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Biomedical subjects

C Bode

Publications and source records attributed to C Bode.

At least 199 records · Page 11Linked to original sources

Antibody-enhanced thrombolysis: targeting of tissue plasminogen activator in vivo.

Tissue plasminogen activator (tPA) was modified by the unidirectional crosslinking reagent N-succinimidyl 3-(2-pyridyldithio)propionate and coupled to iminothiolane-modified anti-fibrin antibody 59D8 by the formation of disulfide bonds at neutral pH. Purification by two affinity-chromatography steps yielded tPA-anti-fibrin antibody conjugate (tPA-59D8) possessing both tPA and anti-fibrin antibody activities. In a quantitative rabbit thrombolysis model, the activity of the purified conjugate was compared with that of tPA alone and that of a conjugate between tPA and a digoxin-specific monoclonal antibody. After correction for spontaneous lysis (10.9 +/- 2.5%), tPA-59D8 was shown to be 2.8-9.6 times more potent than tPA alone. Unconjugated tPA and tPA-digoxin were equipotent. At equivalent thrombolytic concentrations, tPA-59D8 degraded less fibrinogen and consumed less alpha 2-antiplasmin than did tPA alone. This suggests that tPA can be efficiently directed to the site of a thrombus by conjugation to an anti-fibrin monoclonal antibody, resulting in both more potent and more selective thrombolysis.

Animals↗

Effect of acute and chronic ethanol administration in rats on PGE2 formation in microsomes from stomach and small intestine.

Prostaglandin E2 formation and content has been measured in the stomach and small intestine of rats after acute and chronic ethanol ingestion. Chronic ethanol administration for 6 and 12 weeks inhibits PGE2 synthesis and reduces PGE2 content (12 weeks) in all parts of the upper gastrointestinal tract, while after ethanol ingestion up to 1 week PGE2 synthesis is decreased only in the stomach.

Animals↗

Effect of acute and chronic alcohol feeding on prostaglandin E2 biosynthesis in the small intestine of the rat.

The effect of acute and chronic alcohol ingestion on the PGE2 synthesis and PGE2 content in the duodenum and ileum was studied in rats. Following a single oral load of 20% alcohol (v/v; 4 g/kg body weight) the synthesis of PGE2 in isolated microsomes from both parts of the small intestine did not differ from that in control rats during the first 8 hours, but was increased significantly after 24 hours. Feeding a liquid diet containing alcohol (37% of total calories) for 1 week led to enhanced PGE2 synthesis in the duodenum. After feeding the diet for 6 and 12 weeks the rate of PGE2 synthesis was significantly reduced in the duodenum (-73% and -55%) and ileum (-34% and -45%) as compared with the control group. The PGE2 content of the tissue was not significantly changed 24 hours after the single alcohol load and after 1 week of feeding the alcohol-containing diet. However, after 6 and 12 weeks' feeding, the PGE2 content was reduced in both parts of the small intestine. The results suggest a biphasic response to alcohol of PGE2 synthesis in the small intestine. The increased rate of PGE2 synthesis in the initial phase might reflect an adaptive response to the injurious effect of alcohol which cannot be maintained after long-term ingestion of alcohol.

Alcohol Drinking↗

Effect of short- and long-term alcohol feeding in rats on pancreatic enzyme content and enzyme secretion in isolated pancreatic lobules in vitro.

The effect of short- and long-term ethanol intake on digestive enzyme secretion was determined in isolated pancreatic lobules of rats. Groups of male Wistar rats were fed a modified Lieber-DeCarli diet containing either 5% (w/v) of ethanol, isocaloric amounts of a liquid diet in which ethanol was substituted by starch, or solid rat chow; for 3 days, 1, 2, 4, 8 and 12 weeks. Basal and caerulein-stimulated secretion of lipase, amylase, chymotrypsin and trypsin and the enzyme content in the tissue were studied. Feeding the liquid control diet decreased the tissue content of the four enzymes as compared with the values obtained in the group receiving solid rat chow. While basal and stimulated amylase secretion was markedly reduced in the former group, the secretion pattern of the other enzymes exhibited only transient changes. Caerulein-stimulated secretion of lipase and the proteases was increased by ethanol, the effect being more pronounced during the initial phase of the experiment. Alcohol feeding stimulated the basal secretion of these enzymes only in weeks 1-4. In contrast to the other enzymes, basal and stimulated amylase secretion was not enhanced by ethanol feeding. The results suggest that the enzyme secretion of the rat pancreas is distinctly altered by chronic ethanol feeding. However, the response of the pancreatic enzymes is non-parallel, and changes with the duration of alcohol intake.

