Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 613 records · Page 34Linked to original sources

PubMed1997

Role of nitric oxide in pathogenesis of serotonine-induced gastric lesions in rats.

We investigated the role of nitric oxide (NO) in the development of gastric mucosal lesions induced by serotonine (5-HT) in rats. Repeated subcutaneous administration of 5-HT (20 mg kg-1) produced damage in the stomach with severe edema in the submucosa. Gastric lesions induced by 5-HT were prevented by simultaneous administration of aminoguanidine, a selective inducible NO synthase (iNOS) inhibitor, as well as by methysergide, a 5-HT antagonist. In addition, the lesions were inhibited by pretreatment with the antioxidative drugs, such as allopurinol (a xanthine oxidase inhibitor) and hydroxyurea (a neutrophil reducing agent). Following 5-HT treatment, the Ca(2+)-independent NOS activity in the gastric mucosa was significantly increased within 6 h and remained elevated for 2 days thereafter. The serum NOx levels increased 12 h after the administration of 5-HT, reaching a peak 24 h later. Gastric mucosal thiobarbituric acid (TBA) reactants and myeloperoxidase (MPO) activity were also significantly increased after 2 days treatment with 5-HT. Our results suggest that: (1) the repeated administration of 5-HT induced inflammatory gastric lesions in the rat stomach; (2) iNOS is upreguated during 5-HT treatment, and NO produced by iNOS contributes to development of gastric lesions in response to 5-HT, in addition to the oxyradical formation, and (3) the deleterious role of NO in this model may be accounted for by a cytotoxic action of peroxynitrite that is formed in the presence of NO and superoxide radicals.

Animals↗

PubMed1997

Effect of lipopolysaccharides on erythrocyte flow velocity in rat liver.

Although endotoxin exacerbates hepatic microcirculatory disturbance, little is known of the way in which it acts on the hepatic microcirculation. We measured endotoxin-induced changes in hepatic microcirculation and investigated the effect of endotoxin on hepatic microcirculation in rats. After male Wistar rats were anesthetized, a lobe of the liver was observed with an inverted intravital microscope. Erythrocytes (RBC) were labeled with fluorescein isothiocyanate (FITC) and injected. The flow velocity (FV) of FITC-RBC in sinusoids was measured with an off-line velocimeter. Portal pressure (PP) and mean arterial pressure (MAP) were measured with a catheter cannulated in the portal vein and the left carotid artery, respectively. After a small dose (1 mg/kg) of endotoxin had been administered intravenously, FV decreased and PP increased gradually after 30 min. MAP showed no significant change, except for an initial decrease. However, when 5 mg/kg of endotoxin was administered, FV and PP increased, with a peak at 10 min, which was not observed with the small dose. In the late phase, FV decreased and PP increased, as was seen with the small dose. Endotoxin increased serum aspartate aminotransferase and lactate dehydrogenase activities. These results suggest that endotoxin induces hepatic microcirculatory disturbance, which may cause liver injury.

Alanine Transaminase↗

PubMed1997

Elevated levels of type II soluble tumor necrosis factor receptors in the bronchoalveolar lavage fluids of patients with sarcoidosis.

Since tumor necrosis factor (TNF) is known to be involved in granuloma formation in sarcoidosis, and soluble TNF receptors (sTNF-Rs) inhibit TNF action in vivo, we evaluated the levels of sTNF-Rs in the bronchoalveolar lavage fluids (BALF) of 31 subjects using an enzyme-linked immunosorbent assay. Our group consisted of 13 patients with sarcoidosis (7 sarcoidosis patients who received no treatment and 6 who received corticosteroid therapy) and 18 control subjects (11 healthy nonsmokers and 7 asymptomatic smokers). Type II (75-kDa), but not type I (55 kDa) sTNF-R in BALF was elevated significantly in patients with sarcoidosis compared with the healthy nonsmokers (type I: 126.7 +/- 17.6 pg/ml BALF vs 79.4 +/- 16.5 pg/ml BALF, p > 0.05; type II: 98.3 +/- 27.8 pg/ml BALF vs 26.7 +/- 4.9 pg/ml BALF, p < 0.05). Although levels of type I sTNF-R in BALF from sarcoidosis patients were not correlated with any cellular profiles of BALF, concentrations of type II correlated significantly with the numbers of lymphocytes in BALF. We concluded that sTNF-R is a normal constituent of the epithelial lining fluids and that levels of type II sTNF-R are elevated significantly in the BALF from individuals with sarcoidosis. This suggests that sTNF-Rs may influence the local bioactivity of TNF and may also contribute to the pathogenesis of sarcoidosis.

