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Biomedical subjects

K Borch

Publications and source records attributed to K Borch.

At least 55 records · Page 3Linked to original sources
PubMed1994

Localization of a pernicious anaemia autoantibody epitope on the alpha-subunit of human H,K-adenosine triphosphatase.

Four cDNA fragments encoding different portions of the alpha-subunit of human H,K-adenosine triphosphatase (ATPase) were amplified by means of the polymerase chain reaction technique, ligated into the plasmid pGEX-2T, and expressed as glutathione S-transferase fusion proteins in Escherichia coli. The fragments A (residues 163-313), Ba (residues 360-797), Bb (residues 526-797), and C (residues 822-1031) together encompass 77% of the alpha-subunit and cover most of its cytosolic part. The reactivities of autoantibodies in the sera from patients with pernicious anaemia with the recombinant fusion proteins were analysed by immunoblotting. One autoantigenic epitope was found in the NH2-terminal part of the Ba fragment--that is, between residues 360 and 525. No epitope was detected in the other fragments. The Ba fragment was cleaved off from the glutathione S-transferase fusion protein by the action of thrombin and was then further purified. By means of enzyme-linked immunosorbent assay, 28 of 42 sera (67%) from patients with pernicious anaemia were positive against the purified Ba fragment. The present results provide a final proof that the human H,K-ATPase alpha-subunit is a major autoantigen in the parietal cell and that the major epitope is located between residues 360 to 525 on the cytosolic side of the secretory membrane.

Adult↗
PubMed1994

Endogenous hypercholecystokininemia, but not aspirin, reduces the gallstone incidence in the hamster model.

BACKGROUND: Studies in humans and rodents indicate that gallstone development may be prevented by inhibiting gallbladder mucus hypersecretion with non-steroidal anti-inflammatory drugs or by preventing stasis of gallbladder bile with administration of cholecystokinin. METHODS: The effect of oral aspirin and pancreaticobiliary diversion with endogenous hypercholecystokininemia on crystal and gallstone formation was studied in Syrian golden hamsters fed a lithogenic diet for 8 weeks. RESULTS: None of the control animals fed a normal diet developed gallstones or crystals in gallbladder bile. Gallstones developed in 67% of the animals fed a lithogenic diet only. The gallstone prevalence did not differ significantly in animals on a lithogenic diet and a daily aspirin dose of 6 mg/kg (gallstone prevalence, 60%) or 100 mg/kg (gallstone prevalence, 70%), whereas it was significantly lower in animals with endogenous hypercholecystokininemia on a lithogenic diet (gallstone prevalence, 29%). The prevalence of crystals in gallbladder bile did not differ significantly between any of the experimental groups. CONCLUSIONS: It is concluded that in hamsters on a lithogenic diet, aspirin does not prevent gallstone formation, whereas endogenous hypercholecystokininemia reduces the prevalence of stones without affecting the occurrence of crystals in gallbladder bile.

Animals↗
PubMed1994

Human gastric H,K-adenosine triphosphatase beta-subunit is a major autoantigen in atrophic corpus gastritis. Expression of the recombinant human glycoprotein in insect cells.

BACKGROUND: Sera from patients with atrophic corpus gastritis with pernicious anemia frequently contain parietal cell autoantibodies. We have previously demonstrated that the human H,K-adenosine triphosphatase (H,K-ATPase) alpha-subunit constitutes a major autoantigen. The present study investigates whether the human H,K-ATPase beta-subunit is an autoantigen, too, METHODS: The gene of the human beta-subunit was expressed in insect cells by a baculovirus expression system. The reactivity of sera from 42 patients towards the recombinant glycoprotein was analyzed by means of an enzyme-linked immunosorbent assay. RESULTS: Thirty-nine of the 42 sera (93%) scored positive. Autoantibody binding in 41 sera (98%) was eliminated when unglycosylated beta-subunit was used as antigen, and antibody binding in the last serum was decreased by 30%. CONCLUSIONS: The results indicate that the beta-subunit is indeed a major autoantigen and that carbohydrates are involved in binding of the autoantibodies.

Adult↗
PubMed1994

Positive correlation between H,K-adenosine triphosphatase autoantibodies and Helicobacter pylori antibodies in patients with pernicious anemia.

