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Biomedical subjects

M Ota

Publications and source records attributed to M Ota.

At least 199 records · Page 11Linked to original sources
PubMed1994

[Studies on aspoxicillin for its transfer to the skin].

To evaluate the usefulness of aspoxicillin (ASPC) in the field of plastic and reconstructive surgery, we examined its transfer to the skin. 1. After intravenous drip infusion of ASPC for 1 hour at a dose of 2 g in 13 adults and at 1 g in 2 children, the mean serum ASPC concentration 1 hour after termination of the infusion was 70.46 +/- 28.05 micrograms/ml. The mean concentration in the skin tissue 1 hour after infusion in 15 patients was 32.45 +/- 18.47 micrograms/g. The rate of transfer to the skin 1 hour after infusion in the 15 patients was 52.9 +/- 29.7%. 2. The ASPC concentrations in skin tissues and the rates of its transfer to the skin did not differ significantly between 5 patients with facial surgery and 10 with surgery in the trunk or limbs. 3. To prevent postoperative infections, ASPC was intravenously drip infused twice daily for 2 approximately 3 days after operation at a dose of 2 g in adults and 1 g in children. No postoperative infection occurred in any patient, suggesting the effectiveness of this drug. In addition, no side effects or abnormalities in clinical examination values were observed.

Adolescent↗
PubMed1993

Transfusion-associated graft-versus-host disease in an immunocompetent patient following accidental injury.

We report a case of transfusion-associated graft-vs.-host disease (TA-GVHD) in a previously healthy, 58 year old Japanese man following an accidental injury. Despite intensive treatment, the patient died 22 days after the transfusion. Although many cases of fatal TA-GVHD have been reported in immunocompetent patients, only two are known to have developed this disorder unrelated to a surgical procedure. This is the first such case to be confirmed by HLA typing. Our report suggests that TA-GVHD can occur even in a healthy, immunocompetent recipient. Thus, it seems necessary to establish guidelines for the irradiation of cellular blood products before transfusion.

Accidental Falls↗
PubMed1993

Cell-mediated immune-pancytopenia complicating primary Sjögren's syndrome.

A 64-year-old woman with mild bilateral parotid gland swelling and bilateral lower extremity purpura was admitted for evaluation of xerostomia and pancytopenia. The patient had an increased erythrocyte sedimentation rate, pancytopenia, and positive tests for antibodies to nuclear antigen, SS-A, and SS-B. Impaired cell-mediated immunity was also present. Bone marrow aspiration showed a hypoplastic marrow with an increased percentage of lymphocytes. A positive Schirmer's test and keratoconjunctivitis were also noted. A diagnosis of primary Sjögren's syndrome was made by sialography and histological salivary gland findings. Therapy with prednisolone improved the pancytopenia. Addition of the patient's peripheral blood mononuclear cells to cultures of bone marrow mononuclear cells derived from a healthy volunteer dose dependently inhibited colony formation, including mixed hemopoietic colonies. On the other hand, addition of the patient's serum failed to inhibit colony formation by normal bone marrow mononuclear cells. These results suggested that one of the causes of pancytopenia in primary Sjögren's syndrome might be mediated by the inhibition of mononuclear cells to the hemopoietic progenitors.

Blood Physiological Phenomena↗
PubMed1993

Allele frequency distribution of the D1S80 (pMCT118) locus polymorphism in the Japanese population by the polymerase chain reaction.

Population studies among Japanese were carried out at the D1S80 locus by the polymerase chain reaction and subsequent analysis in agarose gel electrophoresis. A total of 58 genotypes and 25 alleles ranging from 16 to 45 repeat units were observed in a population group of 121 unrelated individuals. The alleles with 18, 24 and 30 repeat units were found to be most common. Some large alleles with more than 42 repeat units were first observed in this study. Statistical tests for Hardy-Weinberg equilibrium showed that no significant deviations could be found in this Japanese population sample. The values of the mean exclusion chance and the discriminating power (DP) were calculated to be 0.76 and 0.91, respectively. The observed heterozygosity was 0.91.

Alleles↗
PubMed1993

Comparison of the clinical and immunogenetic features between patients with autoimmune hepatitis and patients with type C chronic active hepatitis.

We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis (C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH. The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH predominantly. Ongoing or past infection of HCV was seen in only 14% of patients with AI-CAH. HLA-DR4 was the most frequently associated with AI-CAH (89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted, disease, and different from C-CAH which is a viral infectious disease.

Adult↗
PubMed1993

Role of vasopressin, the renin-angiotensin system and sex in Dahl salt-sensitive hypertension.