Amylases↗

Usefulness of a simple photometric determination of chymotrypsin activity in stools--results of a multicentre study.

The usefulness of a new photometric test for the determination of chymotrypsin activity in stools was evaluated in a multicentre study. By release of the enzyme from stool particles with a cationic detergent solution after, in most cases, 3 min of homogenization, a photometric measurement of the enzyme activity is possible both in the clear supernatant after centrifugation and in the diluted stool homogenate. The precision of the activity measurement in stool samples with pathologically lowered and normal chymotrypsin activity is good both for in-series (CV = 2.6%, scatter 0.6-5.7%) and for day-to-day determinations (CV = 7.2%, scatter 3.9-13.9%). The results obtained by the photometric determination also exhibit a close correlation with the values measured by pH-stat titrimetry (r = 0.901). The sample-preparation system with a sample-metering chamber is easy to use and gives good agreement with determinations in which the sample metering was done by weighing out the stool (r = 0.961). The photometric test for detection of exocrine pancreatic insufficiency is easy to perform, inexpensive and does not place any undue stress on the patient.

Chymotrypsin↗

Varix of the external jugular vein.

A case of varix involving the left external jugular vein is presented. The pathogenesis of the unusual condition is discussed and the attention of practising physicians drawn to the new differential diagnosis of swelling in the neck.

Adolescent↗

Antibody-directed urokinase: a specific fibrinolytic agent.

A specific fibrinolytic agent was synthesized by covalently coupling urokinase to a monoclonal antibody that was fibrin-specific and did not cross-react with fibrinogen. The antibody was raised against a synthetic peptide representing the seven amino-terminal residues of the beta chain of human fibrin. The urokinase-antifibrin conjugate retained the original binding specificity of the antibody and showed 100-fold increased fibrinolysis in vitro when compared to unmodified urokinase. The presence of human fibrinogen at plasma concentration did not influence these properties.

Antibodies, Monoclonal↗

Effect of ammonia on plasma and cerebrospinal fluid amino acids in dogs with and without portacaval anastomoses.

To elucidate the possible connection between ammonia-induced changes of plasma and cerebrospinal fluid (CSF) amino acid levels and the development of hepatic encephalopathy in dogs, beagle dogs were given an ammonium acetate infusion both before and following portacaval shunt (PCS). During ammonia-induced coma and after recovery in the dogs prior to PCS the plasma and CSF concentrations of most amino acids were decreased. Following PCS the plasma and CSF concentrations of the aromatic amino acids (AAA), phenylalanine and tyrosine, increased and the levels of the branched chain amino acids (BCAA), valine, leucine, and isoleucine, decreased during ammonia-induced coma. The CSF/plasma molar ratio for the AAA exhibited a marked increase after recovery as compared to the value during coma in the Eck-fistula dogs. With respect to the AAA, no correlation was observed between signs of neurologic impairment in the animals and the following parameters: glutamine and methionine levels of CSF, and the plasma molar ratio (Formula: see text). The data obtained do not support the hypothesis that high concentrations of phenylalanine and tyrosine in the brain may be primarily responsible for altered neurotransmission leading to the development of hepatic encephalopathy.

Amino Acids↗

Specific phosphorylation of a protein in calcium accumulating endoplasmic reticulum from rat parotid glands following stimulation by agonists involving cAMP as second messenger.

