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Biomedical subjects

V Gross

Publications and source records attributed to V Gross.

At least 127 records · Page 7Linked to original sources
PubMed1993

Regulation of interleukin-6 (IL-6) expression: evidence for a tissue-specific role of protein kinase C.

The regulation of IL-6 mRNA expression was studied in human blood monocytes and in the human epidermoid carcinoma cell line HEp-2. In human monocytes phorbol-12-myristate 13-acetate (PMA) did not induce IL-6 but it increased IL-1 beta and IL-8 mRNA levels. Furthermore, in monocytes, protein kinase C (PKC) activation by PMA even reduced IL-1-induced IL-6 mRNA, and IL-1-induced IL-6 synthesis was increased by the PKC inhibitor staurosporine. IL-6 synthesis in HEp-2 cells was induced by IL-1, PMA, and calcium ionophore A 23187 but not by dibutyryl-cAMP. PMA-, but not IL-1-induced IL-6 synthesis in HEp-2 cells was inhibited by staurosporine. PMA pretreatment of HEp-2 cells abolished PMA-induced IL-6 but the IL-1 effect was not reduced. These data indicate that IL-6 can be induced by a PKC-independent pathway in monocytes and HEp-2 cells. In monocytes PKC activation does not induce IL-6 and PMA interferes with the IL-1 effect. Transcription factors known to be involved with the regulation of IL-6 expression were studied by gel retardation assays. NF-IL-6 and AP-1 activity were constitutively expressed in monocytes and HEp-2 cells under conditions where IL-6 mRNA was not detectable and levels did not change in response to stimulation by IL-1 or PMA. In contrast, NF-kB was increased by both IL-1 and PMA, but only the effect of PMA, and not that of IL-1, was inhibited by staurosporine. In summary, these results show tissue-specific differences in the regulation of IL-6 expression. Induction of IL-6 in monocytes is PKC independent. In the epithelial cell line HEp-2 IL-6 is inducible by PKC as well as by a PKC-independent pathway.

Alkaloids↗
PubMed1993

PMN-elastase in assessment of patients with inflammatory bowel disease.

PMN-elastase is a proteinase released by activated neutrophils. PMN-elastase was determined in two independent populations with inflammatory bowel disease. In an unselected population of 70 consecutive patients with Crohn's disease and 24 patients with ulcerative colitis with different degrees of disease activity plasma PMN-elastase levels were statistically significantly higher in patients with active than in patients with inactive disease [Crohn's disease: 80.5 +/- 33.2 ng/ml vs 60.1 +/- 24.6 ng/ml (mean +/- SD), P = 0.0017; ulcerative colitis: 98.2 +/- 54.9 ng/ml vs 59.2 +/- 16.8 ng/ml, P = 0.026]. PMN-elastase levels in feces were also higher in patients with active Crohn's disease (23.6 +/- 15.3 ng/g vs 13.6 +/- 12.5 ng/g, P = 0.0021) and active ulcerative colitis (46.5 +/- 60.5 ng/g vs 20.2 +/- 25.0 ng/g, P = 0.46), but the difference reached significance only in Crohn's disease. Correlation of disease activity and PMN-elastase in individual patients showed a statistically significant correlation between plasma and fecal elastase concentrations and disease activity in ulcerative colitis (plasma: r = 0.72, P < 0.001; feces: r = 0.57, P = 0.002). In patients with Crohn's disease only plasma levels of PMN-elastase (r = 0.423, P < 0.001) but not fecal elastase concentrations (r = 0.0083, P = 0.485) correlated significantly with disease activity. Plasma PMN-elastase correlated weakly with fecal PMN-elastase levels in Crohn's disease (r = 0.431, P < 0.01) and in ulcerative colitis (r = 0.515, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Angiotensin-converting enzyme (ACE)-inhibition in cirrhosis. Pharmacokinetics and dynamics of the ACE-inhibitor cilazapril (Ro 31-2848).

