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Biomedical subjects

A Sugiyama

Publications and source records attributed to A Sugiyama.

At least 19 recordsLinked to original sources
PubMed1999

Molecular cloning and chromosomal mapping of mouse intronless myc gene acting as a potent apoptosis inducer.

Our previous findings suggest that the activation of the rat intronless myc gene provides a selective advantage in tumor suppression through apoptosis induction. In the present study, to examine whether intronless myc gene acting as an apoptosis inducer is evolutionarily conserved in mammalian cells, we isolated the mouse intronless myc gene and characterized it. A sequence analysis demonstrated that mouse intronless myc gene, ms-myc, has a linearly opened translatable frame consisting of 1293bp with 90% homology with that of rat s-myc. The chromosomal locus of ms-myc was identified on chromosome 19B by a fluorescent in situ hybridization (FISH) analysis. Gene transfection experiments showed that the transient overexpression of ms-Myc with transactivation activity effectively induces cell death in a wild-type p53-independent manner. In addition, cells stably expressing transfected ms-myc became more susceptible to apoptosis induced by genotoxic stress such as UV-irradiation and hydrogen peroxide compared with untransfected control cells. These observations suggest that the rodents commonly contain an s-myc-type of intronless myc gene with apoptosis-inducing activity.

Amino Acid Sequence↗
PubMed1999

Use of the Harmonic Scalpel in open abdominoperineal surgery for rectal carcinoma.

We describe a technique of open abdominoperineal resection with the use of the Harmonic Scalpel in seven patients. Using this instrument we dissected all pelvic vessels, including the middle hemorrhoidal artery, with no subsequent bleeding. In addition, we divided the levator ani muscles completely in the abdominal procedure alone.

Abdomen↗
PubMed1999

Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils.

The establishment of persisting Helicobacter pylori infection in laboratory animals has been difficult, but in 1996 Hirayama reported the development of a successful Mongolian gerbil model. The present study was undertaken with two aims: to better characterize the normal histological structure and histochemical properties of the gastric mucosa of the Mongolian gerbil; and to evaluate the progression of the histopathological features of H. pylori-induced gastritis in this animal model for one year after the experimental infection. Seventy-five Mongolian gerbils were used. Mongolian gerbils were sacrificed at 2, 4, 8, 12, 26, 38, and 52 weeks after H. pylori inoculation. Sections prepared from stomachs immediately fixed in Carnoy's solution were stained with hematoxylin and eosin and Alcian blue at pH 2.5/periodic acid-Schiff, a dual staining consisting of the galactose oxidase-cold thionin Schiff reaction and paradoxical Concanavalin A staining, and with immunostaining for H. pylori and BrdU. H. pylori infection induced in the Mongolian gerbil a chronic active gastritis, in which a marked mucosal infiltration of neutrophils on a background of chronic inflammation became detectable 4 weeks after inoculation and continued up to 52 weeks. Intestinal metaplasia and gastric ulcers appeared after 26 weeks in some of the animals, whereas others developed multiple hyperplastic polyps. The Mongolian gerbil represents a novel and useful model for the study of H. pylori-induced chronic active gastritis and may lend itself to the investigation of the epithelial alterations that lead to intestinal metaplasia and gastric neoplasia.

Animals↗
PubMed1999

Additional microvascular anastomosis in reconstruction after total esophagectomy for cervical esophageal carcinoma.

BACKGROUND: Maintaining sufficient blood flow to the substitute organ after total esophagectomy is essential for decreasing the risk of anastomotic leakage. Additional venous, or arterial and venous, anastomoses between the vessels of the gastric tube and the vessels in the neck after total esophagectomy are described for 11 patients with cervical esophageal carcinoma. METHODS: The tissue blood flow was measured by laser Doppler flowmetry before and after anastomosis. Venous anastomosis was performed for all 11 patients, and arterial anastomosis was added for 7 patients. RESULTS: A significant increase in tissue blood flow was observed after venous anastomosis alone (mean, 19%; P < 0.05) and after arterial and venous anastomoses (mean 43%; P < 0.01). There was no anastomotic leakage or hospital death. CONCLUSIONS: This procedure may reduce the risk of anastomotic leakage especially in the case of pharyngogastrostomy following total esophagectomy.

