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Biomedical subjects

S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 649 records · Page 36Linked to original sources

Time course study for antigen-induced airway hyperreactivity and the effect of soluble IL-5 receptor.

To study the role of IL-5 in allergic airway hyperreactivity, the time course for the production of cytokines, the infiltration of inflammatory cells and the onset of airway hyperreactivity after three inhalations of antigens were studied in mice. The effect of the soluble alpha-chain of murine recombinant interleukin-5 receptor (sIL-5R alpha) on these phenomena was also examined. Whereas IL-5 and IL-4 were produced in significant amounts, IL-1, IL-2 and gamma-interferon (gamma-IFN) were not detected even after three antigen inhalations. Monocytes and eosinophils but not neutrophils increased significantly after the third antigen exposure. The airway responsiveness to acetylcholine increased after the third aeroantigen-challenge. sIL-5R alpha, administered after each antigen-challenge, suppressed BAL eosinophilia with little effect on airway hyperreactivity.

Acetylcholine↗

Nicotine improves cognitive disturbance in senescence-accelerated mice.

Senescence-accelerated mice (SAM), a murine model of age-related deterioration in learning ability, were studied as to the acetylcholine (ACh) contents in the brain tissues and the effect of nicotine administration. We found that the ACh content of SAM-P/8 (accelerated senescence-prone) mice was lower than that of SAM-R/1 (accelerated senescence-resistant) mice in the midbrain thalamus and the hypothalamus. In addition, an IP administration of nicotine was found to improve learning ability of SAM-P/8 as shown by performance of a passive avoidance task. Nicotine may potentiate cognitive function in SAM-P/8.

Acetylcholine↗

Reduction of visual P300 during transient global amnesia.

Transient global amnesia (TGA) is a syndrome of selective loss of recent memory without other neurological deficits. Auditory and visual P300s were recorded during and after TGA to investigate the contribution of the short-term memory system to P300 generation. The auditory P300 during TGA was comparable to that recorded 1 week and 9 months after TGA. In contrast to the auditory modality, the visual target P300 was reduced in amplitude during TGA and at 1 week after the attack. The P300 to novel visual stimuli was also reduced during TGA. Both target and novelty visual P300 recovered by 9 months after TGA. The results support the notion that the neuronal networks responsible for P300 generation are modality dependent and that brain structures perfused by the posterior circulation are involved in visual P300 generation.

Amnesia↗

Role of intracellular SOD in protecting human leukemic and cancer cells against superoxide and radiation.

Many anticancer drugs have been shown to produce superoxide anion (O2.-) and seem to involve O2.- in their mode of action. Ionizing radiation provokes the decomposition reaction of water, producing a variety of reactive oxygen species, including O2.-. The finding that cancer cells are generally low in SOD activity may offer a theoretical base for radiation therapy and chemotherapy. The purpose of this study was to examine the protective effect of intracellular SOD against cytotoxicity induced by O2.- or radiation and to investigate whether exogenous SOD can protect cells from O2.-(-) and radiation-induced cytotoxicity. For this purpose, xanthine (X) and xanthine oxidase (XOD) were employed as an O2.- (-)generating system, and a linear accelerator was used for ionizing radiation. Cytotoxicity against monolayer cancer cell lines and leukemic cell lines was estimated by measuring the release of lactate dehydrogenase from these cells. The results revealed that the resistibilites to X- and XOD-generated O2.- and radiation correlated with intracellular Cu. Zn-SOD levels and that exogenous SOD could only slightly reduce X- and XOD-induced cytotoxicity while having no influence on radiation-induced cytotoxicity. Thus, intracellular SOD may play a central role in protecting cancer cells against reactive oxygen species generated by anticancer drugs and radiation.

Carcinoma, Squamous Cell↗

Pharmacological studies of platelet-activating factor (PAF)-induced augmentation of response to histamine in guinea-pigs.

