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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 775 records · Page 43Linked to original sources
PubMed1996

Identification of cyclic cystathionine sulfoxide and N-acetylcyclic cystathionine in the urine of a patient with cystathioninuria using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system.

Perhydro-1,4-thiazepine-4,5-dicarboxylic acid sulfoxide (cyclic cystathionine sulfoxide [cyclic cystaSO]) and N-acetylperhydro-1,4-thiazepine-3,5-dicarboxylic acid (NAc-cyclic cysta) have been identified in the urine of a patient with cystathioninuria as new metabolites of cystathionine for the first time using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system (LC/APCI-MS). The concentrations of cyclic cystaSO and NAc-cyclic cysta in the urine of a patient with cystathioninuria have also been determined for the first time using this method: 18.24 +/- 0.79 and 25.23 +/- 0.83 mg/g creatinine, respectively.

Atmospheric Pressure↗
PubMed1996

The effects of proteins on [Ca2+] measurement: different effects on fluorescent and NMR methods.

Previous reports showed that the presence of proteins shifts the apparent dissociation constant (Kd) of a fluorescent dye indicator to Ca2+. To elucidate the sensitivity of Kd of an NMR-sensitive Ca2+ indicator, 5-fluoro-1,2-bis(2-amino-phenoxy)ethane N,N,N'N'-tetraacetic acid (5F-BAPTA) to proteins, and compare with that of a dye indicator, Fura-2, we measured Kd of Fura-2 or 5F-BAPTA using Ca-EGTA buffer with or without proteins. Aldolase (ALD) or bovine cardiac protein (BCP) extracted from bovine hearts was used at concentrations of 10, 25, or 50 mg/ml. ALD significantly increased the apparent Kd of Fura-2 to Ca2+ from 164.1 +/- 5.6 nM (mean +/- SE, N = 8) to 757.2 +/- 2.1 nM (n = 4, P < 0.05) at the concentration of 50 mg/ml. In contrast, Kd of 5F-BAPTA was not markedly changed by ALD (298.4 +/- 3. nM without ALD (n = 8), 385.1 +/- 2.7 nM (n = 4) with 50 mg/ml ALD). BCP (50 mg/ml) also significantly increased Kd of Fura-2 (928.5 +/- 3.3 nM, n = 4, P < 0.05), but did not change Kd of 5F-BAPTA (316.0 +/- 2.9 nM, n = 4). These results indicate that Kd of 5F-BAPTA is much less sensitive to the presence of proteins than Fura-2, and that 19F-NMR coupled with 5F-BAPTA is a more robust method to measure intracellular Ca2+ concentration than a fluorescent method with Fura-2.

Animals↗
PubMed1996

Analysis of antigens recognized by autoantibodies in herpes gestationis. Usefulness of immunoblotting using a fusion protein representing an extracellular domain of the 180 kD bullous pemphigoid antigen.

Herpes gestationis (HG) is a rare pregnancy-associated disease. The aim of this study was to compare various immunohistochemical and immunobiochemical techniques with respect to their diagnostic sensitivity for HG. We studied 43 HG sera; only half of these reacted with the basement membrane zone (BMZ) with both indirect immunofluorescence (IF) and complement IF of normal human skin. 81% of the sera reacted with the epidermal side of 1 M NaCl-split skin. In general, titers of anti-BMZ antibodies in HG sera were lower than those in bullous pemphigoid (BP) sera. Immunoblot analysis of human epidermal extracts showed that 51% of HG sera recognized the 180 kD BP antigen (BP180) and 26% recognized the 230 kD BP antigen (BP230). We also studied the reactivity of HG sera with fusion proteins representing either the NC16a domain of human BP180 or the C-terminal region of mouse BP230. Whereas 79% of HG sera reacted with the BP180 fusion protein, only 5% recognized the BP230 fusion protein. Our results suggest that indirect IF of 1 M NaCl-split skin and immunoblotting of a fusion protein representing the BP180 NC16a domain are more sensitive techniques for the diagnosis of HG than conventional and complement IF or immunoblotting of crude epidermal extracts.

