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Biomedical subjects

M Shinoda

Publications and source records attributed to M Shinoda.

At least 109 records · Page 6Linked to original sources
PubMed1995

Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on thyrotropin-releasing hormone-like immunoreactivity in the cerebral cortex and hippocampus of aged rats.

We investigated the effects of a novel prolyl endopeptidase inhibitor, JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- (phenylmethyl)-1-pyrrolidinecarboxamide), on thyrotropin-releasing hormone (TRH)-like immunoreactivity (TRH-LI) in the cerebral cortex and hippocampus of aged rats. The TRH-LI content of both brain regions in aged rats was significantly lower than that in young rats. A single oral dose of JTP-4819 (3 mg/kg) restored the cortical TRH-LI content in aged rats, while doses of 0.3-3 mg/kg restored it in the hippocampus. Repeated oral administration of JTP-4819 at a dose of 1 mg/kg for 21 days produced a significant increase of TRH-LI in the cerebral cortex, while it did so in the hippocampus at doses of 0.3 and 1 mg/kg. Our findings suggest that JTP-4819 may improve the functioning of TRHergic neurons, which deteriorate with senescence.

Aging↗
PubMed1995

Establishment of a new extrahepatic bile duct carcinoma cell line, TFK-1.

A new human extrahepatic bile duct carcinoma cell line (TFK-1) was established from a surgically resected tumor specimen, which was histologically diagnosed as partly papillary adenocarcinoma and partly differentiated tubular adenocarcinoma. The tumor cells cultured in RPMI-1640 medium supplemented with 10% FBS grew as monolayers showing epithelial-like morphology with a population doubling time of 37 hr during exponential growth at passage 40. Chromosome number was distributed in the range of 72 to 76, with a modal number of 73. Tumor markers (CEA, CA19-9, ST-439, DUPAN-2) were negative in culture supernatant and plasma of SCID mice grafted with TFK-1 cells. Though no point mutation at 12 codon of K-ras was detected, expression of c-erb B-2 product and MUC1 antigen was positive. TFK-1 is the third cell line established from extrahepatic bile duct carcinomas in the world literature, and should provide useful information on various aspects of this type of neoplasm.

Adenocarcinoma↗
PubMed1995

Delayed effects of ethanol, caffeine and nicotine assessed by wheel-running and drinking in mice.

Effects of ethanol, caffeine and nicotine, pleasurable substances, on wheel-running and drinking in mice that were housed under a 12 : 12-hr light-dark schedule (lighting period ; 6 : 00-18 : 00) were investigated. All drug administrations were carried out at 11: 00, a mid-light period. Although ethanol (0.8-2.4 g/kg p.o.) scarcely changed both the wheel-running and drinking during the light period, it was followed by a strong suppression of both behaviors during the coming dark period (18 : 00-6 : 00). The same treatment with caffeine (1-10 mg/kg s.c.) produced significant increase in the drinking during the light period, but suppression of the wheel-running during the dark period. Nicotine (0.1-1 mg/kg s.c.) significantly suppressed the wheel-running, but not drinking, during the dark period. The coadministration of nicotine (0.1-1 mg/kg) with ethanol (2.4 g/kg) reduced the behavioral suppression during the dark period. Whereas nicotine (0.1-1 mg/kg) reduced the increased drinking during light period by caffeine (10 mg/kg), but enhanced the caffeine-induced behavioral suppression during the dark period. These results indicate that the administration of pleasurable substances in the mid-light period results in a delayed effect which is characterized by a suppression of either and/or both wheel-running and drinking during the coming dark period starting 7 hr after the administration, and that nicotine acts to antagonize the effect of ethanol, but contrally to enhance the effect of caffeine.

Animals↗
PubMed1995

Evaluation of acute and sub-acute effects of cocaine by means of circadian variation in wheel-running and drinking in mice.

