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Biomedical subjects

M Shibasaki

Publications and source records attributed to M Shibasaki.

At least 163 records · Page 9Linked to original sources

Interaction of lectins with human IgE: IgE-binding property and histamine-releasing activity of twelve plant lectins.

We examined the IgE-binding reaction and the histamine-releasing response of basophils to a panel of 12 lectins: concanavalin A (Con A), Lens culinaris hemagglutinin (LcH), Pisum sativum agglutinin (PSA), wheat germ agglutinin (WGA), soybean agglutinin (SBA), Bauhinia purpurea agglutinin (BPA), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA-I), Lotus tetragonolobus agglutinin (Lotus A), Ulex europeus agglutinin I (UEA-I), phytohemagglutinin E (PHA-E) and phytohemagglutinin L (PHA-L), IgE from allergic patients bound with high affinity to Con A, LcH, PSA, RCA-I and PHA-E, and with lower affinity to WGA, BPA, Lotus A and UEA-I, but they did not bind to SBA, PNA or PHA-L. There was no apparent individual difference in the reactivity of IgE to these lectins between 10 IgE preparations from allergic patients. The binding to these lectins, except Lotus A and UEA-I, were competitively inhibited by the lectin-specific sugars or glycopeptide. Upon stimulation by Con A, LcH, PSA, WGA, RCA-1 and PHA-E, leukocytes from allergic patients showed a significant release of histamine, but cells from IgE-deficient subjects did not respond to these lectins. The histamine-releasing responses by these lectins were also inhibited by specific sugars or glycopeptides.

Basophils↗

A novel homoisocarbacyclin analog with potent and long-lasting activity.

A synthesis of a novel and chemically stable homoisocarbacyclin analog, TY-11223 (3), has been accomplished. The analog (3), given intravenously or orally, showed potent and long-lasting activities in inhibiting platelet aggregation and, in addition, a good selectivity in biological activities.

Animals↗

Premenstrual asthma with seasonal variation.

A 19-year-old woman had premenstrual asthma (PMA) usually from April through October each year with normal and regular menstrual cycles. When the monthly variation in the patient's PMA between 1984 and 1990 was compared with the monthly admissions of children for acute asthma in a hospital in this region, there was a great similarity in pattern between the two. Although she had high sensitivity to house-dust mites, the monthly pattern of her PMA did not coincide with monthly variations in the number of mites in house-dust in her home.

Administration, Inhalation↗

Haloperidol metabolism in psychiatric patients: importance of glucuronidation and carbonyl reduction.

In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady-state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism.

Adolescent↗

Haloperidol reductase activity in red blood cells from oriental patients on haloperidol.

1. We measured haloperidol reductase activity in red blood cells in 87 samples collected from 50 Japanese psychiatric patients on HAL. HAL reductase activities in the patients were in a range of 7.9-26.1 pmol/hr/10(6) RBC (mean = 13.4, S.D. = 3.4). Interindividual variability was as large as 25.4% (CVs), while intraindividual CVs were small (8.9%). 2. Distribution of HAL reductase activities was normal but their values were slightly lower in the patients than those in the normal controls, though the difference between these two groups was not significant. 3. No significant correlations were found between HAL reductase activity in RBC vs dose of HAL per body weight, or plasma and RBC RHAL/HAL ratio.

Adolescent↗

Pharmacological properties of YM-21095, a potent and highly specific renin inhibitor.

A novel renin inhibitor, YM-21095 [2RS), (3S)-3-[N alpha-[1,4-dioxo-4-morpholino-2-(1-naphthylmethyl)-buthyl]-L- histidil-amino]-4-cyclohexyl-1-[(1-methyl-5-tetrazolyl)thio]-2-but anol), has been synthesized in our laboratories. The aim of this study was to evaluate the pharmacological properties of YM-21095 in in vitro and in vivo experiments. YM-21095 inhibited human renin with an IC50 value of 4.7 x 10(-10) mol/L. YM-21095 was also a potent inhibitor against squirrel monkey renin, but less effective against renins from dog, rabbit, and rat. The effect of YM-21095 is highly specific for renin, since it did not inhibit cathepsin D, pepsin, or angiotensin converting enzyme up to a concentration of 10(-4) mol/L. YM-21095 was resistant to proteolytic actions of the enzymes (pepsin, chymotrypsin, trypsin) and squirrel monkey tissue homogenates (liver, kidney, small intestine). Intravenous infusion of YM-21095 (0.1 to 100 micrograms/kg/min) decreased mean blood pressure and inhibited plasma renin activity in a dose-dependent manner with no effect on heart rate in anesthetized sodium-depleted and sodium-replete squirrel monkeys. The hypotensive effect of YM-21095 in sodium-depleted squirrel monkeys was about ten times as potent as that in sodium-replete squirrel monkeys. Oral administration of YM-21095 to conscious sodium-depleted squirrel monkeys produced dose-related decreases of systolic blood pressure. We conclude that YM-21095 is a potent and highly specific inhibitor of primate renin and produces a blood pressure lowering effect.

