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Biomedical subjects

S Sumi

Publications and source records attributed to S Sumi.

At least 19 recordsLinked to original sources

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

Inhibition of pancreatic adenocarcinoma cell growth by lovastatin.

RAS protein (p21 ras) requires farnesyl (an intermediate of cholesterol synthesis) for activation. Activating mutations of K-ras gene have been detected in most human pancreatic adenocarcinomas. In the present study, the effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, the rate-limiting enzyme of cholesterol synthesis, on the growth of five pancreatic cancer cell lines (human-CAV, MIA Paca2, CAPAN2 and PANC1, and hamster-H2T) in vitro and of two cell lines (CAV and H2T) in vivo was examined. Inhibition of cell growth was observed with lovastatin doses at or above 2.5 micrograms/mL for H2T, CAV, MIA Paca2, and CAPAN2 or 10 micrograms/mL in PANC1. The H2T cell line was studied further to determine the reversibility of growth inhibition. Mevalonic acid (1 mmol/L) reversed lovastatin-induced inhibition of cell growth if it was added with lovastatin (2.5 micrograms/mL). Similarly, removal of lovastatin from the medium within 24 hours after treatment allowed recovery of cell growth. The effect of lovastatin on cell growth was irreversible after 48 hours of exposure. The survival fraction of H2T cells was markedly decreased by 1- or 24-hour exposure to 75 micrograms/mL but not to doses ranging from 0.5 to 60 micrograms/mL of lovastatin. Growth of pancreatic carcinoma xenografts (CAV and H2T) in nude mice was inhibited by a subcutaneous infusion of lovastatin (50 micrograms/h). These results indicate that mevalonic acid or a metabolite in the cholesterol synthesis pathway is necessary for growth of pancreatic cancer cells and suggest that lovastatin should be further examined as a potential therapeutic agent for pancreatic cancer.

Animals

Gallbladder sludge and stone formation in relation to contractile function after gastrectomy. A prospective study.

In a prospective trial to determine whether gastric surgery induces gallbladder sludge and stone formation, 48 patients with gastric cancer were ultrasonographically examined with simultaneous observation on changes in gallbladder contractile function before and serially for 5 years after gastrectomy. Gallbladder sludge formation was induced with a high frequency of 42% 1 month after gastrectomy, with corresponding significant lowering of gallbladder contractile function. Most of gallbladder sludges, however, disappeared within 12 months in relation to the gradual recovery of gallbladder contractile function. Conversely, gallstone developed in nine patients (18.8%), mostly more than 6 months after gastrectomy. Interestingly, gallstone formation was induced in seven patients who were sludge negative. An evolvement of gallbladder sludge into stone was observed in only two patients, who were, however, treated with intravenous hyperalimentation. This study first provides evidence for the relationship between gastrectomy and a considerably high frequency of incidence of gallbladder sludge and stone in relation to changes in gallbladder kinetics after gastrectomy.

Adult

Structural requirements of peptide YY for biological activity at enteric sites.

Peptide YY (PYY) is a colonic hormone consisting of 36 amino acids that is a potent inhibitor of pancreatic exocrine, gastric acid, and insulin secretion. The objective of the present experiments was to characterize the structural requirements of PYY for inhibition of pancreatic exocrine, gastric acid, and insulin secretion, using conscious dogs prepared with gastric and pancreatic fistulas. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (400 pmol.kg-1 x h-1) inhibited cholecystokinin-8-stimulated (25 pmol.kg-1 x h-1) pancreatic exocrine secretion (P < 0.05); however, PYY-(1-10), PYY-(1-20), PYY-(6-36), PYY-(10-36), PYY-(13-36), PYY-(24-36), and PYY-(27-36) did not inhibit pancreatic exocrine secretion. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (200, 400, 800 pmol.kg-1 x h-1) inhibited pentagastrin (0.5 microgram.kg-1 x h-1)-stimulated gastric acid secretion (P < 0.05), as well as 2-deoxy-D-glucose-stimulated insulin release (75 mg/kg) in a dose-related manner. PYY-(6-36), PYY-(13-36), and [Leu31, Pro34] neuropeptide Y did not inhibit either gastric acid secretion or insulin release. In the gastric acid and insulin secretion bioassays, PYY-(1-36) was significantly more potent than PYY-(3-36) and PYY-(4-36); however, in the pancreatic exocrine secretion bioassay, the inhibitory effects of PYY-(3-36) and PYY-(1-36) did not differ significantly. PYY-(4-36) was less potent than PYY-(1-36) on pancreatic exocrine secretion.(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

Release of peptide-YY from the dog pancreas.

