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Biomedical subjects

Y Mano

Publications and source records attributed to Y Mano.

At least 37 records · Page 2Linked to original sources
PubMed2000

Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene.

Clinicopathological and molecular genetic findings on a new Japanese family with oculopharyngeal muscular dystrophy are reported. The family has 54 members, ten of whom are affected (seven male and three female), in 3 generations. Three affected males, one affected female and one unaffected female of seven living siblings in the third generation were examined. Bilateral ptosis developed in the 4th and 5th decades in the three male cases, and in the 7th decade in the female, and this was followed by diplopia, nasal voice, dysphagia and muscle weakness. In addition, severe external ophthalmoplegia, dysphonia, and proximal amyotrophy were prominent in this family. Electromyographs revealed myogenic/neurogenic changes, and computed tomography disclosed selective muscle wasting with fatty replacement, predominantly in the lower extremities. Muscle biopsy in the four affected patients showed variation in fiber size, and the presence of small angulated fibers and occasional rimmed vacuoles. Electron microscopic examination revealed an accumulation of filamentous inclusions in muscle fiber nuclei. DNA analysis identified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11) in the four affected cases examined. All studies were negative in the one unaffected. These results confirm that OPMD is caused by GCG short expansion and provides insights into the genetic mechanisms which may contribute to adult onset myopathy, confined to oculopharyngeal muscles.

Aged↗
PubMed2000

Chondrosarcomatous differentiation in metastatic deposit of serous papillary cystadenocarcinoma.

A rare case of serous papillary cystadenocarcinoma of the ovary showing chondrosarcomatous differentiation in a metastatic deposit late in the clinical course is reported. A 49-year-old female underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for bilateral ovarian tumors. Histological diagnosis was serous papillary cystadenocarcinoma of both ovaries with lymph node metastasis. After six courses of chemotherapy, she was confirmed to be in complete remission following a second laparotomy. Following additional chemotherapy, a third laparotomy disclosed swollen left inguinal lymph nodes. In one of these nodes, approximately 5.0 cm in greatest diameter, the predominant histological features were: chondrosarcoma of the bone and soft tissue, with small foci of serous papillary adenocarcinoma and squamous epithelium. A histological transition between mesenchymal and epithelial areas was identified. Immunohistochemical positivity for broad-spectrum cytokeratin (AE1/AE3), vimentin, epithelial membrane antigen, and S-100 protein was observed in both chondrosarcomatous and epithelial areas. The current evidence may suggest that the chondrosarcomatous differentiation was derived from the metastatic epithelial component.

Cell Differentiation↗
PubMed2000

Fas-mediated cholangiopathy in the murine model of graft versus host disease.

Bile-duct injury observed in hepatic graft versus host disease (GVHD) is regarded as an immune-mediated injury, although its precise mechanism is unclear. However, recent studies have suggested the involvement of Fas-mediated cell death in this immune-mediated cholangiopathy. In this study, we first showed the constitutive expression of Fas receptor by cholangiocytes in situ from normal BALB/c mice, which was upregulated in GVHD mice. Also, we confirmed the Fas protein expression in the isolated cholangiocytes from normal BALB/c mice by immunocytochemistry and immunoblotting. Furthermore, the addition of agonistic Fas antibody-(Jo2)-induced cholangiocyte apoptosis confirmed by DNA-ladder formation and annexin V staining. Cholangiocytes from Fas-deficient mice (MRL lpr/lpr) did not show Jo2-induced apoptosis. Interferon-gamma augmented Fas expression and Fas-mediated cell death, respectively. Following these observations, experimental GVHD was induced by transfer of splenocytes from B10.D2 mice to irradiated (800 rad) BALB/c mice. Liver-infiltrating lymphocytes from the recipient showed dose-dependent cytotoxicity against (51)Cr-labeled cholangiocytes isolated from BALB/c mice. Moreover, the addition of blocking Fas-Fc fusion protein reduced this cytotoxicity to 44.7%. Finally, administration of this Fas-Fc protein to the BALB/c mice, which had been adoptively transferred with splenocytes of B10.D2 mice, prevented the development of hepatic GVHD in vivo. These results showed the involvement of Fas-mediated cell death in cholangiopathy observed in GVHD, and a soluble Fas-Fc protein may have a therapeutic potential for hepatic GVHD.

