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M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 631 records · Page 35Linked to original sources

Effect of cytokine-induced soluble ICAM-1 from human synovial cells on synovial cell-lymphocyte adhesion.

The present study was designed to establish (i) the effects of cytokines on soluble ICAM-1 (sICAM-1) production by human synovial cells (SC) and ICAM-1 expression on these cells, and (ii) the effects of sICAM-1 on lymphocyte-SC adhesion. sICAM-1 production was enhanced in parallel with ICAM-1 expression by IL-1 beta, TNF-alpha and IFN-gamma. IL-4 showed no effects on ICAM-1 expression. In contrast with the transient elevation of cell-associated ICAM-1 by IL-1 beta, which peaked 36 h after stimulation and declined thereafter, sICAM-1 continued to accumulate in culture supernatants even after 48 h. Purified sICAM-1 was obtained from a 48 h culture synovial cell supernatant by affinity chromatography using ICAM-1 monoclonal antibody. The purified sICAM-1 significantly inhibited adhesion of lymphocytes and monocytes to cytokine-stimulated synovial cells. These results suggest that sICAM-1 may modulate chronic synovitis by inhibiting ICAM-1-mediated cell-to-cell adhesion.

Cell Adhesion↗

Characterization of a gene responsible for the Na+/H+ antiporter system of alkalophilic Bacillus species strain C-125.

An alkali-sensitive mutant, 38154, of the alkalophilic Bacillus sp. strain C-125 could not grow at an alkaline pH. The nucleotide sequence of a 3.7 kb parental DNA fragment that recovers the growth of 38154 at alkaline pH has four open reading frames (ORF1-4). By subcloning the fragment, we demonstrated that a 0.25 kb DNA region is responsible for the recovery. Direct sequencing of the mutant's corresponding region revealed a G to A substitution. The mutation resulted in an amino acid substitution from Gly-393 to Arg of the putative ORF1 product, which was deduced to be an 804-amino-acid polypeptide with a molecular weight of 89,070. The N-terminal part of the putative ORF1 product showed amino acid similarity to those of the chain-5 products of eukaryotic NADH quinone oxidoreductases. Membrane vesicles prepared from 38154 did not show membrane potential (delta psi)-driven Na+/H+ antiporter activity. Antiporter activity was resumed by introducing a parental DNA fragment which recovered the mutant's alkalophily. These results indicate that the mutation in 38154 affects, either directly or indirectly, the electrogenic Na+/H+ antiporter activity. This is the first report which shows that a gene responsible for the Na+/H+ antiporter system is important in the alkalophily of alkalophilic microorganisms.

Amino Acid Sequence↗

Gene frequencies and haplotypic associations within the HLA region in 916 unrelated Japanese individuals.

The gene frequencies and haplotypic associations within the HLA region have been investigated in 916 unrelated Japanese individuals. HLA class I and class II antigens were studied by conventional serology, and class II alleles, DRB1, DRB3, DQA1, DQB1 and DPB1 were typed by using polymerase-chain reaction amplification and sequence-specific oligonucleotide probe (PCR-SSOP) method. Thirty DRB1, 3 DRB3, 8 DQA1, 15 DQB1 and 13 DPB1 alleles were found in our population. DR-NJ25, a characteristic antigen in the native American and Asian populations, was observed at 3.0%. This antigen was observed mainly with the DRB1*1403 and 1406 alleles. Twenty-seven out of 30 DRB1 alleles found in this study had a high positive linkage disequilibrium with DQB1 alleles and 20 of them had an exclusive association with one specific DQA1-DQB1 combination. The strong association between DRB1 alleles and HLA-B antigens was the most striking finding in this study. Twenty-eight out of 30 DRB1 alleles had a positive linkage disequilibrium with 24 HLA-B antigens (p < 0.01). The other two alleles, DRB1*0404 and 1402, were very rare, and their frequencies were 0.2% and 0.1%, respectively. The data presented in this population study should be useful for the studies on anthropology, organ transplantation and disease susceptibility.

Gene Frequency↗

Striking conservation of three extended HLA-DR13 haplotypes in the Japanese population.