The objectives of this study were to characterize the distribution of immunoreactive peptide-YY (PYY) in the dog pancreas and to examine whether vagal stimulation can release PYY from the pancreas. Levels of pancreatic polypeptide (PP) were also measured. PYY levels in extracts of the right lobe (0.43 +/- 0.03 ng/mg tissue) and head (0.35 +/- 0.12 ng/mg tissue) of the pancreas were approximately 10- to 20-fold higher than those in extracts of the stomach (0.03 +/- 0.01 ng/mg tissue; P less than 0.05) and left lobe of the pancreas (0.02 +/- 0.01 ng/mg tissue). However, PYY levels in extracts of the pancreas and stomach were significantly lower than PYY levels in extracts of the colonic mucosa (7.63 +/- 0.71 ng/mg tissue). PP levels were significantly (300-fold) higher in pancreatic extracts than in stomach and colonic extracts. Immunoreactive PYY and PP in pancreatic and colonic mucosal extracts coeluted with synthetic PYY and PP standards on HPLC. Electrical vagal stimulation of dogs resulted in a significant (P less than 0.05) release of PYY and PP, which was abolished by atropine treatment (2 mg/kg, iv). PYY levels in the pancreatic veins increased more quickly than in the peripheral veins. The integrated levels of PYY in the pancreatic veins [1.63 +/- 0.30 ng (0-30 min)/ml] were significantly (P less than 0.05) higher than those in peripheral veins [0.86 +/- 0.16 ng (0-30 min)/ml], but lower than those in colonic veins [3.14 +/- 0.22 ng (0-30 min)/ml]. Our results indicate that PYY is primarily produced in the colon; however, the pancreas contains a measurable amount of PYY, which is mainly distributed in the right lobe and head of the pancreas. In addition, PYY can be released from the pancreas in response to vagal stimulation. These data suggest that pancreatic PYY may participate in the regulation of pancreatic and gastrointestinal functions through endocrine and paracrine actions.

Animals

Role of extracellular magnesium in insulin secretion from rat insulinoma cells.

Magnesium (Mg2+) is an abundant intracellular cation that participates in the regulation of the intracellular concentration of ATP. In this study, we examined the relationship between insulin secretion and intracellular free Mg2+ ([Mg2+]i) in a rat-insulinoma cell line (RIN m5F), using a fluorescent dye (Mag-fura-2). KCI, forskolin, and D-glyceraldehyde increased [Mg2+]i and insulin secretion from RIN m5F cells in a dose-dependent fashion. Verapamil, a voltage-dependent Ca2+ channel blocker, inhibited the increase of [Mg2+]i that was evoked by KCI, forskolin, and D-glyceraldehyde. In a Mg(2+)-free buffer, these agents failed to cause an elevation in [Mg2+]i; however, the insulin response to KCI and forskolin was enhanced, compared with that in the presence of Mg2+ (1.25 mM). Our findings suggest that [Mg2+]i is dependent upon extracellular Mg2+, and the influx through the voltage-dependent Ca2+ channel. Mg2+ may competitively inhibit the voltage-dependent Ca2+ channel, which is known to play a role in insulin secretion. An absence of Mg2+ in the extracellular space may result in enhanced insulin secretion. [Mg2+]i may play a role in insulin secretion from RIN m5F cells.

Animals

Circumvention of multidrug resistance in human carcinoma KB cells by polyether antibiotics.