Anastomosis, Surgical↗
PubMed1999

Preoperative assessment of adenylylcyclase activity as a functional marker of islet cell quality after transplantation in rats.

To determine the potential value of measuring adenylylcyclase activity as a pre-transplant functional marker of pancreatic islet cell quality, a production rate of adenosine 3':5'-monophosphate was measured with a fluorometric assay in rat islet cells before transplantation. Islets were stored for different periods of time (0 to 96 hours) and in different preservation solutions. The adenylylcyclase activities of islets stored in University of Wisconsin (UW) solution for 3 hours after isolation were significantly higher than those stored in Hanks' balanced salt solution. Similarly, the adenylylcyclase activities of islets stored for more than 24 hours in UW solution decreased significantly with prolonged storage time. Preoperative adenylylcyclase activity was compared with post-transplant islet function in a rat model of diabetes. Transplant success was evaluated by measuring blood glucose level and body weight. Although all transplants were ultimately successful in this study, the rate at which they achieved euglycemia varied, and this is the property that correlated with pre-transplant basal or forskolin-stimulated adenylylcyclase activity. Additional studies showed that it was feasible to measure adenylylcyclase activity in human islet cells. We conclude that preoperative measurement of basal and stimulated adenylylcyclase activity may provide a useful clinical marker for assessing islet cell quality and differences in preservation media and may predict transplant success. Based on these data, additional studies evaluating the feasibility of using adenylylcyclase activity as a research and clinical marker of islet cell viability are warranted.

Adenylyl Cyclases↗
PubMed1999

Interleukin-10 inhibits hepatic injury and tumor necrosis factor-alpha and interferon-gamma mRNA expression induced by staphylococcal enterotoxin B or lipopolysaccharide in galactosamine-sensitized mice.

BACKGROUND/AIMS: Proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) play a critical role in the pathogenesis of liver injury induced by lipopolysaccharide (LPS) or staphylococcal enterotoxin B (SEB) in D-galactosamine (GalN)-sensitized mice. The aim of this study was to examine the ability of interleukin-10 (IL-10), a recently characterized, highly potent anti-inflammatory mediator, to protect sensitized mice against hepatotoxicity induced by SEB or LPS. METHODS: IL-10 was injected at various concentrations into BALB/c mice treated by GalN/SEB or GalN/LPS. Liver injury was assessed biochemically and histologically. Serum levels of TNF-alpha and IFN-gamma were measured and the expressions of TNF-alpha and IFN-gamma mRNA in the liver and spleen were determined by reverse-transcription polymerase chain reaction. RESULTS: Treatment with IL-10 markedly reduced serum transaminase activities in a dose-dependent manner and reduced hemorrhagic liver damage in sensitized mice exposed to either toxin. IL-10 also inhibited increases in serum TNF-alpha and IFN-gamma concentrations with either toxin. Treatment with IL-10 significantly reduced TNF-alpha mRNA and IFN-gamma mRNA expression in the liver and spleen after administration of either toxin to sensitized mice. CONCLUSIONS: These findings suggest that IL-10 is capable of regulating both T cell- and macrophage-mediated hepatic injury in vivo and that this cytokine might be useful in the treatment of acute liver failure.

Animals↗
PubMed1999

Effects of cytokines on the binding of leukocytes to cultured rat hepatocytes and on the expression of ICAM-1 by hepatocytes.

