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Biomedical subjects

M Ohashi

Publications and source records attributed to M Ohashi.

At least 19 recordsLinked to original sources
PubMed1992

Doxorubicin: an antagonist of muscarinic receptors in guinea pig heart.

While studying the mechanisms of doxorubicin-induced cardiotoxicity, we observed that doxorubicin inhibited the negative inotropic effect of acetylcholine in isolated heart muscle preparations. We therefore examined the effects of doxorubicin on muscarinic acetylcholine receptors. In left atrial muscle preparations isolated from guinea pig heart and stimulated at 2 Hz at 30 degrees C, doxorubicin caused a parallel right-ward shift of the dose-response curves for the negative inotropic effects of acetylcholine. The inhibitory action was reversed by an additional incubation in the absence of doxorubicin. Doxorubicin reversed the carbachol-induced inhibition of developed tension: a high concentration of doxorubicin brought the force back to its original strength. Doxorubicin inhibited specific [3H]quinuclidinyl benzilate (QNB) binding to membrane preparations obtained from ventricular muscle of guinea pig hearts. The pA2 value for doxorubicin obtained in the inotropic study corresponded to the IC50 value for doxorubicin observed in the [3H]QNB binding assay. These results indicate that doxorubicin acts as a weak competitive antagonist on muscarinic acetylcholine receptors.

Animals↗
PubMed1992

Two excited states in aequorin bioluminescence induced by tryptophan modification.

The Ca(2+)-activated photoprotein, aequorin, contains six tryptophan residues and has a bioluminescence emission maximum at 465 nm. On converting the six tryptophan residues to phenylalanine, the mutant aequorins exhibited varied luminescence activities and spectra, but one mutant, with tryptophan-86 replaced by phenylalanine, gave a bimodal emission spectrum, with maxima at 455 nm and 400 nm. This result suggests that tryptophan-86 may be importantly involved in the generation of the product excited state during aequorin bioluminescence.

Aequorin↗
PubMed1992

Anticentromere-protein-B--DNA complex activities in anticentromere antibody-positive patients.

Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often those with scleroderma). In this study, we analysed activities of anti-CENP-B-DNA complex in anticentromere antibody (ACA)-positive patients using DNA immunoprecipitation with purified CENP-B. The activities correlated with ACA titres and were closely associated with Raynaud's phenomenon. Patients with CREST symptoms (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) showed higher activities than those with no symptoms. Our results suggest that autoimmune responses to native CENP-B may have an important role in the pathogenesis of scleroderma.

Autoantibodies↗
PubMed1992

Centromere protein B assembles human centromeric alpha-satellite DNA at the 17-bp sequence, CENP-B box.

We purified 15,000-fold from HeLa cell nuclear extract the centromere antigen that reacts specifically with the 17-bp sequence, designated previously as CENP-B box, in human centromeric alpha-satellite (alphoid) DNA by a two-step procedure including an oligonucleotide affinity column. The purified protein was identified as the centromere protein B (CENP-B) by its mobility on SDS-PAGE (80 kD), and reactivities to a monoclonal antibody raised to CENP-B (bacterial fusion protein) and to anticentromere sera from patients with autoimmune diseases. Direct binding by CENP-B of the CENP-B box sequence in the alphoid DNA has been proved using the purified CENP-B by DNA mobility-shift assay, Southwestern blotting, and DNase I protection analysis. The binding constant of the antigen to the CENP-B box sequence is 6 x 10(8) M-1. DNA mobility-shift assays indicated that the major complex formed between the CENP-B and the DNA contains two DNA molecules, suggesting the importance of the CENP-B/CENP-B box interaction in organization of higher ordered chromatin structures in the centromere and/or kinetochore. Location of DNA binding and dimerization domains in CENP-B was discussed based on the DNA mobility-shift assays performed with a protein fraction containing intact and partial cleavage products of CENP-B.

Autoantigens↗
PubMed1992

Immunogenetic study of three Japanese families with neonatal lupus erythematosus.