We examined the effect of various polyether antibiotics on colchicine resistance in multidrug-resistant KB-C4 cells which exhibit about 4,000-fold resistance to colchicine. As a result, 4 out of 14 polyether antibiotics were found to reverse colchicine resistance. Among them, laidlomycin was the most potent. It potentiated colchicine cytotoxicity on KB-C4 cells about 700-fold at 1 microgram/ml. Degree of potentiation was calculated by dividing of the IC50 value of colchicine in the absence of a polyether antibiotic by the IC50 value of colchicine in the presence of the polyether antibiotic. Monensin, dianemycin, and leuseramycin at 3 micrograms/ml also potentiated the cytotoxicity, about 100-fold. We previously reported that inostamycin is a potent chemosensitizer in KB-C4 cells. Although lysocellin has a structure very similar to that of inostamycin, it didn't reverse colchicine resistance. It slightly increased [3H]vinblastine accumulation in KB-C4 cells and weakly inhibited the [3H]vinblastine binding to KB-C4 plasma membranes.

Anti-Bacterial Agents

Experimental hybrid islet transplantation: application of polyvinyl alcohol membrane for entrapment of islets.

In this study, we first examined in vitro a polyvinyl alcohol membrane to be used to contain hybrid islet cells, and second we tested a bioartificial pancreas with entrapment of pancreatic islets in polyvinyl alcohol membrane in rats with experimentally induced diabetes. The permeability of the polyvinyl alcohol membrane to different substances was studied in a two-cell chamber system. Glucose, insulin, and nutrients passed through the membrane easily, whereas the passage of immunoglobulin G was completely prevented, indicating that this membrane could be effective in protecting the bioartificial pancreas from immunorejection. Approximately 2,000 islets collected from three Sprague-Dawley rats were enclosed in a mesh-reinforced polyvinyl alcohol tube and transplanted into the peritoneal cavity of six Wistar rats with streptozotocin-induced diabetes. Their nonfasting serum glucose levels were significantly decreased for at least 12 days. Six diabetic rats receiving intraperitoneal transplantation of free islets without the tube showed a slight but significant decrease in nonfasting serum glucose levels for only 3 days. One diabetic rat with transplantation of the bioartificial pancreas had a significant and sustained decrease in nonfasting glucose levels from pretransplanted levels of 440-500 mg/dl to a mean value of 162 +/- 13 mg/dl for over 3 months without immunosuppression. The bioartificial pancreas was then removed, and glucose levels gradually increased to over 500 mg/dl. The results of the present study suggest that a bioartificial pancreas with entrapment of islets in a polyvinyl alcohol membrane could be a promising therapeutic approach to diabetes mellitus.

Animals

[CT appearance of small renal angiomyolipoma].

Twenty-six small renal angiomyolipomas (AML) in 21-patients, detected incidentally by ultrasonography, were evaluated with CT. Conventional CT findings of AML were classified into three types by the degree of the fatty areas in the mass. Type 1 is a mainly fat density mass like a lipoma observed in 7 lesions (26.9%). Type 2 is a fatty mass intermixed with areas of tissue density and found in 15 lesions (57.7%). Type 3 is a mass without fatty portion and observed in 4 lesions (15.4%). These latter lesions were indistinguishable from renal cell carcinoma on CT. It is important to diagnose a small lesion of the kidney as AML correctly for proper treatment.

Adult

[Macroscopic tumor thrombus in renal cell carcinoma].

Prognosis of 114 patients treated for renal cell carcinoma from 1972 to 1988 was investigated to evaluate intravenous tumor extension as a prognostic factor. Those in whom presence or absence of macroscopic tumor thrombus was not confirmed were not included in the current patient group. Tumor stages were evaluated according to TNM criteria except that intravenous tumor thrombus was not counted for local staging. Incidence of T3 and T4 tumors, distant metastasis and grade 3 anaplasia (G3) were higher in V+ group (V1 + V2) than in V0 group, which appeared to be a major difference of background making 5-year actuarial survival rates in V1 and V2 patient groups worse than in V0. Therefore, 5-year actuarial survival rates in N0 and M0 cases receiving radical nephrectomy were compared and found 83.3% in V2 group, 54.4% in V1 and 87.3% in V0. Since V1 group included G3 tumors more frequently than the other two groups, 5-year survival rates were further compared after excluding those with G3 tumors and found to be identical among V0, V1 and V2 groups. The current results indicate that macroscopic intravenous extension of renal cell carcinoma is an accompanied phenomenon secondary to high grade and invasive tumors and therefore, not a primary risk factor for prognosis. Accordingly, it is questionable to regard macroscopic tumor thrombus itself as a risk factor for clinical staging.