Antigens, CD↗

PubMed1997

Role of peptide YY in regulation of duodenal motility during the interdigestive period in sheep.

Temporal coordination between duodenal migrating myoelectric complexes (MMC) and pancreatic exocrine secretion, and the effects of porcine peptide YY (PYY) on gastroduodenal motility and pancreatic exocrine secretion were examined during the interdigestive period in conscious mature sheep. Fluid and enzyme secretions from the exocrine pancreas showed a periodic pattern corresponding to the phases of duodenal MMC, although these secretion rates were maintained at a high level during phase II in sheep. Intravenous continuous infusion of PYY at doses ranging from 50 to 200 pmol.kg-1.h-1 or intravenous bolus infusion of PYY at doses ranging from 50 to 200 pmol.kg-1 showed a tendency to prolong the first cycle of the duodenal MMC and significantly shorten the second cycle. However, there was almost no effect on ruminal contractions from the PYY administration. In the pancreatic exocrine secretion, PYY could inhibit only bicarbonate secretion at only the highest dose of 200 pmol.kg-1. These results imply that endogenous PYY may play a physiological role in the regulation of the duodenal MMC cycles in sheep but not in ruminal contractions. PYY seems unlikely to regulate the pancreatic exocrine secretion in normal sheep, because a supraphysiological dose of PYY was required to inhibit the pancreatic exocrine secretion.

Amylases↗

PubMed1997

Fine structure and distribution of lymphatic vessels in the human dental pulp: a study using an enzyme-histochemical method.

The existence of lymphatic vessels in the human dental pulp and their distribution were established by light and electron microscopy using an enzyme-histochemical method. The distinction between lymphatic and blood vessels was made by light microscopy on cryostat sections of undecalcified and decalcified teeth using 5'-nucleotidase(5'-Nase)-alkaline phosphatase double staining. On the tissue surface, 5'-Nase-positive lymphatic vessels were highlighted with good contrast and resolution by backscattered electron imaging using scanning electron microscopy. By transmission electron microscopy, dense granular precipitations resulting from the 5'-Nase reaction were seen on the luminal surface of the lymphatic endothelial cells as well as in the area at the basal side, but were absent in the blood vessels. These lymphatic vessels were more numerous in the central part than in the peripheral odontoblastic layer.

5'-Nucleotidase↗

PubMed1997

Lack of association between variants of the angiotensinogen gene and the risk of coronary artery disease in middle-aged Japanese men.

The renin-angiotensin system is important in cardiovascular remodeling. Although a variant of the angiotensinogen gene is associated with an increased generation of angiotensinogen, it is unclear how this genetic variant might influence the activity of the renin-angiotensin system and thereby contribute to the predisposition to coronary artery disease (CAD). The relation between genetic polymorphisms in the gene-encoding angiotensinogen and the risk of CAD in middle-aged Japanese men was investigated. Two polymorphisms in exon 2 of the angiotensinogen gene, M235T and T174M, were analyzed in 327 patients with CAD and 352 matched control subjects. The genotype distribution of both polymorphisms did not differ between patients with CAD and control subjects. No combination of genotypes of the two polymorphisms was associated with CAD. Results indicate that the M235T and T174M variants of the angiotensinogen gene are not associated with CAD in Japanese men.

Angiotensinogen↗

PubMed1997

Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol.

BACKGROUND & AIMS: The precise pathogenic significance of oxidative injury in the evolution of alcohol-induced liver disease is still obscure. The present report was designed to investigate whether ethanol alters the production of active oxidants and biological activities of hepatocytes. METHODS: The following parameters in rat hepatocytes were investigated by using fluorescence probes in vitro and ex vivo: (1) mitochondrial membrane potential and membrane permeability transition, (2) oxygen radicals generation, (3) membrane barrier function, and (4) glutathione level. RESULTS: Ethanol (50 mmol/L) increased oxidative stress in hepatocytes and subsequently induced an increased mitochondrial permeability transition and a decreased membrane potential. These ethanol-induced alterations were attenuated by an inhibitor of alcohol dehydrogenase and an intracellular oxidant scavenger, whereas they were enhanced by diethyl maleic acid, a glutathione depletor. Ethanol plus diethyl maleic acid but not ethanol alone increased the number of hepatocytes with membrane barrier dysfunction. A continuous infusion of ethanol (50 mmol/L) increased oxidative stress and decreased mitochondrial membrane potential in the pericentral area of isolated perfused rat liver. CONCLUSIONS: Active oxidants generated during ethanol metabolism increase mitochondrial permeability transition and modulate mitochondrial energy synthesis in hepatocytes. Reduction of glutathione level enhances mitochondrial dysfunction and impairs membrane barrier function of hepatocytes.

