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Biomedical subjects

M Yun

Publications and source records attributed to M Yun.

At least 37 records · Page 2Linked to original sources

gamma-Linolenic acid-containing diet attenuates bleomycin-induced lung fibrosis in hamsters.

Although bleomycin (BLM), an antineoplastic drug, is used in the treatment of a variety of tumors, the mechanism(s) that contribute to its induced lung injury and fibrosis are not fully elucidated. Since alterations in the levels of certain fatty acid metabolites have been associated with BLM-induced lung injury, we tested the effects of dietary gamma-linolenic acid (GLA)-containing evening primrose oil on BLM-induced morphological alterations in the hamster lung, the marked elevation of tissue hydroxyproline (a marker for collagen synthesis), and elevated generation of arachidonic acid metabolites (marker of inflammatory mediators). Our data revealed that after 14 d of dietary GLA-containing oil (i) BLM-induced elevation of lung hydroxyproline was suppressed (P < 0.05), (ii) the marked BLM-induced elevation of lung leukotriene B4 (LTB4) (a marker of polymorphanuclear generation of proinflammatory LTB4) was significantly suppressed (P < 0.05). The decrease in LTB4 was accompanied by marked elevations (P < 0.05) of lung prostaglandin E1 (PGE1) and 15-hydroxyeicosatrienoic acid (15-HETrE), both with known antiinflammatory properties. Taken together, data from these studies suggest that dietary GLA-containing oil contributes to tissue elevation of PGE1 and 15-HETrE, which in vivo may attenuate lung inflammation and fibrosis.

Animals↗

Primary and secondary liver/kidney microsomal autoantibody response following infection with hepatitis C virus.

Liver/kidney microsomal autoantibody type 1 (LKM-1), which characterizes a subtype of autoimmune hepatitis, is also found in some patients with chronic hepatitis C virus (HCV) infection. Whether HCV and LKM-1 are accidentally or causally related is unknown. This case report describes a child who became infected by HCV after liver transplantation for end-stage liver disease caused by alpha 1-antitrypsin deficiency. LKM-1 was detected by immunofluorescence, anti-microsomal reactivity by Western blotting, anti-HCV and anti-GOR by immunoenzymatic assays, and HCV RNA by polymerase chain reaction. Two weeks after HCV infection, immunoglobulin (Ig) M LKM-1 appeared, followed by IgG1 LKM-1, with titers increasing to 1/2560; antibodies to a 50-kilodalton liver microsomal protein appeared 2 months later. Sera from day 1 posttransplant became positive for HCV RNA. HCV RNA was also detected in a liver biopsy specimen obtained 3 months after surgery. The patient did not produce anti-HCV and anti-GOR antibodies throughout the study and had no histological evidence of hepatitis. The temporal relationship between HCV infection and LKM-1 production suggests that HCV may trigger a primary autoimmune response. The lack of liver damage attributable to autoimmunity or viral infection may be caused by immunosuppression.

Antibody Formation↗

Pancreatic exocrine deficiency after partial pancreatectomy in conscious dogs.

OBJECTIVE: To describe the secretory responses to physiological stimulation of the exocrine pancreas after partial pancreatectomy in conscious animals. DESIGN: Controlled study. MATERIAL: Thirteen mongrel dogs. INTERVENTIONS: Partial pancreatectomy (n = 4), and creation of gastric and pancreatic (Herrera) fistulas (n = 13). Collections of duodenal juice at 15 minute intervals after an oral meal or during intraduodenal infusion of sodium oleate, and blood samples. MAIN OUTCOME MEASURES: Protein concentration in duodenal juice and cholecystokinin 33/39 concentrations in plasma one and three months after partial pancreatectomy, and secretion of fluid by the pancreas. RESULTS: Pancreatic protein output after a meal was significantly reduced at one and three months in dogs after partial pancreatectomy compared with control animals. Protein output in response to an intraduodenal infusion of oleate was also reduced at both time points. In contrast, secretion of fluid after a meal or during infusion of oleate was unchanged by removal of the distal lobe. There was no correlation between the effects of partial pancreatectomy on protein output and plasma concentrations of cholecystokinin 33/39. CONCLUSION: Pancreatic exocrine deficiency, particularly the reduction in secretion of protein, results directly from the partial pancreatectomy and persists for at least three months after the operation.