OBJECTIVE: To determine the roles of vasopressin, the renin-angiotensin system and sex in the pathogenesis of salt-sensitive hypertension in the Dahl rat. DESIGN: The effects of 12 days' treatment with a non-peptide, orally effective V1 antagonist (OPC-21,268) and captopril, individually or together, were compared in male and female Dahl salt-sensitive rats after 10 days on a high-salt diet. METHODS: OPC-21,268 was given in the food, and captopril was administered with osmotic pumps implanted subcutaneously. RESULTS: Systolic blood pressure (SBP) reached a higher level in untreated males than in untreated females. V1 blockade in males prevented any further increase in SBP during the first week of treatment, but SBP rose thereafter towards the levels found in the untreated males. In females OPC-21,268 had no effect. In males captopril prevented any further increase in SBP. There was no effect of captopril in females during the first week of treatment, but SBP fell to pretreatment levels during the second week. Combined treatment with OPC-21,268 and captopril in males had a smaller antihypertensive effect than either drug alone. In females combined treatment prevented any further increase in SBP. CONCLUSIONS: These findings suggest that both vasopressin and the renin-angiotensin system contribute to the pathogenesis of Dahl salt-sensitive hypertension, but that other factors, possibly including the sympathetic nervous system, are also involved. Sex also affects the severity of this form of hypertension and influences the relative roles of vasopressin and the renin-angiotensin system. It is likely that the gonadal steroid hormones modulate the activity of the pathogenetic factors in this form of hypertension at a central or peripheral level.

Animals↗
PubMed1993

Evidence that nitric oxide can act centrally to stimulate vasopressin release.

Nitric oxide (NO) is the endothelium-derived relaxing factor, which causes relaxation of vascular smooth muscle. NO synthetase, the enzyme for the synthesis of NO from its precursor L-arginine, is also widely distributed in neurons in the brain, and it has been suggested that NO may serve as an important neuromodulator. Because NO synthetase is present in the hypothalamus in relatively high concentration, we have determined whether NO can affect the release of vasopressin in conscious, chronically prepared rats. The intracerebroventricular (i.c.v.) injection of S-nitroso-N-acetylpenicillamine (12.5 and 25 micrograms; SNAP), that spontaneously breaks down to form NO, caused transient dose-related increases in the plasma vasopressin concentration of 1 and 2 microU/ml (p < 0.01), respectively. In control experiments in which N-acetylpenicillamine (25 micrograms), the precursor for the preparation of SNAP, was injected i.c.v. there was a small, 0.4 microU/ml, increase (p < 0.01) in the plasma vasopressin level. The i.c.v. injection of L-arginine (0.5 and 1 mg), also the precursor for the biosynthesis of NO, resulted in dose-dependent increases in the plasma vasopressin concentration similar in magnitude to those caused by SNAP. When D-arginine (1 mg), which cannot serve as a substrate for NO synthetase, was injected i.c.v., there was only a slight delayed increase in the plasma vasopressin concentration. Thus, NO can act centrally to stimulate vasopressin release and may serve as a neuromodulator in the control of vasopressin release.

Animals↗
PubMed1993

[Effect of palonidipine hydrochloride (TC-81), a new dihydropyridine derivative, on various myocardial ischemic models].

The antianginal effects of palonidipine, a novel 1,4-dihydropyridine derivative, and nifedipine on various myocardial ischemic models were compared. (1) Palonidipine at 0.5 mg/kg, p.o. significantly inhibited vasopressin-induced ST depression of ECG in Donryu rats. This activity was about 5 times more potent than that of nifedipine and was long-lasting. (2) Palonidipine at 1 mg/kg, i.d. significantly inhibited ST depression induced by isoproterenol in Wistar rats. This activity of TC-81 was more potent than that of nifedipine. (3) Palonidipine at 3 micrograms/kg, i.v. produced an increase in regional myocardial tissue blood flow in the ischemic region of chronic coronary artery occluded dogs. (4) In isolated dog coronary artery, palonidipine at a concentration of 10(-10) M or greater inhibited the amplitude of 3,4-DAP-induced cyclic contractions in a concentration-dependent manner. This activity was 10-30 times more potent than that of nifedipine. (5) An intracoronary injection of endothelin (30 pmol/kg) reduced the coronary blood flow, subepicardial tissue blood flow, and subepicardial pH in anesthetized dogs. The ST elevation of ECG over 0.1 mV also occurred in 8 of 10 cases. In all the cases, ventricular extrasystoles were noted, and 9 out of 10 animals died. Pretreatment with palonidipine (3 micrograms/kg, i.v.) inhibited endothelin-induced ischemic changes, with a potency greater than that of nifedipine. These results suggest that palonidipine may be useful for the therapy of angina-pectoris.

Angina Pectoris↗
PubMed1993

[Immunological study on Alzheimer's disease using anti-beta-protein monoclonal antibodies].

