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Biomedical subjects

N Ohashi

Publications and source records attributed to N Ohashi.

At least 109 records · Page 6Linked to original sources
PubMed1997

Ehrlichia sennetsu groE operon and antigenic properties of the GroEL homolog.

A clone expressing an immunoreactive 55-kilodalton (kDa) protein of Ehrlichia sennetsu, the causative agent of human Sennetsu ehrlichiosis, was isolated from a gene library of this organism. Sequence analysis of the DNA insert revealed two open reading frames, encoding proteins of 10,620 and 58,225 kDa, respectively. These deduced amino acid sequences were homologous to those of the GroES and GroEL heat shock proteins (HSP) of other bacteria, respectively. Phylogenetic trees based on GroES and GroEL homologs of several bacteria including E. sennetsu showed a relationship similar to that based on 16S rRNA gene sequences. The recombinant and native 55-kDa proteins of E. sennetsu, GroEL homolog, reacted with a monoclonal antibody (SPA807) which recognizes a homologous sequence between human and mycobacterial HSP60 and a polyclonal antibody (SPA804) to cyanobacteria HSP60, but not with antibodies to HSP60 of several other organisms used. Furthermore, anti-recombinant E. sennetsu 55-kDa protein antibody prepared in a rabbit was reactive to HSP60 antigens of other Ehrlichia and Rickettsia species, but not GroEL of E. coli. The recombinant 55-kDa protein would be a useful tool for studying the role of this antigen in the immune response to E. sennetsu infection.

Amino Acid Sequence↗
PubMed1997

The real life of aged persons living alone in a depopulated area--in case of village a in Nagano Prefecture.

Japan adopted a high economic growth policy and developed rapid industrialization since the 1960s. Consequently, Japanese have gotten various positive influences and negative influences. In this paper, we describe various positive influences and also we describe the "real life" of aged persons living alone in depopulated areas as one of the typical negative influences. For the purpose of investigating the actual lives of aged person living alone in depopulated areas, we carried out repeated interviews, research and direct observations of their work and lives in Village A. Village A is located in a mountain area 20 kilometers from Nagano City. The total population of the village was 3,294 in 1993, while it was 6,312 in 1960. The ratio is increasing rapidly year by year. In the village, the number of aged persons over 65 years old living alone, without any family, was 116 in 1994. The highest age is 94 years old. The number is increasing year by year. Through our study, it is made clear that aged persons over 65 years old living alone in the village have to manage everything in their daily lives by themselves to maintain their own safety, while accepting the influences of economic and industrial developments.

Aged↗
PubMed1996

The proportion of free to total prostate specific antigen: a method of detecting prostate carcinoma.

BACKGROUND: Prostate specific antigen (PSA) is the most useful marker for prostate carcinoma (CaP). However, the sensitivity and specificity for PSA are not sufficient for the diagnosis of organ-confined prostate carcinoma. Recent studies have revealed that anti-PSA antibody identifies both PSA complexed to alpha-1-antichymotrypsin and free PSA, whereas anti-gamma-seminoprotein antibody recognizes free PSA exclusively. To enhance the ability of PSA to detect CaP in patients with total PSA levels of 10 ng/mL or lower, we developed the ratio of gamma-seminoprotein and PSA (free/total PSA index). METHODS: We measured free/total PSA indices for 285 patients who had serum PSA levels of 10 ng/mL or lower and who were diagnosed pathologically. RESULTS: Of the 285 patients, 228 had no prostate carcinoma (NC) and 57 had CaP. The mean total PSA level for CaP (5.137 +/- 2.483 ng/mL; mean +/- standard deviation) was significantly greater (P < 0.0001) than that for NC (3.251 +/- 2.129). The mean free/total PSA index for CaP (0.774 +/- 0.468 was significantly lower (P < 0.0001) than that for NC (1.563 +/- 0.938). The sensitivity for the free/total PSA index was similar to that for total PSA (78.9% vs. 75.4%). However, the specificity, positive predictive value, and overall accuracy for the free/total PSA index (75.9%, 45%, and 76.5%, respectively) increased by 15-20% compared with those for total PSA (56.6%, 30.3%, and 60.4%, respectively). CONCLUSIONS: The free/total PSA index improved the specificity of PSA without impairing the sensitivity in detecting CaP among patients with serum PSA levels of 10 ng/mL or lower.

Humans↗
PubMed1996

Laser Spectroscopy of the CCO Radical in the 0.77-μm Region: Analysis of the A(020)kappa3Pi and A3Pii(001) States

The A(020)kappa3Pi-X3Sigma-(000) and A3Pii(001)-X3Sigma-(000) bands of the CCO radical have been investigated by laser spectroscopy with two types of tunable laser system. An analysis was made simultaneously for both the bands to establish line assignments and determine molecular constants for both the A(020) and A(001) states. A coupling constant between these two states was also determined by assuming the interaction to be of Fermi type.