Animals↗
PubMed1996

Development and cytolytic function of intestinal intraepithelial T lymphocytes in antigen-minimized mice.

Intraepithelial T lymphocytes in the small intestine (IEL) consist of alpha beta T-cell receptor (TCR)-bearing T cells (alpha beta-IEL) and gamma delta TCR-bearing T cells (gamma delta-IEL). Development and cytolytic activation of alpha beta-IEL sharply attenuate in germ-free (GF) mice fed a natural diet (Nat-GF), but the number and cytotoxicity of gamma delta-IEL are comparable between conventional (CV) and Nat-GF mice. In this report, we compared the properties of IEL in Nat-GF mice and GF mice fed antigen-minimized diet (AgM-GF mice) of C57BL/6 strain to evaluate an influence of gut antigenic load on IEL development. Numbers of alpha beta-IEL and gamma delta-IEL in AgM-GF mice were less by 1.9- and 1.4-fold than those in Nat-GF mice, respectively. Significant decreases in the proportions of CD4+8-, CD4-8 alpha beta +, and CD4+8+ subsets and a resultant increase in the ratio of CD4-8 alpha alpha + subset were evident in alpha beta-IEL of Nat-GF mice compared with CV mice, but the subset constitution of alpha beta-IEL was similar between Nat-GF and AgM-GF mice. In contrast, relative composition of gamma delta-IEL was not different between CV, Nat-GF, and AgM-GF mice. alpha beta-IEL displayed low cytolytic activity in Nat-GF mice and were almost deprived of their cytotoxicity under the antigen-minimized condition. While gamma delta-IEL were strongly cytolytic in Nat-GF mice their cytolytic activity was remarkably reduced in AgM-GF mice. These results indicate that gamma delta-IEL are activated independently of microbial colonization in the gastrointestinal tract but their activation occurs in response to the exogenous antigenic substances other than live micro-organisms.

Animals↗
PubMed1996

Primary low cerebrospinal fluid pressure syndrome with galactorrhea: findings at MR imaging.

A case of primary low cerebrospinal fluid (CSF) pressure syndrome with galactorrhea is reported. Magnetic resonance imaging demonstrated diffusely enhanced meninges, edematous brain, and enlarged pituitary gland. Coincidental enlargement of pituitary gland and edematous brain due to low CSF pressure compressed the pituitary portal system. The low-perfused anterior lobe of pituitary gland would be the mechanism of galactorrhea.

Adult↗
PubMed1996

Induction of heat shock protein (HSP)-70 in posterior cingulate and retrosplenial cortex of rat brain by dizocilpine and phencyclidine: lack of protective effects of sigma receptor ligands.

The role of sigma receptors in the induction of heat shock protein (HSP)-70 by non-competitive N-methyl-Daspartate (NMDA) receptor antagonists (+)-MK-801 (dizocilpine) and phencyclidine (PCP) was studied. HSP-70 is induced in the posterior cingulate and retrosplenial cortex of rat brain 24 hours after a single administration of dizocilpine (1 mg/kg) or PCP (50 mg/kg). The induction of heat shock protein HSP-70 by dizocilpine or PCP was attenuated partially by pre-treatment with the antipsychotic drug haloperidol (3 mg/kg, i.p., 15 minutes previously). However, pre-treatment with high potent and selective sigma receptor ligands, 4-phenyl-4-(1-phenylbutyl)piperidine (4-PPBP, 3 mg/kg, i.p., 15 minutes previously) and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride) (NE-100, 3 mg/kg, i.p., 15 minutes previously) did not alter the induction of HSP-70 by dizocilpine or PCP. These findings suggest that sigma receptors may not play a significant role in the induction of HSP-70 by non-competitive NMDA receptor antagonists dizocilpine and PCP, and that protective effects of haloperidol on induction of HSP-70 protein by dizocilpine or PCP may be due to other effect(s) except sigma receptors.

Journal Article↗
PubMed1996

Primary structure of the pig homologue of human IHRP: inter-alpha-trypsin inhibitor family heavy chain-related protein.

