Search PubMed⌕ Search

Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 1,225 records · Page 68Linked to original sources

[Anxiolytic effects of lisuride and its agonistic action to central 5-HT1A receptors].

Effects of lisuride, a derivative of ergot alkaloid, on central 5-HT1A receptors were investigated biochemically, behaviorally and electroencephalographically (EEG) in rats and rabbits. Effects of lisuride in water-lick conflict tests were also investigated in rats. Lisuride was found to strongly inhibit the bindings of [3H]8-OH-DPAT to 5-HT1A receptors in the raphe nucleus, hippocampus, cortex, amygdala and hypothalamus of rat brain. Inhibitory effects of lisuride on bindings of [3H]8-OH-DPAT in the hippocampus was almost the same as that of 5-HT (Ki = 0.5 nM) and stronger than those of the 5-HT agonist 5-MeO-DMT (Ki = 2.1 nM) or other ergot derivatives (bromocriptine and pergolide, Ki = 3.0 nM). Lisuride (0.1-0.5 mg/kg, i.p.), like 8-OH-DPAT, dose-dependently induced a 5-HT behavioral syndrome in rats. Lisuride affected locomotor activity in rats, whereas 8-OH-DPAT did not. In hippocampal EEG of rabbits, lisuride (0.01-0.03 mg/kg, i.v.), like 8-OH-DPAT and diazepam, dose-dependently inhibited rhythmical slow activity (RSA) induced by acoustical stimulation (3100 Hz) and also inhibited the RSA increased by administration of anxiogenic FG7142. In water-lick conflict tests, lisuride (0.05-0.1 mg/kg, i.p.), like diazepam, increased the number of shocks. These findings indicated that lisuride acts as a strong agonist on central 5-HT1A receptors and suggested that lisuride might be a potential anxiolytic.

Animals↗

[Interaction of the hypnotic lormetazepam with central benzodiazepine receptor subtypes omega 1, omega 2 and omega 3].

To clarify the action of lormetazepam, 3-hydroxybenzodiazepine, on the benzodiazepine (BZ) receptor subtypes, effects of lormetazepam on motor performance in the traction test and hexobarbital-induced loss of righting reflex in mice and the binding to BZ receptor subtypes were investigated in comparison with those of other BZ hypnotics. Lormetazepam prolonged the duration of hexobarbital-induced loss of righting reflex. The minimal effective dose (1 mg/kg, p.o.) was higher than that of flunitrazepam, lower than those of diazepam and zopiclone, and the same as those of triazolam and brotizolam. Lormetazepam showed the ataxic effect at 10 mg/kg, p.o., but the separation between its effective doses for the hypnotic and ataxic effects was the largest among the hypnotics tested. In the displacement study on [3H]flumazenil binding to cerebellar and spinal cord membranes, lormetazepam bound with a higher affinity to omega 1 receptor (Ki = 10 nM) than to omega 2 receptor (Ki = 29 nM). The GABA-ratios of lormetazepam to omega 1 and omega 2 receptors were 3.9 and 4.0, respectively; and they were higher and lower than those of flunitrazepam to omega 1 and omega 2 receptors, respectively. In the displacement study on [3H] Ro5-4864 binding to kidney membranes, lormetazepam bound with a lower affinity to the omega 3 receptor (Ki = 213 nM) than flunitrazepam. Thus, lormetazepam was suggested to be a potent hypnotic with weaker ataxic effects than other BZ hypnotics, which may be due to its selective and potent agonistic action on central omega 1 receptors.

Animals↗

Effect of TNF-alpha on prolactin secretion from rat anterior pituitary and dopamine release from the hypothalamus: comparison with the effect of interleukin-1 beta.

The effects of human recombinant interleukin-1 beta and -6 and tumor necrosis factor-alpha (TNF-alpha) on the releases of PRL and dopamine were examined using monolayer cultures of rat pituitary cells and hypothalamic cells. The release of PRL from rat pituitary cells in 30 min was increased about 2-fold (p less than 0.05) by 10(5) U/l interleukin-1 beta, 10(5) U/l interleukin-6 or 100 micrograms/l TNF-alpha. TNF-alpha at 100 micrograms/l significantly increased PRL release within 5 min incubation and this effect continued throughout the next 30 min of incubation. Incubation for 5 min with TNF-alpha caused dose-dependent stimulation of PRL release. These cytokines did not modulate [3H]-dopamine release from primary cultures of hypothalamic cells. These results suggest that these cytokines stimulate PRL release directly at the pituitary gland, without modifying the release of dopamine from the hypothalamus.