Adhesions of leukocytes to hepatocytes and sinusoidal endothelial cells mediates the induction and progression of hepatic injury. However, in contrast to endothelial cells, information regarding the regulation of interactions between leukocytes and hepatocytes is limited. In the present study, we investigated the effect of inflammatory mediators including lipopolysaccharide (LPS), staphylococcal enterotoxin B (SEB), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) on the adhesion of polymorphonuclear leukocytes or lymphocytes to primary cultured rat hepatocytes, and on the expression of intercellular adhesion molecule-1 (ICAM-1) gene in hepatocytes. Both polymorphonuclear leukocyte and lymphocyte adhesion to hepatocytes were enhanced after exposure of hepatocytes to IFN-gamma and TNF-alpha, but not after exposure to LPS, SEB or IL-1beta. The adhesion induced by either IFN-gamma or TNF-alpha was inhibited by monoclonal antibodies against ICAM-1 or lymphocyte function-associated antigen-1 (LFA-1). Nonstimulated hepatocytes expressed faintly ICAM-1 mRNA, which increased slightly during the culture period. ICAM-1 mRNA expression was up-regulated to a greater extent by incubating hepatocytes with IFN-gamma or TNF-alpha, and peaked after 12 hr of incubation with TNF-alpha and after 24 hr with IFN-gamma. These results indicate that IFN-gamma and TNF-alpha induce the expression of ICAM-1 on parenchymal hepatocytes and that the LFA-1-ICAM-1 pathway plays an important role in the interaction between hepatocytes and neutrophils or lymphocytes.

Animals↗
PubMed1999

Protective effect of aged garlic extract on the small intestinal damage of rats induced by methotrexate administration.

The methotrexate (MTX) administration to rats causes the damage of small intestine. The small intestinal damage was evaluated by measuring the intestinal permeability of the poorly absorbable compound, fluorescein isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) (FD-4) using the in vitro everted intestine technique and by determining the FD-4 that appeared in plasma using the in situ closed loop intestine technique. The MTX administration to rats fed with the standard laboratory diet increased the small intestinal permeability of FD-4 due to the damage of the small intestine. Interestingly, the permeability of FD-4, when MTX was administered to rats fed with the aged garlic extract containing diet, was depressed almost to the level of control rats without the MTX treatment. The present study showed that the aged garlic extract protected the small intestine from the damage induced by the action of MTX on the crypt cells.

Animals↗
PubMed1999

Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils treated with chemical carcinogens.

Helicobacter pylori (Hp) is thought to be a stomach carcinogen from epidemiological findings. To determine the effects of infection with the bacteria on experimental carcinogenesis, a study of the glandular stomach of Mongolian gerbils (MGs) was performed. Male MGs were treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by inoculation with Hp or infected with Hp followed by N-methyl-N'-nitro-N-nitrosoguanidine administration. Animals were killed at week 50, and their excised stomachs underwent microbiological and histopathological examinations. In addition, a serological investigation was performed. The incidences of adenocarcinomas were significantly higher in animals treated with 60 or 300 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 10 weeks followed by Hp inoculation or Hp followed by 20 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine for 30 weeks than in the respective controls. Moreover, tumour-bearing animals had higher titres of anti-Hp antibodies than tumour-free animals. Of interest was the finding that a dose of 100 p.p.m. N-methyl-N'-nitro-N-nitrosoguanidine given to infected gerbils eradicated the Hp in about half the animals, with a concomitant reduction in the promoting effect. No tumours were found in animals infected with Hp without N-methyl-N'-nitro-N-nitrosoguanidine or non-treated gerbils. Hp infection enhances glandular stomach carcinogenesis in MGs treated with N-methyl-N'-nitro-N-nitrosoguanidine. Animals with high titres of anti-Hp antibodies are at greatest risk of developing neoplasms.

Adenocarcinoma↗
PubMed1999

Mark-release-recapture experiment with adult Anopheles minimus (Diptera: Culicidae) on Ishigaki Island, Ryukyu Archipelago, Japan.

