Biomedical subjects

M Minami

Publications and source records attributed to M Minami.

At least 235 records · Page 13Linked to original sources

PubMed1998

Bremazocine recognizes the difference in four amino acid residues to discriminate between a nociceptin/orphanin FQ receptor and opioid receptors.

We investigated the molecular basis of the discrimination between nociceptin/orphanin FQ receptor (NociR) and opioid receptors (OPRs) by bremazocine, a non-type-selective opioid ligand. Construction of several chimeric receptors between NociR and kappa-opioid receptor (KOPR) and mutant NociRs followed by binding experiments with [3H]bremazocine showed that the mutation of only four amino acid residues of NociR, Ala216, Val279, Gln280 and Val281, to the amino acid residues located at the corresponding position of KOPR, Lys227, Ile290, His291 and Ile292, made it possible for the resultant mutant NociR to bind bremazocine with high affinity. Considering that these four amino acid residues are conserved among mu-, delta- and kappa-OPRs, the present result suggests that bremazocine recognizes the difference in these four amino acid residues to discriminate between NociR and OPRs.

Amino Acid Sequence↗

PubMed1998

Biological monitoring of metabolites of sarin and its by-products in human urine samples.

More than 20,000 passengers of Tokyo underground trains were intoxicated with warfare toxic chemicals. Most of the patients examined had marked miosis and decreased serum cholinesterase activity. Transient increase of serum CPK activity after 3 days of the exposure was the another sign. We intensively analyzed the metabolites in the urine of 4 patients. The following analytic results indicated the exposure to sarin as well as contaminated compounds such as diisopropyl methylphosphonate (DIMP), ethyl methylphosphonate fluoridate (EMPF, or ethylsarin), diethyl methylphosphonate (DEMP), and ethyl isopropyl methylphosphonate (EIMP). (1) Isopropanol (IPA) and ethanol (EtOH) were detected of large quantities in the urine samples, and were thought to be derived from sarin and the sarin counterpart, EMPF, DIMP, DEMP and EIMP. (2) Monoalkyl methylphosphonic acids (isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) also were excreted in large amounts with taking the similar excretion pattern of IPA and EtOH. (3) The metabolite only derived from sarin and ethylsarin is F anions whose integral output in the urine was less than the equimolar level of the excreted (IMPA + EMPA + IPA + EtOH). (4) Other corroborative findings were low lethality: of more than 5,510 patients treated, 11 were acutely dead. (5) Nine exposed males had higher sister chromatid exchange (SCE) rate (5.00 +/- 1.48/cell) than the control (3.81 +/- 0.697/cell), because dialkyl methylphosphonates seemed to have alkylating activity and producing DNA adducts. The SCE rate also increased after the in vitro exposure of lymphocytes to dialkyl methylphosphonates.

Chemical Warfare Agents↗

PubMed1998

Effects of granisetron, a selective 5-HT3 receptor antagonist, on ouabain-induced emesis in ferrets.

The antiemetic effect of granisetron, a selective 5-HT3 receptor antagonist, on ouabain-induced emesis was studied using ferrets. In order to clarify the relationship between ouabain-induced emesis and serotonin (5-HT), we examined its effects on 5-HT release from the isolated ileum. Afferent vagal nerve activity was also determined. An intravenous bolus injection of ouabain (0.1-1.0 mg/kg) produced emesis in a dose-dependent manner. Ouabain-induced emesis was inhibited by pretreatment with granisetron. In the isolated ileum, ouabain induced a concentration-dependent increase of 5-HT. This release of 5-HT was suppressed by granisetron. Increases in vagal nerve discharges were observed immediately after the intravenous administration of ouabain (0.1-1.0 mg/kg). These increases were suppressed by granisetron. Taken together, ouabain activates 5-HT release from the mucosa in the gastrointestinal tract. Released 5-HT may activate the vagal afferent nerves, resulting in vomiting. Granisetron inhibited the ouabain-induced elevation of 5-HT and vagal nerve activity. Ouabain may induce emesis as well as negative chronotropic effects by activating the vagus. Our results suggest that ouabain-induced emesis is in part mediated by the 5-HT3 receptors of the peripheral gastrointestinal tract.

