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Biomedical subjects

M Tsuchiya

Publications and source records attributed to M Tsuchiya.

At least 199 records · Page 11Linked to original sources
PubMed1993

The effects of HA1077, a novel protein kinase inhibitor, on reductions of cerebral blood flow and glucose metabolism following acute and/or chronic bilateral carotid artery ligation in Wistar rats.

The effects of HA1077, a novel protein kinase inhibitor on local cerebral blood flow (LCBF) 2.5 h (acute) after permanent bilateral carotid artery ligation (BCAL) and on LCBF and local cerebral glucose utilisation (LCGU) one week (chronic) after BCAL were studied in conscious Wistar rats. Use was made of quantitative autoradiographic 14C-iodoantipyrine and the 14C-2-deoxyglucose techniques and 24 anatomically discrete regions of the brain. HA1077 (1 or 3 mg/kg) or saline was infused i.v. over a 30 min period. HA1077 significantly increased LCBF after acute BCAL in one of the 23 decreased regions in rats given 1 mg/kg, and in 14 of 23 decreased regions in rats given 3 mg/kg, compared to findings in the saline-treated group. Significant increases in LCBF and LCGU after chronic BCAL were noted in seven of the 13 decreased regions and in four of the 11 decreased regions in rats given 3 mg/kg, as compared to observations in the corresponding saline-treated group, respectively. The LCBF and LCGU reductions in forebrain regions with global ischaemia after acute and/or chronic BCAL were overcome by HA1077. These results suggest that HA1077 may be considered for treatment of subjects with acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Local cerebral glucose utilisation following acute and chronic bilateral carotid artery ligation in Wistar rats: relation to changes in local cerebral blood flow.

The effects on local cerebral blood flow (LCBF) and glucose utilisation (LCGU) of permanent, bilateral carotid artery ligation (BCAL) were studied in conscious Wistar rats. LCBF and LCGU were measured using quantitative autoradiographic 14C-iodoantipyrine and the 14C-2-deoxyglucose (14C-DG) techniques in 24 anatomically discrete regions of the brain. LCBF in the cerebral hemispheres 2.5 h (acute) after BCAL significantly decreased to 25-87% of the sham control, with the exception of the mammillary body. After acute BCAL, there was a heterogeneous accumulation of 14C-DG in the caudate nucleus and cerebral cortices. Only in the lateral geniculate body did LCGU significantly decrease after BCAL. One week (chronic) later, LCBF was significantly decreased in 15 (containing the caudate nucleus and all the cerebral cortices) of 24 structures. LCGU in ten (containing the caudate nucleus and all the cerebral cortices) of 24 structures after chronic BCAL significantly decreased to 66-77% of the sham control, except for regions with neuronal damage in which there was a heterogeneous uptake of 14C-DG. The ratio of LCBF/LCGU in chronic BCAL was unchanged in comparison with values in the corresponding sham-operated group. This model of acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism, is expected to become a pertinent tool for the neurophysiologist.

Animals↗
PubMed1993

Fatal herpes simplex hepatitis type 2 in a post-thymectomized adult.

The authors report an unusual case of herpes simplex type 2 (HSV) hepatitis which presented as part of a systemic HSV infection accompanied by disseminated intravascular coagulation (DIC). The patient was a 49-year-old Japanese male who three months prior to admission underwent surgical resection of his thymus for an invasive thymoma. Postoperatively, he received a course of chemotherapy which included prednisone, cyclophosphamide, vincristine, and pinorubicin. After discharge from the hospital, he was put on a maintenance dosage of prednisone and cyclophosphamide. Two weeks prior to this admission, the patient developed rhinorrhea, chills and general fatigue. Routine follow-up laboratory tests revealed markedly elevated liver enzymes which led to his immediate hospitalization. The tentative diagnosis on admission was fulminant hepatitis with DIC. The patient's condition steadily worsened during his hospitalization and acyclovir was initiated on the 4th hospital day due to the possibility of HSV hepatitis. He died on the same day. Histopathology performed on the liver at autopsy revealed hepatic inclusion bodies of HSV with positive immunohistochemical detection of the HSV type 2 antigen. Our case is the first report of HSV hepatitis associated with the removal of the thymus secondary to thymoma. It supports previous observations of disseminated HSV infection being prevalent in those patients with disorders of cell mediated immunity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Influence of HCV infection and its subtypes on clinical course of alcoholic liver disease.