Movement of adult An. minimus Theobald between larval habitats and feeding sites was investigated by mark-release-recapture in March 1993 on Ishigaki Island, Ryukyu Archipelago, Japan. Unfed (998 females) and fed (1,485 females) cohorts from a laboratory colony were marked with different colors of fluorescent dye, and released near Nishihama stream where larvae were abundant. Overall, 42 fed (2.82%) and 13 unfed (1.30%) females were recaptured. Among these, 12 females were recaptured at a cowshed, the nearest blood meal source. Most females in the fed cohort recaptured at the release point had developing or matured ovaries, whereas 55% at the cowshed were parous. The movement of released females from larval habitat to the cowshed for blood feeding indicated a flight distance > 1 km.

Animals↗
PubMed1999

Antiischemic effects of CP-060S, an inhibitor of pathologically modified sodium channels, assessed in the canine experimental model of angina pectoris.

CP-060S is a novel compound that can inhibit the slow inward calcium current as well as the veratridine-induced, noninactivating sodium current. Antiischemic and cardiovascular effects of CP-060S were assessed by using halothane-anesthetized beagle dogs and compared with the effects of semotiadil, a benzothiazine calcium antagonist. The first or second diagonal branch was narrowed. ECG, unipolar electrograms from both ischemic and nonischemic regions, and systemic and left ventricular pressure were monitored. The left ventricle was electrically driven at 190-240 beats/min for 3 min to induce reversible myocardial ischemia. The severity of ischemia was judged by the magnitude of ST-segment depression. CP-060S (0.1 mg/kg, i.v.) significantly attenuated the pacing-induced ST-segment depression in the ischemic region >2 h, whereas during the sinus rhythm, it showed reversible negative chronotropic, inotropic, and dromotropic effects and induced transient depressor response, which would not necessarily be considered favorable (n = 8). A smaller dose of CP-060S (0.03 mg/kg, i.v.) showed a similar antiischemic and cardiovascular profile, but each effect was less potent than that of the higher dose (n = 7). Semotiadil (0.1 and 0.3 mg/kg, i.v.) also showed cardiovascular suppression similar to that of CP-060S; however, the antiischemic effect was not detected during the whole experimental period (n = 6). Thus the inhibition of the noninactivating sodium current may be the primary reason for the antiischemic effect of CP-060S and could become a new cytoprotective principle in the treatment of patients with ischemic heart disease.

Angina Pectoris↗
PubMed1999

Cariporide, a highly selective Na+/H+ exchange inhibitor, suppresses the reperfusion-induced lethal arrhythmias and "overshoot" phenomenon of creatine phosphate in situ rat heart.

The effects of a highly selective Na+/H+ exchange inhibitor cariporide on the reperfused in situ heart were assessed. Male Sprague-Dawley (SD) rats weighing 200-300 g were anesthetized with pentobarbital sodium (60 mg/kg, i.p.) and divided into four groups; sham-operated (n = 6), vehicle (n = 15), 0.1 mg/kg (n = 15), and 1.0 mg/kg (n = 15) groups. The left coronary artery was ligated for 5 min and then released with ECG and blood pressure monitoring. Cariporide was intravenously given as a bolus 2 min before the reperfusion. The heart was rapidly excised and frozen 3 min after the onset of ventricular fibrillation, otherwise 10 min after the reperfusion. The adenosine triphosphate (ATP), creatine phosphate (CP), and glycogen contents were measured in the reperfused ischemic myocardium by using an enzymatic fluorometric assay technique. The incidence of the lethal ventricular fibrillation was 53% in the vehicle, 27% in the low-dose and 7% in the high-dose group. The concentrations (mean+/-SEM) of ATP, CP (nmol/mg protein), and glycogen (nmol as glucose/mg protein) were 74+/-4, 255+/-19, and 164+/-21 in the sham, 23+/-4, 763+/-70, and 61+/-7 in the vehicle, 27+/-4, 180+/-16, and 104+/-14 in the low-dose, and 32+/-4, 178+/-24, and 108+/-8 in the high-dose groups, respectively, indicating that cariporide significantly blunted CP overshoot as well as glycogenolysis during reperfusion. Thus cariporide can be expected to depress arrhythmogenesis and protect the metabolic status of the heart.

