PubMed Health⌕ Search

Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 613 records · Page 34Linked to original sources
PubMed1997

Identification of a mouse homolog for the human hereditary haemochromatosis candidate gene.

Recently, a novel human major histocompatibility complex (MHC) class I-like gene (HLA-H) was reported as a candidate gene for human hereditary haemochromatosis, a recessive disease of iron metabolism with a remarkably high incidence in northern Europeans. Independently we have isolated this gene in the course of a search for new human MHC class I-related genes and named it MR2. Here we report a mouse homolog of this human gene. The mouse MR2 gene is similar to the human counterpart with an overall predicted amino acid sequence similarity of approximately 66% and it is expressed in various tissues as in human. The extra eight amino acid residues between the alpha1 and the alpha2 domains in the mouse molecule compared to the human counterpart can be explained by the creation of the coding sequence from the intron. While the human gene is located at the site telomeric to the MHC region on human chromosome 6, our study indicated the translocation of the mouse homolog from the site telomeric to the MHC on mouse chromosome 17 to chromosome 13 along with other genes. This mouse gene should be important in clarifying a possible role in iron metabolism.

Amino Acid Sequence↗
PubMed1997

Possible role of coexpression of CD9 with membrane-anchored heparin-binding EGF-like growth factor and amphiregulin in cultured human keratinocyte growth.

CD9 is a protein with 4 transmembrane domains, and functions as a cell surface antigen. We have previously reported that CD9 functions as an up-regulator of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) activity, which is a potent mitogen as well as a soluble HB-EGF. Anti-CD9 antibodies can neutralize the juxtacrine activity of proHB-EGF when both CD9 and proHB-EGF are coexpressed. We demonstrated here: (1) the CD9 gene was transcribed and translated in the cultured human keratinocytes; (2) anti-CD9 antibody inhibited the approximately 50% growth of human keratinocytes in culture; (3) CD9 was coprecipitated with proHB-EGF and membrane-anchored amphiregulin (proAR), and (4) the transient coexpression of CD9 with proHB-EGF or proAR in mouse L cells up-regulated their juxtacrine growth factor activities. These results suggest that CD9 would make a heterodimer and/or trimer complex with proHB-EGF and proAR, and might cooperate with proHB-EGF and proAR for human keratinocyte growth in a juxtacrine manner.

Amphiregulin↗
PubMed1997

Effects of nonsedating antihistamine, astemizole, on the in situ canine heart assessed by cardiohemodynamic and monophasic action potential monitoring.

The possible mechanisms of cardiac adverse effects of astemizole were studied using a halothane-anesthetized in vivo canine model under the cardiohemodynamic and monophasic action potential monitoring. A dose of 0.3 mg/kg of iv astemizole (n = 7), which is close to the recommended dose for clinical use, showed a bradycardic effect and a reversed use-dependent lengthening of repolarization. The increase in the repolarization was greater than in the effective refractory period. These effects persisted even when the plasma drug concentration became undetectable. Additional administration of 3.0 mg/kg of iv astemizole (n = 7) decreased the mean blood pressure, suppressed the cardiac contraction and conduction, and induced early after depolarization-like potential in addition to the qualitatively similar effects compared to those observed by the lower dose. The decrease of the plasma concentration of astemizole followed the pattern predicted by the two-compartment theory of pharmacokinetics, but the drug concentration in the cardiac muscle was estimated to be more than 100 times greater than that in plasma. Our study emphasizes that each cardiac consequence of astemizole overdose may be related to proarrhythmic effects and the monitoring of plasma drug concentration will be less helpful in predicting the cardiac adverse effects of astemizole. The results provide some insights into the clinical cardiotoxicity of astemizole. Drugs or interventions inducing positive chronotropic, inotropic, and dromotropic effects can become good candidates for the treatment of astemizole intoxication, which may attenuate the cardiac effects of astemizole including the lengthening of repolarization.

Action Potentials↗
PubMed1997

Anti-neutrophil cytoplasmic antibody in patients with systemic lupus erythematosus is unrelated to clinical features.

To investigate the incidence, the specificity and clinical significance of positivity for serum anti-neutrophil cytoplasmic antibody (ANCA) in 31 patients with systemic lupus erythematosus (SLE), the indirect immunofluorescence (IIF) technique and enzyme-linked immunosorbent assay (ELISA) were used to measure ANCA. Purified myeloperoxidase (MPO), lactoferrin (LF), cathepsin-G (CTG) and elastase (HLE) served as ANCA antigens for ELISA. Thirteen (42%) of the 31 SLE patients showed positivity for perinuclear, but not cytoplasmic, ANCA by IIF. Five of 31 sera were positive for MPO, 10 for LF, 1 for CTG and 0 for HLE by ELISA. Patients positive for ANCA had a higher score of SLE disease activity index (SLEDAI) than those without ANCA. There was no correlation between ANCA positivity, clinical manifestations, or organic involvement. While the ANCA in patients with SLE reflected disease activity, it was unrelated to organic involvement.