The effects of cocaine on wheel-running and drinking activities in mice, housed under a 12-h light-dark schedule (lighted period; 6:00-18:00 h), were investigated through long continuous observation. Cocaine (20 and 40 mg/kg, sc), administered at 11:00 h, acutely increased wheel-running and drinking, but it was followed by a sub-acute suppression of the spontaneous increment in both of these behaviors during the coming dark period (18:00-6:00 h). Such behavioral accelerating and suppressing effects of cocaine did not change throughout the whole course of administration, which was repeated five times at 3- to 5-day intervals. In addition to these findings, wheel-running and drinking spontaneously increased during the light period and decreased during the dark period on the day after the drug administration. On the other hand, the repeated administration of cocaine at 18:00 h never increased, but rather acutely suppressed both behaviors during the dark period, and no trends in the behavioral changes on the next day were clearly shown. These results suggest that the effects of cocaine on wheel-running and drinking differ depending on the time of day of the administration.

Animals↗
PubMed1995

[The evaluation of cuff-occluded rate of rise of peripheral venous pressure (CORRP) for monitoring blood volume status].

Cuff-occluded rate of rise of peripheral venous pressure (CORRP) was evaluated for perioperative monitoring. We investigated the CORRP in 6 patients undergoing open laparotomy. These patients were given general anesthesia, and monitoring lines were inserted. Heart rate, blood pressure (BP), right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure (PAP), cardiac output (CO) and CORRP were monitored. CORRP is defined as the average rate (in millimeters of mercury per minute) of rise of peripheral venous pressure after proximal occlusion of that vein by a tourniquet (select pressure: 50 mmHg). In the actual measurement of CORRP, only the first 90% of the curve after occlusion of the tourniquet is used. CORRP correlated with RAP (r = 0.69 +/- 0.10), and PCWP (r = 0.79 +/- 0.07). On the other hand, there was no significant correlation between CORRP and BP, or PAP and CO. Snyder et al. described that CORRP seems to be an excellent indicator of acute volume change in the hyper- and hypovolemic canine model. We conclude that in these laparotomy patients, CORRP appears to be a sensitive and minimally invasive method of assessing volume status.

Aged↗
PubMed1995

[Combination chemotherapy with FP versus FEP in patients with advanced gastric cancer. Research group of gastric cancer chemotherapy].

Forty-eight patients with unresectable gastric cancer were enrolled for a randomized trial of FP (n = 24) vs FEP (n = 24) combination chemotherapy with respect to their effects on survival period. Of these, excluding 7 patients, 21 in FP group were treated with 400 mg/m2 UFT po daily and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks, and 20 in FEP group were treated with 400 mg/m2 UFT po daily, 50 mg/m2 etoposide iv and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks. In FP group, 10 PR in primary lesions were observed with an overall response rate of 52.4%. In FEP group, 5 PR in primary lesions were observed with an overall response rate of 35.0%. Toxicities over Grade 3 were anorexia (35%), vomiting (25%), and leukopenia (12%), which were manageable. The 50% survival time in FP and FEP group was 233 and 176 days, respectively. Because of the high response rate and prolongation of the survival period, combination chemotherapy with FP seemed to be useful for the treatment of patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed1994

Novel dual inhibitors of 5-lipoxygenase and thromboxane A2 synthetase: synthesis and structure-activity relationships of 3-pyridylmethyl-substituted 2-amino-6-hydroxybenzothiazole derivatives.

As part of our search for novel antiinflammatory drug candidates, we have designed and synthesized a series of 3-pyridylmethyl-substituted 2-amino-6- hydroxybenzothiazoles. Introduction of a 3-pyridylmethyl group into the 2-amino group (type-A) or the benzene ring (type-B) of 2-amino-6-hydroxybenzothiazoles imparted dual inhibitory activity against the production by glycogen-induced peritoneal cells of rat (in vitro) of leukotriene B4 (LTB4) and thromboxane A2 (TXA2), while not significantly inhibiting that of prostaglandin E2 (PGE2). The observed inhibition of the former two arachidonic acid metabolites was indicated to be the result of a direct action on 5-lipoxygenase and TXA2 synthetase by a cell-free in vitro assay. On the other hand, the inhibitory activities against PGE2 production were for most compounds very weak, indicating that they did not inhibit cyclooxygenase. Structure-activity relationship studies concerning the position of the 3-pyridylmethyl group revealed that type-B compounds generally showed about 10-fold stronger inhibitory activity against TXA2 synthetase than type-A compounds. The position of the 3-pyridylmethyl group played an important role in TXA2 synthetase inhibition. When some of these compounds (8, 13a, 26a (E3040), 26b, 27b, and 28b) were orally administered in the rat TNB/ethanol-induced chronic colitis model (100 mg/kg), the production of both LTB4 and TXB2 in the rat colon was reduced (ex vivo). In addition, one type-B compound, 6-hydroxy-5,7-dimethyl-2-(methylamino)-4-(3-pyridylmethyl)benzothiazole (26a), demonstrated a therapeutic effect at treatments of 100 mg/kg po once daily for 11 days and showed almost comparable activity to sulfasalazine at a dose of 500 mg/kg, the reference drug for inflammatory bowel diseases, in this in vivo model.