The angiotensin-converting enzyme (ACE)-inhibitor, cilazapril, is converted to its active metabolite, cilazaprilat, by ester hydrolysis in the liver. The pharmacokinetics and pharmacodynamics of a single 1 mg oral dose of cilazapril were investigated in 10 healthy volunteers and in 9 cirrhotic patients with compensated cirrhosis and portal hypertension. A significantly increased mean plasma peak concentration (40.0 +/- 13.6 ng/ml vs. 25.5 +/- 7.9 ng/ml; p < 0.05) and a decreased apparent oral clearance (7.8 +/- 6.0 l/h vs. 16.4 +/- 5.4 l/h; p < 0.05) of cilazapril were found in cirrhotic patients compared to healthy volunteers. The plasma concentration of cilazaprilat declined in 2 phases. In both phases the plasma half-life was significantly longer in patients with cirrhosis (1st phase: 2.5 +/- 0.8 h vs. 1.7 +/- 0.6 h; p < 0.05; 2nd phase: 46.2 +/- 16.6 h vs. 28.8 +/- 4.7 h; p < 0.001). Consequently, cilazaprilat concentrations at 24 h were higher in patients than in volunteers (1.42 +/- 0.33 ng/ml vs. 0.87 +/- 0.14 ng/ml; p < 0.001). The predose activity of the ACE (26.3 +/- 7.3 U/l vs. 16.8 +/- 4.5 U/l; p < 0.005) and plasma renin activity (3.3 +/- 3.2 ng/ml/h vs. 1.4 +/- 1.0 ng/ml/h) were higher in patients than in volunteers. Maximum ACE-inhibition occurred at similar times in patients (2.7 h) and volunteers (2.3 h). Maximum ACE-inhibition was slightly higher in volunteers (94.6%) than in patients (90.6%). At later time points (> 24 h), however, ACE-inhibition was more pronounced in patients (at 72 h: 39.6 +/- 6.9% vs. 23.5 +/- 8.2%; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Inflammatory mediators and cytokines--new aspects of the pathophysiology and assessment of severity of acute pancreatitis?

Most attacks of acute pancreatitis are mild and self-limiting. In 10-20% of the cases, however, severe disease with multiple systemic complications develops. During the last few years it has been recognized that activated leukocytes have an important role in the multisystem involvement during acute pancreatitis. Activated leukocytes are thus a pathogenetic factor in the severity of the disease. Activation of polymorphonuclear granulocytes (PMNs) and of monocytes/macrophages is an early event during severe acute pancreatitis. Factors released by activated leukocytes therefore reflect the severity of the disease. Three independent studies have shown that released PMN-elastase is a reliable early prognostic marker that permits correct classification of 80-95% of the patients within the first 24-48 hours. Interleukin-6 (IL-6), mainly secreted by activated monocytes/macrophages, is also an early prognostic parameter (shown in one study), but is not superior to PMN-elastase. Leukocyte activation markers are more reliable than multiple scoring systems in the assessment of the severity of acute pancreatitis. Compared with PMN-elastase or IL-6, increased plasma concentrations of such acute-phase proteins as alpha-1-antitrypsin or CRP, and consumption of the protease inhibitor alpha-2-macroglobulin, are later events that can be detected only 1 to 4 days later. Comparison of the various inflammatory parameters suggests that PMN-elastase is the best early and reliable prognostic marker in acute pancreatitis. The reviewed data underscore the role of activated leukocytes in the pathogenesis of complicated acute pancreatitis.

Acute Disease↗
PubMed1992

[Interleukins].

Interleukins are polypeptide hormones which are primarily but not exclusively synthesized by cells of the immune system (monocytes/macrophages, T- and B-lymphocytes). Up to now 12 interleukins (IL-1 to IL-12) have been described. The central function of the interleukins is the orchestration of the different cells of the immune system during host defence against pathogens. Besides the regulated stimulation of the immune reaction against foreign antigens, interleukins are involved in the stimulation of unspecific inflammatory reactions and in the induction of the acute phase response.

B-Lymphocytes↗
PubMed1992

Inhibition of protein N-glycosylation by 2-deoxy-2-fluoro-D-galactose.

The effects of 2-deoxy-2-fluoro-D-galactose (dGalF) on N- and O-glycosylation of proteins was studied in rat hepatocyte primary cultures and in human monocytes. In hepatocytes, dGalF at concentrations of 1 mM or higher completely inhibited N-glycosylation of alpha 1-antitrypsin and alpha 1-acid glycoprotein, whereas 4 mM-2-deoxy-D-galactose (dGal) only slightly impaired N-glycosylation. In monocytes, 1 mM- or 4 mM-dGalF blocked N-glycosylation of alpha 1-antitrypsin and of interleukin-6, while O-glycosylation of interleukin-6 remained unaffected. In monocytes, dGal had no effect on protein N-glycosylation. Addition of uridine effectively prevented the UTP deficiency induced by dGalF, but had no effect on the inhibition of protein N-glycosylation by dGalF. Using 19F-n.m.r. spectroscopy, 2-deoxy-2-fluoro-D-galactose 1-phosphate (dGalF-1-P), UDP-dGalF and UDP-dGlcF could be identified as the major metabolites of dGalF in hepatocytes as well as in monocytes. In conclusion, compared with dGal, dGalF is a more efficient inhibitor of protein N-glycosylation. The effect is not caused by the depletion of UTP induced by dGalF, but rather by metabolites of dGalF. dGalF is metabolized not only in hepatocytes but also in peripheral blood monocytes, which can be used for ex vivo studies of disturbances in D-galactose metabolism.