HLA class II DNA typing was conducted for 1335 unrelated Japanese individuals. The study on the linkage disequilibrium revealed a striking conservation of HLA DR13 haplotypes. Among these Japanese, 155 were typed for HLA-DR13 serologically, and they were correspondent to three DRB1 alleles, DRB1*1301, 1302 and 1307 defined by using the polymerase-chain reaction and sequence-specific oligonucleotide probe (PCR-SSOP) method. The two alleles, DRB1*1301 and 1307 were exclusively associated with each specific DRB3-DQA1-DQB1 combination which was DRB1*1301-DRB3*0101-DQA1*0103-DQB1*0603, and DRB1*1307-DRB3*0202-DQA1*0501-DQB1*0301, respectively. DRB1*1302, the most common DR13 allele in Japanese, had two significant associations with DRB3*0301-DQA1*0102-DQB1*0604 (DRB1*1302A) and with DRB3*0301-DQA1*0102-DQB1*0605 (DRB1*1302B). In this study, no other DR13 class II combinations were found. Only the DRB1*1302A halotype was associated with the DPB1*0401 allele while the DRB1*1302B haplotype was not. The complete conservation of these DR13 class II haplotypes was found to extend toward the HLA class I region. They were HLA A3-B44-DRB1*1301, A33-B44-DRB1*1302A and A33-B17-DRB1*1302B. Japanese could be characterized with these three extended haplotypes which were remarkably different from those in Caucasian, Black and Asian other than Korean populations.

DNA Primers↗

Long-term graft survival rate of zero-mismatch kidney transplants for HLA-DRB1.

The study of a two-locus association between HLA-B and -DRB 1 revealed a significant 43 linkage disequilibrium. Donor-recipient HLA-DRB1 was determined by these 43 linkages. Zero-mismatch for HLA-DRB1 had a significant effect on the graft survival rate in living related and cadaver transplants. The 5-year graft survival rate was 94% in the zero-mismatch group for HLA-DRB1, 96% for related transplants, 92% for cadaver cases, and 94% in HLA identical siblings. A statistically significant difference was found between the zero-mismatch group for HLA-DRB1 and mismatch groups for HLA-DRB1 or HLA-DR (P < 0.01). The zero-mismatch group for HLA-DRB1 had mismatches for HLA-A and/or HLA-B in 46 of 70 cases (66%). No significant differences in the rejection rate was observed between zero-mismatch and mismatch cases for HLA-A and/or -B in the zero-mismatch group for HLA-DRB1. In the second step, genotyping was conducted in 118 cases. The 5-year graft survival rate was 93% in the zero-mismatch group for HLA-DRB1 and 86% in mismatch group (not a significant difference). We concluded that zero-mismatch transplant for HLA-DRB1 had a better long-term graft survival rate regardless of HLA class I.

Cyclosporine↗

Calcium transients in single myocytes and membranous ultrastructures during the development of cardiac hypertrophy and heart failure in rats.

1. We examined changes in intracellular calcium transients of separated single myocytes from the right ventricle (RV) of the rat heart during the change from adaptation to maladaptation in response to a pressure overload. 2. Right ventricular hypertrophy (RVH) secondary to pulmonary hypertension was induced by a subcutaneous injection of monocrotaline. Developed tensions of the RV-free wall were decreased as RVH progressed. Single myocytes were separated from the RV during different stages of RVH. Fura-2/AM-loaded cells were field stimulated, and changes in calcium transients were measured by Olympus OSP-3 system. We also examined membranous ultrastructures (sarcoplasmic reticulum, mitochondria, surface caveolae) involved in calcium metabolism in the hearts using scanning electron microscopy. 3. We observed characteristic changes in calcium transients during the change from adaptation to maladaptation, and also found that one parameter (amplitude) of calcium transients appeared to be correlated with the changes in the number of sarcoplasmic reticulum. 4. These results provided some insights into the mechanism of calcium handling of hypertrophied heart in response to a pressure overload from adaptation to maladaptation especially when stimulatory frequency was high, and suggested that heart rate control is a very important factor for the treatment of patients with congestive heart failure.

Animals↗

In vitro studies of release of adenine nucleotides and adenosine from rat vascular endothelium in response to alpha 1-adrenoceptor stimulation.

1. Noradrenaline-induced release of endogenous adenine nucleotides (ATP, ADP, AMP) and adenosine from both rat caudal artery and thoracic aorta was characterized, using high-performance liquid chromatography with fluorescence detection. 2. Noradrenaline, in a concentration-dependent manner, increased the overflow of ATP and its metabolites from the caudal artery. The noradrenaline-induced release of adenine nucleotides and adenosine from the caudal artery was abolished by bunazosin, an alpha 1-adrenoceptor antagonist, but not by idazoxan, an alpha 2-adrenoceptor antagonist. Clonidine, an alpha 2-adrenoceptor agonist, contracted caudal artery smooth muscle but did not induce release of adenine nucleotides or adenosine. 3. Noradrenaline also significantly increased the overflow of ATP and its metabolites from the thoracic aorta in the rat; however, the amount of adenine nucleotides and adenosine released from the aorta was considerably less than that released from the caudal artery. 4. Noradrenaline significantly increased the overflow of ATP and its metabolites from cultured endothelial cells from the thoracic aorta and caudal artery. The amount released from the cultured endothelial cells from the thoracic aorta and caudal artery. The amount released from the cultured endothelial cells from the aorta was also much less than that from cultured endothelial cells from the caudal artery. In cultured smooth muscle cells from the caudal artery, a significant release of ATP or its metabolites was not observed. 5. These results suggest that there are vascular endothelial cells that are able to release ATP by an alpha 1-adrenoceptor-mediated mechanism, but that these cells are not homogeneously distributed in the vasculature.