We encountered three Japanese families with neonatal lupus erythematosus. None of the three fathers showed any signs of collagen disease. The three mothers were found to suffer from Sjögren's syndrome; they all tested positive for anti-SSA and SSB antibodies and had lymphocyte infiltration into the small salivary gland. In two families, one child had neonatal lupus erythematosus while a sibling was normal; in the third family, both children had neonatal lupus erythematosus. Thus, a mother with positive anti-SSA and SSB antibodies can give birth to one infant with and one infant without or have two infants with neonatal lupus erythematosus. We conducted HLA typing of all 12 members of the three families in order to clarify the immunologic factors involved. We found no increased frequency of any HLA phenotype in the three mothers and their four children with neonatal lupus erythematosus; however, HLA-DR4 was present in three of the children with neonatal lupus erythematosus.

Adolescent↗
PubMed1992

Juvenile dermatomyositis: a statistical study of 114 patients with dermatomyositis.

We conducted a statistical review of 114 cases of dermatomyositis (DMS) treated primarily at the Department of Dermatology at Nagoya University Hospital over 27 years from 1965 to 1991 in order to determine the primary characteristics of juvenile DMS with the following results. 1) Juvenile DMS was found slightly more often in males than females; the male-to-female ratio was 1.4:1. Therefore, unlike adult DMS with its preponderance of females, there was no clear gender predominance. 2) Muscular manifestations tended to follow the appearance of cutaneous manifestations, but the frequency of minor muscular manifestations was high over the entire course of the disease. 3) Laboratory findings showed increases in serum aldolase and serum creatinine kinase with significant frequency when compared with adult patients (p < 0.01 and p < 0.05, respectively). Elevated serum aldolase most often occurred prior to or at the time of the appearance of muscular manifestations, suggesting its usefulness in early diagnosis. The positive rates for the antinuclear antibody on HEp-2 cells and anti-DNA antibody were significantly lower in children than in adults (p < 0.001 and p < 0.05, respectively). 4) There were no cases of juvenile DMS complicated by malignant tumors, interstitial pneumonia, or pulmonary fibrosis. There were also no deaths, and the rate of "remission or improvement" was significantly higher than in adult DMS cases (p < 0.05). Adult cases which remained the same or worsened usually presented with intractable muscular manifestations. In children, however, the cutaneous manifestations were more difficult to treat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The clinical expression in anticentromere antibody-positive patients is not specified by the epitope recognition of CENP-B antigen.

Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often with scleroderma). From our previous analysis of the reactivity of anticentromere sera, four independent epitopes were identified on recombinant CENP-B. The anticentromere sera displayed heterogeneity in their patterns of reactivity to the four epitopes. We have investigated to what extent this heterogeneity of the target autoepitope on CENP-B accounts for the clinical diversity of anticentromere antibody (ACA)-positive patients. A major autoepitope, epitope I, was recognized by all 40 ACA-positive sera; however, the other three epitopes were recognized differently from case to case. We could not find any significant correlation between the reactivity to CENP-B autoepitopes and the clinical presentation of ACA-positive patients. There was considerable clinical diversity, even among the nine patients showing specificity for the single major autoepitope. In conclusion, we found that, although ACA-positive patients were both clinically and immunologically heterogeneous, in most respects the clinical expression appeared to be independent of the reactivity to the CENP-B autoepitope, a finding which suggests that identification of the target epitope of CENP-B is unlikely to assist in the clinical classification of the disease in ACA-positive patients. The identification of multiple B cell epitopes on CENP-B is consistent with the concept that the self-antigen drives the antibody response. However, factors other than CENP-B autoepitope specificity must determine the clinical expression of ACA responses.

Adult↗
PubMed1992

[Serovar distribution and drug resistance of Salmonella isolated from imported and domestic cases in 1980-1989 in Tokyo].