Animals↗

Gossypol effects on monoamine oxidase (MAO) activity in several organs of term rats.

In order to study the effect of gossypol on the monoamine oxidase (MAO) activity in pregnant rat organs, 20 day pregnant rats were sacrificed, and MAO activity/0.02 g tissue of several organs and total MAO activity/organ, were determined. The control group (n = 5) were injected with vehicle intramuscularly on the 17th, 18th and 19th day of pregnancy, and the gossypol treated group (n = 4) were injected with gossypol acetic acid (GAA) (25 mg/kg of body weight) intramuscularly on the 17th, 18th and 19th day and were decapitated on the 20th day of pregnancy. Maternal liver, uterus, placenta, and fetal liver were collected and examined. In placenta, total MAO activity/organ was significantly (p less than 0.05) lower in the GAA treated group than that in the control group. However, in maternal liver, uterus and fetal liver, there was no significant difference in total MAO activity/organ between the two groups. There was no significant difference in MAO activity/0.02 g tissue (specific activity), weight of organ, protein weight/organ and protein/g tissue between the two groups in maternal liver, uterus, placenta and fetal liver. These results suggest that, after intramuscular injection of GAA, total MAO activity/organ in the placenta of pregnant rats might decrease significantly.

Animals↗

Effects of progesterone and gossypol on monoamine oxidase activity in human term placental explant.

Human placental explant was cultured, using fresh full term placenta delivered by elective cesarean section (n = 10), and monoamine oxidase (MAO) activity was measured in the tissue by the spectrophotometric method. Placentae were obtained from patients without complications in pregnancy. Chorionic villi 2 g was incubated for 3 hr under the 95% air-5% CO2 humidified condition at 37 degrees C. When progesterone was added in the media (100-500 micrograms/ml), MAO activities significantly decreased, compared with the control. The gossypol (100 micrograms/ml) treated group showed no inhibitory or stimulatory effects on MAO activities, compared with the control. However, progesterone (100-500 micrograms/ml) and gossypol (100 micrograms/ml) treated group showed the same value of MAO activities, compared with the control. Those results indicate that gossypol might block progesterone action which is inhibitory against MAO activity. The mechanism of pharmacological function of gossypol was discussed.

Female↗

Effects of aspirin, dipyridamole, and dibutyryl cyclic adenosine monophosphate on platelet-derived growth factor A chain mRNA levels in human saphenous vein endothelial cells and smooth muscle cells.

Aspirin and dipyridamole have frequently failed to control intimal hyperplasia in vascular grafts in animal and clinical trials. These trials were based on the concept that the smooth muscle mitogen, platelet-derived growth factor (PDGF) released from platelets, was a major cause of intimal hyperplasia. Both endothelial and smooth muscle cells (ECs and SMCs), however, can also release PDGF-like SMC mitogens that might cause intimal hyperplasia. We therefore tested whether aspirin and dipyridamole alone or together can affect PDGF-A chain mRNA levels in cultured human saphenous vein ECs and SMCs. Cultures were exposed for 72 hours to 3 x 10(-5) mol/L aspirin and/or 5 x 10(-6) mol/L dipyridamole. Cellular RNA was then extracted, and PDGF-A chain mRNA signal levels were measured by a reverse transcription/polymerase chain reaction method. mRNA for glyceraldehyde-3-phosphate dehydrogenase was used as a constitutively expressed control RNA species. Signal strength on Southern blots of amplified polymerase chain reaction products was measured by densitometry. Neither aspirin nor dipyridamole alone or together reduced the ratio (PDGF-A chain signal/glyceraldehyde-3-phosphate dehydrogenase signal) below that of control cultures. PDGF-A chain expression was not a constitutive artifact of culture because dibutyryl cyclic AMP (5 x 10(-4) mol/L) reduced PDGF-A chain signal from a control index of 1.0 to 0.5 +/- 0.1 (mean +/- SE) (n = 3; p less than 0.05) in EC cultures and to 0.2 (mean) (n = 2) in SMC cultures. These data may explain why aspirin and dipyridamole fail to reduce intimal hyperplasia in some animal and clinical trials despite effective inhibition of platelet aggregation.

Aspirin↗

Excess death of lung cancer among sarcoidosis patients.

