthesis and secretion of M- and Z-type alpha 1-proteinase inhibitor by human monocytes. Effect of inhibitors of glycosylation and of oligosaccharide processing on secretion and function.

The biosynthesis and secretion of M-type and Z-type alpha 1-antitrypsin was studied in human monocytes. In monocytes of PiMM individuals alpha 1-antitrypsin represented 0.08% of the newly synthesized proteins and 0.44% of the secreted proteins. Two molecular forms of alpha 1-antitrypsin could be identified: a 51-kDa intracellular form, susceptible to endoglucosaminidase H, thus representing the high-mannose type precursor form and a 56-kDa form resistant to endoglucosaminidase H which was secreted into the medium. Inhibition of de novo glycosylation by tunicamycin impaired the secretion of M-type alpha 1-antitrypsin by about 75% whereas inhibition of oligosaccharide processing by the mannosidase II inhibitor swainsonine did not alter the secretion of M-type alpha 1-antitrypsin. alpha 1-Antitrypsin secreted by human monocytes was functionally active as measured by complex formation with porcine pancreatic elastase. Even unglycosylated alpha 1-antitrypsin secreted by human monocytes treated with tunicamycin formed a complex with elastase. In monocytes of PiZZ individuals the secretion of alpha 1-antitrypsin was decreased. 72% of newly synthesized M-type alpha 1-antitrypsin, but only 35% of newly synthesized Z-type alpha 1-antitrypsin were secreted during a labeling period of 3 h with [35S]methionine. The 51-kDa form of Z-type alpha 1-antitrypsin accumulated intracellularly, whereas the 56-kDa form was secreted. Inhibition of oligosaccharide processing by swainsonine did not alter the decreased secretion of Z-type alpha 1-antitrypsin, whereas inhibition of de novo glycosylation by tunicamycin blocked the secretion of Z-type alpha 1-antitrypsin completely.

Alkaloids↗

Erythrocyte sodium transport and renal sodium excretion after saline loading in young and adult spontaneously hypertensive (SHR) and normotensive (WKY) rats.

Adult SHR aged 19-21 weeks, subjected to osmotic diuresis, responded to an intravenous 1.8% saline loading (15 ml/kg b.w.) with greater sodium excretion than age-matched WKY. Young (6-7 weeks old) SHR and WKY also responded to saline loading with an increased sodium excretion but there were no differences in the relative changes of sodium excretion between young WKY and SHR. In adult WKY, saline loading induced a faster erythrocyte 22Na uptake as compared with adult SHR or young WKY. This suggests that volume and/or sodium loading increased sodium turnover of red cells only in adult WKY. The sodium transport differences found in erythrocytes of adult SHR and WKY could be caused by some membrane differences or could be due to different hormonal and nonhormonal response(s) to saline loading. If similar alterations would also occur in other tissues, they might be important for the sodium excretion pattern.

Animals↗

[The sodium excretion behavior of anesthetized and conscious spontaneously-hypertensive (SHR) and normotensive (WKY) rats].

Urethane-anesthetized and conscious, immobilized SHR subjected to osmotic diuresis, responded to intravenous saline loading with a larger natriuresis than WKY-rats due to an increased urine sodium concentration without differences in urine flow. Blood pressure and heart rate reactions after saline loading were qualitatively different in anesthetized and conscious rats. The magnitude of these changes was larger in WKY than in SHR in both experimental groups.

Anesthesia↗

Effect of the alpha-glucosidase inhibitor N-hydroxyethyl-1-deoxynojirimycin (Bay m 1099) on the biosynthesis of liver secretory glycoproteins.