Adolescent↗
PubMed1997

Age-related changes in the compound action potentials of the eighth nerve in guinea pigs.

The eighth nerve compound action potential (CAP) in 95 guinea pigs was measured using click stimuli to investigate age-related changes in their neural auditory thresholds. The animals were separated into three groups: group A (n = 43, 86 ears; 2-4 months old); group B (n = 29; 58 ears, 13-15 months old); and group C (n = 23; 46 ears, 23-25 months old). With increasing age, a gradual elevation of CAP thresholds was clearly seen among the three groups. The negative peak (N1) latencies of the CAP were prolonged, and the N1 amplitudes of the CAP decreased. There were significant differences in N1 latencies among the three groups and in N1 amplitudes between groups A and B, and between groups A and C. However, the rate of decline of the thresholds as well as the input-output function curves of the CAP varied in some of the oldest animals, suggesting that there were some individual differences in degenerative aging processes of the auditory system.

Acoustic Stimulation↗
PubMed1997

Effects of a cardioselective M2 receptor antagonist, AF-DX 116, on ventricular arrhythmias in dogs.

AF-DX 116 is a cardioselective M2 receptor antagonist and, thus, it should induce sinus tachycardia. Since normal ventricular automaticity is suppressed by atrial overdriving, AF-DX 116 might become an antiarrhythmic drug and act by increasing the sinus node automaticity. Ventricular arrhythmia models used in this study were induced either by two-stage coronary ligation, digitalis, or adrenaline in beagle dogs. AF-DX 116 (0.3 mg/kg i.v.) tended to increase the sinus rate of the conscious beagles compared to the pre-drug level (although the effect was not significant) but had no antiarrhythmic effect (i.e., there was no decrease in the arrhythmic ratio defined as the number of PVC divided by the total heart rate) on the ventricular tachycardia (VT) induced 24 h after aseptic ligation of the left anterior descending coronary artery. AF-DX 116 did not alter the blood pressure. The drug also did not suppress digitalis-induced VT and did not increase the atrial rate, which was already increased to about 210 beats/min by ouabain. AF-DX 116 decreased the arrhythmic ratio, 9 min after bolus injection, and increased the atrial rate in the adrenaline VT model. The maximum plasma concentration of AF-DX 116 reached nearly 1microg/ml 1 min after the bolus injections in the digitalis and adrenaline arrhythmia experiments, which is close to the maximum concentration expected to be attained in the clinical application of this drug. Although AF-DX 116 increased the heart rate, under the present experimental conditions of increased atrial rate, the extent of tachycardia was not strong enough to suppress the 24-h coronary ligation and digitalis-induced arrhythmias. The late onset of the antiarrhythmic effect of AF-DX 116 on adrenaline-induced arrhythmia cannot be explained by the overdrive suppression mechanism.

Animals↗
PubMed1997

Modulation of cardiac interstitial noradrenaline levels through K(ATP) channels during ischemic preconditioning in rabbits: comparison of the effect of anesthesia between pentobarbital and ketamine + xylazine.

In rabbits, both the stimulation of alpha1-adrenoceptors and ischemic preconditioning (PC) reduce infarct size. One candidate for the mechanism of PC is noradrenaline (NA), which stimulates alpha1-adrenoceptors in the myocardium during PC. Opening of the K(ATP) channel is considered to be another candidate for PC, since a K(ATP) channel blocker, glibenclamide, blocks the infarct size-reducing effect of the PC of 5-min ischemia and 5-min reperfusion in rabbits anesthetized with ketamine + xylazine. However, in rabbits anesthetized with pentobarbital, the infarct size-reducing effect of PC was not blocked by glibenclamide. The effect of glibenclamide on the PC effect thus differs depending on the anesthesia used. Therefore, we speculated that the increase in cardiac interstitial NA levels induced by PC may be modified by the anesthesia used, thus regulating the effect of glibenclamide on the PC effect. In open-chest Japanese white male rabbits anesthetized with pentobarbital or ketamine + xylazine, myocardial interstitial NA levels were measured before and during the PC of 5-min ischemia and 5-min reperfusion in the presence or absence of the K(ATP) channel blocker, glibenclamide (0.3 mg/kg, i.v.), using a microdialysis technique. The NA levels were measured using high-performance liquid chromatography coupled with electrochemical detection. The PC of 5-min ischemia and 5-min reperfusion significantly elevated the interstitial NA level. This increase in the NA level was not blocked by glibenclamide under anesthesia with pentobarbital. Under anesthesia with ketamine + xylazine, the PC did not cause an increase in the myocardial interstitial NA level in either the absence or the presence of glibenclamide. In conclusion, PC elevates the myocardial interstitial NA level, and this elevation is not mediated through the opening of the K(ATP) channel under anesthesia with pentobarbital. Under anesthesia with ketamine + xylazine, PC does not cause an increase in the myocardial interstitial NA level. This may explain the discrepancy in the blocking effect of glibenclamide on the infarct size-reducing effect of PC between anesthesia with pentobarbital and ketamine + xylazine.