This study is to calculate a risk of lung cancer in a cohort of 1411 sarcoidosis cases which were followed for a 3 year period from 1984 to 1987. The physicians were requested to answer the questionnaire about progress of the disease by mail. Excess death was investigated using standardized mortality ratio (SMR). The expected number of deaths was calculated from Japanese sex-age specific mortality rate in 1985, using person-year method. Death from all causes and cancers did not show any excess. SMR being 0.98 and 0.97 respectively. The SMR of lung cancer was 3.26 (male: 5.56, female: 3.03), being statistically significant. The SMR of lung infection was 4.2, with statistical significance. The SMR of other main causes of death in Japan i.e., cerebrovascular accident, ischemic heart diseases and heart failure was less than 0.88. It is probably that sarcoidosis is a risk factor of lung cancer. The SMR of leukemia and uterine cancer was 5.88 and 8.70, respectively, though the observed number of leukemia was too small to conclude how high the cancer risk is among sarcoidosis patients. Gastric cancer, hepatic cancer and colon cancers were not observed.

Adult↗

[Cigarette smoking and mortality among Japanese males in a prospective cohort study].

The relationship between smoking and disease was studied in a prospective cohort study among a Japanese male working population. The relative risk of cigarette smoking was positively associated with mortality for all diseases and major neoplasms. In current smokers consuming 25 to 34 cigarettes per day, relative risk for all diseases, major neoplasms, and lung cancer compared to nonsmokers was 1.38, 2.04, 2.36, respectively. These data suggest that there is a positive relation between smoking and disease mortality in this male working population. As for ex-smokers, estimated relative risk for all neoplasms was between that of current smokers and nonsmokers.

Adult↗

Combination therapy of M2-protocol and interferon-alpha as remission induction in refractory multiple myeloma.

A successful induction of remission in two patients with resistant multiple myeloma using a new combination therapy of modified M-2 protocol and interferon-alpha (IFN-alpha) is described. The first case was a 32-year-old man with K type urinary Bence-Jones protein who became resistant after treatment with melphalan and prednisone (MP protocol). IFN-alpha alone had a marginal response. The modified M-2 protocol proved insufficient. Therefore, IFN-alpha was administered in the interval of M-2 protocol. This combination therapy showed remarkable responses. The second case was a 59-year-old woman with advanced IgA myeloma who was treated with M-2 protocol and became resistant. IFN-alpha alone resulted in a slight response. After addition of IFN-alpha to the modified M-2 protocol, a rapid reduction in the level of serum IgA was found and clinical symptoms including bone pain, anaemia and so on were dramatically improved. No infection and/or intolerable side effects were observed in either case. This combination treatment appears worthy to try in cases of resistant or relapsing myeloma patients.

Adult↗

[Hairy cell leukemia expressing SIgM+, SIgG-, CD11b+ and CD21+ and accompanying lymphadenopathy without splenomegaly].

Hairy cell leukemia (HCL) expressing both surface monocytoid antigen and IgM (kappa) was reported. A 62-year-old male was admitted to our hospital in September 21, 1989 because of leukocytosis. Physical examinations showed axillary and inguinal lymphadenopathy but no hepato-splenomegaly. The leukocyte count was 12,600/microliters with 73% of abnormal cells like large lymphocytes which had abundant cytoplasm and hairy appearance under phase microscopy. They had ruffles with microvilli under electron microscope. Bone marrow puncture showed normocellular marrow with 71.2% of abnormal cells similar to the peripheral blood. Surface markers were CD11b+, CD21+, HLA-DR+, Tac- and IgM (kappa). They were positive for ++acid phosphatase staining, but negative for peroxidase and tartrate-resistant acid phosphatase staining. He was diagnosed as Japanese type HCL. HCL expressing both surface monocytoid antigen and IgM is rare and the clinical features of our case are compared with those reported in Japan.

Antigens, Differentiation, B-Lymphocyte↗

Bilateral enlargement of the aortic valve ring for valve replacement in children. New operative technique.

We report a new technique for the bilateral enlargement of a small aortic anulus in two children by the insertion of a bifurcated teardrop-shaped Dacron fabric lined with a porcine pericardium. Our experience in two children indicates that this technique will permit the insertion of a prosthetic valve that is four sizes larger than that measured with the native anulus intact in children weighing around 15 kg. It entails no risk of distorting the mitral valve, damaging the conduction system, the main coronary arteries or their important trunks, or of leading to left ventricular dysfunction.