Alcohol Dehydrogenase↗

PubMed1997

Endoscopic hemostasis of bleeding duodenal ulcer in a child with Henoch-Schönlein purpura.

A 9-year-old boy with Henoch-Schönlein purpura had a duodenal ulcer. Endoscopic injection with pure ethanol was performed on a pulsating visible vessel in the third part of the duodenum, resulting in complete hemostasis. A bleeding ulcer, although rare, may be a serious gastrointestinal complication of Henoch-Schönlein purpura and may require aggressive intervention.

Anemia↗

PubMed1997

Failure of the nitric oxide synthase inhibitor to stimulate duodenal bicarbonate secretion in streptozotocin-diabetic rats.

We examined the HCO(3)- stimulatory effects of L-NAME (N(G)-nitro-L-arginine methyl ester) in the proximal duodenum of streptozotocin (STZ)-induced diabetic rats and compared with those of 16,16-dimethyl prostaglandin E2 (dmPGE2) and vagal electrical stimulation. Male SD rats were given STZ (70 mg/kg) i.p., and the experiments were done using 1 approximately 6 week STZ-diabetic rats with blood glucose levels of >300 mg/dl. Under urethane anesthesia the HCO(3)- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. Hyperglycemic conditions appeared 1 week after STZ treatment and remained during 6 week-test period. The duodenal HCO(3)- secretory response to L-NAME was significantly decreased in STZ-diabetic rats; the degree of reduction was dependent on the duration of diabetes, and the stimulatory effect disappeared completely in rats after 5 approximately 6 weeks of diabetes. Intravenous administration of L-NAME markedly increased arterial blood pressure with significant decrease in heart rate in normal rats, whereas in STZ-diabetic rats this agent caused only pressor response without any effect on heart rate. STZ-diabetic rats also secreted significantly less amount of HCO(3)- from the duodenum in response to dmPGE2 and vagal electrical stimulation after 5 approximately 6 weeks of diabetes. These all changes observed in STZ-diabetic rats were significantly reversed by daily injection of insulin. These results suggest that 1) L-NAME failed to stimulate duodenal HCO(3)- secretion in STZ-diabetic rats, and 2) impairment of the duodenal HCO(3)- secretory ability in STZ-diabetic conditions is due to both vagal-dependent neuronal dysfunction and decreased sensitivity of the secreting cell.

16,16-Dimethylprostaglandin E2↗

PubMed1997

Effects of proglumide on cholecystokinin-8-induced exocrine and endocrine pancreatic responses in conscious sheep.

The effects of cholecystokinin (CCK)-8, either alone or together with the CCK antagonist, proglumide on both exocrine and endocrine pancreatic responses were examined in conscious sheep. Intravenous infusions of CCK-8 (120 pmol/kg/min for 40 min) with vehicle (0 mumol/kg/min proglumide) significantly increased both amylase output in pancreatic juice and plasma insulin concentrations (P < 0.05). Concomitant infusions of proglumide (5-40 mumol/kg/min for 50 min) inhibited both amylase and insulin secretory responses induced by CCK-8 infusion. The antagonistic effects of proglumide occurred in a dose-dependent manner, and proglumide infusion at dose of 20 mumol/kg/min or above simultaneously inhibited CCK-8-induced amylase and insulin responses. In conclusion, although the type of receptor involved is not characterized at present, exogenously infused CCK-8 acts on B cells via a CCK-receptor-mediated mechanism and induces insulin secretion in sheep.

Amylases↗

PubMed1997

Cloning of chick cellular retinol-binding protein, type II and comparison to that of some mammals: expression of the gene at different developmental stages, and possible involvement of RXRs and PPAR.

We cloned chick cellular retinol-binding protein, type two (CRBP II) cDNA and compared it with those of some mammals. The deduced amino acid sequence showed that chick CRBP II was one amino acid greater in size than those of mammals, and the nucleotide sequence of chick CRBP II shared 72%-75% similarity with those of mammals. RNA blot hybridization analysis showed that CRBP II transcript of 0.7 kb was first detected in the duodenum of day-18 embryonic chick, and exhibited a rapid increase during 24 hr around the hatching. Northern blot hybridization also revealed that the transcripts of two types of retinoid X receptors (RXR alpha and RXR gamma) and peroxisome proliferator-activated receptor (PPAR) were expressed in the chick duodenum at hatching. The organ culture of day 16 embryonic chick duodenum showed that the addition of 9-cis retinoic acid in the medium caused a significant increase in CRBP II mRNA levels. In addition, arachidonic acid, from which putative ligands for PPAR were supposed to be generated, was accumulated around hatching in the duodenum. The results may suggest that the abrupt increase of the CRBP II gene expression in the chick duodenum around hatching may be related with RXRs and/or PPAR.