Journal Article↗
PubMed1996

Synthesis and antifungal activity of alkylthio and alkylsulfonyl derivatives of SM-8668.

Triazole analogues which contained alkylthio or alkylsulfonyl groups where synthesized as derivatives of antifungal SM-8668 and estimated for their in vitro and in vivo activity. Derivatives having pentylthio, heptylthio or nonylthio groups showed excellent efficacy against both candidiasis and aspergillosis. Introduction of a hydrophilic group at the end of their alkyl chain made their activity stronger. Especially, 5-hydroxypentylthio and 7-hydroxyheptylthio derivatives showed the strongest antifungal activity.

Alkylation↗
PubMed1996

Long-term evaluation of recombinant human bone morphogenetic protein-2 induced bone formation with a biologic and synthetic delivery system.

The efficacy of microspheres made of polylactic acid polyglycolic acid copolymer mixed with blood clot as a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2) was evaluated and the long term behaviour of rhBMP-2 in rats was studied. Twenty micro grams of rhBMP-2 in 200 microliter carrier (blood coagulum and polylactic acid polyglycolic acid porous microspheres) were implanted subcutaneously over both sides of the chest muscles in 40 5-week-old male Long Evans rats. The control group were implanted with carrier alone. Specimens were retrieved after 3 days and weekly for 9 weeks. Outcome was measured by signs of bone formation on low power radiographs, and signs of bony growth on histological examination. There were no signs of foreign body or inflammatory reactions to the carrier in either group. In the experimental group signs of bone formation had started to appear by the end of the first week, and there was a gradual increase in both radio-opacity and size during the observation period. Histologically the bony growth was beginning to mature by 4 weeks and was fully mature by 7-9 weeks. In contrast there was no sign of cartilage or bone formation in the control group and the carrier had resorbed by 4-6 weeks. It is concluded that rhBMP-2 implanted in a carrier consisting of blood clot and porous microspheres made of polylactic acid polyglycolic acid induces rapid proliferation of mesenchymal cells that lead to formation of cartilage and bone by 7 days which had matured by 9 weeks. rhBMP-2 in this carrier may be useful clinically because of its capacity to induce early formation of bone.

Animals↗
PubMed1996

CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes.

To determine which cytochrome P450 form is involved in the promethazine [10-(2-dimethylaminopropyl) phenothiazine] metabolism, in vitro analysis using human liver microsomes were performed. Promethazine was mainly biotransformed to ring-hydroxylated, S-oxidized and N-demethylated metabolites. The promethazine hydroxylase in human liver microsomes was inhibited by SKF-525A, propranolol, sparteine, quinidine and anti-CYP2D6 serum suggesting involvement of a P450 related to CYP2D6. Lineweaver-Burk plots for the hydroxylation, S-oxidation and N-demethylation indicated that the hydroxylation occurred with a low K(m) value in human liver microsomes. Microsomes from genetically-engineered human B-lymphoblastoid cells expressing CYP2D6 hydroxylated promethazine most efficiently as compared to other P450 forms, indicating that it was the principal P450 responsible for the metabolism of promethazine in human liver microsomes. The inhibition of CYP2D6-catalysed bufuralol 1'-hydroxylase by various histamine H3 antagonists including promethazine suggested that promethazine and some other histamine H1 antagonists could be inhibitors of this P450 in human liver microsomes.

Antibodies↗
PubMed1996

Paraneoplastic pemphigus: report of a case.

A 56-year-old male with chronic lymphocytic leukemia developed extensive erosive mucocutaneous lesions with histologic acantholysis. Immunopathologic studies showed IgG deposition at the intercellular space, C3 deposition at both the intercellular space and the dermo-epidermal junction, and reactivity of the serum to rat urinary bladder epithelium. Autoantibodies in the serum to human epidermal proteins of 210 kD and 190 kD were shown by Western blotting and to proteins of 250 kD, 210 kD, and 190 kD by immunoprecipitation. All these data suggest the diagnosis of paraneoplastic pemphigus. Repeated plasmapheresis resulted in re-epithelialization of the mucocutaneous lesions and reduction in antibody titer from 1:1280 to 1:20. Although this mucocutaneous disease was established as a new autoimmune bullous disease by Anhalt et al. (1990), cases have rarely been reported from Japan. The present patient demonstrates the major characteristics of paraneoplastic pemphigus.

Autoantibodies↗
PubMed1996

Demonstration of antigenic and genotypic variation in Orientia tsutsugamushi which were isolated in Japan, and their classification into type and subtype.