Animals↗
PubMed1994

Percutaneous transgastric intestinal decompression: the management of malignant bowel obstruction without nasal intubation.

We inserted a long intestinal tube via the percutaneous transgastric route in three patients with an inoperable malignant bowel obstruction. The percutaneous endoscopic gastrostomy technique facilitated this method. The main purpose of our procedure is to achieve direct intestinal decompression without nasal intubation, which is not always possible by venting gastrostomy alone. Palliative intestinal decompression proved to be effective in all patients. This alternative therapeutic strategy for managing bowel obstruction in terminal cancer patients is herein presented.

Cecal Neoplasms↗
PubMed1994

Expression of adhesion molecules and HLA-DR by macrophages and dendritic cells in aphthoid lesions of Crohn's disease: an immunocytochemical study.

The phenotypes and ultrastructure of macrophages and dendritic cells in aphthoid lesions of the colon were immunocytochemically observed in patients with Crohn's disease. Biopsy specimens were endoscopically obtained from both aphthoid and advanced lesions in Crohn's disease patients. Biopsy specimens obtained from patients with infectious colitis and from normal individuals served as controls. Aphthoid lesions contained densely aggregated CD68+ macrophages, which were surrounded by numerous ID-1+ dendritic cells. In the normal controls and infectious colitis patients, however, a few scattered CD68+ macrophages and ID-1+ dendritic cells were noted beneath the surface epithelium. CD3+ lymphocytes were significantly increased in both aphthoid and advanced lesions of Crohn's disease, but the CD4/CD8 ratio was similar in all groups studied. The double immunoperoxidase staining method revealed that both CD68+ macrophages and ID-1+ dendritic cells in the aphthoid lesions simultaneously expressed ICAM-1 and HLA-DR antigens. Electronmicroscopic observation revealed that CD68+ macrophages had numerous vesicles and lysosomal granules and few projections, and that ID-1+ dendritic cells had appreciable cytoplasmic protrusions with a few vacuoles. These findings suggested that the colonic mucosa in Crohn's disease contained two types of macrophage/dendritic cells in the same lineage that expressed intercellular adhesion molecules and class-II MHC antigens. It also appeared that the aphthoid lesions of Crohn's disease featured an increase in macrophages and dendritic cells consistent with immunological activation.

Adult↗
PubMed1994

Purification and characterization of 3 alpha/beta-hydroxysteroid dehydrogenase from mature porcine testicular cytosol.

NADPH-dependent 3 alpha/beta-hydroxysteroid dehydrogenase (3 alpha/beta-HSD) was purified to apparent homogeneity from testicular cytosol of mature pigs. The purified enzyme catalyzes the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) to both 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol. The molecular weight of the enzyme was estimated to be 31 kDa by SDS-polyacrylamide gel electrophoresis and 40 kDa by gel filtration chromatography indicating that the native 3 alpha/beta-HSD is a monomer. The isoelectric point of the purified enzyme was found to be 6.2 by density gradient isoelectric focusing and 6.4 by chromatofocusing. The enzyme reduced both 5 alpha- and 5 beta-DHT, 5 alpha- and 5 beta-dihydroprogesterone, 5 alpha- and 5 beta-dihydrocortisol, prostaglandin E2, 13,14-dihydro-15-keto-prostaglandin E2 and 13,14-dihydro-15-keto-prostaglandin F2 alpha. Moreover, the enzyme caused rapid reduction of other carbonyl compounds including aldehydes, ketones and quinones. The rates of reduction of these compounds are fast relative to the rates of reduction of steroids and prostaglandins. The purified enzyme was inhibited by AgNO3, SH-reagent, quercetin, hexesterol, stilbestrol, disulfiram and divalent cation such as Cu2+, Hg2+ and Cd2+. The two enzymes show certain similarities (e.g. molecular weight, cross-reactivity to a common antibody) and certain striking differences (e.g. pI, effects of various inhibitors and greater enzyme activity towards steroids (neonatal form) or prostaglandins (mature form). Reasons are give for suggesting that these enzymes are closely related to carbonyl reductase.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Detection of norepinephrine distribution in rats with adrenal medulla autotransplants using 125I-meta-iodobenzyl guanidine.