Since the assay of HCV antibody has been developed, it became clear that HCV is involved not only in patients with non-A non-B hepatitis but also in some alcoholic patients. The aim of this study is to examine the prevalence of HCV in chronic alcoholics and to elucidate the influence of HCV and its subtypes on pathogenesis and clinical feature of alcoholic liver disease. To that effect, sera from 100 alcoholics were tested for antibody against C100 of HCV by ELISA and for HCV RNA by reverse transcriptation and the PCR method. The incidence of HCV Ab/RNA was 0%/17% in patients with non specific reactive hepatitis, 0%/0% in fatty liver, 17%/17% in alcoholic hepatitis, 50%/73% in chronic hepatitis, 15%/18% in liver fibrosis and 19%/31% in liver cirrhosis. HCV Ab and RNA were positive in 21% and 31% of alcoholics, respectively. Subtypes of HCV were identified by dot blot hybridization method. Type K1, K2a and K2b were detected in 68%, 25% and 7% of 28 patients with positive HCV RNA, respectively. Type PT was not detected. In addition, serum transaminase activities were evaluated after 4 weeks abstinence. The incidence of normalization of the enzyme activity was lower in patients with positive HCV RNA than that with negative HCV RNA. Furthermore, when it was estimated in relation to HCV subtypes, the incidence of normalization in patients with type K1 was lower than that with type K2. In conclusion, the prevalence of HCV infection in alcoholic patients was much greater than general population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of fatty acid absorption on bidirectional release of immunoglobulin A into intestinal lumen and intestinal lymph in rats.

Effects of absorption of long and middle chain fatty acids on IgA secretion into the intestinal lumen and intestinal lymph and the factors which evoke changes in IgA secretion during the absorptive process were examined in rat small intestine. Bidirectional secretion of IgA from the intestinal mucosa into the intestinal lumen and intestinal lymph was continuously observed in the control condition. Perfusion of oleic acid (a long-chain fatty acid) micelle into the jejunal loop induced a significant increase in IgA output into the intestinal lymph. In contrast, lymphatic output of IgA was significantly decreased when oleic acid micelle was administered intraduodenally. Absorption of octanoic acid, a middle-chain fatty acid, did not produce any significant changes in IgA output into either direction. CR1505, a CCK-receptor antagonist, significantly attenuated the oleic acid-induced increase in IgA secretion into the intestinal lumen, but did not affect the oleic acid-induced decrease in lymphatic IgA secretion. Pluronic L-81, an inhibitor of chylomicron formation and secretion, significantly attenuated the decrease in IgA output into the intestinal lymph during oleic acid absorption without affecting the luminal IgA output. The rate of release of IgA into the intestinal lumen is stimulated by absorption of long-chain fatty acids possibly through the influence of locally released CCK, while the transport process of IgA into lymphatics is controlled by a different mechanism which is closely correlated with the intracellular formation and secretion of chylomicron.

Animals↗
PubMed1993

Genioglossus muscle activity and inspiratory timing in obstructive sleep apnea.

Atypical tongue muscle activity during sleep may contribute to the development of obstructive sleep apnea (OSA). Inspiratory genioglossus (GG) muscle activity was investigated in 10 OSA adults and 4 symptom-free controls. On the basis of overnight monitoring during nonREM sleep, the duration of the inspiratory GG activity and the total GG activity cycle is shorter in patients with OSA. The duration of inspiration and the duration of one total respiratory cycle is also shorter in patients with OSA. The commencement time lag between inspiratory GG activity and the onset of inspiration is shorter in patients with OSA during nonapneic breathing which indicates that inspiratory GG activity is activated relatively later in these patients. Furthermore, the inspiratory GG activity occurs after inspiration during an apnea, but the timing of GG activity onset progressively advances during the apnea. Earlier GG reactivation occurs before inspiration during the first nonoccluded breath at the end of an apnea. During subsequent tidal breathing, the timing of the GG onset progressively decreases after the onset of inspiration until the next obstructive apnea occurs. This observation suggests that the timing relationship between GG inspiratory activity and inspiratory effort is of physiologic importance in the pathogenesis of OSA. Furthermore, it may explain why dental appliances, such as the tongue retaining device, are highly effective in the resolution of OSA in selected patients.