Abdomen↗

PubMed1998

Dental bur fragments causing metal artifacts on MR images.

PURPOSE: Our purpose was to define the role of dental bur fragments in producing metal artifacts on MR images. METHODS: Dental prosthetic reconstructions were made for two dogs. The two lower second premolars were prepared for full-cast crowns by using a diamond bur. The crown margin was placed subgingivally on the right side (1 mm below the free gingival margin) and at the same level as the free gingival margin on the left side. After 1 week, full-cast crowns were cemented in place. MR imaging was performed 7 days later. RESULTS: Metal artifacts appeared in both second premolar regions of the mandible on MR images, with the right side, in which the crown margin was positioned subgingivally, displaying a larger signal distortion than the left side. After removal of the crown, the artifact remained on the right. On histopathologic examination, bur fragments were detected in the gingiva, more on the right than on the left. X-ray fluorescent element analysis showed iron in the gingival tissue containing bur fragments. CONCLUSION: Distortion of MR images was considered to be attributable in part to the damage of the gingiva and in part to the presence of dental bur fragments.

Animals↗

PubMed1998

[Effect of granisetron in preventing emesis due to anti-cancer drug (CDDP) administration pulmo-mediastinal malignancies--comparison of simultaneous infusion with the conventional method of administration].

For patients with pulmo-mediastinal malignancies, the antimetic effect of granisetron was studied in the following two ways. Firstly in the standard method, 40 micrograms/kg of granisetron was infused for 30 minutes, 30 minutes before CDDP infusion. Secondly, in the simultaneous method, granisetron was mixed with CDDP in a 500 microliters infusion bottle, and then infused over 0.5-3 hours. Over a 24-hour time course, significantly effective rates (nausea less than mild, and vomiting 2 times less) were 72.7% in the simultaneous group (n = 22) and 52.6% in the standard group (n = 19). The non-effective rates were 18.2% and 15.8%, respectively. Although the results were not statistically significant, the simultaneous method is easier to perform and it seems to confer a slightly better clinical outcome than the conventional method.

Aged↗

PubMed1998

Increased frequencies of interleukin-2- and interferon-gamma-producing T cells in patients with active Behçet's disease.

PURPOSE: To elucidate the profile of cytokine-producing T cells in patients with active or inactive Behçet's disease (BD), the frequencies of type 1 (Interleukin- [IL] 2, interferon-gamma [IFN-gamma]) and type 2 (IL-4) cytokine-producing CD4+ and CD8+ cells in peripheral blood were investigated, and the effect of immunosuppressive drugs on the profile of cytokine-producing cells was evaluated. METHODS: Fifty-two patients with BD (32 with active and 20 with inactive BD) and 33 healthy control subjects were the subjects in this study. Patients were or were not treated with immunosuppressive drugs. Peripheral blood mononuclear cells were fixed, permeabilized, and stained for intracellular cytokines in combination with cell surface markers CD4 and CD8 for flow cytometric analysis. RESULTS: In nontreated patients with BD, the frequencies of IL-2- and IFN-gamma-producing CD4 and CD8+ cells in active patients were significantly higher than those in inactive patients. Conversely, the frequencies of IL-4 producing CD4+ and CD8+ cells in nontreated patients with active BD were comparable with those in patients with inactive disease and in control subjects. Patients with inactive BD who were treated with immunosuppressive drugs showed significantly lower frequencies of IL-2- and IFN-gamma-producing CD4+ and CD8+ cells than did treated patients with active BD. CONCLUSIONS: The frequencies of type 1 cytokine-producing CD4+ and CD8+ cells increased in patients with active BD. Effective immunosuppressive treatments decreased the population of type 1 cytokine-producing CD4+ and CD8+ cells. These results suggest that type 1 cytokine-producing cells play an important role in the immunopathogenesis of the inflammation in BD.