Animals↗

Mechanical precision in two-dimensional electrophoresis can improve protein spot positional reproducibility.

Current methods for high resolution two-dimensional electrophoresis (2DE) of proteins are capable of separating over 5000 protein spots in one procedure. Running and analysing such 2DE gels requires skilled technical work. However, the variable reproducibility of spot positions means that, even under the best circumstances, one gel cannot be overlain directly on another for precise comparison. Therefore, new and improved technologies that enhance gel-to-gel reproducibility are required. To this end, we have designed and built a research instrument to test whether a precise mechanical device could improve the gel-to-gel reproducibility by reducing the amount of distortion and positional variation between the first and second dimension gels. Other causes of poor reproducibility, including sample type and preparation, gel matrices and running conditions were not varied in order to limit this study to the mechanical variations inherent in current 2DE systems. We found that the sample standard deviation of pooled data for measured protein spot-to-spot distances in the prototype device was 1.3 mm as compared to 4.3 mm in a conventional 2DE system. These improvements support the possibility that greater automation of the multistep 2DE process will enhance reproducibility. This approach seems justified in order to achieve significantly better matching between gels and between results from different laboratories.

Cerebrospinal Fluid Proteins↗

Human cerebrospinal fluid protein database: edition 1992.

Two-dimensional electrophoresis maps of human cerebrospinal fluid proteins are presented in the form of labeled images. 931 protein spots are identified in spinal fluid from a normal volunteer. Distinct spots that represent variants of the same protein, especially posttranslational modifications, are estimated to reduce the 931 different spots to < 200 different proteins. 248 spots of 29 protein groups have been identified and are indicated on enlargements of specific gel regions. The distribution of protein abundance, mass, charge and shape characteristics of these normal 931 spinal fluid spots are graphically profiled. Analysis of the shape parameter "vertical height: width ratio" reveals that a ratio > 3.5 correlates with glycoproteins, enabling their identification simply by image analysis. Proteins that are not present on the normal map, but appear in spinal fluid in patients with schizophrenia and Creutzfeldt-Jakob disease are illustrated on additional maps.

Cerebrospinal Fluid Proteins↗

Effects of gastric inhibitory polypeptide and glucagon on portal venous and hepatic arterial flow in conscious dogs.

Gastric inhibitory polypeptide (GIP) has considerable structural homology with glucagon, which is known to increase liver blood flow. We compared the effects of GIP on portal venous and hepatic arterial flow with those of glucagon in conscious dogs. Injection of GIP significantly increased portal venous flow in a dose-related manner (by 7%, 15%, and 46% at doses of 1, 100, and 500 pmol/kg, respectively). The increase in portal venous flow induced by GIP and glucagon was comparable; however, the increase in portal venous flow after GIP injection reached its peak significantly earlier than that after glucagon injection. Hepatic arterial flow decreased after GIP injection (by 17%, 21%, and 35% at doses of 1, 100, and 500 pmol/kg, respectively), whereas it was not altered by glucagon. Thus, GIP causes significant changes in both portal venous and hepatic arterial flow in conscious dogs. Although structurally related, GIP and glucagon may influence liver blood flow through different mechanisms.

Animals↗

Qualitative and quantitative changes in islet cells of autotransplanted pancreas in dogs in relation to glucose metabolism.

This study was conducted to clarify the quantitative and qualitative changes in the cells of the islets of Langerhans in the autotransplanted pancreas in dogs and to correlate these changes with alterations of glucose tolerance. The left lobe of a canine pancreas was transplanted into the left iliac fossa. The splenic vessels were anastomosed to the left iliac vessels. The pancreatic duct was left open to the peritoneal cavity. Open biopsies of the autotransplanted pancreas were performed 3, 7, 11, and 14 weeks after transplantation. The islets in the transplanted pancreas were examined ultrastructurally; B-cells, A-cells, and D-cells were identified immunohistochemically and their percentages were determined. Intravenous glucose tolerance tests were performed 3, 5, 7, 11, and 14 weeks after operation, and several indexes (K values and integrated response and increased values for baseline serum and immunoreactive insulin) were calculated. Fibrosis of the transplanted pancreas progressed after transplantation. The percentage of B-cells fell significantly (p < 0.01), whereas that of A- and D-cells did not have significant changes. The ultrastructural study revealed an increase in collagen bundles, degranulation of B-cells, and marked preservation of A-cell granules 3 weeks after transplantation. B-Cells with dark cytoplasm were found 7 weeks after operation. In contrast, clusters of immature B-cells were seen in some sections of the pancreas 14 weeks after autotransplantation. The integrated response in baseline serum was increased significantly (p < 0.01), and the K value was decreased significantly (p < 0.01) 11 weeks after autotransplantation when compared with the initial posttransplant period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of ethanol and wine on hepatic arterial and portal venous flows in conscious dogs.