BACKGROUND: Helicobacter pylori is a major cause of gastritis, and the parietal cell H,K-adenosine triphosphatase (ATPase) is a major autoantigen in autoimmune atrophic corpus gastritis, which may eventually lead to pernicious anemia and/or neuropathy. Whether the bacterium induces the autoimmune response is unknown. METHODS: By means of enzyme-linked immunosorbent assay the occurrence of antibodies against porcine H,K-ATPase and H. pylori was determined in sera from 30 patients with pernicious anemia. RESULTS: All sera scored positive against H,K-ATPase, and 25 (83%) scored positive against H. pylori. The titers of antibodies against both antigen preparations inversely correlated with the duration of disease. A possible common epitope in the antigen preparations was tested with a competition assay. There was no indication of a common epitope in either human or porcine H,K-ATPase and H. pylori. CONCLUSIONS: There was a positive correlation and a high incidence of antibodies against H,K-ATPase and H. pylori in sera from patients with pernicious anemia. These antibodies recognized different epitopes.

Aged↗
PubMed1994

Trends in incidence, clinical findings and outcome of acute and elective cholecystectomy, 1970-1986.

OBJECTIVE: To assess time trends in the incidence, clinical findings, and outcome of conventional acute and elective cholecystectomy. DESIGN: Single-institution time series analysis. SETTING: University hospital, Sweden. SUBJECTS: A consecutive series of 2926 patients operated on for acute or chronic gallbladder disease in a defined Swedish population. MAIN OUTCOME MEASURES: Changes in the incidence and outcome of acute and elective cholecystectomy. RESULTS: From period I (1970-1978) to period II (1979-1986), the mean rate of acute operations increased from 10 to 30/100,000 inhabitants/year and that of elective operations decreased from 190 to 120/100,000 inhabitants/year. There was therefore a negative correlation between the rate of elective and acute operations (r = -0.58, p < 0.02). This was strongest when the rate of elective operations in any one year was correlated with the rate of acute operations two years later (r = -0.71, p < 0.01). In both groups the proportion of patients over 70 years old increased significantly. The female:male ratio decreased significantly for acute but not elective operations (mean 2.6 in period I and 1.0 in period II). The length of history and the number of previous admissions to hospital with gallstone disease decreased significantly for both groups, as did prevalence of common bile duct stones detected at cholecystectomy. Morbidity did not seem to change, though a general improvement may have been concealed, because patients were older in period II and postoperative mortality was lower than in period I. Complications were least common among patients with a short or no previous history of symptoms attributable to gallstones. CONCLUSIONS: The rate of elective cholecystectomy seems to have some influence on the future rate of acute cholecystectomy. When symptoms of gallstone disease develop, treatment should not be delayed unnecessarily.

Age Factors↗
PubMed1994

Effects of gastric fundusectomy and antrectomy on gallbladder epithelial proliferation in the hamster.

BACKGROUND: Exogenous administration of cholecystokinin or its analog cerulein induces epithelial hyperplasia in the mouse gallbladder. The effects on the gallbladder of resectional surgery of the stomach with hormonal consequences are not known. METHODS: The effects of gastric fundusectomy and antrectomy on proliferation and growth of the gallbladder epithelium were studied in male Syrian golden hamsters during periods of 5 and 25 days. Sham-operated animals served as controls. RESULTS: Basal plasma gastrin concentrations were significantly increased after fundusectomy and significantly decreased after antrectomy, whereas basal plasma cholecystokinin concentrations were not significantly affected. Five days after fundusectomy, there was a significant increase in the tritiated thymidine DNA labeling index of gallbladder epithelial cells. On day 25, the gallbladder weight and total number of epithelial cells were significantly increased after fundusectomy. Antrectomy significantly decreased the gallbladder weight on day 25, whereas the labeling index and total number of epithelial cells were not significantly affected on days 5 and 25. CONCLUSIONS: These results suggest that gastric fundusectomy at least transiently induces gallbladder epithelial hyperplasia and hypertrophy in the hamster. Although achlorhydria and hypergastrinemia are prominent features, the actual mechanism behind this effect of fundusectomy on the gallbladder needs further clarification.

Animals↗
PubMed1993

Colonic mucosal proliferation after pancreaticobiliary diversion in the hamster.

The effect of pancreaticobiliary diversion (PBD) on the colonic mucosa was studied in hamsters over 5, 10, and 24 days. Sham-operated animals served as controls. At all three time intervals, experimental animals had increased plasma cholecystokinin concentrations and decreased gastrin concentrations. Five days after PBD, there was an increase in scintigraphically measured [3H]thymidine incorporation into colonic tissue. Correspondingly, there was an increase in the [3H]thymidine DNA labeling index of goblet cells in the colonic mucosa. The total number of cells in the colonic crypt columns were significantly increased on days 5, 10 and 24. Whether this proliferative response in the colon is due to increased release of cholecystokinin, enteroglucagon, other aberrations of hormones or growth factors, or simply an increased bile load on the colonic mucosa remains to be clarified. Such further studies may reveal an alternative animal model for studies on risk factors in colonic carcinogenesis.

