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Biomedical subjects

M Ohashi

Publications and source records attributed to M Ohashi.

At least 271 records · Page 15Linked to original sources

Effect of octapeptide somatostatin analogue (SMS 201-995) on plasma 7B2 (a neuroendocrine polypeptide) levels in patients with acromegaly.

We studied the sequential changes of plasma levels of immunoreactive '7B2' (IR-7B2), a neuroendocrine polypeptide, after a subcutaneous injection of 50 micrograms of synthetic octapeptide somatostatin analogue (SMS 201-995) in seven patients with acromegaly due to GH-producing pituitary adenoma. Compared to the basal levels, mean plasma IR-7B2 and GH levels significantly decreased, until 5 and 10 h respectively after the administration of SMS 201-995. The mean (+/- SEM) nadir levels of plasma IR-7B2 and GH were 68.1 +/- 10.1 and 13.1 +/- 6.9%, respectively, compared to mean plasma levels before treatment (100%). Plasma IR-7B2 as well as GH levels did not change significantly when saline was administered subcutaneously to three acromegalic patients. In addition, plasma IR-7B2 levels did not change significantly after the administration of SMS 201-995 in normal subjects or in patients with primary hypothyroidism in whom SMS 201-995 induced a decrease of plasma TSH levels. These results strongly suggest that SMS 201-995 has an unequivocal suppressive effect on the synthesis and/or the secretion of 7B2 in human somatotroph adenoma cells.

Acromegaly↗

Production of immunoreactive inhibin by a virilizing ovarian tumour (Sertoli-Leydig tumour).

A 59-year-old post-menopausal woman was admitted to the hospital with atypical vaginal bleeding and hirsute lower extremities. There was a high serum testosterone level (15.8 nmol/l) and also an appreciable serum immunoreactive inhibin level. No adrenal or ovarian lesions were detected by conventional imaging procedures. Selective blood sampling was performed during venous catheterization and showed that testosterone and inhibin levels were highest in the right ovarian vein. Laparotomy revealed a Sertoli-Leydig tumour in the right ovary, which was excised. Post-operatively, immunoreactive inhibin became undetectable while the testosterone level fell to 2.8 nmol/l. Specific radioimmunoassay showed a high immunoreactive inhibin content in the tumour. These findings indicate that Sertoli-Leydig tumours can produce both testosterone and immunoreactive inhibin, both of which would then inhibit LH and FSH release to produce the symptoms seen in this patient. Thus, assay of inhibin may aid in the differential diagnosis of virilizing tumours.

Female↗

Inhibition by ibudilast of leukotriene D4-induced formation of inositol phosphates in guinea-pig lung.

1. The effects of a novel anti-asthmatic drug, 3-isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine (ibudilast, KC-404) on leukotriene D4 (LTD4)-induced formation of inositol phosphates were studied in slices of guinea-pig lung and hippocampus. 2. In guinea-pig lung, ibudilast inhibited LTD4 (0.01-1 microM)-induced formation of inositol monophosphate (IP1) in a concentration-dependent manner (IC50 = 10 microM) without affecting LTD4 receptor binding. 3. Ibudilast (10 microM) inhibited histamine (0.1-1 mM)-induced formation of IP1 in guinea-pig lung slices but not in hippocampal slices. 4. Inhibition of agonist-induced formation of IP1 by ibudilast was non-competitive. 5. Ibudilast had no effect on either GTP- or calcium-stimulated phosphatidylinositol specific-phospholipase C activity of lung membranes. 6. These results suggest that ibudilast has no direct effect on LTD4 receptors, GTP binding proteins (G proteins) or phospholipase C, but inhibits inositol phosphate formation, possibly by interfering with the coupling between receptors and G proteins.

Animals↗

[Biochemical characteristics, growth on selective media, antimicrobial susceptibility, and diarrheagenic toxin production of enteroinvasive Escherichia coli].