Analysis of Variance↗
PubMed1999

Can the MAP technique be applied to detect delayed afterdepolarization? Electrophysiologic and pharmacologic evidence.

The purpose of this study was to assess whether the monophasic action potentials (MAPs) technique can be applied to detect delayed afterdepolarizations (DADs). The canine isolated, blood-perfused ventricular septum preparation was used to obtain stable MAP signals (n = 8). The preparation was electrically driven by trains of 15 stimuli at each cycle length of 600-300 ms under the monitoring of MAP and papillary muscle contraction. In a basal condition, neither DADs nor premature ventricular contractions (PVCs) were induced by the train stimulation, whereas the coupling interval between electrograms of the last driven contraction and the first spontaneously developed contraction was prolonged by shortening the pacing cycle length. Then 40-45 microg of ouabain was intravenously administered into the blood-donor dog. Both DADs and PVCs were induced in all preparations by the pacing protocol 10-15 min after the ouabain injection; however, PVCs did not occur spontaneously. Small aftercontractions also were detected during the electrical pacing in four preparations. By shortening the pacing cycle length, the DADs were enhanced, the coupling interval was shortened, and the number of PVCs increased. After the administration of ryanodine, verapamil, tetrodotoxin, or lidocaine (n = 4--6), the small aftercontractions disappeared, the DADs attenuated, the coupling interval was prolonged, and the number of PVCs decreased. These observations suggest that PVCs observed in this model may be derived from the DAD-related triggered activity, and moreover, show the feasibility of recording DADs and triggered activity by the MAP technique.

Action Potentials↗
PubMed1999

Electrophysiologic, cardiohemodynamic and beta-blocking actions of a new ultra-short-acting beta-blocker, ONO-1101, assessed by the in vivo canine model in comparison with esmolol.

The purpose of this study was to assess the cardiovascular effects of an ultra-short-acting beta-blocker, ONO-1101, by using halothane-anesthetized beagle dogs in comparison with esmolol. ONO-1101 (n = 6) or esmolol (n = 6) was administered at four infusion rates of 0.3, 3, 30, and 300 microg/ kg/min. Each infusion was performed over a 30-min period, and the parameters were measured at 20-30 min after the start of each infusion. ONO-1101 significantly decreased the heart rate, rate-pressure product, left ventricular contraction, cardiac output, and relative refractory period of the right ventricle, suppressed the AV nodal conduction, and increased the effective refractory period of the right ventricle, whereas no significant change was observed in the preload and afterload of the left ventricle, intrinsic sinus nodal automaticity, His-Purkinje-ventricular conduction, and the monophasic action-potential duration of the right ventricle. The cardiovascular effects of esmolol were comparable to those of ONO-1101, except that the preload of the left ventricle was significantly increased, and the ventricular repolarization phase was shortened by 300 microg/kg/min of esmolol infusion. Meanwhile, ONO-1101 as well as esmolol significantly reduced the isoproterenol-induced increase in heart rate and ventricular contraction, but the inhibitory action of ONO-1101 was 6-8 times greater than that of esmolol. These results suggest that the suppressive effects of ONO-1101 on cardiovascular performance are significantly less potent than those of esmolol at equipotent beta-blocking doses.

Adrenergic beta-Agonists↗
PubMed1999

Cardiovascular effects of optical isomers of cibenzoline, assessed in the canine isolated, blood-perfused papillary muscle and sinoatrial node preparations.

