Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 307 records · Page 17Linked to original sources

PubMed1996

Ethanol retards gastric epithelial restoration in monolayer cultures.

The purpose of this study was to clarify the effect of ethanol on confluent monolayer gastric epithelial cells that had a round cell-free area in the center of the culture dish. Restoration of such "wounding" was evaluated quantitatively every 12 hr using a computer image analyzer with and without ethanol. Without ethanol, restoration was achieved within 48 hr. Exposure to ethanol retarded cellular restoration significantly. Staining for actin and myosin in the control group revealed the presence of lamellipodia and stress fibers. However, in the ethanol group narrowed lamellipodia and few stress fibers were observed. In conclusion, ethanol retarded the migration and proliferation of cultured gastric mucosal cells after in vitro wounding, possibly by damaging the cytoskeletal system.

Actins↗

PubMed1996

Reduction of gap junction protein connexin 32 in rat atrophic gastric mucosa as an early event in carcinogenesis.

This study was conducted to examine the possible relationship among connexin 32 (Cx32) expression, cell proliferation and differentiation in the normal stomach, N-methyl-N'-nitro-nitrosoguanidine (MNNG)-induced atrophic gastritis, and carcinoma in rats. Atrophic gastritis and adenocarcinoma were induced by the administration of MNNG for 8 and 30 weeks, respectively. Cell proliferation was detected by staining with 5-bromo-2'-deoxyuridine (BrdU). The proliferative zone (BrdU-positive zone), located in the lower third of the gastric gland in controls, was elongated in atrophic gastritis. In adenocarcinoma, BrdU-positive cells were distributed diffusely. Cx32 expression was investigated by an indirect immunofluorescence method. In both control and atrophic gastritis specimens, Cx32 fluorescence was abundant in the surface epithelium, but was rarely detected in the glandular portion or the proliferative zone. The length of the Cx32-positive mucosa was significantly less than the control value in atrophic gastritis and no such positive mucosa was visible in adenocarcinoma. The results of this study indicate that the loss of cell-cell communication through the gap junction, associated with elongation of the proliferative cell zone, may be manifested much earlier than carcinoma. We regard this model as useful for investigating the development of atrophic gastritis into gastric carcinoma.

Adenocarcinoma↗

PubMed1996

Cerebrospinal fluid sodium concentration and osmosensitive sites related to arterial pressure in anaesthetized rats.

Intracerebroventricular injection of hypertonic saline induces experimental hypertension. To measure [Na] in the vicinity of osmosensitive sites, we continuously measured [Na] in cerebrospinal fluid ([Na]csf) in the lateral ventricle (LV, n = 6), in the third ventricle (V3, n = 6) and in the medial preoptic nucleus (MPO, n = 6) ([Na]MPO) with a Na-sensitive electrode together with mean arterial pressure (MAP) during infusion of hypertonic artificial cerebrospinal fluid (ACSF, [Na] = 1,000 meq/kg H2O) at 5 "mu"l/min for 3 min into the LV in urethane- anaesthetized rats. [Na]csf in the LV began to increase at the beginning of infusion, reaching a peak of 48 +/- 9 meq/kg H2O (mean +/- SE) around the end of infusion, then recovering to the pre-infusion level by 17 min. [Na]csf in V3 changed similarly to that in the LV without any delay, although the peak value was reduced (61% , P < 0.05). In the MPO, in contrast the increase in [Na]MPO was delayed (3 min, P < 0.002) and the peak reduced even further (to 37%, P < 0.01) compared with that in V3. Thereafter, it remained higher than the pre-infusion level until the end of recovery (P < 0.05). MAP began to increase at the onset of infusion (P < 0.05); the maximum increase of 16 +/- 2 mm Hg (n = 18) was reached at the end of infusion, whereafter this level was almost sustained until the end of the 22-min recovery period. To analyse quantitatively the relationship between MAP and [Na]csf, hypertonic ACSF was infused at 2.5 "mu"l/min into the LV. [Na]csf in the LV and MAP increased at half the rates seen with 5 "mu"l/min. These results suggest that the first increase in MAP after hypertonic infusion into the LV is due to the increase in [Na] in the LV and V3, and that the subsequent sustained increase in MAP is related to the delayed increase in [Na] in the periventricular tissues of the V3.