A total of 40 strains of Orientia tsutsugamushi (34 isolates from patients and trombiculid mites in Japan, and 6 prototype strains of antigenic variants) were examined for classification based on the reactivities with type-specific monoclonal antibodies in indirect immunofluorescence tests, and on the restriction fragment length polymorphism of a polymerase chain reaction (PCR)-amplified 56-kilodalton type-specific antigenic protein gene. By these methods, several antigenic and genotypic variants were found among the strains, and these variants were classified into types and further into subtypes. These results suggest that there are many variants in O. tsutsugamushi, and the methods used here seem to be useful for the systematic classification of the numerous variants. A strain which may be a new type distinguishable from those identified previously was also found in this study. Furthermore, variety in the degree of pathogenicity in mice related to type and/or subtype classification were observed.

Animals↗
PubMed1996

No alteration in DNA topoisomerase I gene related to CPT-11 resistance in human lung cancer.

Mutations and reduced expression of DNA topoisomerase I (topo I) gene have been shown to be important in the acquisition of resistance to camptothecin and its analogues in vitro, but their significance has not been verified in vivo. We investigated possible topo I gene mutations and topo I mRNA expression levels in 127 samples obtained from 56 patients with lung tumors, including patients who had developed clinical resistance to topo I inhibitors. No mutations were detected in any of the samples examined and expression levels did not differ significantly between clinically resistant cases and others. However, the topo I mRNA expression level was significantly higher in small cell lung carcinomas than in non-small cell lung carcinomas (P < 0.05). These results suggest that topo I mRNA levels may affect CPT-11 sensitivity in human lung cancer. However, topo I gene mutations and reduced topo I mRNA expression may not be the main mechanism of clinically acquired resistance to camptothecin analogues in vivo.

Adult↗
PubMed1996

Structure-activity relationships of 3-methyl and 3,3-dimethyl analogs of 2-(2,4-difluorophenyl)-3-(omega-substituted alkyl)sulfonyl-1-(1H-1,2,4-triazol-1-yl)-2-propanols.

3-Methyl and 3,3-dimethyl analogs of 2-(2,4-difluorophenyl)-3-(omega-substituted alkyl)sulfonyl-1-(1H-1,2,4-triazol-1-yl)-2-propanols were synthesized and evaluated for their antifungal activities against Candida albicans and Aspergillus fumigatus. The 3,3-dimethyl analogs were found to have more potent activity both in vitro and in vivo than the corresponding 3-mono-methyl analogs. The prophylactic efficacy of the lead compounds against murine systemic candidiasis and aspergillosis was improved significantly by dimethylation of the 3-position.

Animals↗
PubMed1996

Hyperglycemia decreases dehydroepiandrosterone in Japanese male with impaired glucose tolerance and low insulin response.

Recent studies indicate that experimentally induced hyperinsulinemia may reduce serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S). Serum DHEA and DHEA-S decrease in diabetic patients, but the mechanism by which hyperglycemia decreases DHEA and DHEA-S is unknown. In this study, we investigated the effect of hyperglycemia on DHEA and DHEA-S in impaired glucose tolerance (IGT) by means of the 75g-oral glucose tolerance test (OGTT). We selected 30 male IGT patients receiving diet therapy only, whose insulinogenic Index was under 0.3. Oral glucose challenge significantly reduced DHEA (P = 0.0001) and DHEA-S (P < 0.05) at 60 and 120 min after OGTT. Setting the value of DHEA and DHEA-S at time zero as 100%, we calculated the DHEA and DHEA-S values at 60 and 120 min after OGTT as %DHEA(-S) 60 min and %DHEA(-S) 120 min, respectively. DHEA and DHEA-S at time zero showed no correlation with BMI, HbA1c, the sum of insulin values (sigma IRI) or the area under the curve of plasma glucose (AUC). We found decreases in %DHEA 60 min (r = -0.411, P < 0.05), %DHEA-S 60 min (r = -0.508, P < 0.01) and %DHEA-S 120 min (r = -0.393, P < 0.05) as AUC increased, but sigma IRI showed no correlation with %DHEA(-S) 60 min or %DHEA(-S)120 min. We conclude that the depression of DHEA and DHEA-S after OGTT is attributable to hyperglycemia in male Japanese IGT with low insulin response.

Dehydroepiandrosterone↗
PubMed1996

Depression of dehydroepiandrosterone in Japanese diabetic men--comparison between non-insulin-dependent diabetes mellitus and impaired glucose tolerance.