Animals↗

PubMed1997

Revascularization with split duro-encephalo-synangiosis in the pediatric moyamoya disease--surgical result and clinical outcome.

Dural arteries are potential donor arteries for cortical revascularization. In this report, a technique of indirect anastomosis using a split dura is presented. At surgery, the dura near the branches of the middle meningeal artery was split into outer and inner layers, and the split surface of the outer layer was attached to the cortical surface (split duro-encephalo-synangiosis; split DES). This procedure, combined with standard encephalo-duro-arterio-synangiosis, was applied to 25 hemispheres in 18 patients with pediatric Moyamoya disease (mean age, 6 years). Postoperative superselective angiograms demonstrated effective cortical revascularization through the dural arteries in addition to the supply from the scalp arteries. All the patients were symptom free by 1.5 years after surgery. Postoperative reversible ischemic neurological deficit and infarction were seen in three (12%) and one (4%), respectively. The follow-up period ranged from 1 to 12 years (mean, 6.5 years). Thirteen of 16 (81%) patients led normal lives and three were mildly handicapped due to mental retardation that existed preoperatively. The split DES is a useful technique to extend the area of revascularization of ischemic hemispheres in Moyamoya disease.

Adolescent↗

PubMed1997

Nitric oxide, prostaglandin, and sensory neurons in gastric mucosal blood flow response during acid secretion in rats.

1. The mechanism underlying the increase of gastric mucosal blood flow (GMBF) during acid secretion induced by pentagastrin was investigated in anesthetized rats, in relation to nitric oxide (NO), prostaglandin (PG), and sensory neurons. 2. An intravenous infusion of pentagastrin at 60 micrograms/kg/h (submaximal dose) produced an increase of acid secretion and GMBF as determined by laser Doppler flowmetry, and the GMBF response was totally attenuated when the acid secretion was inhibited by omeprazole or when the luminal H+ was removed by mucosal perfusion with glycine (200 mM). 3. Prior administration of NG-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, IV), a NO synthase inhibitor, significantly mitigated the GMBF response to pentagastrin, without any influence on acid secretion, and this effect was antagonized by coadministration of L-arginine (500 mg/kg IP). 4. The increase of GMBF during pentagastrin infusion also was significantly mitigated by indomethyacin (5 mg/kg, SC) or sensory deafferentation following capsaicin pretreatment, had no effect on the acid secretion, and was totally inhibited by the combined treatments with indomethacin plus L-NAME in addition to sensory deafferentation. 5. Pentagastrin infusion for 8 hr did not by itself cause any macroscopic damage in the stomach, but additional treatments with L-NAME, and indomethacin plus sensory deafferentation provoked severe lesions in the gastric mucosa. 6. These results suggest that the increase of GMBF induced by submaximal dose of pentagastrin totally depends on luminal H+. This process seems to be mediated by endogenous NO and PGs, as well as capsaicin-sensitive sensory neurons, and to play a pivotal role in maintaining mucosal integrity during acid secretion.

Animals↗

PubMed1997

Irritant action of monochloramine in rat stomachs: effects of zinc L-carnosine (polaprezinc).

1. Effects of a novel zinc compound (polaprezinc), N-(3-aminopropionyl)-L-histidinato zinc, on the mucosal ulcerogenic response induced by ammonia (NH4OH) and monochloramine (NH2Cl) were examined in rat stomachs. 2. Oral administration (1 ml) of NH4OH (> 600 mM) and NH2Cl (> 60 mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs, whereas hypochlorous acid (HClO) even at 120 mM did not cause any macroscopic damage. 3. Pretreatment of the animals with polaprezinc (2-12 mg/ml, 1 ml, PO) showed a dose-dependent inhibition against gastric lesions induced by NH4OH (1,800 nM) or NH2Cl (120mM), and this effect was significant at > 6 mg/ml in either case. These lesions were also significantly prevented by prior administration of dmPGE2 (2 micrograms/ml, 1 ml, PO). 4. Mucosal application of NH4OH (300 mM) and NH2Cl (10 mM) caused a marked reduction of transmucosal potential difference (PD) in ex vivo stomachs of anesthetized rats. The reduced PD responses caused by NH4OH and NH2Cl were prevented dose dependently by preexposure of the mucosa to polaprezinc, but not affected by dmPGE2. 5. Mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery (1 ml per 100 g body wt), followed by severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were attenuated by prior application of polaprezinc as well as taurine (25 mg/ml, 1 ml), while dmPGE2 prevented the lesions without affecting the reduced PD response. 6. These results suggest that (a) NH2Cl damages the gastric mucosa at much lower concentrations than NH4OH, (b) polaprezinc protects the stomach against injury caused by either NH2Cl or NH4OH, and (c) the mechanisms underlying the protective action of polaprezinc remain unclear but may be different from those of dmPGE2.