Animals↗
PubMed2000

Differential effects of nitric oxide on the activity of prostaglandin endoperoxide H synthase-1 and -2 in vascular endothelial cells.

A number of studies have demonstrated that prostacyclin and nitric oxide (NO) regulate blood pressure, blood flow and platelet aggregation. In this paper, we have examined the possible relationship between NO and prostaglandin endoperoxide H synthase (PGHS)-1 and -2 activities in cultured bovine aortic endothelial cells. In the non-activated condition endothelial cells expressed PGHS-1 activity alone. When these cells were pretreated with aspirin to inactivate their PGHS-1 and then activated by serum and phorbol ester (TPA) for 6 h, the cells expressed PGHS-2 activity alone. The PGHS activity was assessed by the generation of 6-ketoprostaglandin F1alpha (6-ketoPGF1alpha), a stable metabolite of prostacyclin, after the treatment of these cells with arachidonic acid. The simultaneous addition of NOC-7, a NO donor, with arachidonic acid did not affect the production of 6-ketoPGF1alpha in PGHS-1 expressed cells, but attenuated it in PGHS-2-expressed cells. The inhibitory effect of NOC-7 on PGHS-2 activity was dose dependent, and the different effects of NOC-7 on the activities of PGHS isozymes were also observed in other NO donors. To confirm the different effect of NO on PGHS isozymes demonstrated in the cultured endothelial cells, we carried out an ex vivo perfusion assay in aorta isolated from normal and lipopolysaccharide (LPS)-treated rats. In the aortae isolated from normal rats, where dominant expression of PGHS-1 was expected, the NO donor did not affect the PGHS activity, while in aortae isolated from LPS-treated rats, where PGHS-2 was dominantly expressed, the NO donor dramatically inhibited the PGHS activity, suggesting that NO suppressed PGHS-2 activity alone. The inhibitory effect of NO on PGHS-2 activity was not mediated by cyclic GMP (cGMP), since (a) methylene blue, an inhibitor of soluble guanylate cyclase did not abolish the inhibitory effect of the NO donor on PGHS-2 activity, and (b) 8-Br-cGMP, a permeable cGMP analogue, failed to mimic the effect of NO donors. These data suggest that the effect of NO on prostacyclin production in endothelial cells was dependent on the expression rate of PGHS-1 and PGHS-2 in the cells.

3T3 Cells↗
PubMed2000

[ADL and actual life styles of all Japanese centenarians as determined by a visitation interview survey].

A visiting interview survey was performed on all centenarians living in Japan to investigate their Activities of Daily Life (ADL). 2,851 centenarians, 92.9% of all subjects completed the interview. They were divided into three groups, good ADL (almost independent in daily life), moderate ADL (almost independent in indoor life), and inferior ADL (bed fast) by the condition of ADL. Some factors of health conditions, family size, frequency of use of public welfare services, and life styles were compared among these three groups. Both the good and the moderate ADL groups accounted for about 20% each, and the inferior ADL group was about 60% of the subjects. The condition of ADL of men was better than that of women. The inferior ADL group showed a significantly higher percentage of chronic diseases. High ratios of cerebral vascular disease and dementia were seen in this group, and many had no teeth. While two thirds of all the centenarians lived at home, over 90% of the good ADL group lived at home. The mode of family size was three including the person oneself. An average of 21% of men and 27% of women used public health welfare services. However 40% of the centenarians in the inferior ADL group used those services. Men had better dietary habits for health than women. The good ADL group showed the most desirable dietary habits among the three groups and had the highest percentage of drinkers and smokers. Men practiced a greater number of ideal habits for longevity than women. Of the ADL groups, centenarians in the good ADL group had the highest percentage of ideal habits for longevity. The centenarians who maintained good ADL had the following characteristics: There were fewer people under medical treatment. They had maintained their own teeth. Almost all of them were living at their home with their family. They had continued good dietary habits and daily life for health and longevity. For the maintenance and improvement of ADL of centenarians, adequate social welfare support in a local area for centenarians and their family seemed to be vital in addition to health management and guidance of healthy life style of the aged.