A total of 70 strains of enteroinvasive Escherichia coli (EIEC) belonging to 8 different O serogroups including O28ac O29, O121, O124, O136, O143, O144, and O164, was studied for their biochemical characteristics, growth on selective isolation agar, antimicrobial susceptibility, and diarrheagenic toxin production. Among the biochemical characteristics examined, all EIEC strains gave negative lysine decarboxylation and all but one belonging to O124 serogroup, were non-motile, regardless of their O serogroups. The one motile O124 strain had a H30 antigen. Some close correlations were also observed between their O serogroups and biochemicals such as utilization of sodium acetate and mucate, ornithine decarboxylation, arginine dihydrolation, gas production from glucose, and lactose fermentation. Among the selective isolation agars, MacConkey and Deoxycholate-hydrogen sulfide-lactose (DHL), and modified Shigella-Salmonella (SS) agars supported growth of the EIEC strains well, whereas SS agar was remarkably inhibitory for strains of some O serogroups. Antimicrobial susceptibility was tested for nine drugs including chloramphenicol (CP), tetracycline (TC), streptomycin (SM), kanamycin (KM), ampicillin (ABPC), sulfamethoxazole-trimethoprim (ST), nalidixic acid (NA), fosfomycin (FOM) and norfloxacin (NFLX). Forty-one of the 70 strains (58.6%) were found to be resistant to the 6 drugs, such as CP, TC, SM, KM, ABPC or ST. None of the strains were resistant to NA, FOM or NFLX. Among the resistant strains recognized, the strains which showed the resistant patterns of CP.TC.SM.ABPC, CP.TC.SM, TC.SM.ST, TC.SM, and SM appeared to be prevalent. None of the strains gave positive reactions for the production of diarrheagenic toxins of heat-labile enterotoxin, heat-stable enterotoxin, and verocytotoxins 1 and 2.

Anti-Bacterial Agents↗

[The serotype distribution of Campylobacter jejuni strains among gastroenteritis in hospitals over 7 year period in Tokyo].

Campylobacter jejuni strains isolated from gastroenteritis at 4 general hospitals of Tokyo Metropolitan during the period from 1981 to 1987 were serotype according to the slide agglutination test (TCK system) developed by the Tokyo Metropolitan Research Laboratory of Public Health. Two thousand four hundred seventy-nine strains isolated from sporadic cases among infants and children, 1,962 (78.5%) were typed by 33 typing sera numbered TCK 1 through TCK 33 and leaving 537 strains (21.5%) untypable. Out of the typable strains, 1,643 strains reacted with only single serum, while 319 strains reacted with 2 or more antisera. The most common serogroups included TCK 21, 20, 7, 1, 4, 23, 24, 10, 30 and 12. Out of the 1,250 strains isolated from sporadic cases among adults, 974 strains (77.9%) were typed and 276 strains were untypable. The most common serogroups were similar to those of infants and children. Serogroups TCK 1, 7, 4 and 21 were consistently the common serogroups every year during the 7 year study. Isolation frequency of serogroup TCK 30 have increased remarkably since 1986, while TCK 23, 14 and 9 have decreased.

Adult↗

Antigenic characterization of small, round-structured viruses by immune electron microscopy.

Small, round-structured viruses (SRSVs) detected from nonbacterial gastroenteritis outbreaks in Tokyo and Saitama Prefecture, Japan, during the period from 1977 to 1988 were tentatively classified into nine antigenic patterns from SRSV-1 (S-1) to SRSV-9 (S-9) by cross-immune electron microscopy (IEM). S-1 and S-2 appeared pattern specific, while S-3 to S-9, distinguishable from each other in their reactivity, appeared somewhat antigenically related. Their antigenic relatedness to the Norwal, Hawaii, and Otofuke agents was also examined by IEM by using antisera to these agents. S-3 appeared most closely related to the Norwalk agent. S-4 and S-5 were related to the Norwalk agent and, presumably, were distantly related to the Hawaii and Otofuke agents. S-6 and S-7 were related to the Hawaii and Otofuke agents. S-8 and S-9 were related to the Otofuke agent and, presumably, were distantly related to the Hawaii agent. The prevalence of each antigenic pattern in 38 outbreaks was examined: S-8 was implicated in 24% of the outbreaks S-5 in 16%, S-4 in 13%, S-9 in 13%, S-6 in 11%, and others in 5%.

Antigens, Viral↗

Expression of c-fos and c-myc proto-oncogenes in human adrenal pheochromocytomas.

We examined c-fos and c-myc expressions in pheochromocytoma tissues from six patients. All samples contained c-fos and c-myc transcripts, whereas mRNA from bovine adrenal medulla, as a control, did not contain these transcripts at detectable levels. Southern blot analysis revealed no amplification and no rearrangement of c-fos and c-myc genes. We also examined the gene expression of insulin-like growth factor-II (IGF-II), a mitogen for rat pheochromocytoma cells exerted by autocrine or paracrine fashion. All samples from the pheochromocytomas contained IGF-II transcripts as well as c-fos and c-myc transcripts. The constitutive expressions of c-fos and c-myc genes may be interpreted to mean that pheochromocytoma is in a state of growth stimulation in vivo by growth factors, including IGF-II.

Adrenal Gland Neoplasms↗

Metabolism of diltiazem. III. Oxidative deamination of diltiazem in rat liver microsomes.