Adenine Nucleotides↗

Prevalence of IgE antibody to crude and purified allergens of Japanese cedar pollen among different troops of Japanese monkeys (Macaca fuscata).

We measured specific IgE antibodies to the crude allergen as well as two purified allergens (Cry j I and Cry j II) of Japanese cedar (Cryptomeria japonica--CJ) pollen in the serum of 276 Japanese monkeys in nine troops. Of 45 monkeys with CJ specific IgE in eight of nine troops, 23 (51%) were found to have IgE to both Cry j I and Cry j II, 21 (47%) only to Cry j I, and one (2.2%) only to Cry j II. The positive rate of specific IgE antibody to each allergen varied among the troops.

Allergens↗

The roles of the C-terminal domain and type III domains of chitinase A1 from Bacillus circulans WL-12 in chitin degradation.

The mature form of chitinase A1 from Bacillus circulans WL-12 comprises a C-terminal domain, two type III modules (domains), and a large N-terminal domain which contains the catalytic site of the enzyme. In order to better define the roles of these chitinase domains in chitin degradation, modified chiA genes encoding various deletions of chitinase A1 were constructed. The modified chiA genes were expressed in Escherichia coli, and the gene products were analyzed after purification by high-performance liquid chromatography. Intact chitinase A1 specifically bound to chitin, while it did not show significant binding activity towards partially acetylated chitosan and other insoluble polysaccharides. Chitinases lacking the C-terminal domain lost much of this binding activity to chitin as well as colloidal chitin-hydrolyzing activity. Deletion of the type III domains, on the other hand, did not affect chitin-binding activity but did result in significantly decreased colloidal chitin-hydrolyzing activity. Hydrolysis of low-molecular-weight substrates, soluble high-molecular-weight substrates, and insoluble high-molecular-weight substrates to which chitinase A1 does not bind were not significantly affected by these deletions. Thus, it was concluded that the C-terminal domain is a chitin-binding domain required for the specific binding to chitin and that this chitin-binding activity is important for efficient hydrolysis of the sufficiently acetylated chitin. Type III modules are not directly involved in the chitin binding but play an important functional role in the hydrolysis of chitin by the enzyme bound to chitin.

Amino Acid Sequence↗

Properties of two different Na+/H+ antiport systems in alkaliphilic Bacillus sp. strain C-125.

Na+/H+ antiport was studied in alkaliphilic Bacillus sp. strain C-125, its alkali-sensitive mutant 38154, and a transformant (pALK2) with recovered alkaliphily. The transformed was able to maintain an intracellular pH (pHin) that was lower than that of external milieu and contained an electrogenic Na+/H+ antiporter driven only by delta psi (membrane potential, interior negative). The activity of this delta psi-dependent Na+/H+ antiporter was highly dependent on pHin, increasing with increasing pHin, and was found only in cells grown at alkaline pH. On the other hand, the alkali-sensitive mutant, which had lost the ability to grow above pH 9.5, lacked the delta psi-dependent Na+/H+ antiporter and showed defective regulation of pHin at the alkaline pH range. However, this mutant, like the parent strain, still required sodium ions for growth and for an amino acid transport system. Moreover, another Na+/H+ antiporter, driven by the imposed delta pH (pHin > extracellular pHout), was active in this mutant strain, showing that the previously reported delta pH-dependent antiport activity is probably separate from delta psi-dependent antiporter activity. The delta pH-dependent Na+/H+ antiporter was found in cells grown at either pH 7 or pH 9. This latter antiporter was reconstituted into liposomes by using a dilution method. When a transmembrane pH gradient was applied, downhill sodium efflux was accelerated, showing that the antiporter can be reconstituted into liposomes and still retain its activity.

Alanine↗

Neuromyelitis optica.

An 11-year-old girl developed sudden visual loss in her left eye, preceding subacute myelitis by 9 months. Multifocal lesions in the central nervous system were demonstrated by magnetic resonance imaging. Although unilateral blindness is unusual, the clinical findings predominantly involving the optic nerve and spinal cord were consistent with the diagnosis of neuromyelitis optica (NMO). This case provides additional evidence to support the view that NMO is a variant of multiple sclerosis.