The pig counterpart of human IHRP has been isolated from pig serum, and cDNA clones encoding this counterpart were isolated and characterized. The amino acid sequence of pig IHRP predicted from the nucleotide sequence of its cDNA shows reasonable homology to that of human IHRP. The nucleotide sequence of pig IHRP cDNA is identical to that of the mRNA partially determined to be the heavy chain of pig ITI [Buchman et al. (1990) Surgery 108, 560-566]; it is one of the major mRNAs induced in pig liver on cardiogenic shock. Thus we concluded that the reported mRNA should code for IHRP and not for the heavy chain of ITI. The pig IHRP also seems to be identical to pig-MAP, which was recently reported to be a major acute phase serum protein in pig [Gonzalez-Roman et al. (1995) FEBS Lett. 371, 227-230]. The results suggest that IHRP might be involved in acute phase reactions.

Acute-Phase Proteins↗
PubMed1996

Isolation and characterization of the human inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1).

Inter-alpha-trypsin inhibitor (ITI) family heavy chain-related protein (IHRP) is a novel human glycoprotein that shows significant homology in amino acid sequence to proteins of the ITI family heavy chains from human plasma. Three overlapping clones that encode the human inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1) were isolated and characterized. The IHRP gene spans 15 kb and is composed of 24 exons from 27 to 207 bp in size with consensus splice sites. The gene codes for the precursor of IHRP, which is similar to inter-alpha-trypsin inhibitor (ITI) family heavy chains. Two major transcription initiation sites were identified in the 5'-flanking region. They contain putative promoter elements, but no typical TATA box. Some exons of this gene showed significant similarities to those of the ITI-H1 gene in nucleotide length and in intron phasing. The tissue-specific transcription of this gene may be due to the presence of binding sites for the hepatocyte nuclear factors LF-A1, HNF-5, NF-IL6, and C/EBP. This gene was found to be localized very close to another unknown gene related to EST (GenBank accession #: R54643, R50663, R50563, H27139, and R54913).

Base Sequence↗
PubMed1996

Intrathecal catheterization in the rat. Improved technique for morphologic analysis of drug-induced injury.

BACKGROUND: The authors previously described an in vivo model suitable for investigation of functional impairment induced by intrathecally injected local anesthetic. However, meaningful histologic analysis could not be performed because catheterization, per se, induced morphologic changes in control animals. In the current experiments, the authors sought to identify an alternative, less reactive, catheterization technique for intrathecal drug administration. METHODS: Twenty-five rats received an intrathecal infusion of normal saline through a catheter composed of either 28-gauge polyurethane, 32-gauge polyimide, 32-gauge polyurethane, PE-10 polyethylene, or PE-10 polyethylene that had been stretched to twice its original length. Seven days after infusion, sensory function was assessed using the tail-flick test, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. RESULTS: There was no significant difference in sensory function among groups. Animals in which 28-gauge polyurethane, 32-gauge polyimide, PE-10, and double-stretched PE-10 had been implanted had moderate to severe nerve injury in 11%, 14%, 23%, and 8% of fascicles, respectively, whereas none of the animals in which 32-gauge polyurethane was implanted had any evidence of moderate or severe damage. CONCLUSIONS: Morphologic changes induced by intrathecal catheterization in the rat can be minimized by the use of 32-gauge polyurethane tubing.

Animals↗
PubMed1996

Follicular dendritic cells in vitro are not susceptible to infection by HIV-1.

OBJECTIVES: To investigate whether follicular dendritic cells (FDC) are target cells for HIV-1 infection. DESIGN: Based on the principle that if FDC are true target cells, HIV-1 particles will bind to the surface of FDC and then invade their cytoplasm and nuclei. METHODS: Freshly isolated tonsilar FDC were exposed to two strains (HE and JR-FL) of HIV-1 and cultured. They were then examined for HIV-1 replication, using p24 antigen-capture enzyme-linked immunosorbent assay, immunolabelling, and polymerase chain reaction (PCR) amplification. We used FDC clusters as the FDC source, since the culture system for FDC clusters has various advantages over other methods for the successful long-term culture of FDC. RESULTS: After 2 h incubation, particles of both HIV-1 strains bound to the surfaces of FDC, as well as to CD4+ T cells, although FDC do not have CD4 receptors. The FDC gradually released the particles into the culture supernatant. More HIV-1 particles were bound to fresh FDC than to dedifferentiated FDC or to control fibroblasts. However, HIV-1 particles bound to the FDC did not seem to enter the cells. We found no evidence of HIV-1 proviral DNA synthesis in FDC. CONCLUSIONS: Our results suggest that FDC are not readily infected with HIV-1 in situ, although we found that FDC in vitro were not infected by HIV-1.