Anesthesia↗

PubMed1996

Non-carcinogenicity of 2,2'--(4-aminophenyl)imino-bisethanol sulfate in a long-term feeding study in Fischer 344 rats.

2,2'-[(4-aminophenyl)imino]bisethanol sulfate (4APE) was administered at dietary levels of 0 (control), 300, 1000 and 3000 ppm to groups of 50 male and 50 female Fischer 344/DuCrj rats for 104 wk. As slight body weight retardation was observed in the male 3000 ppm group in the preliminary 13-wk feeding study, this dose was selected for the highest exposure level. Mean body weights of both sexes in the 3000 ppm group were lower than those of the controls from wk 2 to termination. However, there were no treatment-related clinical signs or adverse effects on survival rate, food consumption or haematology data. Very slight but statistically significant increases in relative thyroid weights were found in males of the 3000 ppm group, but there was no significant treatment-related increase in the incidence of any non-neoplastic or neoplastic lesions. Thus, under the experimental conditions used, 4APE was not carcinogenic in Fischer 344 rats of either sex.

Animals↗

PubMed1996

Medium-term liver and multi-organ carcinogenesis bioassays for carcinogens and chemopreventive agents.

To bridge the gap between long-term carcinogenicity tests and short-term screening assays such as the Ames test, several types of medium-term bioassay for rapid detection of carcinogenic agents have been developed using male F344 rats. The liver model, in which diethylnitrosamine initiation and acceleration of carcinogenesis by partial hepatectomy are essential components, requires only 8 weeks of animal experimentation and a few weeks for quantitative analysis of hepatic preneoplastic lesions. Using the model, a total of 250 chemicals have been analyzed and the efficacy of the system for hapatocarcinogens has thereby been well established. Other models are so-called multi-organ bioassays for detection of carcinogenic agents in multiple organs within relatively short periods. Among these, the DMBDD bioassay with 5 known carcinogens as initiators has been found to be most applicable and has now been introduced for practical use. Data from these bioassays and several single organ carcinogenesis systems have demonstrated that carcinogenic and modifying effects of individual exogenous agents may markedly differ from organ to organ. Therefore, research into chemoprevention should be based on a whole body level analysis. The present medium-term systems are very useful for this purpose.

Animals↗

PubMed1996

Effects of rebamipide on bile acid-induced inhibition of gastric epithelial repair in a rabbit cell culture model.

BACKGROUND: Anti-ulcer agents exert various functional effects on gastric epithelial cells. AIM: The effects of a novel gastro-cytoprotective agent (rebamipide) on epithelial restoration following bile acid damage were assessed using primary cultured rabbit gastric epithelial cells. METHODS: Rebamipide was added to complete confluent cell sheets with deoxycholic acid just after creating a cell-free wound (2 mm2). The restoration was monitored and analysed by phase contrast microscopy and an image analyser for 48 h. The migration speed was measured during the initial 3 h after wounding. Cell proliferation was detected by staining for bromodeoxyuridine (BrdU) at 12-h intervals. The labelling index was calculated per unit area. The major cytoskeletal protein actin was detected by immunohistochemical staining. RESULTS: In the controls, restoration was completed 48 h following wounding. Deoxycholic acid retarded this process. The addition of rebamipide to deoxycholic acid abolished the bile acid-induced retardation. The migration speed was 26 microns/h in the controls. 15 microns/h in the deoxycholic acid group and 27 microns/h in the deoxycholic acid plus rebamipide group. In the controls, BrdU-positive cells, which were rarely detected in the initial 24 h, were maximal at 36 h (labelling index 1.7%). In the deoxycholic acid group, proliferation was inhibited (peak labeling index; 0.5% at 48 h). Actin-containing stress fibres were detected throughout the cells and the periphery of the lamellipodia in the controls, and were disrupted in the deoxycholic acid-treated group. Rebamipide prevented these effects. CONCLUSIONS: Deoxycholic acid significantly retarded restoration by the inhibition of both cell migration and proliferation, potentially through an effect on the cytoskeleton. Rebamipide protected the mucosal cells from bile acid mediated injury.