Adult↗
PubMed1993

Heterogeneity of hepatic acetaldehyde adducts in guinea-pigs after chronic ethanol administration: an immunohistochemical analysis with monoclonal and polyclonal antibodies against acetaldehyde-modified protein epitopes.

The formation of acetaldehyde (AcH) adducts was immunohistochemically demonstrated in the livers of experimental animals after chronic ethanol consumption. Recently, we established a hybridoma producing monoclonal antibody against the adduct. Although the polyclonal antibody obtained from a rabbit immunized with adducts had affinities for AcH adducts produced with 20 microM, 1 mM and 10 mM of AcH, the monoclonal antibody could recognize only those produced with 1 and 10 mM of AcH, suggesting that there is a difference of antigenicity between the adducts formed with a high concentration of AcH and those modified with a low concentration of AcH. AcH adducts in the liver of guinea-pigs fed ethanol for 90 days were detected by immunohistochemical staining with the polyclonal and monoclonal antibodies. The staining of liver specimens with polyclonal antibody was observed around both the portal and perivenular areas, whereas the reactions to monoclonal antibody were localized only in the perivenular area. These data suggest that AcH adducts are able to be formed around both portal and perivenular areas in the liver and that the perivenular area might be exposed to a higher concentration of AcH than the portal area after ethanol intake.

Acetaldehyde↗
PubMed1993

Binding sites for calcitonin gene-related peptide in regenerating gastric mucosa.

To clarify the effector sites and significance of calcitonin gene-related peptide (CGRP) in the gastric mucosa, the specific binding sites of CGRP in the rat stomach were studied with autoradiography of soluble compounds and in vitro autoradiography. Binding sites for CGRP in the stomach were seen on the vascular smooth-muscle cells of the arterioles and venules, on the nonvascular smooth-muscle cells of the muscularis mucosae, and on the longitudinal layer of the muscularis propriae. After acetic acid treatment, the number of silver grains was significantly increased in the regenerated mucosa. These data support the significant role of CGRP in the regulation of cytoprotection of the stomach through an increase in the microcirculatory blood flow and through extended smooth-muscle relaxation.

Acetates↗
PubMed1993

Increased chemiluminescence and ulcer development in the low blood flow state of the gastric tube for esophageal replacement.

Peptic ulcers in the gastric tube for esophageal replacement develop in spite of reduction of acid secretion after truncal vagotomy and often result in serious conditions such as bleeding and perforation. Thirteen cases of gastric tube ulcers were detected endoscopically from 1985 to 1990 in our hospital. Most of these ulcers developed within 20 cm of the anastomosis (esophagogastrostomy), which was an especially hypoxic and ischemic area. Ischemic change due to decreased blood supply is suggested as a causative factor in ulcer development. Recent studies indicate that chemiluminescence (ChL) activity may increase even in the low-flow hypoxic condition. Therefore, we investigated the ChL of regional blood in the hypoxic gastric tube in dogs. The ChL activity of the blood sample collected from the ischemic region in the gastric tube significantly increased after construction of the gastric tube, compared with systemic blood from the femoral vein, and the number of leukocytes decreased in the ischemic region. We believe that oxygen radicals derived from neutrophils adhering to the vascular endothelium may play an important role in the damage to endothelial cells of the gastric tube and suggest the possibility of their causative effects in the process of ulcer formations.

Anastomosis, Surgical↗
PubMed1993

Xanthine oxidase-mediated intracellular oxidative stress in response to cerulein in rat pancreatic acinar cells.