Adult

Experimental studies on the interrelationship between organs mediated by peptide YY: effect on splanchnic circulation and exocrine pancreas in dogs.

Peptide YY (PYY) which is most likely to mediate colonic inhibition on digestive organs is also a potent vasoconstrictor. However, very little is known about the effect of circulating PYY on splanchnic blood flow. This study examined the effect of systemic administration of peptide YY on splanchnic circulation and exocrine pancreas in dogs. Under secretin stimulation, intravenous administration of PYY (0.1, 0.5, 1 and 2 micrograms/kg) significantly decreased pancreatic secretion volume and blood flows in the pancreatic tissue, the superior mesenteric artery and the celiac artery in a dose-related manner. At the same time, PYY increased mean blood pressure. Under secretin plus cholecystokinin stimulation, PYY (1 micrograms/kg) significantly inhibited pancreatic secretion volume and protein output. This study first shows that PYY potently reduces celiac arterial blood flow as well as intestinal blood flow at such doses that PYY inhibits exocrine pancreatic secretion.

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 human cholecystokinin-33 on pancreatic blood flow in dogs.

We have examined the effect of synthetic human cholecystokinin (CCK-33 and CCK-8) on pancreatic blood flow and protein output in anesthetized dogs. Human CCK-33 and CCK-8 increased pancreatic blood flow and protein output in a dose-related manner. There were no significant differences in increasing pancreatic blood flow between human CCK-33 and CCK-8, and increases in blood flow were closely related to the increase of the pancreatic enzyme secretion. L-364,718 (20 nmol/kg) caused a potent inhibition of CCK-stimulated pancreatic blood flow as well as protein output. The degree of inhibition by L-364,718 was dependent on the amount of CCK infused. This study demonstrates that increasing effect on pancreatic blood flow may be one of the biological actions of CCK mediated via CCK receptor. The CCK-33, one of longer molecular forms of CCK, is an important biological stimulator of pancreatic blood flow as well as of exocrine pancreatic secretion.

Animals

Interstitial deletion of the short arm of chromosome 4 in a boy with mild psychomotor retardation and dysmorphism.

A 17-month-old boy is reported with 46,XY,del(4) (p15.2p15.32). He had mild psychomotor retardation and multiple minor anomalies, without growth retardation or microcephaly, which differs from the classical 4p--syndrome (Wolf-Hirschhorn syndrome). The activity of dihydropteridine reductase, a genetic marker for chromosome 4p15.3, was half that in a normal control.

Chromosome Deletion

Probable assignment of the dihydropteridine reductase gene to 4p15.31.

We report the dihydropteridine reductase (DHPR) activity in cases with interstitial deletion of the short arm of chromosome 4. Case 1 with the segment 4p15.32-4p16 deleted has normal DHPR activity. Case 2 with 4p15.2-4p15.32 deleted has reduced DHPR activity, less than 50% of normal.

Chromosome Banding

Acute megakaryoblastic leukemia in Down syndrome, following thrombocytopenia with antiplatelet antibody.

We report a case of acute megakaryoblastic leukemia (AMKL) with antiplatelet antibody in a boy with Down syndrome. When the patient was admitted, his platelet count was 1.3 X 10(4)/mm3 and antiplatelet antibody in the plasma was detected. Two months after admission, blasts, which showed positive reaction to both antiplatelet monoclonal antibody and platelet peroxidase, increased.

Autoantibodies