Actins↗

PubMed1996

Dysfunction of cholinergic and dopaminergic neuronal systems in beta-amyloid protein--infused rats.

Accumulations of beta-amyloid protein are characteristic and diagnostic features of the brain of Alzheimer's disease patients; however, the physiological role of this protein in CNS is unknown. We have previously reported that continuous infusion of beta-amyloid protein into rat cerebral ventricle impairs learning ability and decreases choline acetyltransferase activity, a marker enzyme of cholinergic neuron. In this study, the effects of beta-amyloid protein infusion on the release of neurotransmitters in cholinergic and dopaminergic neuronal systems were investigated by using an in vivo brain microdialysis method. Nicotine-stimulated release of acetylcholine and dopamine in these animals was significantly lower than that in vehicle-infused rats. Further, dopamine release induced by high-K stimulation was decreased in beta-amyloid protein-infused rats compared with vehicle-infused rats. These results suggest that the release of the two transmitters, acetylcholine and dopamine, was decreased by beta-amyloid protein and that learning deficits observed in the beta-amyloid protein-infused rats are partly due to the impairment of neurotransmitter release. Furthermore, continuous infusion of beta-amyloid protein may be a useful method to produce the animal model of Alzheimer's disease.

Acetylcholine↗

PubMed1996

Platelet-derived growth factor accelerates gastric epithelial restoration in a rabbit cultured cell model.

BACKGROUND & AIMS: Growth factors play an important role in gastric wo und repair. The aim of this study was to assess the role of platelet-derived growth factor (PDGF) in gastric epithelial restoration. METHODS: PDGF-BB (1-50 ng/mL) was added to confluent cultures of rabbit gastric epithelial cells after wounding. Regrowth of the epithelial cells was monitored for 48 hours. The speed of cell migration was measured, and cell proliferation was detected by using a 5-bromodeoxyuridine (BrdU) staining technique. The labeling index was calculated for a 0.05-mm(2) area around the wound. RESULTS: After wounding, cells at the wound edge formed lamellipodia and showed ruffling movements. The addition of PDGF-BB significantly accelerated cell migration and proliferation as well as gastric restoration. Migration speed was 21 microm/h in control cultures and 32 microm/h and 40 microm/h in cultures containing 10 ng/mL and 50 ng/mL of PDGF-BB, respectively. In control cultures, BrdU-positive cells were rarely detected in the initial 24 hours after wounding, and maximum labeling occurred at 36 hours (labeling index, 3.4%). Cultures containing PDGF-BB showed maximum labeling at 24 hours (labeling index, 6.9%). CONCLUSIONS: PDGF-BB dose-dependently accelerated the migration rate and proliferation of cultured gastric epithelial cells after wounding. Therefore, PDGF-BB may play a role in gastric epithelial cell restoration during healing of gastric mucosal lesions.

Animals↗

PubMed1996

The effect of postoperative analgesia with continuous epidural bupivacaine after cesarean section on the amount of breast feeding and infant weight gain.