The main metabolites of diltiazem in rats are acidic metabolites having a carboxyl group which may be formed by oxidative deamination of the dimethylaminoethyl group of diltiazem. In order to identify the enzymes responsible for the deamination and formation of acidic and neutral metabolites [14C]diltiazem was incubated with microsomal and mitochondrial preparations from the liver of SD male rats. Both acidic and neutral metabolites were formed only in the presence of an nicotinamide adenine dinucleotide phosphate generating system. Their formation was remarkable, especially in the microsomes, and inhibited by SKF 252-A, but not by pargyline and iproniazid. The production of neutral metabolites surpassed that of acidic ones. Structural analysis by gas chromatography-mass spectrometry showed that the neutral metabolites are aldehydes which have not been detected in vivo. The results suggest that the dimethylaminoethyl group of diltiazem is oxidized to an aldehyde group by microsomal cytochrome P-450 in the liver. Subsequently, the aldehyde group would be dehydrogenated to the carboxyl group.

Animals↗

Decreased levels of steroid 21-hydroxylase [P450(c21)] and its mRNA in an adrenocortical adenoma associated with 21-hydroxylase deficiency.

Adrenocortical adenoma incidentally found in a 37-yr-old female patient, with simple virilizing form of 21-hydroxylase deficiency, was studied. Cultured adenoma cells revealed excessive secretion of 17 alpha-hydroxyprogesterone in response to 10(-8) M ACTH, compared with those of 11-deoxycortisol and cortisol, which indicated impaired activity of the 21-hydroxylase. To elucidate the molecular mechanisms of this defective 21-hydroxylase in the adenoma, we analyzed the gene encoding specific cytochrome P450 (P450c21) for steroid 21-hydroxylation and its expression. DNA and RNA were extracted from the adrenal adenoma and were hybridized with a probe of human P450c21 gene, by Southern and Northern blot analysis. In Southern blot analysis with Taq I, Bgl II or Bam HI, there was no difference between the pattern of restriction fragments in DNA from the adenoma and normal peripheral leucocytes. Northern blot analysis of the adenoma showed the same size of P450c21 mRNA as in the normal adrenal gland, but the amount was low--about a half that of the normal adrenal. In Western blot analysis with polyclonal antibody to P450c21, only a small amount of P450c21 protein was detected in the adenoma, although it was found to be of the same molecular weight as that in the normal adrenal gland. In view of these findings it is conceivable as one of possibilities that a mild and small mutation in the structural or promotor region of the P450c21 gene may cause the decreased 21-hydroxylase activity in this adenoma.

Adenoma↗

Structure-receptor binding relationships of sarafotoxin and endothelin in porcine cardiovascular tissues.

The specific binding of 125I-sarafotoxin S6b was observed in the microsomal fractions from porcine thoracic aorta, and two vasoconstrictive peptides with strikingly homologous structures, sarafotoxin (SRT) and endothelin (ET), interact with a common receptor of the vasculature. The order of the potency of an each endothelin or sarafotoxin analogue as a competitor against 125I-sarafotoxin S6b binding was ET-1 greater than ET-2 greater than SRT S6b greater than ET-3 much greater than SRT S6c. The hydrophobic carboxyl-terminal tail and intramolecular disulfide bridges are essential for the binding activity. In addition, Ser4, Ser5 and Lys9 seem to be important for the activity while the 6th residue does not affect the activity.

Amino Acid Sequence↗

[The development of visible light-cured composite resin. Kinds of fillers to be mixed with cyclophosphazene system monomers and its amount and its physical properties].

A visible light-cured composite resin was developed. Cyclophosphazene monomer, 4 PN-(TF)1-(EMA)7 was prepared as a monomer. The ratio of brush abrasion, mechanical properties, water sorption, thermal expansion coefficient and the surface of abrasion were examined after mixing with fillers of different particle size (R-972, OX-50 and VL-30). The ratio of brush abrasion showed a tendency to be small when more than 50 wt% of VL-30 with a large particle size was mixed with 4 PN-(TF)1-(EMA)7 monomer. However its abrasion surface was rough compared with that of the microparticle filler. When the microparticle filler (50 wt% of OX-50) was mixed with the monomer, its mechanical properties were good for the mixture with 50 wt% OX-50. In that case, the ratio of brush abrasion was 0.268, compressive and transverse strength, 124.3 and 86.3 MPa respectively, hardness, 43.2 Hk, water absorption 14.2 micrograms/mm3 and thermal expansion coefficient, 47.4 x 10(-6)/degrees C.

Composite Resins↗

[Structure and function of the receptor for human atrial natriuretic peptide in cultured human skin fibroblasts].