An acute increase in airway response to histamine produced by platelet activating factor (PAF) was investigated pharmacologically in guinea-pigs. (1) The airway response to histamine (3 micrograms/kg) measured as pulmonary pressure was increased 8 min after injection of PAF at a dose of 25 ng/kg without affecting the numbers of leukocytes (macrophages, eosinophils, neutrophils and lymphocytes) in bronchoalveolar lavage fluid and airway capillary permeability. (2) To investigate the mechanism responsible for the PAF (25 ng/kg)-induced airway hyperresponsiveness to histamine, the effects of CV-3988 (a PAF-antagonist), ONO-1078 (a leukotriene (LT) antagonist), AA-861 (a 5-lipoxygenase inhibitor), indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane A2 (TXA2) synthetase inhibitor) and S-1452 (a TXA2 receptor antagonist) were examined. Simultaneously, to investigate the direct antagonistic effects of these drugs on PAF-induced response, the effects of above agents on PAF (150 ng/kg) induced bronchoconstriction were examined. CV-3988 completely inhibited both reactions, while ONO-1078 and AA-861 had no effect on both reactions. OKY-046, S-1452 and indomethacin inhibited PAF-induced bronchoconstriction more potently than PAF-induced airway hyperresponsiveness. These results indicate that inflammatory response is not involved in the onset of PAF-induced acute airway hyperreactivity. Results also suggest that TXA2 but not LT may play a role in the onset of this airway hyperreactivity and the role of TXA2 in hyperreactivity is less important than in PAF-induced bronchoconstriction.

Animals↗

An unusual buried polar cluster in a family of fungal lipases.

The stability of globular proteins arises largely from the burial of non-polar amino acids in their interior. These residues are efficiently packed to eliminate energetically unfavorable cavities. Contrary to these observations, high resolution X-ray crystallographic analyses of four homologous lipases from filamentous fungi reveal an alpha/beta fold which contains a buried conserved constellation of charged and polar side chains with associated cavities containing ordered water molecules. It is possible that this structural arrangement plays an important role in interfacial catalysis.

Amino Acid Sequence↗

Tetraplegic wheelchair basketball.

Tetraplegic wheelchair basketball was started in the Kanagawa Rehabilitation Center (KRC) as a recreational sport for tetraplegics in 1980. In this game, there are two goals on each side, thus we call it 'twin basketball'. One goal is of ordinary height and the other is low. Three ways of shooting and two ways of dribbling are allowed according to the player's level of tetraplegia and technical skill. The first official game was held in 1983. Since then, the game has been taken up in several areas of Japan. The first All Japan championship game was held in 1987, ten teams including 98 tetraplegics attending. Five years later, in the sixth championship game, 18 teams including 171 tetraplegics attended. As official physicians, we have examined the physical condition and technical skills of all players since 1987. All players are classified, and assigned points from 1 to 4.5. The total number of points of five players in one team are limited to 11.

Adolescent↗

Electroencephalographic activity associated with shifts of visuospatial attention.

The neural processes underlying shifts of visuospatial attention were studied in normal adults by non-invasive recording of brain electrical activity. Event-related evoked potentials (ERPs) were recorded during target detection tasks with targets preceded by central or peripheral directional cues in the visual field, which are hypothesized to provoke voluntary and reflexive shifts of spatial attention. Reaction time to targets varied as a function of cue type and cue-target interval, indicating that the tasks induced shifts of spatial attention across the visual field. Event-related evoked potential recordings showed that central cues elicited negative potential shifts starting 240 ms after cue onset over posterior scalp sites contralateral to the cued visual field, which spread to anterior scalp sites over time. After 500 ms post cue, negative potentials were more negative in right temporal parietal sites regardless of cue direction. Peripheral cues enhanced the N1 component (140-200 ms post cue) over the contralateral hemisphere. Following N1 enhancement, a sustained negative potential shift appeared after 460 ms post cue at posterior scalp sites contralateral to cued field and spread over the temporal and central regions. These results suggest that the neural processes underlying spatial selection are initiated in the posterior region and that other cortical activities are recruited in a serial fashion. Symmetrical early activation of each contralateral hemisphere suggest independent involvement of the hemispheres in the early stages of shifting attention toward the contralateral visual field. A predominant contribution of the right hemisphere to sustained spatial attention was demonstrated in the late stage of cue processing at the right temporal and parietal regions. Different ERP patterns generated by central and peripheral cues support the hypothesis that distinct neural systems are involved in voluntary and reflexive mechanisms of attention shift.

Adult↗

Mutations and polymorphisms of the gene encoding the beta-subunit of the electron transfer flavoprotein in three patients with glutaric acidemia type II.

Electron transfer flavoprotein (ETF) is a heterodimeric enzyme composed of an alpha-subunit and a beta-subunit and contains a single equivalent of FAD per dimer. ETF deficiency can be demonstrated in individuals affected by a severe metabolic disorder, glutaric acidemia type II (GAII). In this study, we have investigated for the first time the molecular basis of beta-ETF deficiency in three GAII patients: two Japanese brothers, P411 and P412, and a third unrelated patient, P485. Molecular analysis of the beta-ETF gene in P411 and P412 demonstrated that both these patients are compound heterozygotes. One allele is carrying a G to A transition at nucleotide 518, causing a missense mutation at codon 164. This point mutation is maternally derived and is not detected in 42 unrelated controls. The other allele carries a G to C transversion at the first nucleotide of the intron donor site, downstream of an exon that is skipped during the splicing event. The sequence analysis of the beta-ETF coding sequence in P485 showed only a C to T transition at nucleotide 488 that causes a Thr154 to Met substitution and the elimination of a HgaI restriction site. HgaI restriction analysis on 63 unrelated controls' genomic DNA demonstrated that the C488T transition identifies a polymorphic site. Finally, transfection of wild-type beta-ETF cDNA into P411 fibroblasts suggests that wild-type beta-ETF cDNA complements the genetic defect and restores the beta-oxidation flux to normal levels.