Administration, Oral↗

Stereocontrolled synthesis of exocyclic olefins using arene tricarbonyl chromium complex-catalyzed hydrogenation. I. Efficient synthesis of carbacyclin and its analogs.

An efficient synthesis of carbacyclin and its analogs (2-7) is described in which the stereospecific 1,4-hydrogenation of a 1,3-diene to an internal monoene plays a key role. That is, arene.Cr(CO)3 complex-catalyzed 1,4-hydrogenation of the dienes 13 and 58, obtainable from the Corey lactone in good yields, under high H2 pressure afforded the exocyclic olefins 14 and 61 stereospecifically in excellent yields, and these intermediates were converted to therapeutically useful carbacyclin (2) and its analogs 3-7 in a usual way.

Animals↗

Overexpression of glucose transporter modulates insulin biosynthesis in insulin producing cell line.

Glucose transporter (GT) has been suggested to be involved in the insulin biosynthesis. However, the functional relationship between GT and insulin biosynthesis is not well understood. In this report, we have generated rat pancreatic B cell lines (RINr) that stably overexpress a cDNA encoding the brain type GT. These cell lines showed 3- to 4-fold increase in insulin mRNA and protein. These results suggest that GT might have some relationship to the insulin biosynthesis in the pancreatic B cells.

Animals↗

Reduced haloperidol/haloperidol ratios in plasma: polymorphism in Japanese psychiatric patients.

We measured plasma concentrations of haloperidol (HAL) and its metabolite, reduced haloperidol (RHAL), by high performance liquid chromatography (HPLC) in 45 Japanese psychiatric patients receiving HAL. Plasma levels of HAL had a highly positive correlation with daily dose per body weight. Plasma RHAL/HAL ratios had also a dose-dependent relationship, but their distribution was nonnormal and a bimodal pattern with an antimode at 0.7 was apparent by probit analysis. There were 8 subjects (18%) with high RHAL/HAL ratios (mean = 1.26, SD = 0.41) and 37 subjects (82%) with low RHAL/HAL ratios (mean = 0.42, SD = 0.13). RHAL/HAL ratios showed little intraindividual variability (+/- 10.6%), while interindividual variability was large. This may suggest that pharmacogenetic factors are involved in the metabolism of HAL and RHAL.

Adolescent↗

Measurement of haloperidol reductase activity in red blood cells and reduced haloperidol/haloperidol ratios in plasma in oriental psychiatric patients.

1. The authors established a method for measuring haloperidol (HAL) reductase activity in human red blood cells. 2. Characteristics of the HAL reductase in red blood cells were examined. This enzyme reaction was NADPH dependent, and the optimum pH was at 8.2-8.9. Vmax and Km were calculated as 25-150 pmol/hr/10(6) RBC and 160-2600 microM respectively. 3. HAL reductase activities in red blood cells from 14 patients treated with HAL were in a range of 9.7-20.8 pmol/hr/10(6) RBC. So far we did not find any significant correlation between HAL reductase activities and reduced HAL/HAL ratios in plasma.

Adult↗

Relationship between asthma and seasonal allergic rhinitis in schoolchildren.

The relationship between sensitization to common allergens and the development of asthma and seasonal allergic rhinitis (SAR) was investigated in a total of 419 schoolchildren in a farming community where allergens of both Dermatophagoides farinae (Df) and orchard grass (OG) pollen predominate. Twelve subjects (2.9%) were found to have asthma and 35 subjects (8.4%) SAR. There was no significant association between occurrences of asthma and SAR. The incidence of asthma correlated with DF-specific IgE levels but not with OG-specific IgE levels, whereas that of SAR correlated with OG-specific IgE levels but not with Df-specific IgE levels. No significant correlation was detected between IgE antibody levels against Df and OG. These results suggest that asthma occurs independently of SAR.

Adolescent↗

[Effects of intra-arterial infusion of degradable starch microspheres on liver tissue blood flow].

The effects of intra-arterial infusion of degradable starch microspheres (DSM) on liver tissue blood flow were estimated in rat with liver carcinoma induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) administration. Tissue blood flow of tumor and normal liver was measured simultaneously by Laser blood flowmeter. Tissue blood flow of tumor and normal liver was 13.3 +/- 6.9, 13.2 +/- 4.3 (ml/min/100 g), respectively. After intra-arterial infusion of DSM, tissue blood flow of both tumor and normal liver decreased to the same degree as that at hepatic artery occlusion and then gradually recovered. This gradual recovery of tissue blood flow was supposed to express the process of resolution of DSM by alpha-amylase. The recovery time of tissue blood flow following intra-arterial infusion of DSM was 27.3 +/- 4.0 min (DSM 20 mg/kg) and 70.0 +/- 23.6 min (DSM 30 mg/kg) in tumor and 20.0 +/- 3.3 min and 36.5 +/- 18.0 min, respectively, in normal liver. Thus, the blocking effect of blood flow by DSM was different between tumor and normal liver and proved to be more persistent in the former.