Animals↗
PubMed1992

High concentrations of soluble tumor necrosis factor receptors in ascites.

Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy-related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor-alpha concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy-related (p55: 26.0 +/- 8.6 ng/ml; p75: 20.5 +/- 17.4 ng/ml; mean +/- S.D.) and infected ascites (p55: 25.1 +/- 10.9 ng/ml, p75: 22.6 +/- 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 +/- 4.4 ng/ml; p75: 6.0 +/- 2.6 ng/ml). Patients with infected or malignancy-related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 +/- 15.2 ng/ml to 10.7 +/- 1.9 ng/ml and from 20.2 +/- 14.4 ng/ml to 7.5 +/- 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Epidermal growth factor stimulates Ca2+ uptake of human erythrocytes.

To examine the functional significance of epidermal growth factor (EGF) binding sites present on the human erythrocyte membrane [Engelmann et al. (1992) Am J Hematol 39:239-241], the effect of EGF on 45Ca2+ uptake and on 22Na+ efflux from these cells has been studied. In all cases media contained 1.25 mM Ca2+, whereas Na+ and K+ were varied. In 140 mM Na+/5 mM K+ medium EGF (250 ng/ml) stimulated 45Ca2+ uptake by 50%-90% in quin-2-loaded cells, and by up to threefold in untreated cells. Increasing extracellular K+ up to 75 mM at the expense of extracellular Na2+ stimulated the EGF-induced 45Ca2+ uptake by about twofold compared to 145 mM Na+ medium both in quin-2-loaded and in untreated cells. In 145 mM K+ medium, however, no EGF-induced 45Ca2+ uptake was detectable in quin-2-loaded cells, while in untreated cells Ca2+ entry was stimulated twofold by EGF. After increasing intracellular Na+ from 6 mmol/l cells to 18 mmol/l cells in untreated cells suspended in 145 mM K+ medium, 45Ca2+ uptake induced by EGF gradually increased. In contrast, in 140 mM Na+/5 mM K+ as well as in 70 mM Na+/75 mM K+ medium, 45Ca2+ uptake accelerated by EGF was largely unaffected by a modified red cell Na+ content. When 22Na-loaded untreated red cells were suspended in 145 mM K+ medium EGF stimulated red cell 22Na+ efflux by more than threefold. In 140 mM Na+/5 mM K+ as well as in 70 mM Na+/75 mM K+ medium, no 22Na+ efflux induced by the growth factor was evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoquinolines↗
PubMed1992

Evidence for continuous stimulation of interleukin-6 production in Crohn's disease.

Increased serum concentrations of acute-phase proteins can be found in active inflammatory bowel disease. Because interleukin 6 (IL-6) is one of the main mediators of acute-phase protein synthesis by the liver, the serum concentrations of IL-6 and the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and alpha 1-acid glycoprotein were determined in 70 patients with Crohn's disease (CD) and 23 patients with ulcerative colitis (UC). Disease activities were determined by established clinical activity indices. Serum IL-6 concentrations were significantly (P less than 0.005) increased in patients with CD (mean +/- SEM, 6.8 +/- 0.9 U/mL) compared with patients with UC (mean, less than 4 U/mL) and healthy controls (mean, less than 4 U/mL). Of patients with CD, 68.5% had serum IL-6 concentrations of greater than or equal to 4 U/mL, compared with 21.7% of patients with UC and 0% of healthy controls. There was a tendency toward higher serum IL-6 concentrations in patients with active CD than in patients with inactive disease. However, these differences were not statistically significant. There was no correlation between IL-6 serum concentrations and clinical activity indices, possibly because of the short circulatory lifetime and rapid hepatic clearance of IL-6 from the portal venous blood. In contrast to serum IL-6, acute-phase proteins, which have a longer circulatory lifetime, were significantly correlated with clinical activity indices. Only the follow-up of individual patients with initially highly active disease showed a further increase in IL-6 levels during acute exacerbations of the inflammatory process. The results show that most patients with even moderately active CD have significantly increased serum concentrations of IL-6, most probably reflecting a continuous stimulation of IL-6-producing cells.

