Biomedical subjects

Y Ikarashi

Publications and source records attributed to Y Ikarashi.

At least 73 records · Page 4Linked to original sources

PubMed1997

Limiting dilution analysis of T-cell progenitors in the bone marrow of thymic lymphoma-susceptible B10 and -resistant C3H mice after fractionated whole-body X-irradiation.

Earlier studies from this laboratory using Thy 1 congenic B10 strain mice suggested that a depletion of T cell progenitors (pre T cells) in the bone marrow in addition to the destruction of the thymus after fractionated whole body X-irradiation (IR) are the two main critical factors that cause differentiation arrest of initially repopulating intrathymic radio-resistant T cell progenitors, which then lead to the appearance of preneoplastic, prelymphoma cells, and eventually to highly neoplastic thymic lymphomas under the influence of the thymic environment. In order to explore the significance of the depletion (or reduction) of T cell progenitors in the bone marrow during pathogenesis of radiation-induced thymic lymphomas, we compared the pool size of pre T cells in the bone marrow and the spleens as well as the profiles of the regenerating thymocyte populations between thymic lymphoma induction-susceptible B10 and -resistant C3H strain mice following irradiation. The results indicated that irradiation severely depleted the pre T cells in the bone marrow and the spleens of both lymphoma induction-susceptible and -resistant mice. They also showed that in C3H mice the differentiation and maturation of intrathymic T cell progenitors which initially repopulated the depleted thymus seemed to proceed normally in spite of the poor cellularity, while this process was greatly suppressed in B10 mice. These data indicate that a depletion of pre T cells in the bone marrow combined with atrophy of the thymus in the irradiated mice is necessary, but not sufficient for development of thymic lymphoma. Implication of these findings on the possible mechanism of radiation-induced thymic lymphomagenesis is discussed.

Animals↗

PubMed1997

[Cytotoxicity of chemicals used in household products: estimation of eye irritating potency of 25 chemicals tested during 1991-1996].

Cytotoxicity potential of chemicals was evaluated by determining the concentrations inducing 50% reduction of neutral red (NR) uptake into Chinese hamster fibroblast V79 cells compared with control culture (IC50). The results of cytotoxicity test for surfactants with the data produced by the in vivo Draize eye and skin irritation test were compared. There was a good correlation between cytotoxicity and eye irritation score obtained from the Draize test. In contrast, no correlation was observed between Draize skin irritation score and cytotoxic potential of chemicals. Therefore, the NR cytotoxicity test was regarded as a possible in vitro model for predicting eye irritation. Based on the IC50 values in the NR cytotoxicity test, the eye irritation classification (weak, moderate and strong) for each chemical used in household products has been established. We evaluated the cytotoxicity of 25 chemicals used for antimicrobial, rubber accelerator, rubber antioxidant, ultraviolet absorber etc. in household products, and estimated the eye irritating potency of these test chemicals according to the criterion.

Animals↗

PubMed1996

Effects of hepatic nerve stimulation on blood glucose and glycogenolysis in rat liver: studies with in vivo microdialysis.

In vivo microdialysis was applied to investigate the effects of hepatic nerve stimulation on glycogenolysis in rat liver under anesthesia. We analyzed the norepinephrine (NE) outflow and glucose output from the liver through the measurement of NE and glucose in the microdialysis dialyzate, as well as the plasma glucose level. Stimulation of the hepatic nerves (10 Hz, 20 V, 2 ms, 20 s every minute) increased NE outflow and glucose output from the liver. The blood glucose level increased by 1.5-1.6 times over the basal level at the end of the 10 min intermittent stimulation. Bilateral adrenalectomy and pancreatectomy did not abolish the glycogenolysis that was induced by the nerve stimulation. Phentolamine an alpha-antagonist, reduced the effects of nerve stimulation on the glucose output and the plasma glucose level. Phentolamine caused an increase in the NE outflow. Quinacline, an inhibitor of phospholipase A2, inhibited the glycogenolytic nerve effects without any inhibition of the NE outflow. These data show that hepatic nerve stimulation produces glycogenolysis via alpha-adrenergic mechanism and partly mediated by eicosanoids, and that microdialysis is a useful and simple method for the study of liver metabolism in physiological conditions.

Adrenalectomy↗

PubMed1996

Hypothalamic cholinergic activity associated with 2-deoxyglucose-induced hyperglycemia.