Hyperglycemia is known to reduce dehydroepiandrosterone (DHEA) circulating levels; however, the mechanism by which hyperglycemia decreases DHEA is not elucidated. In this study, serum DHEA and DHEA sulfate (DHEA-S) levels were compared in 50 men with non-insulin-dependent diabetes mellitus (NIDDM) and 50 age-matched men with impaired glucose tolerance (IGT) receiving only diet therapy. Serum concentrations of DHEA and DHEA-S in the NIDDM group were significantly lower than in the IGT group (7.8 and 9.7 nmol/l vs 3.4 and 4.9 mumol/l, respectively; p < 0.01) but there was no significant difference in immunoreactive insulin between the two groups. When the results from both groups were combined, HbA1C was significantly inversely related to DHEA (r = -0.243, p < 0.01) and DHEA-S (r = -0.305, p < 0.01). Immunoreactive insulin showed no correlation with DHEA and DHEA-S. Multiple regression analysis showed that HbA1C was independently negatively related to both DHEA and DHEA-S. We conclude that hyperglycemia may decrease serum DHEA and DHEA-S in Japanese men with NIDDM, but the depression of DHEA(-S) is independent of serum insulin level.

Dehydroepiandrosterone↗
PubMed1996

Magnetic resonance imaging of brain death.

Fifteen patients with clinical diagnosis of brain death were examined by magnetic resonance (MR) imaging. Aortography with intraarterial digital subtraction angiography (IADSA) was also performed in nine patients. MR imaging indications of the flow void phenomenon were evaluated in the cavernous portion of internal carotid artery (ICA) and the middle or anterior cerebral artery, and compared with the IADSA findings. The relative intensities of gray and white matters were also measured. MR imaging showed that flow voids were absent in the ICA in all eight patients in whom non-filling was confirmed by IADSA. In one patient, IADSA demonstrated intracranial flow despite the diagnosis of brain death and the flow void pattern was normal. Serial MR imaging showed disappearance or abnormality of flow voids after brain death in six patients and absence before brain death in one. Spotty flow voids became visible in the unilateral ICA of one case after brain death. Partial residual flow voids may be caused by to-and-fro blood movement which was demonstrated by transcranial Doppler sonography. The normal flow void pattern was seen in none of these patients, therefore absence of flow voids indicates cessation of intracranial blood flow. Proton density and T2-weighted MR images showed dissociated intensity changes between white and gray matters, which were thought to be characteristic of brain death. In conclusion, MR imaging can achieve non-invasive diagnosis of the non-filling phenomenon in patients with brain death.

Adult↗
PubMed1996

[Three cases of lung metastases of renal cell carcinoma treated with a combination of interferon-alpha, 5-fluorouracil and leucovorin].

Three patients with lung metastases of renal cell carcinoma (RCC) were treated with a combination of interferon-alpha, leucovorin and 5-fluorouracil. All patients were male between 60 and 66 years and had been treated by nephrectomy prior to the combination therapy. Interferon-alpha was administered at the dose of 9 x 10(6) IU intramuscularly 3 times/week, leucovorin at 30 mg/m2 per day intravenously (day 1 to 5) and 5-fluorouracil at 500 mg/m2 daily by continuous infusion intravenously (day 1 to 5) followed by weekly bolus therapy. One patient achieved complete response for 17 months and the other two achieved stable disease for 6 and 16 months. Side effects related to this therapy were diarrhea, stomatitis, alopecia, leucocytopenia and thrombocytopenia. Grade 3 stomatitis occurred after the continuous administration of 5-fluorouracil in one patient; he recovered by discontinuation of 5-fluorouracil. Combination therapy with interferon-alpha, leucovolin and 5-fluorouracil might be effective for the treatment of lung metastases of RCC.

Aged↗
PubMed1996

[Ocular metastasis necessitating enucleation of an eyeball after surgery for primary lung cancer].

A 68-year-old man was referred because of an abnormal shadow in the right upper lung field on a chest X-ray film. After the diagnosis of adenocarcinoma of the lung, left upper lobectomy was done. Histologically, adenocarcinoma with foci of squamous cell carcinoma was seen. About 11 months after that operation, he suddenly noticed a decrease in visual acuity on the left side. The fundus of the eye was tested and metastatic choroidal cancer was suspected. To prevent rupture, the eyeball was enucleated. The choroidal tumor appeared to have components of squamous cell carcinoma from primary lung cancer. About 7 months after enucleation of his eyeball, the patient was disease-free with no decrease in his quality of life. As a result of a recent increase in the incidence of lung cancer, it is important to pay attention to ophthalmological tests in patients with primary lung cancer.

Adenocarcinoma↗
PubMed1996

[Effective administration of recombinant granulocyte colony-stimulating factor to prevent granulocytopenia due to combination chemotherapy for testicular germ cell tumors].

A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.

Adult↗