The purpose of this study is to determine the effect of postoperative analgesia on the amount of breast feeding and infant weight gain. Thirty parturients undergoing elective cesarean section under spinal anesthesia were randomly allocated to receive postoperative pain management with (S-E group, n = 15) or without epidural bupivacaine (S group, n = 15). Epidural analgesia was performed for 3 days with a continuous epidural infusion (0.7 mL/h) of 0.25% bupivacaine. Diclofenac was available on demand in all patients. The weight of milk fed by breast and the infant weight were measured for 11 days after cesarean section. In the S-E group, the visual analog pain score after surgery was significantly lower and both the weight of milk fed by breast and the infant weight during the study were significantly more than the respective values in the S group. The S group required a larger dose of diclofenac after the operation than did the S-E group. We suggest that satisfactory postoperative pain relief with continuous epidural bupivacaine for 3 days after cesarean section improved the amount of breast feeding and the gain of infant weight.

Adult↗

PubMed1996

Effect of aging on arteriolar dilatation induced by prostaglandin E(1) incorporated in lipid microspheres.

To investigate the effect of aging on vasodilation of arterioles induced by prostaglandin E1 incorporated in lipid microspheres (lipo-PGE(1)), we measured the diameter of the anterior ciliary artery in patients aged <65 years (young group) and in patients aged >65 years (elderly group). An eyelid retractor was affixed to the right eyelid while patients were under general anesthesia, and changes in the diameter of the arteriole were continuously monitored by surgical stereomicroscopy for 10 min after the intravenous (i.v.) injection of lipo-PGE(1) (0.2 mu g/kg). We also measured mean arterial pressure (MAP) and heart rate (HR) during the study. The diameter of the arteriole in the young group began to increase significantly 1 min after the injection (p < 0.01), reaching the maximal increase (42.3 +/- 7.4% above the preinjection level) at 3 min after continuous dilatation at the end of the study. In the elderly group, the diameter began to increase 2 min after the injection (p <0.01), reached the maximal value (33.2 +/- 12.7% above the preinjection level) at 5 min, and then gradually decreased to the baseline value. MAP decreased continuously after the injection in both groups; there was no significant difference between the groups. HR in the young group began to increase after the injection and then returned to the baseline level, but in the elderly group it showed continuous increase throughout the study. These results suggest that aging impaired the vasodilatory response to lipo-PGE(1) in the anterior ciliary artery.

Adult↗

PubMed1996

Lack of chemoprevention effects of the monoterpene d-limonene in a rat multi-organ carcinogenesis model.

Modifying effects of dietary administration of the monoterpene d-limonene were examined using a multi-organ carcinogenesis model. Groups of twenty F344 male rats were treated sequentially with N-diethylnitrosamine (DEN, i.p.), N-methyl-N-nitrosourea (MNU, i.p.), 1,2-dimethylhydrazine (DMH, s.c.), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, in drinking water) and dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) during the first 4 weeks (DMBDD treatment), and then d-limonene was administered in the diet, at the dose of 2.0, 1.0 or 0.5%. The maximal tolerable dose was 2.0% under the present conditions. Further groups were treated with DMBDD or 2.0% d-limonene alone as controls. All surviving animals were killed at week 28, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. The incidences and/or multiplicities of renal atypical tubules and adenomas were increased in animals fed 2.0% d-limonene. The immunohistochemical reactivity for alpha2u-globulin in the proximal tubules was greater in rats fed d-limonene than in the carcinogen alone group. No enhancing or inhibitory effect was noted for tumor development in other organs. The present results indicate a lack of any chemopreventive effect of d-limonene in any organ of male rats under the present experimental conditions.

1,2-Dimethylhydrazine↗

PubMed1996

Dose-dependent induction of mammary carcinomas in female Sprague-Dawley rats with 2-amino-1-methyl-6-phenylimidazol[4,5-b]pyridine.