The effects of ethanol and wine on hepatic arterial and portal venous flows were examined in conscious dogs. Ethanol was given intravenously or intragastrically, and red wine (ethanol: 14%) was given intragastrically over 30 min. Intravenous ethanol (0.8 g/kg) and intragastric ethanol (14% vol/vol) increased hepatic arterial flow, which remained elevated for 60 min after the cessation of ethanol administration. Ethanol also increased portal venous flow. Portal venous flow returned gradually toward basal levels after the cessation of intravenous ethanol infusion, whereas it remained elevated even after the cessation of intragastric ethanol. Intragastric wine increased hepatic arterial and portal venous flows. In contrast to intragastric ethanol, hepatic arterial flow continued to rise after the cessation of intragastric wine infusion, while portal venous flow returned toward basal levels. We conclude that, though both ethanol and wine increase hepatic blood flow, the responses of hepatic arterial and portal venous flows differ substantially among intravenous ethanol, intragastric ethanol and intragastric wine.

Animals↗

[Immunohistochemical and ultrastructural study on the islet of autotransplanted pancreas in dogs].

This study was conducted to clarify the quantitative and qualitative changes of the islet cells of Langerhans in the autotransplanted pancreas. The left lobe of the canine pancreas was autotransplanted to the left iliac fossa with pancreatic duct left open to the peritoneal cavity. Fibrosis of transplanted pancreas progressed after transplantation. B-cell ratio was decreased significantly (p less than 0.01) whereas A-cell ratio and D-cell ratio showed no significant changes. Ultrastructural study revealed the increase of collagen/bundle, degranulation of B-cells and well preservation of A-cell granules at 3 weeks after operation. B-cells with dark cytoplasm were found at 7 weeks after operation which indicate the dysfunction of B-cells. In contrast, clusters of immature B-cells appeared on some sections obtained from the pancreas 14 weeks after autotransplantation. On the other hand, K-values were decreased significantly 7 weeks after operation (p less than 0.05). sigma BS (integrated response value of serum glucose level during IVGTT) was increased significantly (p less than 0.01) in addition to the decrease of K-values (p less than 0.01) at 11 weeks after operation. It proved that any indices at 14 weeks after operation showed no significant changes from the control group. It might be possible to speculate that relatively well preservation of glucose tolerance at 14 weeks after operation is associated with some clusters of immature B-cells observed ultrastructurally.

Animals↗

Effect of human epidermal growth factor (hEGF) on splanchnic circulation in dogs.

The effect of intravenous administration of human epidermal growth factor on the splanchnic blood flows was examined in anesthetized dogs, using an ultrasonic transit-time volume flow meter. Human epidermal growth factor (0.1, 0.5 and 1 microgram/kg) significantly increased blood flows in the portal vein (36.9 +/- 7.4% at 1 microgram/kg) and the superior mesenteric artery (49.0 +/- 16.8% at 1 microgram/kg). Systemic blood pressure monitored simultaneously was significantly decreased (8.4 +/- 1.2% at 1 microgram/kg). This study is the first to demonstrate that intravenous administration of epidermal growth factor increases the portal venous blood flow.

Animals↗

Effect of synthetic physalaemin on splanchnic circulation in dogs.