Monoclonal antibodies (TB1 & TB2), which were obtained by immunization of 24 amino acids in BALB/c mice, bound specifically to the amyloid senile plaque and amyloid-angiopathic lesions of brain tissues of patients with Alzheimer's disease (AD) or with senile dementia of Alzheimer type (SDAT), and strongly reacted with the 1st part (Asp-Ala-Glu-Phe-Arg-His-Asp) of beta-protein. Western blotting and two-dimensional immunoelectrophoresis of cerebrospinal fluid (CSF) and serum revealed bands of 125 and 20 kilodaltons. The positive frequency of 125 and 20 KD bands detected by two-dimensional immunoelectrophoresis was higher in the serum of AD and SDAT patients (12 cases) than in that of normal control patients. ELISA employing various anti-amyloid precursor protein (APP) antibodies was performed using the extract of the human neuroblastoma cell line (NB39) which produces APP. In the near future, we hope to measure APP in CSF and sera from patients with Alzheimer's disease.

Aged↗
PubMed1993

[Molecular biological analysis of HLA class II gene in autoimmune hepatitis among Japanese].

The frequencies of HLA B54, DR4, DR53 and DQ4 were significantly higher in patients with autoimmune hepatitis than in healthy controls. HLA-DR4 was most frequently associated with autoimmune hepatitis. To define the HLA class II gene which has the susceptibility or resistance to autoimmune hepatitis, we performed HLA class II genotyping using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. The frequency of DRB1*0405 was significantly higher in autoimmune hepatitis than in controls. However, there was no significant difference in the frequency of the DR4 associated Dw-allele between the patients and the controls who were DR4-positive. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-associated Dw-alleles compared with the DR2-positive controls. Comparison of the amino acid residues of DRB1 chain suggested that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among Japanese.

Asian People↗
PubMed1993

Association of primary biliary cirrhosis with human leukocyte antigen DPB1*0501 in Japanese patients.

To investigate the relationship between distribution of human leukocyte antigen alleles and susceptibility to primary biliary cirrhosis among Japanese, we performed serological typing and human leukocyte antigen DP genotyping in 47 Japanese patients with primary biliary cirrhosis. Serologically, the frequency of human leukocyte antigen DQ3 was significantly higher in the patients than in healthy controls, whereas frequency of DR52 was significantly lower in the patients. Human leukocyte antigen DP genotyping using the polymerase chain reaction-restriction-fragment-length polymorphism method showed that the frequency of human leukocyte antigen DPB1*0501 (85.1%) was significantly higher in patients than in healthy controls but that the frequency of DPB1*0402 was significantly lower in patients. The positive association of human leukocyte antigen DPB1*0501 with primary biliary cirrhosis was stronger than that of serological human leukocyte antigen DQ3, which can be explained by its linkage to DPB1*0501. In addition, three of seven DPB1*0501-negative patients had DPB1*0202, suggesting that the human leukocyte antigen DPB1 amino-acid chain plays an important role in the immunogenesis of primary biliary cirrhosis among Japanese patients. Comparative analysis of amino acid sequences from DPB1 alleles indicated that a Leu at position 35 of the DPB1 chain likely contributes to the susceptibility to primary biliary cirrhosis among the Japanese.

Adult↗
PubMed1993

[Two cases of MERRF (myoclonus epilepsy associated with ragged red fibers) showing different clinical features in the same family].

A 73-year-old woman (patient 1) developed progressive mental deterioration at age 63, and seizures at age 70. On examination, she showed severe dementia, tonic clonic convulsion, hypotonia and muscular wasting. There was neither myoclonus nor cerebellar ataxia. Brain CT revealed a low density area in the right occipital lobe. A 44-year-old man (son of the patient 1) developed unsteady gait at age 15, muscle twitching at age 18 and then noticed speech disturbance at age 35. He had no history of convulsive seizure. Neurological examination showed cerebellar ataxia, myoclonus in the extremities and mild muscular weakness. His intelligence was normal. Brain CT showed moderate atrophy of the pons and the cerebellum. Both cases showed the same mitochondrial DNA mutation as reported previously in patients with MERRF. However, the clinical features, the age of onset and the brain CT findings were totally different between these 2 cases. In the progress of mitochondrial genetic analysis, atypical forms in MERRF like the patient 1 would increase in number, and the wide variation of clinical symptoms should be considered.

Adult↗
PubMed1993

cAMP-dependent phosphorylation of nuclear proteins in mouse submandibular gland following testosterone administration.

