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Biomedical subjects

B Kommerell

Publications and source records attributed to B Kommerell.

At least 73 records · Page 4Linked to original sources

sn-1,2-Diacylglycerols and phorbol diesters stimulate thromboxane synthesis by de novo synthesis of prostaglandin H synthase in human promyelocytic leukemia cells.

We studied the regulation of thromboxane (TX) synthesis in promyelocytic leukemia cells during macrophage differentiation. Cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) showed rates of TXB2 synthesis from exogenous arachidonic acid that exceeded that of control cells by a factor of up to 81. Cells treated with sn-1,2-dioctanoylglycerol (diC8) showed similarly high TXB2 synthesis rates when diC8 was added concomitantly with a subthreshold concentration of TPA or when given in multiple doses. These activities depended on de novo synthesis of prostaglandin H (PGH) synthase because: microsomal PGH synthase activity showed large increases in Vmax values, and mass measurements of PGH synthase revealed the presence of PGH synthase in differentiating cells whereas the enzyme was undetectable in control cells. These results indicate that macrophage differentiation is associated with stimulation of TXB2 synthesis that requires both activation of protein kinase C and de novo synthesis of PGH synthase.

Arachidonic Acid↗

[Drug therapy of peptic ulcer. What is coming up?].

Prostaglandin-E analogues inhibit gastric acid secretion after oral administration. Therefore, these drugs are tested in clinical trials and one of them--Misoprostol--has recently been registered. With regard to healing rate of peptic ulcers and improvement of clinical signs and symptoms the prostaglandin analogues are superior to placebo but only equally effective or even slightly inferior to H2-receptor blockers. Side effects such as diarrhea or uterotropic actions will probably limit their broad application. The exact therapeutic effectiveness of prostaglandin analogues in treatment of peptic ulcer remains to be evaluated in greater detail. The substituted benzimidazole omeprazole is the first drug which exerts a long lasting and almost complete suppressive effect on gastric acid secretion in humans. This unique inhibition leads to a significant and more rapid healing rate of duodenal ulcers compared to treatment with H2-blockers. Additionally, peptic ulcers resistant to H2-blocker therapy can be treated effectively with omeprazole. In spite of these promising results the exact therapeutic effectiveness of this drug requires further evaluation.

Alprostadil↗

Chronic ursodeoxycholic acid- and chenodeoxycholic acid-feeding-induced changes of colon mucosal cell proliferation in rats.

Hyperproliferation has been suggested to play a major role in bile acid-dependent colorectal tumor promotion. Effects of chronic feeding of chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) were tested on cell proliferation in the colon of male noninbred Wistar rats. By use of a dynamic method measuring actual rates of cell production, proliferation was modulated by both bile acids only in the proximal part of the colon. UDC feeding produced mild hyperproliferation of basal crypt cells (cell position 5-8: 7.6 +/- 2.0 vs. 3.5 +/- 1.3 cells/1,000 cells/hr--P less than .05; cell position 9-12: 18.1 +/- 10.7 vs. 10.3 +/- 2.9--P less than .05; cell position 13-16: 18.1 +/- 8.9 vs. 9.1 +/- 2.3--P less than .05). This finding reflected a characteristic compensatory response to superficial cell damage. However, CDC application did not effect cell regeneration in this crypt area but led to a striking drop of cell renewal in higher crypt cell positions (positions greater than or equal to 17), where no proliferation was detectable. These data suggest that CDC exerts its tumor-promoting effect by other means than hyperproliferation.

Animals↗

Pre-S1 proteins in sera of patients positive for HBsAg and antibodies to hepatitis delta virus.

Infection with the hepatitis Delta virus results in a reduction in hepatitis B virus replication. To study the question as to whether expression of large surface (pre-S1) protein is changed in patients with previous and chronic hepatitis Delta virus infection, sera of 25 HBsAg- and anti-HD-positive patients were analyzed by the Western blot technique using an antibody directed against a pre-S1 fusion protein. Pre-S1 proteins were present only in 3 of the 25 sera. This finding suggests that the expression of pre-S1 proteins and HBsAg is regulated independently, and that pre-S1 proteins are not necessarily required for the envelope of hepatitis Delta virus.

Antibodies, Viral↗

Effect of colchicine on in vivo and in vitro ethanol metabolism in the rat.