Adolescent↗

PubMed1998

Effect of 5-hydroxytryptamine on intracellular calcium dynamics in cultured rat vascular smooth muscle cells.

The present study elucidated the precise mechanism of 5-hydroxytryptamine (5-HT)-induced increase of intracellular Ca2+ concentration ([Ca2+]i) in cultured vascular smooth muscle cells isolated from rat aortic media. [Ca2+]i was measured using fluorescent Ca2+ indicator, fura-2. 5-HT caused a dose-dependent increase in [Ca2+]i, which was completely inhibited by ketanserin. alpha-Methyl-5-HT had an equipotent effect to 5-HT. Diltiazem at 10 microM partially suppressed the 5-HT-induced increase in [Ca2+]i. 5-HT also augmented Mn2+ influx, when monitored by Mn2+ quenching of fura-2 fluorescence. When extracellular Ca2+ (1.3 mM) was removed, a decrease in resting level and a small, transient increase in [Ca2+]i were observed. 5-HT stimulation also induced an increase in the production of inositol triphosphate. 5-HT-induced increase in [Ca2+]i was significantly, but partially inhibited by staurosporin and H-7. Phorbol 12-myristate 13-acetate induced an increase in [Ca2+]i, which was abolished by removal of extracellular Ca2+. 5-HT-induced increase in [Ca2+]i was not affected by the pretreatment with pertussis toxin (PTX), and was not accompanied by a change in cyclic AMP content. These results suggest that, in cultured rat aortic smooth muscle cells, 5-HT increases [Ca2+]i via 5-HT2 receptor subtype by inducing influx of extracellular Ca2+ partially through L-type voltage-dependent Ca2+ channel, as well as by mobilizing Ca2+ from its intracellular stores. Activation of protein kinase C may be positively involved in the regulatory mechanism of Ca2+ influx, but PTX-sensitive G protein and cyclic AMP seem to be not involved.

Animals↗

PubMed1998

Ameliorative effects of docosahexaenoic acid on serum lipid changes in stroke-prone spontaneously hypertensive rats.

It has been shown that docosahexaenoic acid (DHA) has numerous physiological actions. However, the precise mechanism of these actions is still obscure, and DHA is not yet regarded as a drug. The present study was undertaken to elucidate the effects of long-term administration of DHA on the serum lipid concentrations in stroke-prone spontaneously hypertensive rats (SPSHR). SPSHR was selected because serum lipid derangement is one of the primary risk factors in the development and maintenance of hypertension. DHA-treated SPSHR showed significantly lower blood pressure when compared with that of non-treated SPSHR; total cholesterol, triglyceride, low density lipoprotein and lipid peroxide levels were significantly decreased in DHA-treated SPSHR. On the other hand, the high density lipoprotein concentrations tended to increase in DHA-treated SPSHR when compared with those in non-treated SPSHR. These findings suggest that long-term administration of DHA has a protective effect against serum lipid derangement in SPSHR. This DHA-induced amelioration of serum lipid changes in SPSHR might be associated with mechanisms involving the antihypertensive action induced by DHA.

Animals↗

PubMed1998

[Non-real-time computed tomography-guided percutaneous ethanol injection therapy for hepatocellular carcinoma undetectable by ultrasonography].

The purpose of this study was to evaluate the feasibility of non-real-time CT-guided percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC, 37 lesions) untreatable by ultrasonography-guided (US)-PEIT. The HCC lesion was localized on the lipiodol CT image with a graduated grid system. We advanced a 21 G or 22 G needle in a stepwise fashion with intermittent localization scans using a tandem method to position the tip of the needle in the lesion. Ethanol containing contrast medium was injected with monitoring scans obtained after incremental volumes of injection, until perfusion of the lesion was judged to be complete. A total of 44 CT-PEIT procedures were performed. The average number of needle passes from the skin to the liver in each CT-PEIT procedure was 2.3, the average amount of ethanol injected was 14.4 ml, and the average time required was 49.3 minutes. Complete perfusion of the lesion by ethanol on monitoring CT images was achieved in all lesions with only a single or double CT-PEIT procedure without severe complication. Local recurrence was detected only in 5 lesions. At present, it is more time-consuming to perform CT-PEIT than US-PEIT because conventional CT guidance is not real-time imaging. However, it is expected that this limitation of CT-PEIT will be overcome in the near future with the introduction of CT fluoroscopy. In conclusion, CT-PEIT should prove to be a feasible, acceptable treatment for challenging cases of HCC undetectable by US.