A total of 6,816 strains of nontyphoidal Salmonella isolated from oversea travellers (imported cases) and domestic healthy individuals and sporadic cases (domestic cases) in Tokyo from 1980 to 1989 were studied for their serovar distribution and antimicrobial sensitivity. The serological typing results showed that the Salmonella strains were classified into 22 O groups and 156 serovars. Among serovars identified, S. ser. Anatum, S. ser. Derby, S. ser. Blockley, S. ser. Agona and S. ser. Typhimurium were predominant in imported cases, while S. ser. Litchfield, S. ser. Typhimurium, S. ser. Hadar, S. ser. Infantis and S. ser. Thompson were predominant in domestic cases. It was also noticed that isolation rates of S. ser. Hadar and S. ser. Blockley have tended to increase noticeably in recent years in both cases. From antimicrobial sensitivity testing, 739 (28.1%) of 2,628 strains isolated from imported cases and 1,047 (25.0%) of 4,188 strains isolated from domestic cases were found to be resistant to any one of the drugs tested (CP, TC, SM, KM, ABPC, ST, NA, FOM and NFLX). From 1980 to 1983 the resistance rate was less than 20% for both cases and then the rate was increased year by year, and it became greater than 40% in 1989. Serovars of a high resistant rate during this period were S. ser. Hadar (96.3%), S. ser. Blockley (92.0%), S. ser. Typhimurium (75.7%), S. ser. Kentuckey (64.1%), S. ser. Krefeld (59.3%), and S. ser. Panama (58.3%) for the imported cases and S. ser. Hadar (97.5%), S. ser. Blockley (57.4%), S. ser. Litchfield (44.6%), S. ser. Enteritidis (44.4%), S. ser. Muenchen (42.2%) and S. ser. Typhimurium (40.9%) for the domestic cases. Drug resistance patterns of the resistant isolates varied up to as much as 50 patterns. Prevalent patterns recognized were TC.SM, CP.TC.SM.KM, TC, CP.TC.SM.KM.ABPC and SM for imported cases and TC.SM, TC, TC.SM.KM, SM, and CP.TC for the domestic cases. 21(12.4%) of 170 drug resistant strains were isolated from imported cases from 1988 to 1989 were found to have conjugative transmissible R plasmids.

Antibodies, Bacterial↗
PubMed1992

[Serological studies on Campylobacter jejuni/coli: establishment of national reference system for serological typing in Japan].

In order to establish a national reference system for Campylobacter serotyping in Japan, 7 local institutes of public health collaborated to prepare 30 serogrouping antisera including 26 antisera of Lior's serogrouping system and 4 antisera of TCK serogrouping system which was developed by the Tokyo Metropolitan Research Laboratory of Public Health. A total of 603 strains (92.2%) out of 654 isolates from 23 outbreaks of C. jejuni throughout Japan were serogrouped by the 30 antisera. Out of 1,198 strain isolated from sporadic cases of Camplyobacter gastroenteritis, 883 (73.7%) were typed and 298 strains (24.9%) were untypable. The remaining 17 strains belong to rough form were not used for serogrouping. A hundred thirteen out of 883 strains have reacted with more than one typing serum. Among C. jejuni isolated from 7 prefecture, Lior's serogroup 4 was most common followed by Lior's serogroup 4, 2, 11, 1 and TCK serogroup 1 and 12. We conclude from the experiment described above that this Lior's serogrouping system by combining with TCK serogroup for Campylobacter jejuni/coli is useful in epidemiological investigations in Japan.

Campylobacter coli↗
PubMed1992

Lack of effect of carbonyl cyanide m-chlorophenylhydrazone on KB-5246 accumulation by Staphylococcus aureus.

The accumulation of KB-5246 in a quinolone-susceptible strain of Staphylococcus aureus was about 70 times that of norfloxacin. Carbonyl cyanide m-chlorophenylhydrazone increased the accumulation of norfloxacin about eightfold, but it did not influence that of KB-5246. The low efflux of KB-5246 from S. aureus may contribute to its potent antibacterial activity.

Anti-Infective Agents↗
PubMed1992

Helicobacter pylori-associated ammonia production enhances neutrophil-dependent gastric mucosal cell injury.