The effect of the alpha-glucosidase inhibitor N-hydroxyethyl-1-deoxynojirimycin (Bay m 1099) on the glycosylation and secretion of alpha 1-antitrypsin (three complex type oligosaccharide chains) and of alpha 1-acid glycoprotein (six complex type oligosaccharide chains) was studied in rat hepatocyte primary cultures. In the presence of 4 mM Bay m 1099 the processing of high-mannose to complex type oligosaccharides was partially inhibited leading to the secretion of alpha 1-antitrypsin and alpha 1-acid glycoprotein carrying a mixture of both high-mannose and complex type oligosaccharides. The major part of alpha 1-antitrypsin secreted by Bay m 1099 treated cells still carried two complex type oligosaccharide chains, the majority of alpha 1-acid glycoprotein carried three to five. Despite its effects on protein glycosylation Bay m 1099 did not lead to pronounced changes in the synthesis or secretion of alpha 1-antitrypsin, alpha 1-acid glycoprotein or albumin. At concentrations of Bay m 1099 lower than 0.5 mM no inhibitory effect on oligosaccharide trimming could be observed. After removal of Bay m 1099 from hepatocytes its inhibitory effect on protein glycosylation was immediately reversible.

1-Deoxynojirimycin↗

O- and N-glycosylation lead to different molecular mass forms of human monocyte interleukin-6.

The biosynthesis and secretion of human interleukin-6 (IL-6) was studied in monocyte cultures stimulated with endotoxin. After labeling with [35S]methionine and immunoprecipitation with a specific antiserum one major (24 kDa) and four minor (27.5, 23.3, 22.5 and 21.8 kDa) molecular mass forms of IL-6 could be found in the cells and media. Incubation of monocyte media with sialidase and subsequently with endo-alpha-N-acetylgalactosaminidase, which cleaves Gal(beta 1-3)Gal-NAc from serine or threonine, led to the formation of only two forms of IL-6 with apparent molecular masses of 25 and 21.8 kDa. The latter had an electrophoretic mobility indistinguishable from that of 125I-labeled recombinant human IL-6. The results suggest that human monocyte IL-6 carries O-glycosidically bound carbohydrates with a Gal(beta 1-3)Gal-NAc core to which only sialic acid is bound. Differences in O-glycosylation are the major cause for the molecular heterogeneity of IL-6. A small part of IL-6 (27.5 kDa form) is in addition N-glycosylated. Incubation of monocytes with tunicamycin and 1-deoxymynnojirimycin and treatment of IL-6 with endoglucosaminidase H suggested that the 27.5 kDa form of IL-6 carries at least one N-linked complex-type oligosaccharide chain.

1-Deoxynojirimycin↗

Detection of biliary origin of acute pancreatitis. Comparison of laboratory tests, ultrasound, computed tomography, and ERCP.

Fifty consecutive patients with acute pancreatitis were assessed with respect to a biliary origin of the disease. Endoscopic retrograde cholangiopancreaticography, surgery, and autopsy were used to define biliary pancreatitis. Ultrasound, computed tomography, and several laboratory tests (SGOT, SGPT, alkaline phosphatase, and bilirubin) were analyzed for their ability to detect a biliary origin of the disease. Ultrasound and computed tomography could not reliably make the diagnosis in the 10 patients found to have biliary disease. Receiver-operator-characteristic curves revealed that none of the laboratory tests assessed had sufficient sensitivity and specificity to determine the diagnosis, although all tests showed higher mean values in biliary pancreatitis. SGPT gave the best discrimination (positive predictive value 53%, negative predictive value 94%, cut off 40 units/liter). Therefore, initial ERCP is suggested for a reliable diagnosis of biliary origin of acute pancreatitis.

Acute Disease↗

Relapsing pancreatitis as initial manifestation of cystic fibrosis in a young man without pulmonary disease.

In young adults with acute pancreatitis a wide etiologic spectrum has to be considered. Among the possible causes, cystic fibrosis is rare. Besides the typical clinical triad of pancreatic exocrine insufficiency, chronic obstructive pulmonary disease, and elevated sweat chloride levels, there is a wide spectrum of variants of the cystic fibrosis syndrome. Especially mild manifestations of the disease may, therefore, escape proper identification. Here we describe a young man who presented initially with recurrent acute pancreatitis without pulmonary disease and without a family history of cystic fibrosis, in whom the diagnosis of cystic fibrosis was established by slightly elevated sweat chloride levels and obstructive azoospermia. Five years after the first attack of pancreatitis the patient developed pancreatic exocrine insufficiency.

Adult↗