The dose-dependence of 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induction of mammary carcinomas was investigated in female Sprague-Dawley (SD) rats given PhIP in the diet for 48 weeks at concentrations of 0, 25, 100 and 200 ppm in experiment 1, and 0, 12.5, 50 in experiment 2. Yields of ductular lesions, including intraductal papillomas and carcinomas, as well as papillo-tubular and solid-tubular carcinomas, showed dependence on the dose, with the respective total incidences being 0, 4.8, 25, 72.2 and 0, 10 and 35%. There was thus no apparent carcinogen exposure threshold. The present results confirmed the carcinogenicity demonstrated in a previous study using F344 rats and revealed the SD rat strain to be more susceptible.

Adenocarcinoma↗

PubMed1996

Dose-dependent induction of 8-hydroxyguanine and preneoplastic foci in rat liver by a food-derived carcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, at low dose levels.

Male F344 rats were administered 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the diet at doses of 200, 50, 12.5, 3.2, 0.8, 0.2 and 0.05 ppm for six weeks, and partially hepatectomized 1 week after the beginning of MeIQx administration. Quantitative values for glutathione S-transferase placental form (GST-P)-positive foci in the liver were dose-dependently increased by the MeIQx treatment. 8-Hydroxyguanine (8-OHG) levels assessed after 1 week of dietary MeIQx administration were also dose-dependently increased, although the effect was no longer observed at the end of the treatment period. The correlation between numbers of GST-P-positive foci at week 6 and 8-OHG levels at week 1 was linear, values for both parameters being higher than the control levels even in the 0.8 ppm dose group. These findings indicate that, in addition to the previously reported MeIQx-DNA adduct formation, DNA modifications due to oxidative damage may play an important role in MeIQx liver carcinogenesis in rats.

Animals↗

PubMed1996

Thermoregulatory response in female patients during lower abdominal surgery in the head-down tilt position.

BACKGROUND: The head-down tilt (HDT) position suppresses sympathetic nervous activity. We investigated the effect on thermoregulation of the HDT position during lower abdominal surgery under general anaesthesia. METHODS: Tympanic membrane temperature was measured to assess core temperature, and forearm-fingertip and calf-toe temperature gradients were used to assess peripheral vasoconstriction in 30 female patients less than 60 years of age. RESULTS: During surgery in the HDT position (n = 10), the tympanic membrane temperature was similar to that of patients in the supine position (n = 10) (36.2 degrees C and 36.2 degrees C), but in patients operated in the HDT position and premedicated with an angiotensin converting enzyme inhibitor (5 mg of enalapril, n = 10) it was reduced (35.7 degrees C, P < 0.05). In both groups of patients operated in the HDT position, forearm and calf skin-surface temperature gradients were lower by 2.3 degrees C than those in patients operated in the supine position (P < 0.05). CONCLUSIONS: During lower abdominal surgery the head-down tilt position does not augment core hypothermia in spite of suppressed peripheral vasoconstriction, and the renin-angiotensin system may be of importance for thermoregulation.

Adult↗

PubMed1996

Effects of transforming growth factors on the wound repair of cultured rabbit gastric mucosal cells.

We have evaluated the role of two different transforming growth factors in the restoration of rabbit primary cultured gastric mucosal cells using a new wound repair model. After forming confluent monolayer cell sheets, a wound with a constant size (2 mm2) was made using a rotating silicon tip. Either TGF alpha (0.1 - 100 ng/mL or TGF beta 1 (0.1 - 10 ng/mL) was added to the medium and the process of wound repair was monitored and analysed quantitatively by an image analyser. Cell proliferation was examined by BrdU staining. After wounding, the cells fronting the wound formed lamellipodia and migrated towards the centre of the wound. In the control group, the wound healed completely 48 h after wounding. TGF alpha promoted wound healing and wound healed within 36 h in the presence of TGF alpha. TGF alpha increased the number of proliferative cells and they appeared in an earlier phase of healing than in controls. TGF beta did not have any effect on the wound repair process. In conclusion, TGF alpha promotes mucosal cell repair processes in the rabbit primary cultured gastric mucosal wound repair model in a dose-dependent manner by accelerating migration and proliferation. TGF alpha may modulate the healing process of a gastric ulcer or erosion in vivo.