The role of neutrophil and its chlorinated oxidant were investigated in Helicobacter pylori-induced gastric mucosal injury in vitro. Luminol-dependent chemiluminescence (ChL) was used to detect neutrophil-derived oxidants. ChL activity was significantly elevated when neutrophils were incubated in H. pylori, indicating that H. pylori actually elicits oxidative burst of neutrophils. To assess whether H. pylori-activated neutrophils exert the cytotoxicity for gastric mucosal cells, rabbit gastric mucosal cell was monolayered in culture wells and labeled with a fluorescence dye, 2',7'-bis(2-carboxyethyl)-5(6)carboxy-fluorescein, which is retained in the intracellular space as long as the cell membrane is intact. Labeled cells were coincubated with neutrophils and H. pylori. We inferred from the cytotoxicity index (specific %cytotoxicity), which was calculated from fluorometrical measurements of supernatant and lysate, that the mucosal cells were significantly damaged by H. pylori-activated neutrophils. This injury was largely attenuated by eliminating urea from the incubation mixture or by acetohydroxamic acid, a potent urease inhibitor. Additionally, the scavengers of neutrophil-derived oxidants, including taurine, methionine, and catalase, also attenuated this injury. Cultured mucosal cells that were exposed to the solution containing monochloramine (an oxidant yielded by reaction of hypochlorous acid and ammonia) were highly damaged compared with cells exposed to hypochlorous acid or hydrogen peroxide at physiological concentrations. These data suggest that H. pylori-activated neutrophils promote gastric mucosal cell injury and that monochloramine plays a unique and important role in this process.

Ammonia↗
PubMed1992

Novel disease-modifying antirheumatic drugs. I. Synthesis and antiarthritic activity of 2-(4-methylphenyl)benzothiazoles.

A series of 2-(4-methylphenyl)benzothiazoles was synthesized and evaluated using an adjuvant-induced arthritic rat model. This class of desired compounds affecting the immune response was found using hemagglutination assay. 4-Acetoxy-2-(4-methylphenyl)benzothiazole (7m), KB-2683, was most potent in the adjuvant-induced arthritic rat model and selected for further evaluation. In contrast to nonsteroidal antiinflammatory drugs, compound 7m showed no antiinflammatory or analgesic activities. It did, however, show an immunomodulatory activity in enhanced delayed type hypersensitivity.

Animals↗
PubMed1992

Disordered expression of adrenal steroidogenic P450 mRNAs in incidentally discovered nonfunctioning adrenal adenoma.

In order to elucidate the steroidogenesis of clinically nonfunctioning adrenocortical adenoma, we studied the aldosterone, cortisol (F) and dehydroepiandrosterone (DHEA) content and the expression of mRNA of cytochrome P450 for side chain cleavage (P450scc), 17 alpha-hydroxylase (P450c17). 21-hydroxylase (P450c21) and 11 beta-hydroxylase (P450c11) in four clinically nonfunctioning adrenocortical adenomas discovered incidentally in asymptomatic patients (Cases 1, 2, 3 and 4). The results were compared with those in normal adrenal glands. In the adenomas from cases 1 and 2, the abundance of steroidogenic P450s mRNA were similar to those in normal adrenal glands, except P450c11 mRNA expression in the adenoma from case 1 which was slightly higher than normal. The steroid content was normal level, except for higher F in the adenoma from case 1 and lower aldosterone in case 2 adenoma than normal. The adenoma from case 3 contained much less P450scc, P450c17 and P450c21 mRNA, while the amount of P450c11 mRNA was slightly greater than in normal adrenals. The adenoma showed normal aldosterone, high F and low DHEA content compared with normal adrenal glands. In the adenoma from case 4, the accumulation of all four P450 mRNAs decreased, whereas aldosterone, F and DHEA content in the adenoma was similar to that of normal adrenal glands. These data indicated that nonfunctioning adrenocortical adenoma showed similar or decreased expression of steroidogenic P450 mRNAs that the normal adrenal gland. This decreased expression of steroidogenic P450 mRNAs may be at least partly concerned with the absence of clinical symptoms in patients with nonfunctioning adenoma.

Adenoma↗
PubMed1992

Thermal coefficients of paste-paste type pulp capping cements.