Stimulation of secretion in exocrine cells by agonists involving cAMP as second messenger is associated with the phosphorylation of a specific membrane-associated 22.4-kDa protein (protein III) (Jahn et al.). Here it is shown by subcellular fractionation of rat parotid gland lobules that protein III is associated with the endoplasmic reticulum. The submicrosomal fractions containing protein III, also contain the ATP-dependent microsomal calcium pump activity. Protein III in microsomal subfractions can be phosphorylated in vitro with catalytic subunit from cAMP-dependent protein kinase. Phosphorylated protein III contains exclusively P-serine. Protein III can be removed from ER-membranes with acid chloroform-methanol or Triton X-114, but not by high salt wash indicating that it is tightly associated with the membranes. Protein III is smaller than phospholamban and, in contrast to phospholamban, resistant to heating in SDS. A relationship between phosphorylation of protein III and microsomal calcium sequestration is discussed.

Animals↗

The effect of cimetidine treatment on ethanol formation in the human stomach.

Ethanol concentrations were determined in the gastric juice of 53 patients treated with a nasogastric tube. Significant ethanol concentrations ranging from 1 to 27 mmol/l were found in a subgroup of 29 patients receiving cimetidine (n = 22) or antacids (n = 7). The mean ethanol concentration in these patients was higher 1-2 h after a liquid meal (means +/- SEM, 6.95 +/- 2.6) than in the fasting state (3.44 +/- 2.1; p less than 0.05). In the second subgroup of 24 patients, who were not treated with cimetidine or antacids, ethanol concentrations in gastric juice of more than 1 mmol/l were found in 6 cases, with maximal ethanol values of 2.2 mmol/l. The alcohol concentration correlated significantly with the pH of the gastric juice. It is assumed that an increase in the yeast and/or bacterial population in the stomach due to the reduction of gastric acidity induced by cimetidine or antacids is responsible for the enhanced production of ethanol.

Antacids↗

Jejunal microflora in patients with chronic alcohol abuse.

The types and numbers of bacteria were examined in aspirates from the jejunums of 27 chronic alcoholics and 13 hospitalized control patients of comparable age distribution without alcohol abuse or diseases of the liver. Samples of jejunal juice were aspirated in the fasting state. The mean number of microorganisms obtained during anaerobic incubation was distinctly higher in the alcoholics (log10, mean +/- SD: alcoholics 4.9 +/- 2.2, controls 3.2 +/- 1.5, p less than 0.025). A similar difference was found for the number of aerobic bacteria (alcoholics 4.7 +/- 1.9, controls 3.3 +/- 2.1, p less than 0.05). Significant counts (greater than 10(5)/ml) of bacteria obtained during anaerobic incubation were more frequent in the alcoholics (48.1%) than in the controls (7.6%, p less than 0.001). Coliform microorganisms were cultured much more frequently from the jejunal fluid of the alcoholics (alcoholics 55.6%, controls 15.4%, p less than 0.025). In addition the incidence of Gram-negative anaerobic bacteria and endospore-forming rods was higher in the aspirates from alcoholics (p less than 0.05). In both groups the number of microorganisms in jejunal fluid correlated closely with the pH found in the gastric juice. No correlation was found between the numbers or types of microorganisms in the jejunum and the type or degree of liver disease in the alcoholics. It is concluded that bacterial overgrowth might contribute to functional and/or morphological abnormalities of the small intestine commonly found in patients with chronic alcohol abuse.

Actinomyces↗

[Diagnostic value of lipase and isoamylase determination. Monitoring studies in patients with proven and suspected pancreatitis].

Changes of lipase (turbidimetric evaluation), total amylase and isoamylases (inhibition test) were determined in 93 patients with proven or suspect pancreatitis. In 35 patients with established acute pancreatitis 143 sera were investigated in the course of disease. Lipase and pancreatic amylase were increased in these samples significantly more often (thus longer in the course of disease) than total amylase. Eight patients with chronic pancreatitis and exocrine insufficiency showed very low lipase and pancreatic amylase activities whereas total amylase was normal. Observations in the course of two groups of patients with suspect (but not established) pancreatitis showed superior organ specificity of lipase and pancreatic amylase when compared to total amylase. However, no relevant difference of the diagnostic validity of both enzymes could be demonstrated.