Acute Disease↗
PubMed1992

Evidence for the production of high amounts of interleukin-6 in the peritoneal cavity of patients with ascites.

The ascites and serum concentrations of interleukin-6 (IL-6) and interleukin-1 (IL-1) were determined in 21 patients with hepatic ascites and in 9 patients with malignancy-associated ascites. There was no evidence for bacterial peritonitis in any patients. All ascites samples contained high amounts of immunoreactive IL-6 [hepatic ascites 1730 +/- 2130 pg/ml (mean +/- SD), 1160 pg/ml (median); malignant ascites 4020 +/- 1510 pg/ml (mean), 3820 pg/ml (median)] but no IL-1. The mean ascites to serum ratios of IL-6 were 96 (median 49) in patients with hepatic ascites and 587 (median 480) in patients with malignant ascites. Ascites IL-6 was biologically active as determined by the B9 cell bioassay. The results indicate that even in the absence of infection IL-6 is produced in high amounts in the peritoneal cavity of patients with hepatic or malignant ascites.

Adult↗
PubMed1992

Value of endoscopic retrograde cholangiopancreatography in determining the cause but not course of acute pancreatitis.

We have recently shown that ERCP is the most useful technique for detecting a biliary origin of acute pancreatitis and can be done without side effects. We now report on a second series of 50 patients with acute pancreatitis in whom ERCP, computed tomography (CT), ultrasound (US), and clinical and laboratory assessment were performed within the first 24 to 48 hours of hospitalization. A score for ERCP, CT and US was used to assess the severity of the disease. Patients were followed up until discharge or death and their condition classified according to outcome as mild (less than or equal to 1 complication), severe (greater than 1 complication) or fatal. ERCP was superior in detecting choledochal stones (ERCP 100%, US 25%, CT 50%) and dilated intrahepatic ducts (ERCP 75%, US 75%, CT 37%) but not gallbladder stones (ERCP 70%, US 100%, CT 60%). When the ERCP severity score was calculated there was no relevant difference between patients thereafter having a mild course (0.66 +/- 0.91, range 0-3), a severe course (1.3 +/- 0.80, range 0-3), or a fatal outcome (1.0 +/- 1.1, range 0-3). In contrast, the CT score was different in all three groups (mild: 3.0 +/- 1.9; severe: 5.3 +/- 3.2; lethal: 6.3 +/- 3.1) as was the US score (mild: 1.5 +/- 1.3; severe: 3.2 +/- 2.3; lethal: 4.4 +/- 1.4). It is concluded from these results that ERCP is of value in defining the origin of acute pancreatitis. When a biliary origin is detected this can lead to immediate treatment using endoscopic sphincterotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Human recombinant C5a enhances lipopolysaccharide-induced synthesis of interleukin-6 by human monocytes.

The effect of human recombinant C5a (hrC5a) on the synthesis of interleukin-6 (IL-6) was studied in human monocytes. Monocytes incubated in the absence of hrC5a and of bacterial lipopolysaccharide (LPS) produced only low amounts (less than 100 U/2 x 10(6) cells/16 h) of IL-6 activity. LPS in concentrations from 10 pg ml-1 to 10 ng ml-1 greatly stimulated the synthesis of IL-6 to about 50.000 U/10(6) cells/16 h. When hrC5a was added to the monocyte media maximal IL-6 synthesis was reached at lower LPS concentrations, i.e. at 0.1 ng ml-1 LPS in the presence of 100 ng ml-1 hrC5a. Maximal IL-6 production was not significantly enhanced by hrC5a. Metabolic labelling with [35S]-methionine followed by immunoprecipitation of IL-6 showed that the increased IL-6 activity in the medium of hrC5a treated monocytes was due to a stimulation of the de novo synthesis of IL-6. Increased amounts of IL-6 mRNA were found in monocytes treated with LPS and hrC5a compared with monocytes stimulated only with LPS. HrC5a prolonged the elevation of IL-6 mRNA levels after stimulation of monocytes with LPS. HrC5a thus enhanced the LPS-induced synthesis of IL-6 by human monocytes.

Cells, Cultured↗
PubMed1992

Interleukin-8 and neutrophil activation in acute pancreatitis.