Thermal coefficients of four kinds of commercially available paste-paste type pulp capping cements were examined. Control reference samples were made of dentin. A thermal coefficient analyzer was used, heating specimens for a few nanoseconds by a xenon flash bulb and measuring thermal changes by using a thermocouple. Thermal coefficients were examined by this non-steady state method. Thermal conductivities of all cements were almost the same or lower than that of dentin. Therefore, when each cement was heated, the penetrating energy was almost the same or lower than that of dentin. The thickness of the cements was converted into that of the dentin by using the obtained thermal conductivity. The 1-mm thickness of the examined cements were equal to between 0.97-mm and 2.10-mm thicknesses of lost dentin. The use of a pulp capping cement provided better pulp protection from thermal stimuli than did the same thickness of dentin.

Calcium Hydroxide↗
PubMed1992

Significance of tubuloreticular structures in infants with neonatal lupus erythematosus and their mothers with Sjögren's syndrome.

Four infants with neonatal lupus erythematosus who had annular erythema on the trunk and face reacted positively to tests for anti-Ro(SS-A)/La(SS-B) antibodies. Electron microscopic examination of vascular endothelial cells in the annular erythema revealed the presence of tubuloreticular structures. Once anti-Ro(SS-A)/La(SS-B) antibodies had turned negative, these tubuloreticular structures were no longer evident in the vascular endothelial cells in the same area where annular erythema had been present. Mothers of these 4 infants reacted positively to anti-Ro(SS-A)/La(SS-B) antibodies, but had no sicca syndrome. A biopsy taken from the minor salivary gland of the lip of each mother revealed marked periductal mononuclear cell infiltration. Primary subclinical Sjögren's syndrome was confirmed. Tubuloreticular structures were also observed in the vascular endothelial cells in the region of the minor salivary gland. These findings suggest that the presence of tubuloreticular structures may be related to anti-Ro(SS-A)/La (SS-B) antibodies.

Adult↗
PubMed1992

Utility of the latex agglutination nephelometric immunoassay (Albusure Test) in screening for microalbuminuria in patients with diabetes mellitus.

All diabetic patients should be screened for early signs of diabetic nephropathy, because it is a prognostic factor in the disease. The albusure test (AT), a latex agglutination nephelometric immunoassay, is a rapid and low cost test for the detection of microalbuminuria of 30 mg/L or more. We compared the results of AT and of radioimmunoassay (RIA) for urinary albumin to evaluate the clinical utility of AT using fresh urine samples from 74 diabetic patients without persistent proteinuria and from 11 healthy subjects. Urinary albumin levels were 6.0 +/- 2.3 mg/L in the healthy subjects, 11.0 +/- 8.7 mg/L in the AT-negative group (n = 61), and 38.1 +/- 10.2 mg/L in the AT-positive group (n = 13). Using a cut-off value of 30 mg/L by RIA, the rate of coincidence between AT and RIA was 89.2%, although five subjects were false-positive by AT, and three were false-negative. These results show that AT may provide a useful monitor for microalbuminuria, a reliable early marker of diabetic nephropathy.

Adult↗
PubMed1992

Clinical characteristics of chronic cutaneous graft-versus-host disease in Japanese leukemia patients after bone marrow transplantation: low incidence and mild manifestations of skin lesions.

We investigated the incidence of chronic graft-versus-host disease (GVHD) and skin and oral lesions in chronic GVHD in 90 Japanese leukemia patients surviving over 100 days after bone marrow transplantation (BMT) from HLA-compatible siblings. The clinical characteristics of chronic cutaneous GVHD occurring in eight of these patients are summarized. There were some differences from previous reports in the USA and Europe. The incidence (8/29: 28%) of skin lesions in chronic GVHD was low in contrast to the previously reported high incidence (79-90%). Cutaneous manifestations in six out of eight patients with chronic GVHD tended to be mild, and lichen-planus-like eruptions in the skin and scleroderma-like lesions, which are well known as representative cutaneous manifestations of chronic GVHD, were rare. Furthermore, our statistical analysis indicated that there was no relationship between pretransplant total body irradiation and GVHD prophylaxis or acute GVHD and the onset of chronic cutaneous GVHD. The present study suggests that the differences from previous reports in the USA and Europe concerning chronic cutaneous GVHD may be attributable to differing genetic backgrounds in Japanese and western populations.

Acute Disease↗