Acute Disease↗

Serum apolipoprotein AI synthesis in rat hepatocytes and its secretion as proform.

Rat hepatocytes in monolayer or suspension culture synthesize serum lipoprotein AI. It is secreted into the serum-free culture medium. Synthesis and secretion processes were studied in the presence of radiolabelled amino acids. The synthesis product of the hepatocytes and the secretion product from the medium were isolated by immunoprecipitation with a mono-specific rabbit antiserum against rat apolipoprotein AI. The intracellular and secreted products were homogeneous and identical in polyacrylamide gel electrophoresis but had reduced electrophoretic mobility as compared to native apolipoprotein AI. They were submitted to automated Edman degradation. They were present in their proform, the N-terminus of which is extended by a hexapeptide. In the presence of rat serum the proform is proteolytically transformed into the mature form of apolipoprotein AI.

Amino Acid Sequence↗

A serum proteinase converts proapolipoprotein AI secreted by rat hepatocytes to the mature apolipoprotein.

Apolipoprotein AI integrated into the high-density lipoprotein particle in serum was synthesized in the rat hepatocyte in the presence of radiolabelled amino acids and isolated from the cells in primary culture (suspension) as its proform, with the N-terminus extended by a hexapeptide segment. The primary secretion product is this proform which is only further proteolytically processed in the presence of the serum fraction with density higher than 1.21 g/ml. The secretion product and the proteolytically converted product were characterized by Edman degradation of their respective amino-acid sequences after radiolabelling with [3H]valine and [3H]phenylalanine, the positions of which are well established in the preproform and in the N-terminus of mature rat apolipoprotein AI. The products from the lysed cells and their culture medium were purified by immunoprecipitation, sodium dodecyl sulfate gradient gel electrophoresis and subsequent electroelution of the apo AI band. The proform sediments associated with a particle of density 1.16-1.20 g/ml. The serum proteinase which is inhibited by phenylmethanesulfonyl fluoride, but not by sulfhydryl reagents, is presumably a serine proteinase.

Animals↗

Salivary secretion in chronic pancreatitis with special reference to albumin and lactoferrin.

Saliva from one parotid gland was collected under citric acid stimulation in three groups consisting of 69 control subjects and two groups consisting of 25 patients with chronic and relapsing chronic pancreatitis. Mixed saliva was collected under mechanical stimulation from 10 patients and 6 control subjects. Flow rates and the contents of bicarbonate, amylase and protein were determined. In a subgroup of patients and controls albumin and lactoferrin were measured. Wide inter- and intraindividual variations of secretory values were observed and normal values (which are reported in detail) were highly dependent from conditions of stimulation. Secretory patterns were not significantly different between patients and control subjects. It is concluded that the alterations leading to an elevation of albumin and lactoferrin and a fall in other secretory values are restricted to the exocrine pancreas and do not affect salivary glands in chronic pancreatitis.

Adult↗

The effect of storage at - 80 degrees C on the activities of cytoplasmic, mitochondrial and microsomal enzymes in rat liver.

The effect of storage at - 80 degrees C for 1-28 days on the activity of 12 enzymes in intact liver tissue, liver extract and isolated hepatic microsomes was investigated. To find optimal conditions for tissue homogenization for this study the effects of three types of homogenization on the activity of 10 enzymes from different cell compartments were compared. The activities of glucokinase and phosphofructokinase decreased markedly during storage of both supernatant and liver tissue. Storage of liver tissue increased the activity of mitochondrial enzymes or isoenzymes. While this effect can be explained by additional disintegration of liver tissue caused by freezing and thawing for enzymes like glutamine dehydrogenase, other mechanisms may be involved in the prolonged increase observed in the activity of citrate synthase and xanthine oxidase during storage. The activity of a number of enzymes from the cytosol, mitochondria and microsomes decreased more markedly in the stored liver samples than in the stored supernatant or in the stored microsomal pellet. Cytochrome P 450 content remained stable throughout the whole storage period in both intact liver tissue and isolated microsomes.

Animals↗