Cells, Cultured↗
PubMed1996

Comparison of direct negative chronotropic and positive inotropic effects of sematilide to those of E-4031 and MS-551 and the reverse frequency-dependent prolongation of cardiac refractoriness of sematilide.

Direct cardiac effects of sematilide, a new class III antiarrhythmic drug, were compared with those of E-4031 and MS-551 in canine isolated blood-perfused heart preparations. Doses of sematilide, E-4031, and MS-551 causing a 10% decrease in the spontaneous sinoatrial beating rate were 58 +/- 15, 9 +/- 5, and 84 +/- 10 micrograms (n = 5); those causing a 10% increase in developed tension of the papillary muscle were 485 +/- 49, 17 +/- 2, and 267 +/- 50 micrograms (n = 6); and those causing a 10% prolongation of effective refractory period (ERP) of the atrioventricular node were 68 +/- 10, 11 +/- 2, and 53 +/- 15 micrograms (n = 5), respectively. There were few effects on atrio-His or His-ventricular intervals. Also, in in situ open-chest dog hearts, the percent increases in ERP of the atrioventricular conduction system caused by 1 mg/kg of sematilide were 21 +/- 3, 16 +/- 2 and 9 +/- 1% at cycle lengths of 800, 600, and 400 ms, respectively (p < 0.01; n = 8). These results indicate that (a) sematilide, as well as E-4031 and MS-551, has direct negative chronotropic and positive inotropic effects and prolongs cardiac refractoriness without affecting conduction velocities; (b) quantitatively, the cardiac effects of sematilide were almost identical to those of MS-551 and five to ten times less potent than those of E-4031; (c) and prolongation of ERP of the atrioventricular conduction system by sematilide occurred in a reverse frequency-dependent manner.

Animals↗
PubMed1996

Antiarrhythmic effects of optical isomers of disopyramide on canine ventricular arrhythmias.

Disopyramide is an effective class I antiarrhythmic drug and widely used for the treatment of arrhythmias, but it has anticholinergic side effects. In vitro studies demonstrated that dextrorotatory (D-) disopyramide has a stronger anticholinergic action, whereas the levorotatory (L-) isomer has a stronger Na channel blocking action. Because the antiarrhythmic mechanism of disopyramide suppressing digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmias is the drug-induced Na channel block, we examined the antiarrhythmic efficacy of D- and L-disopyramide on two arrhythmia models. On ouabain-induced ventricular tachycardia (VT), L-disopyramide 3 mg/kg decreased the arrhythmic ratio (number of ectopic beats/total heart rate), whereas the same dose of the D-isomer was ineffective and a higher dose (5 mg/kg) was needed to suppress the arrhythmia. The effective plasma concentrations (IC50) decreasing the arrhythmic ratio to 50% of the control were 5.3 and 11.3 mu g/ml for L- and D-disopyramide, respectively. We obtained similar results using 24-h two-stage coronary ligation VT. The IC50 were 8.9 and 22.2 mu g/ml for the L- and D-isomers, respectively. Our results indicate that L-disopyramide is about twice as strong an antiarrhythmic drug as the D-isomer.

Action Potentials↗
PubMed1996

Effects of dofetilide, a class III antiarrhythmic drug, on various ventricular arrhythmias in dogs.