Animals↗
PubMed1993

Effects of pancreaticobiliary diversion and gastric fundectomy on azaserine-induced pancreatic carcinogenesis in the rat.

The effects of pancreaticobiliary diversion (PBD) and gastric fundectomy on the pancreas in azaserine-treated rats were studied over 14 months. Sham-operated azaserine-treated animals served as controls. A significant increase in pancreatic weight and total DNA and protein content was found in PBD-operated and fundectomized animals. DNA flow cytometry showed a significantly increased ratio of tetraploid to diploid cells in pancreatic tissue in both experimental groups. Mean values of all these variables were significantly higher after PBD than after fundectomy. Acidophilic atypical acinar cell foci of the pancreas were observed in all of the experimental and 75% of the control animals. The volume density of these foci was significantly higher in each experimental group than in the controls. The volume density, radioactive thymidine labeling index, and mitotic index of the foci were significantly higher after PBD than after fundectomy. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. It is concluded that not only PBD with endogenous hypercholecystokininemia, but also fundectomy with endogenous hypergastrinemia lasting about half of the life span in rats, induces pancreatic hypertrophy and enhances the development of precancerous pancreatic changes after azaserine treatment. In comparison with PBD, fundectomy caused less pronounced changes and no observable neoplasia.

Animals↗
PubMed1993

Pancreatic hypertrophy with acinar cell nodules after longterm fundectomy in the rat.

The effect of gastric fundectomy with hypergastrinaemia on the pancreas in rats was studied for 14 months. Rats with hypercholecystokininaemia that had had a pancreaticobiliary diversion (PBD) operation and sham operated rats served as controls. Fundectomised rats showed a significant increase in pancreatic weight and total DNA and protein content compared with sham operated rats. DNA flow cytometry showed a significantly higher ratio of tetraploid to diploid nuclei in pancreatic tissue after fundectomy than after sham operation. Mean values of all these variables were significantly lower after fundectomy than after PBD. Acidophilic atypical acinar cell foci of the pancreas were diagnosed in both fundectomised and PBD operated rats, but not in sham operated controls. The volume density and 3H-thymidine labelling index of the acidophilic atypical acinar cell foci were significantly lower after fundectomy than after PBD. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. In conclusion, fundectomy lasting about half of the life span in rats causes pancreatic hyperplasia and hypertrophy, as well as development of acidophilic atypical acinar cell foci. Although hypergastrinaemia is a prominent feature, it may not be the only factor responsible for this pancreaticotrophical effect of fundectomy.

Animals↗
PubMed1992

Effects of gastric fundectomy and antrectomy on the exocrine pancreas in the hamster.

The effect of gastric fundectomy and antrectomy on growth of the exocrine pancreas was studied in hamsters over 5 and 25 d. Sham-operated animals served as controls. After 5 d, basal plasma gastrin concentrations were significantly increased in fundectomized animals (80.3 +/- 20.6 pmol/L) and significantly decreased in antrectomized animals (11.6 +/- 1.1 pmol/L) as compared with the controls (20.0 +/- 1.7 pmol/L). Similar differences were present among the 25-d groups, whereas basal plasma cholecystokinin (CCK) concentrations did not differ significantly between any groups at any time. At 5 d after fundectomy, there was a significant increase in pancreatic tissue [3H]-thymidine uptake and total DNA content, both of which were reduced 5 d after antrectomy. Autoradiography showed significantly increased [3H]-thymidine labeling index of acinar, intralobular duct, and centroacinar cells of the pancreas at 5 d after fundectomy. The increased intralobular duct cell labeling index persisted 25 d after fundectomy. Labeling indexes after antrectomy did not differ significantly from those in the controls, although antrectomized animals had the lowest values in all three cell compartments at 25 d. At 25 d, pancreatic wet wt and total DNA and protein content were significantly increased after fundectomy and significantly reduced after antrectomy. These findings indicate that fundectomy in the hamster induces pancreatic exocrine tissue hyperplasia and hypertrophy, whereas antrectomy leads to retardation of pancreatic growth.

Animals↗
PubMed1992

Endogenous hypercholecystokininemia model in the hamster: trophic effect on the exocrine pancreas.