Physalaemin has been reported as one of the most potent vasodilator and hypotensive peptides (1-4). In spite of these studies, however, the effect of the peptide on splanchnic circulation is not known precisely. In the present study, the effect of synthetic physalaemin on superior mesenteric arterial blood flow, portal venous blood flow and pancreatic capillary blood flow was investigated in dogs. Dose dependent increases of superior mesenteric arterial blood flow and portal venous blood flow were induced in response to physalaemin (0.1-10.0 ng/kg). Superior mesenteric arterial blood flow and portal venous blood flow attained maximal increases of 77 +/- 8.9% and 70 +/- 8.6%, respectively, at a dose of 5 ng/kg. Physalaemin caused a dose-related decrease in systemic arterial blood pressure. Pancreatic capillary blood flow did not show significant change with the administration of physalaemin. These data suggest that physalaemin may play some physiological roles in the regulation of splanchnic circulation.

Amino Acid Sequence↗

Role of sulphated tyrosine residue in influencing the biologic activity of human cholecystokinin-33.

To evaluate the role of the sulphated tyrosine residue in position 27 in human cholecystokinin-33, parallel bioassay of the sulphated form of human cholecystokinin-33 and the unsulphated form of human cholecystokinin-33 was performed on the pancreatic protein secretion. Both peptides increased the protein output in a dose-related manner. However, the sulphated form possessed a considerably higher activity than the sulphated form. The relative potency of the unsulphated human cholecystokinin-33 compared to that of the sulphated human cholecystokinin-33 (taken as 1.0) was 0.08. From the results, it was suggested that the sulphated tyrosine may play an important role in controlling the activity of the longer molecular forms as well as that of the smaller forms of cholecystokinin.

Animals↗

Effect of synthetic human cholecystokinin-33 on exocrine pancreas.

Synthetic human cholecystokinin-33 was first evaluated with respect to the biological activity on the pancreatic protein secretion. Human cholecystokinin-33 increased pancreatic protein secretion in a dose-related manner. The relative molar potency of this substance compared to that of synthetic cholecystokinin-8 (taken as 1.0) was 0.92. This study supports the concept that longer molecular forms of cholecystokinin are quantitatively important mediators of biological action of cholecystokinin on the pancreas.

Animals↗

Effects of intravenous ethanol on hepatic and pancreatic blood flow in dogs.

Changes in hepatic and pancreatic blood flow in response to ethanol infusion were determined simultaneously and continuously in anesthetized dogs, using a transit-time ultrasonic flowmeter and a laser-Doppler flowmeter. In addition, the effect of intravenous ethanol on exocrine pancreatic secretion was investigated. With a background infusion of secretin, ethanol (1.3 g/kg body wt) was infused intravenously over a 40-min period. Ethanol infusion significantly increased blood flow in the common hepatic artery (by 49%, at the time of the cessation of ethanol infusion), and this increased flow was maintained for 60 min after the cessation of ethanol infusion. In contrast, blood flow in the portal vein was not altered significantly by ethanol. Pancreatic blood flow and secretion showed no significant difference from those seen in the controls. Our data suggest that intravenous ethanol induces a redistribution of the splanchnic blood flow. The increased hepatic arterial flow seen in response to ethanol may play an important role in preventing ethanol-induced hypoxic liver damage.

Animals↗

Effects of synthetic human gastric inhibitory polypeptide on splanchnic circulation in dogs.

Changes in blood flow in the celiac artery, superior mesenteric artery, and pancreas in response to an intravenous injection of synthetic human gastric inhibitory polypeptide (GIP) were determined simultaneously and continuously in anesthetized dogs, using a transit-time ultrasonic flowmeter and a laser-Doppler flowmeter. Injection of GIP significantly increased superior mesenteric arterial flow in a dose-related manner (by 9%, 43%, and 139% at 30 s after an injection at the doses of 3, 50, and 800 pmol/kg, respectively). In contrast, celiac arterial flow was not significantly altered by GIP at any of the three doses. Calculated vascular resistance in the superior mesenteric artery decreased after GIP infusion, whereas that in the celiac artery was not changed by GIP. Pancreatic blood flow decreased significantly after GIP injection at the doses of 50 and 800 pmol/kg (by 11% and 17%, respectively). Our data indicate that there is a substantial difference in the hemodynamic responses to GIP among splanchnic organs, and suggest that GIP acts specifically on the mesenteric vasculature.

Animals↗