Since colchicine has been used in the treatment of alcoholic cirrhosis of the liver, the effect of this drug on ethanol metabolism in the rat has been investigated. The acute intraperitoneal injection of colchicine (500 micrograms per kg body weight) did not significantly influence in vivo ethanol elimination rate nor the ethanol peak blood concentrations following an acute dose of ethanol (3 g per kg body weight). Cytoplasmic hepatic alcohol dehydrogenase activity was not changed by in vitro colchicine. However, an approximate 30% inhibition of hepatic microsomal ethanol oxidation was observed by colchicine at a concentration of 4 microM and more. In addition, when colchicine was given chronically in a daily dose of 50 micrograms per kg body weight for 3 weeks, again in vivo ethanol disappearance from the blood was not affected by the drug. These data indicate that neither acute nor chronic colchicine administration alters in vivo ethanol elimination. But the question is raised whether colchicine can decrease hepatic acetaldehyde concentration following a therapeutic dose in vivo by inhibiting the hepatic ethanol metabolizing enzyme system. This could be a possible explanation for the observation that alcoholics improve their liver function under colchicine therapy although they continue to drink.

Alcohol Dehydrogenase↗

[Composition of gallbladder and bile duct calculi].

The composition of gallbladder and bile duct stones removed at the time of cholecystectomy was analysed in a consecutive series of 45 patients. The type of stones at the two sites was similar in all but two patients. Cholesterol content differed by more than 20% in only six patients. Cholesterol stones were found in the gallbladder of 33 patients, in the bile duct of 36 patients (73 and 80%, respectively); mixed stones in eight and five patients, respectively (18 and 11%); brown-pigment stones in three patients each (7%); black-pigment stones in one patient each (2%). Bile duct stones overlooked during cholecystectomy are thus suitable for litholysis, e.g. by irrigation with monooctanoin, in the majority of cases.

Bile Duct Diseases↗

Gilbert's syndrome: diagnosis by typical serum bilirubin pattern.

Analysis of serum unconjugated and conjugated bilirubin fractions by routine diazo procedures does not allow a definite diagnosis of Gilbert's syndrome. By the alkaline methanolysis procedure of Blanckaert followed by thin-layer chromatography we were able to discriminate Gilbert's syndrome even in the presence of normal serum bilirubin concentrations from healthy subjects, patients with chronic persistant hepatitis and patients with chronic hemolysis. The relative proportion of unconjugated bilirubin in serum was 95 +/- 2% in patients with Gilbert's syndrome (n = 28), 84 +/- 5% in healthy subjects (n = 29), 75 +/- 6% in patients with chronic persistant hepatitis (n = 7) and 85 +/- 3% in patients with chronic hemolysis (n = 9). The difference between Gilbert's syndrome and the control groups with normal or elevated serum bilirubin was highly significant (p less than 0.001). In Gilbert's syndrome, unconjugated bilirubin ranged between 90 and 99%, in healthy subjects between 72 and 90%, in patients with chronic persistant hepatitis between 68 and 85% and in patients with chronic hemolysis between 81 and 89% of total. An overlap was only seen in one patient with Gilbert's syndrome and in 2 healthy subjects at the 90% level. We conclude that in most patients with Gilbert's syndrome provocation tests are no longer necessary.

Adolescent↗

Isomers of bilirubin glucuronide in serum and bile before and after relief of common duct obstruction.

Isomers of bilirubin glucuronide with the bilirubin acyl group attached to the C1-, C2-, C3- and C4-positions of the glucuronyl residue are present in bile of patients with extrahepatic cholestasis, whereas in normal bile only C1-isomers are found. In the present study, these bilirubin glucuronide isomers, and the fractions of unconjugated bilirubin, and bilirubin mono- and diconjugates were determined in serum and bile of 8 patients before and after relief of common duct obstruction by endoscopic papillotomy. Before papillotomy we found 39.6% C1-isomers (median value), 22.2% C2-isomers, 19.3% C3-isomers and 11.4% C4-isomers in the bile. The values in serum before papillotomy were comparable. Twenty-four hours after papillotomy, the level of C1-isomers in bile increased significantly to 56.3% (P less than 0.05) with a concomitant decrease of the non-C1-isomers. In contrast, in serum the isomers of bilirubin glucuronide did not change significantly at 24 h after papillotomy. Before papillotomy, the fraction of unconjugated bilirubin in bile was 3.6% of the total, with 15.8% bilirubin monoconjugates and 75.5% bilirubin disconjugates. After papillotomy, unconjugated bilirubin decreased to 1.6% (n.s.) and bilirubin monoconjugates to 11.9% (n.s.), while bilirubin diconjugates increased to 86.1% (P less than 0.05). In serum, the elevated fractions of bilirubin diconjugates and monoconjugates decreased from 38.4 to 32.2% (P less than 0.05) and from 29.6 to 23.4% (n.s.), respectively. In parallel, the fraction of unconjugated bilirubin in serum increased from 24.1 to 37.0% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Chronic ethanol consumption selectively stimulates rectal cell proliferation in the rat.