Adenosine Triphosphatases↗
PubMed1997

Biparental alleles of HLA-G are co-dominantly expressed in the placenta.

HLA-G is the only major histocompatibility complex molecule expressed in the human placenta and thus has been considered to be necessary for maintenance of pregnancy. We investigated whether HLA-G expression is regulated in a parent-of-origin allele-specific manner. Of six first trimester and three third trimester placentas, three first trimester and two third trimester placentas showed heterozygosity at the PstI polymorphic site in the 3'-untraslated region. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed biallelic expression of HLA-G in all the informative cases, indicating that HLA-G is not imprinted during the gestational period, at least at the transcriptional level. As HLA-G has been postulated to be polymorphic not only at the DNA sequence level but also at the peptide level, co-dominant expression of the gene suggests that each parental allele is involved in the allogenic response during pregnancy.

Alleles↗
PubMed1997

Effect of regional myocardial perfusion abnormalities on regional myocardial early diastolic function in patients with hypertrophic cardiomyopathy.

Nonuniform hypertrophy of the left ventricle is an important factor in regional diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). However, the effect of myocardial perfusion abnormalities on regional diastolic dysfunction has not been established in patients with HCM. We investigated the relationship between regional myocardial perfusion abnormalities and regional early diastolic function in 31 patients with HCM and 8 control patients. Short-axis images of the left ventricle recorded by cine magnetic resonance imaging were divided into ten blocks. The time-to-peak-wall-thickness-thinning rate (TPWR) and the wall thickness were measured in each block. Of the 310 blocks from the patients with HCM, 242 (78%) showed normal thallium-201 uptake (group 1), 40 (13%) showed slightly decreased uptake (group 2), and 28 (9%) showed markedly decreased uptake (group 3). There was no difference in the regional wall thickness among the three groups. The TPWR was longer in patients with HCM than in control patients. It was significantly longer in group 3 (190+/-45ms) than in group 1 (167+/-36 ms) and group 2 (160+/-31 ms). (P < 0.01). The linear regression slope of the relationship between the TPWR and the regional wall thickness was significantly steeper in group 3 than in groups 1 and 2 (P < 0.05). In conclusion, abnormalities in regional myocardial perfusion, in addition to regional hypertrophy, contributed to the regional early diastolic dysfunction in patients with HCM.

Adult↗
PubMed1997

Evaluation of left ventricular ejection fraction from radial long-axis tomography: a new reconstruction algorithm for ECG-gated technetium-99m sestamibi SPECT.

UNLABELLED: Radial long-axis tomography can provide views similar to contrast left ventriculography (LVG) including the basal and apical areas of the left ventricle, not possible in routine short-axis tomography. We applied this method to ECG-gated Tc-99m Sestamibi (MIBI) myocardial SPECT images to estimate the left ventricular ejection fraction (LVEF). METHODS: ECG-gated Tc-99m MIBI SPECT was performed with a temporal resolution of 10 frames per R-R interval. LVEF was calculated on the basis of left ventricular volume estimates at end diastole (ED) and end systole (ES) with using an ellipsoid body model. To validate this method, LVEF's derived from ECG-gated Tc-99m MIBI SPECT were compared with those from LVG in 11 patients with coronary artery disease. RESULTS: There was a close linear correlation between LVEF values calculated from Tc-99m MIBI SPECT and those from LVG (r = 0.89, p < 0.001), although the gated SPECT underestimated LVEF compared to LVG. The technique showed excellent reproducibility (intra-observer variability, r = 0.96, p < 0.001; inter-observer variability, r = 0.71, p < 0.005). CONCLUSION: The radial long-axis tomography technique gives a good estimate of LVEF, in agreement with estimates based on LVG. ECG-gated Tc-99m MIBI SPECT can, therefore, be applicable to assess myocardial perfusion and ventricular function at the same time.

Adult↗
PubMed1997

Mitochondrial DNA and nuclear DNA indicate that the Japanese Fasciola species is F. gigantica.