Aged↗

PubMed1998

Granisetron, a 5-HT3 receptor antagonist, inhibited cisplatin-induced 5-hydroxytryptamine release in the isolated ileum of ferrets.

We investigated the influence of granisetron, a 5-HT3 receptor antagonist, on the increase in 5-hydroxytryptamine (5-HT) release induced by cisplatin from the isolated ileum of the ferret, a species known to vomit in response to cisplatin. 2-Methyl-5-HT, a selective 5-HT3 receptor agonist, increased the release of 5-HT from the ferret ileum in a concentration-dependent manner within the range of 10(-7) to 10(-6)M. The 5-HT release induced by 2-methyl-5-HT was significantly inhibited by a concomitant perfusion with granisetron (10(-6)M). Cisplatin also increased the 5-HT release from the ferret ileum within the range of 10(-8) to 10(-6)M, in a concentration-dependent manner. Granisetron (10(-6)M) also significantly inhibited the cisplatin-induced 5-HT release. Since the cisplatin-induced 5-HT release was significantly inhibited by tetrodotoxin, the possible involvement of an interneuron pathway in the cisplatin-induced 5-HT release mechanism was suggested in the ileal tissue. It is likely that granisetron inhibited the cisplatin-induced 5-HT release from the gut EC cells by producing blockade of an EC cell 5-HT3 receptor.

Animals↗

PubMed1998

Docosahexaenoic acid inhibits blood viscosity in stroke-prone spontaneously hypertensive rats.

Increased blood viscosity facilitates the formation of thrombosis. This is an important risk factor in the occurrence of cerebral infarctions. The present study was undertaken to elucidate whether docosahexaenoic acid (DHA) inhibits blood viscosity, hematocrit and fibrinogen in the disease animal model, stroke-prone spontaneously hypertensive rats (SHRSP). An attempt was also made to clarify the effect of DHA on blood pressure in SHRSP. Blood viscosity, hematocrit and fibrinogen in non-treated SHRSP increased significantly when compared with levels in age-matched non-treated Wistar Kyoto rats (WKY). SHRSP rats which were administered DHA for 5 weeks displayed significant decreases in blood viscosity, hematocrit and fibrinogen when compared with the values in non-treated SHRSP. The blood pressure of DHA-treated SHRSP was significantly lower than that of non-treated SHRSP. A positive correlation existed between blood pressure and blood viscosity. These findings suggest that decreased blood viscosity induced by DHA appears to be associated with the reduction of thrombosis formation and hypotensive action in SHRSP.

Aging↗

PubMed1998

[Flow cytometric analysis of helper T cell subsets (Th1 and Th2) in healthy adults].

To estimate frequency of T helper (Th) 1, Th2, and other related subsets in T cells among healthy Japanese, we determined the frequencies of interferon (IFN)-gamma- and/or interleukin (IL)-4-producing cells in stimulated peripheral blood lymphocytes (PBL) from 51 healthy adults of various ages by three-color flow cytometry using FITC-labeled anti-IFN-gamma, PE-conjugated anti-IL-4, and peridinin chlorophyll protein (PerCP)-labeled anti-CD4 or anti-CD3 antibody. As a result, proportions (mean +/- SD) of IFN-gamma-single positive (conveniently called Th1), IL-4-single positive (Th2), and double-positive cells (Th0) in CD4+ PBL, and homologous cell populations in CD3+ PBL (Th1 type, Th2 type, and Th0 type cells) were 21.3 +/- 8.2%, 2.7 +/- 1.1%, 1.9 +/- 1.0%, 39.5 +/- 13.5%, 1.7 +/- 0.8%, and 1.8 +/- 1.0%, respectively. Percentages of Th1 and Th2 were roughly consistent with those reported previously. Proportions of Th1, Th2, Th1 type, and Th2 type cells were found to increase with the age, whereas there were no significant difference in sex at least in 20s. Furthermore, positive correlation was seen between Th1 and Th1 type (r = 0.79), Th2 and Th2 type (r = 0.87), and Th0 and Th0 type (r = 0.86). Frequencies of these subsets in each donor were maintained at substantially the same levels for at least 3 months, suggesting existence of particular and stable Th1/Th2 balance among healthy individuals. As reported, 6 patients with atopic dermatitis examined in this study showed significantly lower frequencies of Th1 (11.0 +/- 2.5%) as compared with healthy donors (p < 0.01), implying usefulness of the immune test.