Intralobular oxygen radical formation was examined in cerulein-stimulated rat pancreatic acinar cells by digital imaging microscopic fluorography using a hydroperoxide-sensitive fluorescent probe, dichlorofluorescin (DCFH) diacetate. The isolated pancreatic acinar cells loaded with DCFH diacetate were microscopically observed, and the dichlorofluorescein (DCF) fluorescence yielded by DCFH oxidation via hydroperoxides was digitally processed. Within the initial 20 min after the application of cerulein (10 microM), intracellular oxidative stress was observed as indicated by the increase in DCF fluorescence intensity and reached its maximum at 60 min. DCF fluorescence intensity was then gradually decreased until 80 min, followed by a marked increase in propidium iodide (PI) fluorescence, suggesting irreversible cell death. Allopurinol (1 microM), a xanthine oxidase inhibitor, significantly attenuated the early increase of DCF fluorescence intensity as well as the late cell damage. Treatment with hyperbaric oxygen (PO2 300 mm Hg) also significantly attenuated both the increase of DCF fluorescence and the number of PI-positive cells. The results suggest that xanthine oxidase-mediated oxygen radicals may play an important role in cerulein-induced intracellular oxidative stress in pancreatic acinar cells of rats.

Animals↗
PubMed1993

Changes of proliferative activity and phenotypes in spontaneous differentiation of a colon cancer cell line.

We examined the alterations of proliferative activity and c-myc expression of a colon cancer cell line (Caco-2) during its spontaneous differentiation. Caco-2 cells were cultured in various types of media and the degree of differentiation was monitored in terms of dome formation in cell monolayers and expression of alkaline phosphatase (ALP) activity. In Caco-2 cells cultured with Eagle's minimum essential medium (EMEM) containing 10% fetal calf serum (FCS), dome formation was demonstrated and ALP activity was markedly increased after the cells reached confluence. Five-fold reduction of c-myc mRNA and a marked decrease in S-phase cells were observed in the differentiated cells. These changes were not induced in FCS-free EMEM. The addition of insulin and transferrin to FCS-free EMEM did not induce cell differentiation or reduction of c-myc mRNA expression. When Caco-2 cells were cultured with three different serum-free media, the induction of dome formation and the increase of ALP activity were observed to varying degrees. Expression of c-myc mRNA in the cells cultured with one serum-free medium decreased to a level similar to that in fully differentiated cells cultured with EMEM containing 10% FCS. These results suggest that a spontaneous switch from a proliferative state with high c-myc expression to differentiated phenotype occurs after cells reach confluence and depends on the culture conditions.

Cell Differentiation↗
PubMed1993

Attenuation of endotoxin-induced intestinal microcirculatory damage by eicosapentanoic acid.

The major objective of this study is to investigate whether oral administration of eicosapentanoic acid (EPA) has any preventive effect on endotoxin-induced microcirculatory damage of rat small intestine. EPA in a daily dose of 300 mg/kg was orally given to male Wistar rats for 3 wk. Submucosal microvessels of the ileum were observed by intravital microscopy equipped with a high-speed video camera system after the intra-arterial infusion of endotoxin at a dose of 2 mg.kg-1.h-1. The number of sticking leukocytes was significantly increased at 30 min after the treatment of endotoxin especially along the smaller branch of intestinal venules. It reached the maximal plateau at 45 min after treatment. The pretreatment of EPA significantly attenuated the increase in sticking leukocytes induced by endotoxin. A platelet-activating factor (PAF) antagonist 2-[N-acetyl-N-(2-methoxy-3-octadecylcarbamoyloxy propoxycarbonyl) aminomethyl]-1-ethylpyridinium chloride (CV-6209) significantly prevented the increased leukocyte sticking to the same extent as EPA treatment. Thirty minutes after endotoxin infusion, red blood cell (RBC) velocity was significantly decreased in both arterioles and venules. RBC velocity appeared to be continuously decreased thereafter and reached its minimum value at approximately 60 min. EPA treatment was revealed to prevent the decrease in RBC velocity of microvessels induced by endotoxin. CV-6209 also significantly attenuated the decreased RBC velocity. The remarkable elevation of PAF content in the ileal mucosa as observed by endotoxin infusion was also significantly attenuated by administration of EPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Nitric oxide mediates vasoactive effects of endothelin-3 on rat mesenteric microvascular beds in vivo.