The viability of autologous adrenal medullary transplants was evaluated using 125I-meta-iodobenzyl guanidine (MIBG), an adrenal medullary scanning agent. Bilateral cavities in the caudate nuclei were made stereotaxically in Wistar rats. One week later, the left adrenal medulla was resected by microsurgery, followed by reoperation of the cranium and implantation of a 0.5-1.0 mm diameter fragment of the adrenal medulla into the right caudate nucleus. Six weeks after the second operation, MIBG was administered intravenously. Specimens from both cerebral hemispheres, from the right adrenal medulla and blood were analysed by radioactivity counting. The radioactivity present in the blood of the transplanted group of 11.40 +/- 2.35 cpm mg-1 (mean +/- S.E.M.) was significantly higher than in the control group of 4.97 +/- 1.16 cpm mg-1 (P < 0.05). Radioactivity present in the right hemisphere of the transplanted group was 0.66 +/- 0.03 cpm mg-1, also significantly higher than in the control group which was 0.47 +/- 0.04 cpm mg-1 (P < 0.01). Autoradiography revealed increased radioactivity in the area of the transplants, which was also confirmed histologically.

3-Iodobenzylguanidine↗
PubMed1994

Myxoid leiomyoma of the vulva mimicking aggressive angiomyxoma.

A case of vulvar leiomyoma with extensive myxoid change in a 40 year old female is described. The tumor had a unique connection with a non-degenerative leiomyoma that compressed the rectum and the bladder. Scattered smooth muscle cells in a loose myxoid stroma were immunoreactive for desmin. Fibroblast-like spindle cells were immunoreactive for vimentin but not for desmin. The initial, although incorrect, pathological diagnosis of the tumor was aggressive angiomyxoma based on the similarity in both clinical and pathological aspects with this more invasive tumor. Myxoid vulvar leiomyoma should also be differentiated from angiomyofibroblastoma. The key to the differential diagnosis is the presence of interlacing smooth muscle cells and an awareness of tendency toward myxoid change in vulvar leiomyomas.

Adult↗
PubMed1994

Purification and characterization of 5 alpha-dihydrotestosterone 3 beta-hydroxysteroid dehydrogenase from mature pig testicular cytosol.

NADPH-dependent 5 alpha-dihydrotestosterone 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was purified to apparent homogeneity from mature pig testicular cytosol. The purified enzyme catalyzed the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) to 5 alpha-androstane-3 beta, 17 beta-diol. The molecular weight was estimated to be 31 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 28 kDa by gel filtration chromatography, indicating that the native 3 beta-HSD is a monomer. The isoelectric point of the purified enzyme was 5.8 as determined by chromatofocusing. The purified enzyme reduced not only 5 alpha-DHT but also 5 beta-DHT, 5 alpha(or 5 beta)-androstanedione, 5 alpha(or 5 beta)-dihydroprogesterone, prostaglandin E1, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glyceladehyde, xylose and glucuronic acid. Moreover, the enzyme reduced other carbonyl compounds including aromatic aldehydes, aromatic ketones and quinones such as 4-nitrobenzaldehyde, 4-benzoylpyridine, phenylglyoxal, cyclohexanone and 9,10-phenanthrenequinone at high rates when compared with steroids, prostaglandins and sugars. The purified enzyme was inhibited by AgNO3, SH-reagent, disulfiram, hexesterol, stilbestrol, disulfiram and divalent cations such as Cu2+, Hg2+, Cd2+ and Co2+. Furthermore, the enzymatic properties of the purified enzyme, including catalytic activity, inhibitory effects by various agents and immunological properties, were compared with those of 3 alpha/beta-HSD enzymes from pig testicular cytosol.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

[Protective effects of sesamol and its related compounds on carbon tetrachloride induced liver injury in rats].