Using Syrian golden hamsters, we studied the effect of pancreaticobiliary diversion (PBD) on plasma cholecystokinin (CCK) and exocrine pancreatic tissue over 5, 10, and 24 days. As compared with sham-operated controls, PBD-operated animals had increased plasma CCK concentrations by 228, 318, and 207% at 5, 10, and 24 days, respectively. Correspondingly, pancreatic wet weight increased by 24, 61, and 87%; total pancreatic protein by 6, 57, and 73%; and total pancreatic DNA by 35, 52, and 98%, respectively. At 5 days, but not at 10 and 24 days, there was a significant increase in the pancreatic tissue DNA concentration (p less than 0.01) and [3]H-thymidine incorporation into DNA (p less than 0.02). Autoradiography showed increased [3]H-thymidine labeling index in acinar cells at 5 and 10 days after PBD (p less than 0.01 and p less than 0.005). Although not significant, ductal cell labeling index was also increased at 5 and 10 days. These findings provide evidence that, as in the rat, PBD in the hamster induces hypercholecystokininemia with ensuing pancreatic hyperplasia and hypertrophy. The hamster model may be useful for studies on the effect of endogenous CCK on pancreatic ductal cell carcinogenesis and diseases of the gallbladder, neither of which can be studied in the rat.

Animals↗
PubMed1992

Extracorporeal shock wave lithotripsy of bile duct stones: a single institution experience.

Extracorporeal shock wave lithotripsy treatment with Dornier HM3 or MPL 9000 machines was applied in 37 patients with problematic bile duct stones. General anaesthesia was not required. After one extracorporeal shock wave lithotripsy session 14/37 patients (38%) were spontaneously stone free, and additional endoscopic extraction (eight of 37) and retreatments with extracorporeal shock wave lithotripsy (seven cases) increased the stone free rate to 29/37 (78%). In three patients with intrahepatic stones, the bile ducts could not be evaluated decisively at cholangiography and ultrasonography, but they were all symptom free at 15 to 38 months follow up. If these three patients are added to the radiologically stone free patients, the overall clinical success rate was 32/37 (86%). There were no serious complications, hospital admissions, or 30 day mortality as a result of extracorporeal shock wave lithotripsy or endoscopic procedures. It is concluded that extracorporeal shock wave lithotripsy is a valuable adjunct to the non-surgical treatment of bile duct stones.

Aged↗
PubMed1992

Gastric fundic epithelial proliferation after pancreaticobiliary diversion. Studies with quantitative histological analysis and autoradiography in the hamster.

The effect of pancreaticobiliary diversion (PBD) with hypercholecystokininemia on the gastric fundic mucosa was studied in the Syrian golden hamster over 5 and 24 days. Sham-operated animals served as controls. Basal plasma gastrin concentrations were significantly decreased on days 5 and 24. Five days after PBD, there was a significant increase in the scintigraphically measured [3H]-thymidine incorporation into fundic tissue. Correspondingly, there was a significant increase in the number of cells with [3H]-thymidine-labeled DNA in the proliferative zone of the fundic mucosa. The total number of cells in the gastric pits, the number of cells in the proliferative zone and the proliferation index were also significantly increased 5 days after PBD. Although the mean values of all variables were higher after PBD than in the control group on day 24, these increases were not significant. It is concluded that PBD at least transiently stimulates gastric fundic epithelial proliferation in the hamster. Whether this is an effect of hypercholecystokininemia remains to be definitely proven in further studies.

Animals↗
PubMed1992

Effects of gastric fundectomy and antrectomy on the colonic mucosa in the hamster.

The effects of gastric fundectomy and antrectomy on the colonic mucosa were studied in hamsters over 5 and 25 days. Sham-operated animals served as controls. Basal plasma gastrin concentrations were significantly increased after fundectomy and significantly decreased after antrectomy. Five days after fundectomy, there was a significant increase in scintigraphically determined colonic tissue [3H]-thymidine uptake and [3H]-thymidine labeling index of goblet cells, both of which were reduced 5 days after antrectomy. After fundectomy, the labeling index was maximal in differentiating-proliferative cells in the midportion of the colonic crypts, whereas the labeling index of the immature proliferative cells at the base of the crypts did not differ from that in the controls. On day 25, the crypt size and the number and percentage of goblet cells in the crypts were significantly increased in fundectomized animals. The number and percentage of goblet cells in antrectomized animals were significantly reduced on day 25. It is concluded that fundectomy in the hamster induces colonic mucosal hyperplasia with goblet cell proliferation, whereas antrectomy leads to retardation of colonic goblet cell proliferation.

Achlorhydria↗
PubMed1992

Spontaneous rupture of the spleen.

A 40-year-old woman with bronchial asthma was admitted as a medical emergency with suspected myocardial infarction. Spontaneous splenic rupture was diagnosed during hospitalization and splenectomy successfully performed. No histopathologic changes or signs of previous injury or adhesions were found.

Adult↗