It has been suggested that leucocytes play an important role in the pathogenesis of complicated pancreatitis. Indeed, increased plasma concentrations of neutrophil elastase as a marker of neutrophil activation could be detected in patients with a severe course of the disease. Recently, interleukin-8 (IL-8) has been described as a novel neutrophil activating peptide. To determine the role of IL-8 in acute pancreatitis we measured its serum concentrations by a specific enzyme-linked immunosorbent assay in 10 patients with acute pancreatitis daily during the first week of hospitalization. IL-8 levels were compared with plasma concentrations of neutrophil elastase and the clinical course of the disease. Three of the patients had uncomplicated pancreatitis, while seven showed various extrapancreatic complications. Patients with complicated pancreatitis had statistically significant (P less than 0.05) higher mean values of IL-8 (121 +/- 41 pg/ml-1 vs. 13 +/- 6 pg ml-1, mean +/- SEM) and neutrophil elastase (547 +/- 35 ng ml-1 vs. 250 +/- 20 ng ml-1) than patients with uncomplicated disease. There was a positive correlation (r = 0.52, P less than 0.0001) between IL-8 and neutrophil elastase in the lower concentration range of IL-8 (less than 100 pg ml-1). At IL-8 levels greater than 100 pg ml-1 neutrophil elastase was always greatly elevated; however, under these conditions the relationship between IL-8 and elastase was no longer linear. No measurable IL-8 concentrations were found when plasma elastase was less than 200 ng ml-1. During follow-up, initially elevated IL-8 concentrations decreased in correlation with clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1991

Inflammatory mediators in chronic inflammatory bowel diseases.

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of unknown etiology. They are characterized by an activation of intestinal mononuclear cells. Cytokines play a crucial role in the regulation of the functions of these cells. An increased synthesis of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha), which are primarily synthesized by activated monocytes/macrophages has been described in patients with IBD. The synthesis of interleukin-2 (IL-2) and of interferon gamma (IFN gamma), which are produced by lymphocytes, on the other hand, has been found to be decreased. The published data are, however, not quite consistent. In patients with IBD there is not only a stimulation of the local cytokine production in the gut. The blood levels and the synthesis of the cytokines IL-1, IL-6 and TNF alpha by peripheral blood mononuclear cells are also increased, in particular in patients with Crohn's disease. Drugs, which are commonly used for the treatment of IBD impair the synthesis of these cytokines in monocytes/macrophages.

Colitis, Ulcerative↗
PubMed1991

[Hepatology. New research results in its significance for the understanding of liver diseases].

By two exemplary clinical situations--acute viral hepatitis, acute-phase reaction of the liver--the significance of basic research for the understanding of clinical phenomena and for the development of new diagnostic and therapeutic procedures is demonstrated. The very different phenomena following infection with the hepatitis-B-virus can be explained by the variation in the interactions of virus and liver cell, by the immune reaction of the host, and by mutants of the virus. The reaction of the liver to an extrahepatic infection is mediated by interleukin-6, and characterized by an alteration in protein metabolism. The synthesis of acute-phase proteins is increased. The proteins confine the local injury and establish the homeostasis of the organism.

Acute-Phase Proteins↗
PubMed1991

Scintigraphic assessment of leukocyte infiltration in acute pancreatitis using technetium-99m-hexamethyl propylene amine oxine as leukocyte label.

The infiltration of leukocytes has been linked to the pathophysiology of complicated or severe pancreatitis. We have tested the ability of leukocyte scintigraphy using technetium-99m-hexamethyl propylene amine oxine (HM-PAO) as label to demonstrate the localization of leukocytes in the pancreas during acute pancreatitis. Twenty-eight patients with acute pancreatitis (eight with biliary, 13 with alcoholic, and seven with unknown origin) were studied with leukocyte scintigraphy using planar imaging and single photon emission computed tomography (SPECT). Fourteen patients had a mild (group I), II a severe (group II), and three a lethal outcome (group III) of pancreatitis. All patients of group III, six of group II, and two of group I had a positive leukocyte scan. Thus, the sensitivity of leukocyte scintigraphy for the detection of a lethal course of acute pancreatitis was 100%, of a severe course 54%, and of a severe or lethal course 64%. The specificity of a negative scan for a mild pancreatitis was 86%. Comparison of the results of leukocyte scintigraphy with those of contrast enhanced CT showed that six of eight patients with pancreatic necrosis in CT had a positive leukocyte scan, but only five of 20 patients without detectable pancreatic necrosis in CT. In summary, leukocyte infiltration into the pancreas during pancreatitis can be demonstrated by noninvasive leukocyte scintigraphy using technetium-99m-HM-PAO as label. A correlation between the severity of the disease and leukocyte infiltration exists.

Acute Disease↗