Sesamol is a kind of antioxidant and exists in sesame oil. This paper describes the protective effect of sesamol against carbon tetrachloride (CCl4)-induced liver injury in rats. Sesamol had a significant effect in case of intraperitoneal, subcutaneous and oral administration. In order to examine the relationship between the chemical constitution of sesamol and its protective effect, the protective effects of 20 kinds of sesamol related compounds against liver injury induced by CCl4 were investigated in rats. Consequently, significant protective effects were found in methylenedioxybenzene, isosafrole, safrole, methylenedioxyaniline and methylenedioxyacetophenone. These five compounds had a methylenedioxy group had protective effects, it was considered that the protective effects of the methylenedioxy group were influenced by substituent groups on 4 position of methylenedioxy phenyl compounds. In addition, sesamol, methylenedioxybenzene and isosafrole showed significant protective effects against cholestasis induced by CCl4.

Animals↗
PubMed1994

[A comparison between wheel-running and ambulatory activities in young, adult and old rats based on long-term observation].

It has been considered that spontaneous motor activity (SMA) represented by wheel-running activity (WRA) or ambulatory activity (AA) is one of the most basic indicators in the behavioral-pharmacological test in small rodents. Since various differences are noticeable between WRA and AA in their characteristics or drug responses, both activities may be not considered as the same category of SMA. The main purpose of this study was to elucidate the background difference between WRA and AA in three different aged groups, based on their long-term observation. AA data obtained by Gundai type Ambulo-drinkometer were applied for comparison with WRA data obtained by Wheel-drinkometer. WRA, AA and drinking behavior all showed clear diurnal rhythms characterized by nocturnal animals under light-dark condition (LD = 12:12 h). WRA and AA, in particular the former, tended to decrease according to the aging. More than 30 days habituation was required in order to obtain stable daily WRA level in adult rats. AA of young rats was higher than the other aged rats. The present results suggest that indicators, conditions, measurement apparatus, age etc have to be considered in behavioral-pharmacological observations using WRA or AA.

Aging↗
PubMed1994

Morphological changes of somatostatin neurons in the suprachiasmatic nucleus by hypophysectomy of the rat.

After hypophysectomy, behavioral circadian rhythmicities in the rat became indistinct and phase shift was observed. Therefore, it was thought that the suprachiasmatic nucleus (SCN), which is the circadian oscillator in mammals, was affected by hypophysectomy. We investigated the effects of hypophysectomy on SCN neurons using immunohistochemical staining. Wistar-Imamichi strain male rats were hypophysectomized at 60 days old. Their brains were fixed by acrolein perfusion at 10, 30 and 60 days after the operation, and then vasopressin (AVP)-, vasoactive intestinal polypeptide (VIP)- and somatostatin (SRIH)- neurons in the SCN were stained immunohistochemically. Ten days after the operation, SRIH-neurons were not found in the SCN. At 30 and 60 days after the operation, a few SRIH-positive cell bodies were recognized. In contrast, AVP- and VIP- neurons did not change in morphology in comparison with normal rats. These results suggest that hypophysectomy produces an essential change in SRIH neurons in the SCN, and that such change is responsible for the abnormal behavioral rhythms.

Animals↗
PubMed1994

Impaired interleukin-2 production in active ulcerative colitis is reversed by calcium ionophore plus phorbol myristate acetate and related to altered intracellular Ca2+ responses.

Phytohemagglutin in (PHA)-induced IL-2 production in vitro by peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) from patients with active UC (n = 24, n = 8, respectively) was significantly less than that in controls (n = 13, n = 8, respectively) and inactive patients (n = 11). In contrast, PBMC from inactive disease showed no significant difference when compared with the controls. Depressed IL-2 production in active UC was not reversed by the addition of anti-CD3 monoclonal antibody plus phorbol myristate acetate (PMA), but was largely reversed by adding calcium ionophore plus PMA. Using a fluorescent Ca2+ probe fura-2, we found that after PHA stimulation LPMC from patients with active UC showed a lower magnitude of rise in intracellular free calcium concentration ([Ca2+]i) than control cells. These results suggest that impaired PHA-induced IL-2 production in active UC may be related to some alterations of the early signaling events that cause elevation of the [Ca2+]i.

Adult↗