Adult↗

PubMed1998

Effect of docosahexaenoic acid on intracellular calcium dynamics in vascular smooth muscle cells from normotensive and genetically hypertensive rats.

The effects of DHA treatment on intracellular Ca2+ dynamics in aortic smooth muscle cells isolated from young stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar Kyoto rats (WKY) were investigated. The resting intracellular Ca2+ concentration ([Ca2+]i) before stimulation and the peak [Ca2+]i induced by 5-HT, angiotensin II and depolarizing concentration of KC1 were higher in SHRSP than in WKY. When added to the culture medium for 2 days, DHA at a concentration of 30 microM significantly suppressed the peak [Ca2+]i induced by these stimulants in aortic smooth muscle cells isolated from WKY, whereas smooth muscle cells of SHRSP were refractory to the suppression. DHA had no suppressive effect on the 5-HT-induced increase in the inositol triphosphate production. The present study indicates that DHA can suppress receptor-mediated Ca2+ influx, at least, through the voltage-dependent channel, in vascular smooth muscle cells. Since the intracellular Ca2+ plays an important role in regulating vascular tone, the suppressive effect of DHA on [Ca2+]i in vascular smooth muscle cells may be contributed to the beneficial properties of DHA on cardiovascular disorders. The precise mechanisms of action remain to be elucidated.

Animals↗

PubMed1997

Sister chromatid exchanges of human peripheral blood lymphocytes induced by N,N-diethylaniline in vitro.

N,N-Diethylaniline is a reagent used in organic synthesis and is an important intermediate in the manufacturing of dyes. To evaluate its genotoxicity, we examined whether it can induce sister chromatid exchanges (SCEs) in human lymphocytes. We found that N,N-diethylaniline significantly increased the frequency of SCEs both in the absence and presence of S-9 mix. The SCEs from cultures treated by N,N-diethylaniline in the presence of S-9 mix displayed a marked increase which was about 5-fold greater than the control. ANOVA analyses indicated that there is a dose-response relationship between doses of N,N-diethylaniline and the frequency of SCEs, especially in the presence of S-9 mix. The results suggested that N,N-diethylaniline has genotoxicity.

Adult↗

PubMed1997

Inhibitory effects of anesthetics and ethanol on muscarinic receptors expressed in Xenopus oocytes.

Anesthetics (and ethanol) are known to produce amnesia as well as immobilization. Recent identification of a nonimmobilizing (nonanesthetic) agent (F6 or 1,2-dichlorohexafluorocyclobutane) that impairs learning and memory suggests that distinct mechanisms may be responsible for these two actions of anesthetic agents. Muscarinic receptors are believed to play a role in memory and learning, and we asked if a specific subtype of these receptors is affected by anesthetics as well as the new nonanesthetic. We investigated the effects of halothane, a novel halogenated anesthetic compound F3 (1-chloro-1,2,2-trifluorocyclobutane) and ethanol on acetylcholine-induced current mediated by a muscarinic m1 receptor expressed in Xenopus oocytes. We also studied the effects of halogenated nonanesthetic compounds, F6 and F8 (2,3-chlorooctafluorobutane) on muscarinic m1 receptors. Halothane, F3, F6 and ethanol inhibited muscarinic m1 receptor-induced Ca2+-dependent Cl- currents at pharmacologically relevant concentrations. F8 had no effect on acetylcholine-induced muscarinic m1 receptor function. The protein kinase C inhibitor, bisindolylmaleimide I (GF109203X), enhanced the acetylcholine-induced current and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), inhibited this current. GF109203X abolished the inhibitory effects of halothane, F3 and ethanol on muscarinic m1 receptors but had no effect on actions of F6. These results demonstrate that anesthetics and a nonanesthetic inhibit the function of muscarinic m1 receptors and suggest activation of protein kinase C as the mechanism of action of anesthetics and ethanol on these receptors.