Amino Acid Metabolism, Inborn Errors↗

Stereospecificity of trans-dihydrodiol oxidation by dimeric and monomeric dihydrodiol dehydrogenases from mammalian tissues.

The stereochemical course in the enzymatic oxidation of trans-dihydrodiols of benzene and naphthalene by dimeric dihydrodiol dehydrogenase of monkey kidney was compared with that by monomeric dihydrodiol dehydrogenase of rat liver. The monkey kidney and rat liver enzymes each oxidized about half of the racemic dihydrodiol of benzene added to the reaction mixture, but almost all the substrate was disappeared in the reaction mixture containing both enzymes. The CD spectra of the unreacted dihydrodiols of benzene and naphthalene in reaction mixtures containing the rat liver enzyme showed the negative sign of Cotton effect, while those in reaction mixtures containing the monkey kidney enzyme gave the positive sign of Cotton effect. Thus, the monkey kidney dimeric enzyme selectively oxidized (-)-[1R,2R]-dihydrodiols of aromatic hydrocarbons, in contrast to the stereo-specificity of the rat liver enzyme for the (+)-[1S,2S]-isomers. The (+)-[1S,2S]- and (-)-[1R,2R]-dihydrodiols of benzene were separately prepared from the racemic form by using the two enzymes, and were used as substrates to determine the stereospecificity of dihydrodiol dehydrogenases from other mammalian tissues. The dimeric enzymes from pig liver and rabbit lens also exhibited specificity for the (-)-isomer, which was opposite to that of the monomeric enzymes from human and mouse liver, although aldehyde reductase and aldose reductase oxidized both (+)- and (-)-isomers.

Alcohol Oxidoreductases↗

Current progress in crystallographic studies of new lipases from filamentous fungi.

Lipases from filamentous fungi have been studied extensively over many years. They exhibit properties attractive for industrial applications, e.g. in laundry detergents, tanning and paper industries and stereospecific organic synthesis. Enzymes from the fungi Rhizomucor miehei and Geotrichum candidum have been among the first neutral lipases to be characterized structurally by X-ray diffraction methods. In this paper we report a preliminary account of crystallographic studies of three other fungal lipases homologous to that from R. miehei and obtained from Humicola lanuginosa, Penicillium camembertii and Rhizopus delemar. These newly characterized structures have important implications for our understanding of structure-function relationships in lipases in general and the molecular basis of interfacial activation.

Amino Acid Sequence↗

Eosinophil cationic protein in the sera of patients with Mycoplasma pneumonia.

In 1985 we reported that eosinophilia was found in many children with Mycoplasma pneumonia. We measured the serum concentrations of eosinophil cationic protein (ECP) produced by eosinophils in 25 children with Mycoplasma pneumonia, 25 with asthma and 11 with no disease (normal controls). The mean concentrations (+/- SD) of serum ECP in children with Mycoplasma pneumonia, with asthma and the normal controls were 18.7 +/- 12.6, 23.7 +/- 12.2 and 6.5 +/- 1.4 micrograms/ml, respectively. When compared with those of normal controls, these higher serum concentrations of ECP in children with Mycoplasma pneumonia and asthma were statistically significant (P < 0.001). The data were directly correlated with the presence of eosinophilia (r = 0.349). There was no relationship between the amount of ECP and the age of children with Mycoplasma pneumonia. These results suggest that ECP may work as a factor causing a persistent cough similar to asthma in children with Mycoplasma pneumonia.

Adolescent↗

Cyclic haemopoiesis at 7- or 8-day intervals.

We report a patient with severe anaemia and cyclic oscillations of reticulocyte and leucocyte counts, as well as serum iron (Fe), unsaturated iron-binding capacity (UIBC), ferritin, C-reactive protein (CRP) levels and temperature, at regular intervals of 7 or 8 d. After treatment with prednisolone, anaemia was corrected and the cyclic oscillations of these parameters ceased; whereas treatment with indomethacin, recombinant granulocyte-colony stimulating factor (G-CSF) and erythropoietin (Epo) were unsuccessful.