In order to clarify the role of the hypothalamic cholinergic system in the regulation of peripheral glucose metabolism, we investigated hypothalamic cholinergic activity after administration of 2-deoxyglucose (2-DG). Intravenous administration of 2-DG (500 mg/kg) caused marked hyperglycemia; the level of plasma glucose increased by 2.1 times over the initial levels at 20 min. For evaluation of the cholinergic activity, we analyzed extracellular levels of acetylcholine (ACh) and choline using brain microdialysis, as well as measuring their tissue levels in the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamus (LH) of rats killed by microwave. In the microdialysis perfusate, extracellular levels of ACh and the metabolite choline were increased by 2-DG administration. In the tissue, a dose dependent decrease in the ACh content and a corresponding increase in the choline content were observed in both hypothalamic nuclei 20 min after administration of 2-DG. These data show that cholinergic activity is increased after 2-DG administration. Both the plasma glucose increment and the fluctuation of ACh and choline content were reduced in pentobarbital anesthetized rats. In 6-hydroxydopamine (6-OHDA) pretreated rats, the hypothalamic content of norepinephrine (NE) was reduced to one-third of that in controls, but there was no significant effect on the hyperglycemia or increase in hypothalamic tissue choline levels following 2-DG. Our results suggest the involvement of the hypothalamic cholinergic system in 2-DC-induced hyperglycemia.

Acetylcholine↗

PubMed1996

Evaluation of skin sensitization potential of nickel, chromium, titanium and zirconium salts using guinea-pigs and mice.

Contact sensitization capacity of four metal salts, nickel sulphate (NiSO4), potassium dichromate (K2Cr2O7), titanium chloride (TiCl4) and zirconium chloride (ZrCl4), was evaluated using guinea-pigs and mice. In the guinea-pig sensitization tests, we set up an injection concentration to 1% for all chemicals, and changed the challenge concentration. Guinea-pigs were sensitized with NiSO4, K2Cr2O7 and TiCl4. Among the test metal salts, K2Cr2O7 showed the highest sensitization rate and strongest skin reactions. ZrCl4 did not cause any sensitization responses under our experimental conditions. Minimum challenge concentration to cause a skin response was < 0.25% for K2Cr2O7, 0.5% for NiSO4 and 2% for TiCl4, respectively. A sensitive mouse lymph node assay (SLNA) also determined NiSO4 and K2Cr2O7 as a sensitizer. In the SLNA, TiCl4 caused mild lymph node responses, but was classified as a non-sensitizer as well as ZrCl4. Considering these results, the order of sensitization potential was K2Cr2O7 > NiSO4 > ZrCl4. NiSO4- and K2CrO7-sensitized animals did not show any reactions to ZrCl4 and TiCl4. No cross-reaction among these metal salts was found.

Administration, Topical↗

PubMed1996

Incubation with IgE increases cholinergic neurotransmission in human airways in vitro.

Airway cholinergic hyperresponsiveness is frequently observed in asthmatic patients. Recent reports suggest the possible involvement of IgE in hyperresponsiveness, although the exact mechanism is still uncertain. In this study, we examined whether incubation with IgE could facilitate the cholinergic function in human airways. Bronchi were obtained from 20 patients undergoing lung resection. Cholinergic contractile responses were induced by electrical field stimulation (EFS) or exogenous acetylcholine (ACh), and they were assessed by isometric tension measurement. EFS-induced ACh release from cholinergic nerves was also measured by high performance liquid chromatography. Incubation with IgE significantly enhanced EFS-induced bronchial contraction and ACh release as compared with the values of the bronchi incubated with heat inactivated IgE (control) (p < 0.05, respectively), but it did not alter the contractile responses induced by exogenous ACh. Pretreatment with the muscarinic M2-receptor agonist pilocarpine reduced the EFS-induced ACh release in the control tissues (p < 0.05), but not in the tissues incubated with IgE. The M2-receptor antagonist methoctramine significantly enhanced the EFS-induced contraction in control bronchi (p < 0.05), but this augmentation was not observed in the tissues incubated with IgE. These results suggest that IgE itself can enhance cholinergic bronchial contraction via facilitation of ACh release from cholinergic nerves and that this augmentation is related to autoreceptor M2 dysfunction at nerve endings.

Acetylcholine↗

PubMed1995

Application of a novel, plastic formed carbon as a precolumn packing material for the liquid chromatographic determination of acetylcholine and choline in biological samples.