Dofetilide, a new class III antiarrhythmic agent, was tested in various kinds of canine ventricular arrhythmias to compare its effects with those of other class III agents. Ventricular arrhythmia models used were induced by two-stage coronary ligation, digitalis, epinephrine, coronary ligation and reperfusion, and programmed electrical stimulation (PES). Dofetilide (100 micrograms/kg intravenously) did not suppress automaticity arrhythmias induced by two-stage coronary ligation and epinephrine or the coronary ligation and reperfusion arrhythmias, but suppressed the reentry arrhythmia induced by PES in dogs with old myocardial infarction (MI). This effect was associated with a prolongation of QT interval. Dofetilide also showed antiarrhythmic effect in some dogs with digitalis arrhythmia. Dofetilide increased QT interval and showed negative chronotropic effect like that of other class III drugs, but was different in antiarrhythmic profiles from those of other class III agents such as D-sotalol, E-4031, and MS-551 in that it did not prevent the occurrence of ventricular fibrillation (VF) immediately after coronary reperfusion and had some antiarrhythmic effects on digitalis arrhythmia.

Animals↗
PubMed1996

Age-related alterations in the auditory brainstem responses and the compound action potentials in guinea pigs.

The auditory brainstem response (ABR) and the eight nerve compound action potential (CAP) were measured using click click stimuli to investigate the age-related alteration in the auditory function in 66 guinea pigs consisting of four age groups. With advancing age, a gradual elevation of the thresholds in both the ABR and CAP was clearly seen, together with the prolonged latencies for waves I, II, III, and IV to clicks at 95 dBpeSPL in the ABR. There were some individual differences in either threshold elevation or latency prolongation of both the ABR and CAP in aged guinea pigs. These findings suggest that the effect of individual differences on degenerative aging processes of the auditory system should be considered in selected aged animals, although a significant elevation of the neural auditory threshold is clearly found with advancing age as a whole.

Action Potentials↗
PubMed1996

The gene for multiple familial trichoepithelioma maps to chromosome 9p21.

Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease characterized by the presence of many small tumors predominantly on the face. To map the causative gene, we performed linkage analysis with microsatellite markers in three American families. We found a significant linkage of a gene for MFT to chromosome 9p2l. The maximum combined lod score was 3.31 at D9S171 at theta = 0. The disease locus was defined to a 4-cM region between IFNA and D9S126. Because several tumor suppressor genes including p16 and p15 have been mapped to this region, the gene for MFT may also be a tumor suppressor.

Chromosome Mapping↗
PubMed1996

Low frequency of loss of heterozygosity at the nevoid basal cell carcinoma locus and other selected loci in appendageal tumors.

Previous studies of loss heterozygosity (LOH) have revealed distinct patterns of allelic loss in some skin tumors. In basal cell carcinomas (BCCs) loss of heterozygosity is virtually restricted to chromosome 9, whereas in squamous cell carcinomas (SCCs) and actinic keratoses loss is more widespread involving chromosomes 3, 9, 13, and 17. Because there are histological similarities between BCCs and some appendageal tumors, and because lines of evidence suggest that BCCs are appendageal in origin, we carried out a limited allelotype in 41 appendageal tumors. The overall frequency of allelic loss was low (4 out of 247 informative loci; 1.6%). LOH was seen in a proliferating trichilemmal cyst (17p), a sebaceous epithelioma (17q), an eccrine porocarcinoma (17q), a trichoepithelioma (9q), and in two basal cell carcinomas showing eccrine or granular cell differentiation that were originally misdiagnosed (9Q). The pattern of loss in this mixed group of appendageal tumors shows differences from both BCCs and SCCs, and further emphasizes the unique genetic profile and behavior of BCCs. The finding of 9q loss in BCCs with eccrine or granular cell differentiation shows that 9q loss occurs in differential histological subtypes of BCCs.

Basal Cell Carcinoma↗
PubMed1996

Bony anomalies in a patient with reticulate acropigmentation of Kitamura.

Reticulate acropigmentation of Kitamura [RAPK] is a rare pigmentary genodermatosis. This is a case report of a 23-year-old Saudi female who started manifesting the disorder in the 2nd decade. The patient had bony abnormalities in the form of absence of terminal phalanges of the 2nd, 3rd and 4th toes. These bone anomalies are extremely rare, and the association has never been described before in the literature.

Acrodermatitis↗