In order to clarify whether the vasoactive effects of endothelin-3 (ET-3) on microvessels are associated with the endothelium-derived relaxing factor (EDRF) in vivo, the authors examined the effects of L-NG-monomethyl arginine (L-NMMA), an analog of L-arginine, on low-dose ET-3 induced hemodynamic changes in the mesenteric microcirculation of male Wistar rats. The intravital observation revealed that ET-3 100 pM induced a remarkable and periodic vasoconstriction in arterioles, and the constriction was sustained for approximately fifteen minutes. No remarkable change was observed in the microvessels after the superfusion of 1 pM ET-3. Superfusion of 1 pM ET-3 with 100 microM L-NMMA elicited the vasoconstriction in arterioles, and the arteriolar diameter recovered to the control level within ten minutes in spite of continuing the superfusion. The vasoconstriction induced by low-dose ET-3 with L-NMMA was suppressed by the additional superfusion of 200 microM L-arginine. The present study suggests that the recovery of arteriolar diameter after the ET-3-induced constriction may be mediated by nitric oxide at least in the early phase.

Animals↗
PubMed1993

Thymectomy in human renal transplantation.

We reviewed 17 patients submitted to thymectomy via the suprasternal notch (Yoshimatsu Method I), which was performed before transplantation in 12 patients and after transplantation in 5 patients. There were no complications of thymectomy. Graft survival of our patients with thymectomy was better than that for the overall allograft survival in Japan transplant registry for the same period. Pathologic studies revealed that involution of the cortex was not observed in 5 thymuses removed from recipients who had thymectomy after transplantation even though 2 of them had received 6.4 g and 3.5 g of prednisolone for 19 months and 32 months, respectively.

Humans↗
PubMed1993

Revaluation of endoscopic laser therapy for treatment of early cancer in the stomach.

The efficacy and safety of the endoscopic laser therapy for eradication of early cancer in the stomach was revaluated in fourty-eight patients. In 37 of the 42 patients (88%) treated with the laser therapy alone, the procedure was effective and the complete eradication was confirmed at the end of the follow-up period. In seven of fourteen patients with the incomplete treatment, residual cancer cells were successfully removed by repeated laser therapy. The endoscopic mucosal resection was effective in 21 of the 30 patients (70%) with the early gastric cancer. Interestingly, six of the eleven cases with incomplete treatment with the endoscopic mucosal resection underwent the laser therapy and the complete eradication was achieved in all patients. Although the endoscopic mucosal resection is now the main method for the endoscopic treatment of the early gastric cancer, these data favor offering the endoscopic laser therapy as the combined method with the mucosal resection therapy.

Adult↗
PubMed1993

Antioxidant activities of dihydrolipoic acid and its structural homologues.

The relationships between structure and antioxidant activity of dihydrolipoic acid (DHLA) were studied using homologues of DHLA: bisonor-DHLA (a derivative which lacks two carbons in the hydrophobic tail), tetranor-DHLA (which lacks four carbons) and a methyl ester derivative. It was observed that: i) DHLA homologues with shorter hydrocarbon tails (i.e., bisnor- and tetranor-DHLA) had greater ability to quench superoxide radicals (O2-); ii) no differences among homologues with different chain lengths were found for peroxyl radical (ROO.) scavenging in aqueous solution, and iii) DHLA was the best membrane antioxidant in terms of ROO. scavenging and lipid peroxidation inhibition. Differences among the DHLA homologues in their antioxidant properties in polar and apolar environments generally agreed with differences in their partition coefficients. The methyl ester was the least effective antioxidant both in aqueous phase and in membranes. Tetranor-DHLA was found not only to be less effective in preventing ROO.-induced lipid peroxidation, but also to induce lipid peroxidation in the presence of residual iron. Thus, the complexity of biological systems seems to complicate generalizations on the correlation of molecular structure with antioxidant activity of DHLA.

Animals↗