A novel carbon material, plastic formed carbon (PFC), was prepared by mixing various amounts of pure graphite with an organic binder and pyrolysing the mixture to a "glassy carbon" at a modest final temperature of 1000-1400 degrees C. This preparation procedure allows more convenient and precise control of the final graphite adsorption characteristics. Various PFC materials were constructed and tested both as bulk adsorbents and as precolumn packings for the direct determination of ACh and Ch in brain tissue homogenates. The PFC precolumns prepared from 12.5-50% graphite, by mass, were capable of selectively removing interfering species while not adsorbing any of the desired quaternary amine analytes. The usually large solvent front was also dramatically reduced with these precolumns. These PFC precolumns are useful for the direct determination of ACh and Ch in brain tissue homogenates and other biological samples.

Acetylcholine↗

PubMed1995

Pentobarbital protects against CA1 pyramidal cell death but not dysfunction of hippocampal cholinergic neurons following transient ischemia.

Effects of pentobarbital on the release of acetylcholine (ACh), the area of CA1 pyramidal cell soma and the immunoreactivity of choline acetyltransferase (ChAT) in the hippocampus following ischemia were investigated. Five minute ischemia significantly decreased the KCl-, atropine-induced and basal release of ACh and the area of CA1 pyramidal cell soma in the hippocampus. Moreover, ChAT immunoreactivity, a marker of pre-synaptic terminal survival in the cholinergic neurons, was lowered 14 days after ischemia-recirculation. Although treatment with pentobarbital (50 mg/kg) 30 min before ischemia provided complete protection against hippocampal CA1 pyramidal cell death, pentobarbital failed to improve the decrements of ACh release and the low ChAT immunoreactivity over the test period. Our study thus showed discrepancies between pre-synaptic neurochemical estimation and post-synaptic morphological observation of the effect of pentobarbital on ischemic damage.

Acetylcholine↗

PubMed1995

Immunohistochemical and neurochemical studies of hippocampal cholinergic neurones after ischaemia.

We investigated alterations in cholinergic neurones in the gerbil hippocampus after ischaemia. The cholinergic function of acetylcholine (ACh) release fluctuated over the test period. Choline acetyltransferase (ChAT) immunoreactivity decreased slightly on day 1 and no ChAT immunoreactivity was observed on or after day 4 after ischaemia. Since ChAT immunoreactivity is a marker of cholinergic terminal survival, post-ischaemic cholinergic dysfunction on and after day 4 was accompanied by the destruction of terminals. However, dysfunction of the cholinergic system without destruction of the terminals is possible since mild ischaemia decreases ACh release in spite of retaining intact ChAT immunoreactivity. In the morphological study, delayed neuronal death in the stratum pyramidale was observed from day 4. The present study shows that presynaptic cholinergic dysfunction occurs in the early stage prior to pyramidal cell death.

Acetylcholine↗

PubMed1995

Studies on the tumor-promoting activity of additives in biomaterials: inhibition of metabolic cooperation by phenolic antioxidants involved in rubber materials.

For the detection of tumor-promoting activities of phenolic antioxidants, the inhibitory activities on the intercellular gap-junctional communication were investigated using the V79 metabolic cooperation (MC) assay. Among eight antioxidants, 4,4'-butylidene-bis(3-methyl-6-tert-butyl-phenol), 2,2'-methylene-bis(4-methyl-6-tert-butylphenol) (MBMBP), and styrenated phenol (SP) showed stronger inhibitory activities than lithocholic acid, which is known to be a tumor promotor. However, 4,4'-thio-bis(3-methyl-6-tert-butylphenol), Irganox 1010, and 1330 did not inhibit at any concentrations. When the single-electron oxidation potentials were compared among antioxidants, the electrochemical ease estimated with the first oxidation potential was correlated with the cytotoxic potentials (r = 0.88), but not with the inhibitory activities in an MC assay. The tumor-promoting activity of MBMBP was also investigated using an in vitro, two-stage Balb/c 3T3 transformation assay. MBMBP did not show initiating activity, but significant promoting activity at concentrations of both 1 and 2.5 micrograms/ml were noted. These concentrations were close to the lowest effective inhibitory concentration (1.3 micrograms/ml) of MBMBP in an MC assay. In conclusion, there is a possibility that the phenolic antioxidants that show inhibitory activities in an MC assay contribute to the enhancement of tumor incidence induced by biomaterials.

Animals↗

PubMed1995

Cognitive function in rats with alcohol ingestion.