Adult↗

Thyroid cancer in a case with the Alagille syndrome.

A 19-year-old woman with the Alagille syndrome developed papillary thyroid carcinoma with lung metastasis. She was diagnosed as having Alagille syndrome at the age of 8. Following total thyroidectomy and lymph nodes dissection, iodine-131 therapy was conducted for local and distant metastases. This is the first report of a case of thyroid cancer accompanying Alagille syndrome.

Adult↗

A study of urinary metabolites in patients with dicarboxylic aciduria for differential diagnosis.

Dicarboxylic aciduria (DCA-uria) is a relatively common finding in the screening of organic acidemias by gas chromatography/mass spectrometry (GC/MS). A considerable number of patients with DCA-uria are involved in disturbances of mitochondrial and peroxisomal fatty acid beta-oxidation. The differential diagnosis of DCA-uria was investigated using a combination of organic acid analysis by GC/MS, carnitine determination, acylcarnitines by fast atom bombardment/mass spectrometry (FAB/MS) and acylglycines by stable-isotope dilution analysis. The relative distribution of urinary metabolites was examined in 46 patients with DCA-uria of different origins, including physiological ketosis of childhood, disorders of propionic acid metabolism, glutaric aciduria type II, Zellweger syndrome and patients who were clinically diagnosed as having Reye syndrome. Zellweger syndrome seemed to be distinguishable from other disorders by the high sebacic acid/adipic acid ratio of DCA-uria and increased excretion of 4-hydroxyphenyllactic acid and 2-hydroxysebacic acid. The mild form of glutaric aciduria type II was often missed by current organic acid analysis alone, but was readily diagnosed by acylcarnitine and acylglycine determination. The ratio of free/total carnitine was low in most of the DCA-uria patients except for two of five cases of Zellweger syndrome and one of three cases of Reye syndrome. The acylcarnitine analysis by FAB/MS showed adipyl-, suberyl-, sebacyl- or dodecanedioylcarnitine as major peaks in most of these patients, although these were not specific. Disease-specific peaks were detectable only in congenital organic acidemias such as glutaric aciduria type II, methylmalonic acidemia and propionic acidemia.

Amino Acid Metabolism, Inborn Errors↗

Roles of FliK and FlhB in determination of flagellar hook length in Salmonella typhimurium.

The length of flagellar hooks isolated from wild-type and mutant cells with various hook lengths were measured on electron micrographs. The length of the wild-type hook showed a narrow distribution with a peak (+/- standard deviation) at 55.0 +/- 5.9 nm, whereas fliK mutants (so-called polyhook mutants) showed a broad distribution of hook lengths ranging from 40 to 900 nm, strongly indicating that FliK is involved in hook length determination. Among pseudorevertants isolated from such polyhook mutants, fliK intragenic suppressors gave rise to polyhook filaments. However, intergenic suppressors mapping to flhB also gave rise to hooks of abnormal length, albeit they were much shorter than polyhooks. Furthermore, double mutations of flhB and flgK (the structural gene for hook-associated protein 1; HAP1) resulted in polyhooks, suggesting another way in which hook length can be affected. The roles of FliK, FlhB, and HAP1 in hook length determination are discussed.

Bacterial Proteins↗

Association analysis of restriction fragment length polymorphism for alpha 2-adrenergic receptor genes in essential hypertension in Japan.

Recently, restriction fragment length polymorphism (RFLP) of alpha 2-adrenergic receptor gene (alpha 2-C10) digested with Bsu36I restriction enzyme has been reported in US populations. Therefore, we examined the association of this RFLP with essential hypertension by comparing the frequency of specific alleles for this gene in Japanese populations. The distribution of this RFLP was compared with that in US populations. Subjects were hypertensive patients with a family history of essential hypertension (n = 56) and normotensive subjects whose parents had no history of essential hypertension (n = 46). DNA was prepared from leukocytes. RFLP was determined by use of Southern blot analysis with an alpha 2-C10 probe and Bsu36I. The frequencies of the major (12-kb) and minor (5.8-kb) alleles were 0.30 and 0.70 in hypertensive patients and 0.38 and 0.62 in normotensive subjects, respectively. The difference between observed alleles in all subjects in each group was not significant (chi 2 = 1.33, P > .1). The difference between the overall allelic frequency in Japan and that reported in US populations was significant. This study found no evidence for an association between alpha 2-adrenergic receptor gene/Bsu36I RFLP and essential hypertension in Japan. However, the findings showed that the allele frequency in Japan differed from that reported in US populations.

Adult↗