Cultured human skin fibroblasts possessed the high-affinity and low-capacity binding sites for [125I]alpha-human atrial natriuretic peptide (hANP), in which the dissociation constant and maximal binding capacity were computed to 68.7 +/- 11.3 pM and 7.3 +/- 1.2 fmols/mg protein, respectively, from Scatchard plot analysis. The specific [125I] alpha-hANP binding sites of cultured human fibroblast were displaced by unlabeled atriopeptin I, a truncated analogue, to the same extent as the case of alpha-hANP. In human adrenal membrane fractions, [125I] alpha-hANP binding sites were suppressed only by unlabeled alpha-hANP, while the high concentrations of atriopeptin I could slightly inhibit the binding sites for alpha-hANP. As it was reported that atriopeptin I had more significant affinity to the low-molecular weight ANP receptor (60-70 KD) than that to the high-molecular weight form (130-140 KD), the specific bindings may be attributed by the low-molecular weight ANP receptor in cultured human fibroblasts. Furthermore, alpha-hANP up to 10(-8)M failed to induce the significant cGMP formation in cultured human skin fibroblasts. The molecular weight of [125I]alpha-hANP binding sites of human fibroblasts was identified only at the region of 67 KD and no radioactive band was visualized around the region of large molecular weight ANP receptor in the SDS gel electrophoresis of a crosslinked [125I]alpha-hANP-receptor complex. In contrast, the affinity labeling of [125I]alpha-hANP to the human adrenal membrane fractions showed that 135 KD binding sites were responsible to the human adrenal ANP receptor. In conclusion, cultured human skin fibroblasts have a high-affinity low-capacity receptor for ANP. The molecular weight of ANP receptor is approximately 67 KD, and ANP-specific guanylate cyclase may not be linked to the receptor, suggestive that so-called C receptor may be localized in cultured human fibroblasts.

Adrenal Glands↗

The heterogeneity of anticentromere antibodies in immunoblotting analysis.

We tested anticentromere antibody positive sera from 37 patients by immunoblotting techniques. Three antigenic polypeptides were recognized when immunoblotted against protein extracts from HeLa cell nuclei or from chromosomal segments enriched with centromere region. These were a 17 kDa (CENP-A recognized by 34 sera), an 80 kDa (CENP-B recognized by 33 sera), and a 140 kDa polypeptide (CENP-C recognized by 26 sera). There was no disease specific pattern of antigenic polypeptides, although Raynaud's phenomenon was frequent in patients with anti-CENP-B reactivities (p less than 0.01). The heterogeneity of the anticentromere antibody response in Japanese patients shows anticentromere antibody may not be a disease specific autoantibody and diagnostic marker.

Autoantibodies↗

[Two cases of Turner's syndrome with spondyloepiphyseal dysplasia like bone appearance].

We report two cases of mosaic karyotype (45XO/46XiXq) Turner's syndrome with unique bone appearance. The cases were 44 and 34 year-old women and latter was complicated by Hashimoto's thyroiditis (hypothyroidism). Following the systemic bone surveys, we found the patients showed not only osteoporotic bone change and short stature, but also spondyloepiphyseal dysplasia (SED) like bone appearance (thinness of vertebral bodies, irregularity of vertebral end-plates, shortness of femoral necks, Coxa valga, Coxa magna and hypoplasia of acetabula). Those findings can not be explained by degenerative bone changes like osteoporosis, rather are suggestive the sequelae of malgrowth of the bone system in Turner's syndrome.

Adult↗

Okadaic acid and dinophysistoxin-1, non-TPA-type tumor promoters, stimulate prostaglandin E2 production in rat peritoneal macrophages.

Okadaic acid and dinophysistoxin-1 isolated from a black sponge, Halichondria okadai are non-12-O-tetrade-canoylphorbol 13-acetate (non-TPA)-type tumor promoters of mouse skin. Okadaic acid at concentrations of 10-100 ng/ml stimulated prostaglandin E2 production in rat peritoneal macrophages. Dinophysistoxin-1 (35-methylokadaic acid) stimulated prostaglandin E2 production as strong as okadaic acid, but okadaic acid tetramethyl ether, an inactive compound as a tumor promoter, did not. Okadaic acid at 10 ng/ml (12.4 nM) stimulated prostaglandin E2 production as strongly as TPA at 10 ng/ml (16.2 nM) 20 h after incubation. Unlike TPA-type tumor promoters, okadaic acid required a lag phase before stimulation. The duration of this lag phase was dependent on the concentration of okadaic acid. Indomethacin inhibited okadaic acid-induced preostaglandin E2 production in a dose-dependent manner, and its inhibition was more strongly observed in okadaic acid-induced prostaglandin E2 production. Cycloheximide inhibited okadaic acid-induced release of radioactivity from [3H]arachidonic acid-labeled macrophages and prostaglandin E2 production dose dependently, suggesting that protein synthesis is a prerequisite for the stimulation of arachidonic acid metabolism. These results support our idea that tumor promoters, at very low concentrations, are able to stimulate arachidonic acid metabolism in rat peritoneal macrophages.

Animals↗