Animals↗

PubMed1996

Monoclonal antibodies to rabbit hepatocyte myosin that cross-react with human liver myosin.

We prepared polyclonal and monoclonal antibodies against myosin purified from rabbit hepatocytes. Immunoblotting analyses revealed that the polyclonal antibody and four (HM1, HM2, HM3 and HM4) of five monoclonal antibodies reacted with myosin heavy chain. Chymotryptic cleavage of myosin yielded a 130 kDa fragment comprising the tail portion of the myosin heavy chain and a 67 kDa fragment comprising the ATP-binding active site of the myosin head. All active antibodies reacted with epitopes localized in the 130 kDa fragment. Monoclonal antibodies HM3 and HM4 and the polyclonal antibody reacted strongly with myosin heavy chains from a human liver homogenate prepared from a surgically resected liver specimen. Immunocytochemical analyses showed that myosin is localized along the plasma membrane as well as around the bile canaliculi in both rabbit and human hepatocytes. Immunocytochemical analyses on liver blocks obtained from those patients who suffered various types of diseases accompanying cholestasis clearly indicated a marked increase in pericanalicular myosin. This altered myosin localization is analogous to that observed in phalloidin-treated liver. Thus, myosin localization, determined using these antibodies, can provide a valid morphological basis for diagnosing the pathological state of the patient liver.

Adult↗

PubMed1996

Effects of bezafibrate on ethanol oxidation in rats.

Bezafibrate is used to lower serum lipid levels in humans. Fibrate derivatives induce an enzyme participating in the beta-oxidation by peroxisomes. We gave ethanol (2 g/kg) orally to bezafibrate-treated (300 mg/kg) male rats of the Wistar strain. Blood ethanol levels were remarkably lower and ethanol elimination stood at 432.6 mg/kg/hr (control, 336.6 mg/kg/hr) in the bezafibrate group (p < 0.01). Blood acetate levels were conversely higher in the bezafibrate group. The fatty acid beta-oxidation activity of liver peroxisome in bezafibrate-treated, clofibrate-treated, or gamma-linolenic acid-treated rats for 4 days was assayed. The activity was 5.8-fold higher in rats given bezafibrate, 5.4-fold in the clofibrate (p < 0.01), and 2.0-fold in the gamma-linolenic acid (p < 0.05). Alcohol dehydrogenase and aldehyde dehydrogenase activity of cytosol in the liver was not induced by the hypolipidemic drugs, but aldehyde dehydrogenase activity in the liver homogenate was induced. From foregoing results, bezafibrate induced in the organism beta-oxidation by peroxisomes and increased H2O2 production, which led to augmented ethanol metabolism by catalase.

Acetates↗

PubMed1996

Evaluation of ethanol on gastric epithelial restoration in vitro.

Ethanol exerts damaging effects on gastric mucosa and delays ulcer healing. To investigate the effect of ethanol on the wound repairing process, we used a wound repair model using primary cultured gastric mucosal cells. A confluent monolayer gastric mucosal cell sheet consisting mainly of mucous cells was wounded to make a cell-free area of constant size. Cell-free area was restored with time after wounding and monitored every 12 hr using a computer image analyzer to observe epithelial cell restoration quantitatively in the presence and absence of ethanol (2.0%). It was found that, although the control wound was completely repaired in 36 to 48 hr, the group treated with 2.0% ethanol showed a significant delay of repair. In the control, 5-bromodeoxyuridine-positive cells appeared around the wound in 24 to 36 hr. In contrast, the group treated with 2.0% ethanol showed no 5-bromodeoxyuridine-positive cells during the experiment. In conclusion, 2.0% ethanol retarded the repair of gastric mucosal restoration by inhibiting the initial gastric cell migration, followed by inhibition of proliferation of cells.

Animals↗