Anesthetics, Inhalation↗

PubMed1997

The beta-amyloid epitope masking activity in human brain is identified as albumin.

Human brain homogenate proteins were analyzed for binding and processing activity in relation to brain beta-amyloid precursor protein (APP). The homogenate was purified by arginine-Sepharose 4B affinity chromatography, which traps proteins with affinity to certain groups of arginine residue, such as serine proteases and zymogens. A 69 kDa protein that masks epitope(s) of brain APP was found in a weakly bound fraction. The nature of the 69 kDa brain protein was identified as albumin by N-terminal amino acid sequencing and Western blot analysis using anti-human albumin antibody. Western blot analysis with domain-specific anti-APP antibodies revealed that the masking activity is complete for beta-amyloid epitope(s), but incomplete for cytoplasmic and extracellular domain epitopes, suggesting that the interaction site of the albumin is beta-amyloid itself. Therefore, it seems that brain albumin is not merely a carrier protein for beta-amyloid in cerebrospinal fluid, but also a modulator which interferes with processing of beta-amyloid precursor protein and its peptides.

Aged↗

PubMed1997

Type 2 interleukin-1 receptor mRNA is induced by kainic acid in the rat brain.

The in situ hybridization technique was used to examine the expression of type 2 interleukin-1 receptor (IL-1R2) mRNA in the rat brain following the systemic injection of kainic acid at a convulsive dose. The expression of IL-1R2 mRNA was not detected in any brain regions of the saline-injected control rats. 8 h after the systemic injection of kainic acid, weak expression of IL-1R2 mRNA was observed in the dentate gyrus and basolateral amygdaloid nucleus. At 12 and 24 h after the injection of kainic acid, IL-1R2 mRNA was markedly induced in various brain regions including the CA1 and CA3 fields of the hippocampus, dentate gyrus, basolateral amygdaloid nucleus, piniform cortex, claustrum, tenia tecta, arcuate hypothalamic nucleus, dorsomedial hypothalamic nucleus, suprachiasmatic nucleus, tuberal magnocellular nucleus and supramammillary nucleus. In these regions, the signals of IL-1R2 mRNA were observed on likely neuronal cells. Around the mediodorsal thalamic nucleus and the paraventricular thalamic nucleus, dispersed intense signals were observed on the non-neuronal cells. In addition, the expression of the mRNA on the venules was observed at 12 h. The strength of signals significantly decreased by 48 h after the injection. These findings revealed the spatiotemporal induction of IL-1R2 mRNA in the rat brain following the systemic administration of kainic acid, which has shown to cause neuronal degeneration, suggesting the pathological roles of IL-1R2 in the brain.

Animals↗

PubMed1997

Beta2-adrenoceptors on the glial cells mediate the induction of interleukin-1beta mRNA in the rat brain.

Interleukin-1beta mRNA was induced by i.c.v. injection of the beta-adrenoceptor agonist isoproterenol. Lower doses of procaterol, a beta2-adrenoceptor agonist showed stronger induction of the mRNA than isoproterenol. These inductions were primarily observed in the glial cells. On the other hand, the beta1-adrenoceptor agonist dobutamine induced expression of this mRNA only in the meninges. These results suggest the existence of a system for regulation of interleukin-1beta gene expression via beta2-adrenoceptors in the brain parenchyma.

Adrenergic beta-Agonists↗