Animals↗

Synthesis of cis-bicyclo[4.3.0]non-2-ene derivatives. The potent homoisocarbacyclin analogs.

Synthesis of homoisocarbacyclin has been achieved efficiently by a general strategy with stereo- and regiochemical control. One of homoisocarbacyclin derivatives, 3-oxa homoisocarbacyclin analog (4), was shown to be potently active in inhibiting gastric ulcer. Another analog, conjugated diene derivative (5), was found to have a biological profile similar to prostacyclin.

Anti-Ulcer Agents↗

[The plasma levels of haloperidol and reduced haloperidol in Japanese psychiatric patients].

We measured plasma levels of haloperidol (HAL) and its metabolite, reduced haloperidol (RHAL), in 30 psychiatric patients receiving haloperidol. HAL and RHAL levels were measured by reversed-phase high-performance liquid chromatography. The results were as follows. (1) Plasma levels of HAL had a highly positive correlation with daily dose per body weight (r = 0.902). (2) Distribution of individuals in relation to RHAL levels appeared to have a bimodal pattern. Of these 30 patients studied, 7 were identified as extensive metabolizers (23%). (3) RHAL/HAL ratios showed small intra-individual variance, while inter-individually they varied largely. The mean RHAL/HAL ratio in 30 patients was 0.692; when the 7 extensive metabolizers were excluded, it was 0.491. (4) In the individuals with clinical improvements, plasma levels of HAL and RHAL were 7.45 +/- 4.46, 3.96 +/- 2.16 ng/ml (mean +/- SD), respectively. Patients showing high plasma levels of HAL and RHAL (greater than 30 ng/ml) became aggravated during HAL treatment.

Adolescent↗

Late anaphylactic reaction to cuttlefish.

A 10-year-old girl exhibited a late-onset systemic anaphylactic reaction, three and one-half hours after ingestion of cuttlefish. The late reaction was not preceded by an early-phase reaction but occurred seven days after an immediate anaphylactic reaction to this allergen. The patient had a high level of specific IgE antibody against cuttlefish.

Allergens↗

Relation between frequency of asthma and IgE antibody levels against Dermatophagoides farinae and total serum IgE levels in schoolchildren.

The relation between the frequency of wheezing illness and IgE antibody levels against Dermatophagoides farinae (Df) and total IgE levels was examined in 457 randomly selected schoolchildren. From the response to the ATS-DLD-78-C respiratory symptoms questionnaire, 14 subjects (3.1%) were found to have asthma syndrome (recurrent episodes of attacks of shortness of breath with wheezing) and 17 subjects (3.7%), wheezing syndrome (only wheezing). The percentage of the asthma syndrome increased with increasing levels of Df-specific IgE, and there was an intimate correlation between the percentage of asthma syndrome and Df-specific IgE levels (r = 0.97; p less than 0.001), whereas such association was not found between the two (r = -0.19; p greater than 0.5). Similar relations were found between the frequencies of the specific syndromes and total IgE levels. There was a significant correlation between total IgE levels and Df-specific IgE levels in the total population (r = 0.7; p less than 0.001). These results suggest that allergic reaction greatly contributes to the development of asthma in children.

Animals↗

Genetic analysis of human lymphocyte proteins by two-dimensional gel electrophoresis. VIII. Genetic polymorphism of cytosol polypeptide with molecular weight of 20,000.

We describe a genetic polymorphism of cytosol polypeptide with mol. wt. of 20,000 detected in lymphocytes and erythrocytes by two-dimensional gel electrophoresis. Three different electrophoretic phenotypes (type 1-1, 2-1, and 2-2) of the polypeptide have been identified in a Japanese population. Family studies indicate that the phenotypes are determined by two common alleles at a single autosomal locus. The polypeptide is present in the cytosol of various kinds of cells and is abundant in erythrocytes. The data on a gel filtration of the erythrocyte cytosol proteins on a Sephadex G-100 column suggest that the polypeptide exists as a dimer in cells. In nine out of 79 individuals, the phenotypes of the polypeptide were different from those of glyoxalase 1 (GLO1) which has similar properties in subunit size, cell distribution, and allele frequencies. These data indicate that the polypeptide with mol. wt. of 20,000 is a new polymorphic cellular polypeptide. We propose that the polypeptide be temporarily designated as cytosol polypeptide with mol. wt. of 20,000 (CP20) and that the gene for CP20 be designated as CP20. The gene frequencies of two common alleles (CP20(1) and CP20(2) are 0.955 and 0.045, respectively, in a Japanese population.

Blood Proteins↗