Aortic Valve↗

[Intravaginal administration of CDDP for adenocarcinoma].

Single vaginal administration of CDDP was done in a case of adenocarcinoma when relapse in the vaginal stump followed surgery for uterine corpus carcinoma. A tumor the size of a large fingertip in the vaginal stump was completely eliminated via 15-time (75 mg) CDDP vaginal administration, suggesting that this treatment was effective against adenocarcinoma. The only side effect over the whole body was slight pain developing in the external genitalia.

Adenocarcinoma↗

[Role of eosinophils in the late asthmatic response].

The occurrence of late asthmatic response (LAR) is effectively prevented by corticosteroids, but not all by beta-adrenergic drugs. LAR is considered to be of great clinical and therapeutic importance and to be involved in the progression of bronchial asthma into a severe or even an intractable form. However the exact mechanism of the occurrence of LAR remains obscure in many respects. LAR is believed to be due to type I allergy. In guinea pigs, a positive bronchial inhalation challenge following passive sensitization with allogeneic antibody does not induce LAR or eosinophilic infiltration of lung tissue. This experimental fact led us to surmise that LAR would seem likely to be elicited in passively sensitized animals if pronounced eosinophilic infiltration can be induced concurrently and to conduct an experiment with conjoined inhalation of platelet activating factor (PAF). PAF, which has a chemotactic activity for eosinophils, was administered to passively sensitized animals in attempt to examine a role of eosinophils in LAR. A goodly number of animals developed LAR on additional PAF inhalation. These animals, when compared with those without LAR, showed a significantly larger proportion of eosinophils in BALF (p less than 0.05) with an upward tendency for the proportion of neutrophils. Histologically, there was noted a striking association between LAR and eosinophilic infiltration of the bronchial submucosa. These results suggest that anti-IgE antibody is deeply involved in the elicitation of LAR, stressing the importance of eosinophilic infiltration.

Animals↗

[Studies on EDTA-dependent pseudoneutropenia].

The phenomenon of EDTA-dependent pseudoleukocytopenia was observed in seven patients during the period from September 1989 to March 1990. The pseudoleukocytopenia was found to have come from aggregation of neutrophils. The aggregations were composed of neutrophils only, and did not include other granulocytes, monocytes and lymphocytes. The aggregations showed their maximum in size from 30 to 180 minutes after venipuncture at room temperature. The aggregated neutrophils were again dispersed by incubating at 37 degrees C for 30 minutes. The degree of aggregation was found to be dependent on the concentration of EDTA. Neutrophil aggregation was not recognized in the blood films when sodium citrate or heparin was used as an anticoagulant. The results of mercaptoethanol agglutination test and immunocytochemical staining suggest that IgM antibody may play an important role in the formation of neutrophil aggregation. Four of the seven patients had suffered from hepatic disorder. However, the mechanism of EDTA-dependent neutrophil aggregation remains uncertain.

Adult↗

Ventilatory effects of percutaneous magnetophrenic stimulation.

This study was conducted with the purpose of elucidating the ventilatory effect of percutaneous magnetic stimulation of the phrenic nerve and investigating the possibility of clinically utilizing this effect as the mechanism of an artificial respirator. A magnetic stimulator consisting of a flat circular coil generating strong magnetic fields up to a maximum of 1.3 Tesla was developed. Formed from 1.8 mm diameter copper wire, this coil is 40 mm in diameter, 14 mm in thickness and has an inductance of 24 microH. The appurtenant current generator can deliver more than 5000 A to the coil. The capacitor terminal voltage (Vc) of the generator was used as a parameter of the intensity of the stimulus. Ventilatory effects were assessed mainly by diaphragmatic electromyogram and by transdiaphragmatic pressure, ventilation flow and tidal volume measurements. Magnetic stimulation was applied percutaneously to a unilateral phrenic nerve in dogs as well as human subjects and also to a median nerve of the forearm in human subjects. The range of stimulatory intensity Vc necessary to obtain ventilatory effects was 400-500 V, and the tidal volume thus obtained corresponded to normal breathing at rest for both dogs and humans. No pain was felt in the vicinity of point of application of the stimulator and there were no significant adverse effects such as changes in the ECG or heart rate. These results indicated that percutaneous magnetic stimulation of the phrenic nerve could produce adequate ventilatory effects in control applications.

Animals↗