For elucidation of the taxonomic status of the Japanese Fasciola species, whole mitochondrial DNA of Fasciola hepatica from Australia, F. gigantica from Malaysia, and Fasciola sp. from Japan was digested with three four-base-cutting endonucleases: HinfI, MspI, and RsaI. The resulting digestion patterns showed that for each enzyme there were some bands specific for each geographical isolate and that the Japanese Fasciola sp. shared more bands with F. gigantica than with F. hepatica. Nucleotide sequences of two regions, the second internal transcribed spacer (ITS2) of the nuclear ribosomal RNA cluster and mitochondrial cytochrome c oxidase subunit I (COI), were also compared among them. The ITS2 sequence was highly conserved among the three isolates. F. gigantica and the Japanese Fasciola sp. were identical, but they differed from the Australian F. hepatica at six sites, one of which was a deletion. The COI sequence was less conserved but implied a similar relationship between the isolates. There seems no reason to regard the Japanese Fasciola sp. as anything other than a strain of F. gigantica.

Animals↗
PubMed1997

Transplantation of genetically marked cardiac muscle cells.

We examined the possibility that cardiomyocytes could be genetically marked or modified before being grafted to the heart under conditions applicable to the clinical setting. We used a replication-defective recombinant adenovirus carrying the beta-galactosidase reporter gene, and delivered it to cultured murine fetal cardiac myocytes. Virtually all fetal cardiomyocytes in a primary culture expressed beta-galactosidase 24 hours after recombinant adenovirus infection. These cells were transplanted to the hearts of syngenic adult recipient mice. Expression of the beta-galactosidase gene in the grafted cells was demonstrated by staining with 5-bromo-4-chloro-3-indoyl-beta-D-galactosidase, resulting in a blue color at the histochemical level and an electron-dense deposit on transmission electron microscopic analysis. Gene expression was recognized from 7 days to 12 weeks after transplantation. Implanted cardiomyocytes aligned themselves along the layers of the host myocardium. Formation of gap junctions was demonstrated by transmission electron microscopy. Neither inflammation nor fibrous scar tissue was detectable by histologic analysis. This study demonstrates that ex vivo gene transfer to the heart by means of the adenoviral vector is possible.

Adenoviridae↗
PubMed1997

In vivo regulation of serotonin 5-HT2A receptors in rat brain by subchronic administration of sigma receptor ligand NE-100.

In the present study, we examined the effect of the novel sigma receptor ligand NE-100 on 5-hydroxytryptamine-2A (5-HT2A) receptor binding in rat brain using an in vivo approach. Rats received intraperitoneal injections of either vehicle (1 ml/kg) or NE-100 (3 mg/kg) twice daily for 14 days. The in vivo binding of [3H]RP 62203, a selective 5-HT2A receptor radioligand, to 5-HT2A receptors in the rat brain was examined at 1, 3 or 7 days after final treatment. The specific binding of [3H]RP 62203 in the frontal cortex, parietal cortex and occipital cortex 1 day after subchronic administration of NE-100 was significantly increased as compared to animals treated with vehicle. In contrast, specific binding in the frontal cortex and parietal cortex 3 days after subchronic administration of NE-100 was significantly decreased as compared with the vehicle treated group. Seven days after the last injection of NE-100 or vehicle, there were no significant differences between the NE-100 and vehicle treated groups in [3H]RP 62203 binding in all the regions examined except for the hippocampus. These findings indicate that subchronic treatment with NE-100 may regulate the in vivo binding characteristics of 5-HT2A receptors in the cerebral cortex of rat brain.

Animals↗
PubMed1997

Endotoxin induced increases in rat plasma pituitary-adrenocortical hormones are better reflected by alterations in tumor necrosis factor alpha than interleukin-1beta.

In order to assess the relative cytokine contribution to endotoxin stimulation of pituitary-adrenocortical hormone secretion, we measured plasma levels of interleukin-1beta (IL-1beta), tumor necrosis factor (TNF alpha), adrenocorticotropin (ACTH) and corticosterone following lipopolysaccharide (LPS) challenge in rats. LPS administration induced robust increases in both plasma ACTH and corticosterone levels at 3 h after i.p. injection; while ACTH decreased towards control levels, corticosterone remained at peak concentrations at 6 h after LPS injection. Basal levels of plasma IL-1beta were below the sensitivity of the ELISA and basal levels of plasma TNF alpha were 0.25+/-0.12 pM. Small but highly variable non-significant increases in plasma IL-1beta levels were seen at 3 h and 6 h after injection of LPS. The lack of functional consequences of the small increases in IL-1beta levels was demonstrated by unchanged levels of [125I]IL-1alpha binding in liver at 3 h after LPS injection. In contrast, dramatic increases in plasma TNF alpha concentrations were observed at 3 h and decreased to non-injected control levels at 6 h after LPS injection. There was a significant positive correlation between ACTH and TNF alpha after LPS injection, while no correlation was seen between ACTH and IL-1beta. These data demonstrate differential regulation of IL-1beta and TNF alpha by endotoxin treatment and suggest that TNF alpha may be a more potent mediator of LPS-induced ACTH secretion in rat.

Adrenocorticotropic Hormone↗