Ammonium Chloride↗

PubMed1997

Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis.

The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.

Helicobacter Infections↗

PubMed1997

CD18/ICAM-1-dependent nitric oxide production of Kupffer cells as a cause of mitochondrial dysfunction in hepatoma cells: influence of chronic alcohol feeding.

The present study was designed to monitor the process for hepatoma cell injury induced by Kupffer cells. The non-activated Kupffer cells isolated from male Wistar rats reduced the mitochondrial membrane potential in the cocultured AH70 cells, which was indicated by the decreased rhodamine 123 (Rh123) fluorescence. Increased level of nitrite and nitrate in the medium and induction of iNOS in Kupffer cells were observed after coculture with AH70 cells. Incubation with either NG-monomethyl-L-arginine or aminoguanidine attenuated the increased nitric oxide (NO) production of Kupffer cells and the decreased Rh123 fluorescence of AH70 cells. Fluo-3, a calcium-sensitive probe, fluorescence in Kupffer cells increased after coculture with AH70 cells. Addition of TMB-8, a calcium inhibitor, or monoclonal antibody directed against ICAM-1 or CD18 prevented the increases in fluo-3 fluorescence and NO production of Kupffer cells and Kupffer cell-induced mitochondrial dysfunction in AH70 cells, suggesting the involvement of calcium mobilization and CD18/ICAM-1. It is therefore suggested that the Kupffer cell-mediated mitochondrial dysfunction of hepatoma cells largely depends on NO production by iNOS, and that the NO production by Kupffer cells is triggered by CD18/ICAM-1-dependent interaction with hepatoma cells and subsequent calcium mobilization. In other series of experiments, male Wistar rats fed ethanol for 4 weeks were used. The NO production and calcium mobilization of Kupffer cells and reduction of the mitochondrial membrane potential in cocultured hepatoma cells were diminished in the case of Kupffer cells isolated from chronically ethanol-fed rats, while CD18 and ICAM-1 expression was still observed. Thus, the present study further suggests that NO-dependent anti-hepatoma cell activity of Kupffer cells is suppressed in chronically ethanol-fed animals.

Alcoholism↗

PubMed1997

Lack of association of angiotensin converting enzyme gene polymorphism or serum enzyme activity with coronary artery disease in Japanese subjects.

The association of an insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene or the serum activity of ACE with coronary artery disease (CAD) was investigated in Japanese men and women. The ACE genotype of 947 CAD subjects who underwent coronary angiography and of 893 control subjects was determined by polymerase chain reaction analysis. No association of the DD genotype or the D allele with CAD was observed in men or women. In a low risk group (defined by a body mass index below the median value and the absence of a history of hypertension, diabetes mellitus, and hypercholesterolemia), there was also no association between the ACE gene polymorphism and CAD. No significant difference in serum ACE activity was detected between CAD subjects and controls of all genotypes or of the same genotype, whereas a significant association was apparent between serum ACE activity and ACE genotype for both CAD subjects and controls among both men and women. These results indicate that the ACE I/D polymorphism and genotype associated variation in serum ACE activity are not risk factors for CAD in Japanese men or women.

Adult↗

PubMed1997

Primary non-Hodgkin's lymphoma of the larynx.

Three cases of primary non-Hodgkin's lymphoma of the larynx are described. Histologically, two tumours belonged to the category of low grade B-cell lymphomas of the small cell type (extranodal marginal zone B-cell lymphoma and lymphoplasmacytoid lymphoma), and the third was classified as a peripheral T-cell lymphoma of unspecified type. The clinical stage was IE in two cases, and IV in another case. In two cases, complete remission was obtained with radical radiotherapy. But in the other case, which was histologically lymphoplasmacytoid lymphoma, the response to radiotherapy was poor, and surgery was required. There was no relapse subsequent to treatment. Primary non-Hodgkin's lymphoma of the larynx is rare. Several reported cases have clinical features similar to those of MALT-type lymphomas arising in other extranodal sites. Although most of the reported cases have been cured with radiotherapy, in some cases dissemination to other extranodal sites may occur. Therefore careful periodic evaluation is imperative.

Adult↗