The effect of alcohol ingestion on learning disturbances was tested in rats. Rats were fed either an alcohol solution or a nonalcohol solution. The concentration of acetylcholine in the whole brain was significantly lower in rats fed with alcohol than rats fed without alcohol. Passive avoidance learning shows a lower tendency in rats with alcohol compared to rats without alcohol, but the alcohol and control groups did not differ in passive avoidance learning. We suggest that alcohol may disturb acetylcholine metabolism in the brain.

Animals↗

PubMed1995

Cytotoxicity of medical materials sterilized with vapour-phase hydrogen peroxide.

A new sterilization system using vapour-phase hydrogen peroxide (VPHP) was recently developed. The cytotoxicity of various medical materials sterilized by the VPHP sterilization system was investigated. After VPHP sterilization, polystyrene, polyurethane (PU8), blend material of silicone and polyurethane (Sil/PU6), poly(methyl methacrylate) (PMMA), fluorosilicone acrylate and poly(2-hydroxyethyl methacrylate) (HEMA) showed strong cytotoxicity, whereas polyethylene and polypropylene did not. Although the cytotoxic potential of most materials is reduced by extension of the aeration time, HEMA and PMMA still retained strong cytotoxicity after 12 h aeration. Addition of catalase to the cell culture eliminated the cytotoxicity of sterilized polystyrene and PU8. Hydrogen peroxide (H2O2) residues remaining in the sterilized materials were determined. Large amounts of H2O2 (5.1-186 micrograms) were detected in HEMA, PU8, Sil/PU6 and PMMA. In contrast, silicone and polyethylene contained low levels of H2O2. The amounts of residual H2O2 in the materials decreased with increasing aeration time, but the elimination rate of H2O2 differed among the test materials. The cytotoxic potential of the VPHP-sterilized materials correlated with the amounts of residual H2O2 present. These results indicated that the cytotoxicity of VPHP-sterilized materials was caused by the residual H2O2. To generalize the developed VPHP sterilization system for various medical devices, it is important to validate the aeration of materials for removal of cytotoxic residuals.

Acrylates↗

PubMed1995

Decrease of norepinephrine and preservation of acetylcholine in the hypothalamus of VMH obese rats.

We investigated to find which types of neuronal disturbance in the hypothalamus are responsible for ventromedial hypothalamic nucleus (VMH) lesion-induced development of obesity. We found that in VMH-lesioned obese rats, the contents of norepinephrine (NE) and dopamine in the hypothalamus were selectively decreased, but that the serotonin and acetylcholine levels were unchanged from those in sham controls. Also, the content of NE in the lateral portion of the hypothalamus was decreased. Our results show that disturbance of the hypothalamic noradrenergic and dopaminergic neurons, but not of the serotonergic or cholinergic neurons, contributes to the development of VMH lesion-induced obesity.

Acetylcholine↗

PubMed1995

[Therapeutic effect of IGN-2098, a new antiulcer drug (H2-antagonist), in the ulcer diminishing period against acetic acid-induced gastric ulcer in rats].

The effects of IGN-2098 on the healing process of acetic acid-induced gastric ulcer was investigated in comparison with the other histamine H2-receptor antagonists, famotidine and roxatidine acetate HCl, in rats. Ulcer was induced by the injection of acetic acid solution (20%, 0.05 ml). From the 4th day to 17th day after the ulcer induction, drugs were orally administered twice a day. On the 18th day after the ulcer induction, rats were sacrificed to measure the ulcer index macroscopically and to take pictures of the stomachs. Judging from the photographs, the prominence of ulcer the edge was graded into 4 classes, which showed a significant correlation with the histological amount of connective tissue at the ulcer edge. All drugs accelerated the healing of the ulcer, and the effect of IGN-2098 was the most remarkable. In addition, IGN-2098-treatment exhibited more marked inhibition against the prominence of the ulcer edge as compared with the control group. Based on these results, it is concluded that IGN-2098 may be a useful drug for the clinical treatment of ulcer and that the healing acceleration by IGN-2098 without prominence of the ulcer edge may induce no relapse of the ulcer after healing.

Acetates↗

PubMed1995

Recipient-derived T cells participate in autoimmune-like hepatic lesions induced by graft-versus-host reaction.