Cell proliferation was examined in the gastrointestinal tract of 30 pair fed rats having received an isocaloric liquid diet containing 36% of total calories either as ethanol or carbohydrates for four weeks. Utilising the metaphase arrest technique with vincristine, cell proliferation was measured as crypt cell production rate. This was selectively increased in the rectal mucosa of ethanol fed rats (19.1 +/- 2.0 vs 9.1 +/- 1.8 cells/crypt/h; p less than 0.005). There was a concomitant increase in proliferative compartment size (48.1 +/- 5.6% vs 30.1 +/- 8.5% of crypt population size; p less than 0.001). Serum gastrin concentrations were also found to be significantly increased after ethanol feeding (172 +/- 51 vs 106 +/- 27 pmol/l; p less than 0.01). The ethanol dependent proliferative changes in the rectal mucosa are predictive of higher susceptibility of this site to carcinogenesis, supporting experimental and epidemiological data. Increased gastrin concentrations may partly explain the observed rectal hyperproliferation. Other possible causes cannot, however, be excluded.

Alcohol Drinking↗

Colonic absorption of sulfated and nonsulfated bile acids in rat.

Absorption of sulfated and nonsulfated chenodeoxycholic and glycochenodeoxycholic acid was studied in the colon and the data were compared with the absorption rates in the ileum. Absorption of nonsulfated chenodeoxycholic acid in the colon was in the same range of magnitude as in the ileum. Glycochenodeoxycholic acid absorption in the colon was lower than in the terminal ileum. Sulfated bile acids were not absorbed in the colon. In the ileum, absorption of sulfated bile acids was significantly (p less than 0.01) lower than the absorption of nonsulfated bile acids. Little absorption of sulfated bile acids in the ileum and lack of absorption in the colon both contribute to the rapid turnover and excretion of bile acid sulfates.

Animals↗

[Frequency of delta infections in Heidelberg].

The frequency of delta infection was studied in sera of 203 patients with acute hepatitis B, further 461 hepatitis B virus surface antigen-(HBsAg)-positive patients and 117 HBsAg-negative controls by determination of anti-delta by a competitive enzyme immunoassay. Sera have been collected since 1974. None of the sera of acute hepatitis B was anti-delta-positive whereas seven of the HBsAg-positive carriers were anti-delta-positive. Two of the anti-delta-positive patients had chronic hepatitis, four had liver cirrhosis. One of the anti-delta-positive patients with liver cirrhosis died of liver failure. Risk factors included Italian origin and parenteral routes of infection. All sera of 19 relatives of three anti-delta-positive index cases remained anti-delta-negative.

Antibodies, Viral↗

Diagnostic accuracy of computerized B-scan texture analysis and conventional ultrasonography in diffuse parenchymal and malignant liver disease.

The use of a diagnostic system for ultrasonic liver tissue characterization based on computerized B-mode image analysis is clinically tested and compared with the results of conventional realtime and static grey scale liver ultrasound as independently assessed by three experienced observers. The diagnostic classes, normal, diffuse parenchymal and malignant disease, are clearly differentiated by computerized image analysis which is superior to subjective evaluation of liver echograms. Computerized analysis also renders a reliable and clinically useful diagnostic subclassification of diffuse parenchymal disease into echopattern changes prevalent in chronic hepatitis, cirrhosis/fibrosis, fatty infiltration and a mixed state of cirrhosis/fibrosis with fatty infiltration which cannot be achieved by conventional liver ultrasound.

Computers↗