A clinically available racemic mixture of the optical isomers of cibenzoline possesses a potent sodium channel-blocking action in addition to the moderate calcium channel-blocking action. It has been reported that the S(-)-isomer inhibits sodium channels more potently than calcium channels, whereas the R(+)-isomer suppresses the sodium channels as well as calcium channels, and that the calcium channel-blocking potency of these isomers is similar. This study was designed to assess the effects of each optical isomer of cibenzoline on ventricular contraction, coronary blood flow, and sinus node automaticity by using the canine isolated, blood-perfused papillary muscle and sinoatrial node preparations. Each isomer showed negative inotropic and chronotropic effects as well as coronary vasodilator action in a dose-dependent manner. The negative inotropic effect of S(-)-cibenzoline was 1.8 times more potent than that of R(+)-cibenzoline, whereas there was no significant difference between the isomers in the negative chronotropic and coronary vasodilator effects. These results suggest that the difference of the inotropic effects between the optical isomers of cibenzoline is mainly derived from the extent of the sodium channel-blocking action, whereas the vasodilator and negative chronotropic effects may chiefly depend on the calcium channel inhibition.

Animals↗
PubMed1999

Modulation of AV nodal and Hisian conduction by changes in extracellular space.

Previous studies have demonstrated that the extracellular space (ECS) component of the atrioventricular (AV) node and His bundle region is larger than the ECS in adjacent contractile myocardium. The potential physiological significance of this observation was examined in a canine blood-perfused AV nodal preparation. Mannitol, an ECS osmotic expander, was infused directly into either the AV node or His bundle region. This resulted in a significant dose-dependent increase in the AV nodal or His-ventricular conduction time and in the AV nodal effective refractory period. Mannitol infusion eventually resulted in Wenckebach block (n = 6), which reversed with mannitol washout. The ratio of AV nodal to left ventricular ECS in tissue frozen immediately on the development of heart block (n = 8) was significantly higher in the region of block (4.53 +/- 0.61) compared with that in control preparations (2.23 +/- 0.35, n = 6, P < 0.01) and donor dog hearts (2.45 +/- 0.18, n = 11, P < 0.01) not exposed to mannitol. With lower mannitol rates (10% of total blood flow), AV nodal conduction times increased by 5-10% and the AV node became supersensitive to adenosine, acetylcholine, and carbachol, but not to norepinephrine. We conclude that mannitol-induced changes in AV node and His bundle ECS markedly alter conduction system electrophysiology and the sensitivity of conductive tissues to purinergic and cholinergic agonists.

Acetylcholine↗
PubMed1999

Characteristic transfer of colostral components into cerebrospinal fluid via serum in neonatal pigs.

In order to evaluate the possibility of modification of brain function by colostral suckling, the characteristic transfer of colostral components into serum and cerebrospinal fluid (CSF) has been studied by SDS electrophoresis, immunoblot and ELISA methods in nonsuckling pigs. Total protein concentrations in the serum increased immediately after oral administration of bovine colostrum, reaching a peak value (7.0 +/- 0.7 g/dl) at 24 h after administration, corresponding to a 3-fold increase compared to preinfusion levels. IgG and other macromolecular components (MW 19, 000-58,000) were recognized in serum by electrophoretic and ELISA analysis. Total protein concentrations in the CSF collected from the cisterna magna also increased steeply after colostral administration, reaching a maximal value (54.1 +/- 5.0 mg/dl) at 4 h, corresponding to a 4-fold increase compared to preinfusion levels. Two colostral components (MW 19,000 and 31,000) in serum were confirmed to be present in the CSF by electrophoresis. The component of MW 19,000 was identified by immunoblot as beta-lactoglobulin. IgG in serum transferred from colostrum could not be detected in the CSF by ELISA. Lactoferrin administered into the intestine was also detected in the CSF via serum. These results indicate that some components of colostrum can be transported into the CSF via the serum, suggesting the possibility of modification of immature brain functions by colostral suckling in neonatal pigs.

Animals↗