Autoimmune-like hepatic lesions were induced by injection of CD4+ T cells from B10.Thy-1.1 mice into MHC class II-disparate (B10.Thy-1.1 x bm12)F1 mice. Hepatic lesions characterized by mononuclear cell accumulation in the portal area of the central vein and around interlobular bile ducts were observed in these recipients. The morphologic features of the lesions resembled primary biliary cirrhosis. The origin of T cells invading at the site of the hepatic lesions was immunohistochemically analyzed. It was shown that many recipient-derived T cells were present at the lesions and that some of them infiltrated the bile duct epithelia. Furthermore, the lesions were weakened when recipient-type T cells were depleted by thymectomy and the administration of anti-Thy-1.2 monoclonal antibody. Recipient-derived T cells were observed to take part in the formation of autoimmune hepatic lesions. These findings suggest the possibility that the tolerance of self-reactive T cells is abrogated by the graft-versus-host reaction.

Animals↗

PubMed1995

Studies on the tumor-promoting activities of additives in biomaterials: inhibition of metabolic cooperation by additives such as pigments and phenolic antioxidants.

The inhibitory activities on the intercellular gap-junctional communication were investigated using the V79 metabolic cooperation (MC) assay for the detection of tumor-promoting activities of additives such as pigments and phenolic antioxidants. Among six pigments, four chemicals showed inhibitory activities. The inhibitory potencies were ranked in the following order: sudan I > purple 201 > blue 204 > green 202. Sudan I and purple 201 showed stronger inhibitory activities than lithocholic acid, which is known to be a tumor promotor. However, quinizarine and red 225 did not inhibit at any concentration. Relating to eight phenolic antioxidants, four chemicals also showed inhibitory activities. Combining the present findings with previous ones, there are many factors that have tumor-promoting activities via inhibitory action on gap-junctional intercellular communication in biomaterials.

Animals↗

PubMed1995

[Twenty-eight days repeated dose toxicity test of N-(fluorodichloromethylthio)phthalimide in rats].

N-(Fluorodichloromethylthio)phthalimide (Fluor-folpet) has been widely used as an anti-mold and anti-bacterial agent. In this study, 28 days repeated-dose oral toxicity study of fluor-folpet was carried out in Slc:Wistar rats. An oral toxicity study for fluor-folpet, the twenty-eight days test, repeated-dose, oral administration, was performed as follows: Five week-old rats, male and female, 10 rats, each/group, were treated with intragastric administration of fluor-folpet with a dose of 0 (1% Sodium CMC, control), 20, 80 and 320 mg/kg, body weight. Recovery test, for 14 days after the last treatment, was examined for the control and the 320 mg/kg groups. The 320 mg/kg groups, both males and females, showed significantly reduced their body-weight gain compared with the control group. In the 320 mg/kg group, five out of 20 male rats and four out of 20 female rats died from dyspnea during the treatment period. In the female rats in the 320 mg/kg group, serum ChE level was decreased to 50% of control level and gamma-GT was increased in a dose-dependent manner, but these serum levels recovered after 14 days non-treatment period. No histopathological change, relating to the treatment, in liver was observed. Increased weight of the kidney and vacuolation in renal tubules were found in both sexes of 320 mg/kg group. Hyperkeratosis and hyperplasia of the stomach epithelium were observed at the dose more than 80 mg/kg in male, and more than 20 mg/kg in female. A supplemental study, repeated-dose, oral administration in rats carried out to examine the dyspnea revealed that severe acute toxic damages in epithelium of nasal cavity and meatus nasopharyngeus were induced by intragastric administration of fluor-folpet. Fluor-folpet is shown to be cytotoxic. In conclusion, the no-observed-effect level (NOEL) for fluor-folpet was not found under the experimental conditions employed in this repeated-dose toxicity study.

Administration, Oral↗

PubMed1994

Increase of hypothalamic cholinergic activity in 2-deoxyglucose hyperglycemia.

Under inducement of hyperglycemia by intravenous administration of 2-deoxyglucose (2-DG), the contents of choline and acetylcholine (ACh) in the ventromedial hypothalamic nucleus (VMH), lateral hypothalamus (LH) and paraventricular nucleus (PVN) were analyzed after a microdissection of the microwave treated brains. After the administration of 2-DG, the content of choline in those hypothalamic nuclei increased markedly, and the ACh decreased in both the LH and the PVN. The increment of plasma glucose was reduced in the adrenodemedullectomized rats, and simultaneously the increment of the choline in the LH further augmented. These results suggest the contribution of hypothalamic cholinergic neurons in 2-DG-induced hyperglycemia.

Acetylcholine↗