The effect of androgen on protein kinase activities was studied in chromosomal proteins from female mouse submandibular gland. The protein kinase activities in the nuclei were stimulated 3 h after testosterone administration. The in vitro addition of cAMP in the nuclei resulted in the enhancement of the androgen-sensitive protein kinase activities. SDS-PAGE analysis revealed that nonhistone proteins having molecular weights of 20-30 kDa and around 43 kDa were phosphorylated after androgen treatment. The addition of cAMP stimulated phosphorylation of nonhistone proteins having molecular weights with 15-25 kDa, 30 kDa and 35 kDa and the intensity of phosphorylation of these nonhistone proteins was enhanced after androgen treatment. These results suggest that androgen-sensitive protein kinases including cAMP-dependent protein kinase were present and that phosphorylation of nonhistone proteins by these protein kinases may be involved in mediating androgen-induced gene activation.

Animals↗
PubMed1993

Dual roles of 90-kDa heat shock protein in the function of the mineralocorticoid receptor.

Association of the 90-kDa heat shock protein (HSP90) is required for the high-affinity ligand-binding of the glucocorticoid receptor (GR), but not for that of the androgen receptor [Ohara-Nemoto, Y., Nemoto, T., & Ota, M. (1991) J. Biochem. 109, 113-119]. In the present study, we investigated the ligand- and HSP90-binding characteristics of the mineralocorticoid receptor (MR), which shares to some degree the ligand-binding specificity of the GR. A truncated human MR (designated MR351) starting from Gly-351 was translated in vitro with rabbit reticulocyte lysate. Scatchard analysis revealed the presence of a single class of high-affinity binding sites for [3H]aldosterone (Kd = 0.35 +/- 0.2 nM), comparable to those of the native receptor in target tissues. Glycerol gradient centrifugation and immunoadsorption analyses showed that MR351 associated with rabbit HSP90. Exposure to 0.4 M NaCl induced the dissociation of HSP90 from MR351 and simultaneously enhanced binding of MR351 to DNA-cellulose. Moreover, when measured at 10 nM, HSP90-free MR351 showed only 9% of the [3H]aldosterone-binding found in the presence of HSP90. On the other hand, when MR351 was expressed in Escherichia coli as a protein tagged with a histidine hexamer at the N-terminus (designated H6MR351), specific binding of [3H]aldosterone was detected. The binding affinity (Kd = 338 +/- 45 nM) was, however, 1,000-fold lower than that of MR351 translated in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Central carbachol stimulates vasopressin release into interstitial fluid adjacent to the paraventricular nucleus.

We have used an in vivo double microdialysis probe technique in conscious rats to determine whether the application of carbachol to one paraventricular nucleus (PVN) can result in increased local release of vasopressin from that PVN. Experiments were carried out 24 h after placement of microdialysis probes lateral to each PVN. When both probes were perfused initially with 0.9% NaCl, vasopressin was detected in the outflow (dialysate) from both probes. When carbachol (100 micrograms/ml) was included in the perfusate of one probe for the first 10 min of a 30-min collection period, while the other probe continued to be perfused with saline alone, there was a seven-fold increase in the concentration of vasopressin in the dialysate from the carbachol-perfused probe; the vasopressin concentration in the dialysate from the contralateral probe increased only slightly. The plasma vasopressin concentration was also elevated. When one of the paired probes was perfused with carbachol (100 micrograms/ml) for 30 min, there were similar increases in the concentration of vasopressin in the dialysate from both probes and a sustained increase in the plasma vasopressin concentration. Thus, vasopressin is released into the interstitial fluid adjacent to the PVN under basal conditions, and this release can be substantially increased when vasopressin secretion to the periphery is stimulated.

Animals↗
PubMed1992

A possible association between basic amino acids of position 13 of DRB1 chains and autoimmune hepatitis.

Fifty-one patients with autoimmune hepatitis have been studied for HLA association by conventional serology and also by modified polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping. HLA-DR4 was significantly associated with autoimmune hepatitis (46 of 51 patients, 90.2%). DNA typing of the DRB1 gene for 43 DR4-positive patients by using the PCR-RFLP technique revealed that of 43 patients, 33 had DRB1*0405 (Dw15), five had DRB1*0406 (DwKT2), four had DRB1*0403 (Dw13a), two had DRB1*0401 (Dw4), two of 43 had DRB1*0407 (Dw13b) and one had DRB1*0408 (Dw14b). Thus, there was no significant difference in Dw frequencies between DR4-positive patients and DR4-positive healthy subjects. These findings suggest that the DR4-specific sequence (Val 11 and His 13 at amino acid positions 11 and 13, respectively), but not particular Dw-associated DR4 sequence, in the first domain of the DRB1 chain contributes to susceptibility to autoimmune hepatitis among Japanese. Interestingly, all five of the DR4-negative patients had the DR2 specificity (DRB1*1502 or 1601). Taken together, these results imply that the basic amino acids at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), are most important for determining the predisposition to autoimmune hepatitis.

Amino Acid Sequence↗