Blindness↗

Removal of cat major allergen (Fel d I) from futon (Japanese bedding) with a home washing machine.

We evaluated the removal of a cat major allergen (Fel d I) from futons (Japanese bedding) with the use of a large-sized home washing machine. Before and after washing a futon that had been used in a home with a cat, a small amount of cotton was collected from the futon and Fel d I was extracted from the cotton. The levels of Fel d I were assayed by a sandwich enzyme-linked immunosorbent assay (ELISA). We found that washing reduced the Fel d I level in futons by more than 95%. In conclusion, washing of futons is an effective method for elimination of their cat allergens.

Allergens↗

Polymorphic ventricular tachycardia with cardiac sarcoidosis: treatment with low-dose metoprolol and cibenzoline.

A 38-year-old female had felt exertional dyspnea for six months. Physical examination and laboratory data including angiotensin-converting enzyme, failed to diagnose sarcoidosis. Her chest X-ray showed cardiomegaly but no hilar lymph node enlargement. Holter ECG showed nonsustained and sustained ventricular tachycardias, monomorphic or polymorphic tachycardia. Echocardiography and contrast left ventriculography showed left ventricular dilatation and generalized hypo- and akinesis. Endomyocardial biopsy revealed myocardial sarcoidosis. Administration of corticosteroids, metoprolol of 20 mg/day and cibenzoline of 300 mg/day was markedly effective for the treatment of ventricular tachycardia. This patient is alive for one year after treatment and the combination therapy seems to contribute to good prognosis.

Adult↗

Toxicokinetics of zenarestat, an aldose reductase inhibitor in animals and man.

1. The relationship between dose and plasma concentrations is important in extrapolating toxicity between species. Therefore, we determined this relationship for zenarestat in animals and man. 2. The biopharmaceutics of zenarestat was assessed prior to toxicity testing. The bioavailability of zenarestat in rat administered zenarestat in 0.5% (w/v) methyl cellulose suspension and aqueous solution was similar. Bioavailability in dog administered zenarestat treated with excipients and in aqueous solution was similar. 3. Cmax increases dose-relatedly both in animals and man. AUC increased almost in proportion to the dose in mouse, rat and man, but increased to a greater extent at the highest dose in dog. Cmax, AUC and C24h were not significantly different during/after multiple dosing. 4. After 13 and 53 weeks of toxicity testing, plasma concentrations were not significantly different between the days and sexes except at 560 mg/kg in the female rat and at 56 mg/kg in the female dog in 13 week toxicity tests. 5. The exposure of zenarestat in man, administered 300 mg b.i.d., seemed to be no more than that in animals at non-toxic doses.

Administration, Oral↗

Effects of head elevation on intracranial hemodynamics in patients with ventriculoperitoneal shunts.

The present study was performed to investigate the effects of head elevation on intracranial hemodynamics in patients with ventriculoperitoneal (VP) shunts. The series included 35 hydrocephalic patients and five individuals without hydrocephalus who were used as controls. The hydrocephalic patients were divided into three groups: 15 patients who received VP shunts with a differential-pressure valve (DP group); 11 who received VP shunts with a variable-resistance valve (VR group), and 13 hydrocephalic patients (Hyd group) who had not received shunts (four underwent VP shunts later). The cerebral blood flow (CBF) of patients in the supine and upright positions was measured by technetium-99m hexamethylpropylenamine oxide (HMPAO) single-photon emission computerized tomography in each patient, using the subtraction technique. Cerebral perfusion pressure (CPP) was taken as the difference between the mean arterial blood pressure and ventricular fluid pressure, both referenced to the level of the foramen of Mono. The patients' heads were elevated stepwise from supine to upright. Percent changes of the mean CBF in the upright position (% delta mCBFupr) were 24.9% +/- 4.3% (mean +/- standard error of the mean) in the DP group, 6.2% +/- 2.7% in the VR group, 3.5% +/- 2.6% in the Hyd group, and 4.5% +/- 2.2% in the control group. Patients in the DP group showed a pathological increase in CPP with head elevation, whereas those in the Hyd and VR groups showed a physiological decrease in CPP. Three patients with differential-pressure valves, whose % delta mCBFupr was markedly high, developed low-intracranial pressure syndrome. In conclusion, shunted patients with a DP valve showed pathological intracranial hemodynamics in the upright position. This pathological hemodynamic stress in patients with long-standing differential-pressure valve implantation may induce pathological changes in the brain such as subependymal gliosis.

Adolescent↗