Activities of Daily Living↗
PubMed1999

Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer.

This retrospective study of ovarian cancer aimed to elucidate whether expression of apoptosis-related proteins, bcl-2, p53 or MDM-2, is associated with resistance to chemotherapy, especially cisplatin (CDDP) based chemotherapy. Expression of bcl-2, p53 and MDM-2 was assessed by immunohistochemical staining of tumour tissues collected at initial surgery prior to treatment with CDDP-based chemotherapy. Among 66 patients with advanced ovarian cancer with measurable tumour following surgery and evaluable for response to chemotherapy, 42, 45 and 56% were positive for bcl-2, p53 and MDM-2, respectively. Significantly fewer tumours of patients who had a complete response to chemotherapy (CR) showed positivity for bcl-2 (2/20) than for p53 (6/20) and MDM-2 (8/20, P < 0.001). There was an inverse correlation between bcl-2 staining and initial response to chemotherapy, especially in serous and endometrial adenocarcinomas. In patients with stage III-IV, serous or endometrioid adenocarcinomas, significantly poorer survival was seen for those with bcl-2 positive tumours than those with negative bcl-2 staining (P = 0.0064). p53 and MDM-2 were not correlated with initial response to chemotherapy. Multivariate analysis revealed that bcl-2, residual tumour size and histology were significant independent prognostic factors. These results suggest that bcl-2 can be a possible predictor of response to chemotherapy and prognosis in patients with advanced ovarian carcinoma.

Antineoplastic Agents↗
PubMed1999

Preoperative determination of several serum tumor markers in patients with primary epithelial ovarian carcinoma.

This study was designed to evaluate the clinical significance of the use of preoperative serum tumor markers in primary epithelial ovarian cancer. Subjects comprised 111 patients with primary epithelial ovarian cancer. Lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), carcinoembryonic antigen (CEA), CA19-9, tissue polypeptide antigen (TPA), CA125 and sialyl TN (STN) serum levels were measured within 7 days before surgery. The tumor marker values were compared with the histopathologic diagnosis. The overall agreement between the test results and the actual outcome was calculated using Student's t test and analysis of variance (ANOVA). Survival curves were constructed according to the Kaplan-Meier method, and differences in survival were assessed with the log-rank test. The prognostic significance of tumor markers for survival was assessed in a multivariate analysis with the Cox proportional hazards model. Of the tumor markers examined in this study, CA125 showed the highest positive rate (77.6%), followed by 63.2% for STN and 55.9% for CA19-9. When the positive rate was compared according to histologic types, serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid adenocarcinoma and clear cell carcinoma showed the highest positive rates for CA125 (94.1%), CA19-9 (76.9%), CA125 (91.7%) and STN (75.0%), respectively. Regarding the distribution of tumor marker levels according to the FIGO stage, LDH, HBDH, TPA and CA125 were correlated with the clinical stage while CEA, CA19-9 and STN did not show any correlation. From analyses of tumor marker levels according to histologic types, all patients with a ratio of CA125 to CEA of >1, 000 had serous cystadenocarcinoma and a ratio of CA125 to CA19-9 of >50 showed serous cystadenocarcinoma or endometrioid adenocarcinoma. On the other hand, all patients with a ratio of LDH or HBDH to CA19-9 of <1.0 had mucinous cystadenocarcinoma or clear cell carcinoma. From univariate analysis, the survival time of patients with elevated CA125, TPA or STN was significantly shorter than that of patients with normal CA125, TPA or STN levels. When the Cox's proportional hazard model was used, we identified age, clinical stage, clear cell carcinoma and serum STN as independent prognostic factors. Serum CA125, TPA or STN may give significant prognostic information in epithelial ovarian carcinoma. It is noteworthy that STN has been identified as an independent prognostic factor and has a high rate of positivity in clear cell carcinoma.

Adenocarcinoma↗
PubMed1999

Gains of 1q21-q22 and 13q12-q14 are potential indicators for resistance to cisplatin-based chemotherapy in ovarian cancer patients.

The mechanism of drug resistance in ovarian cancer is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In our attempt to find characteristic genetic changes in drug-resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers using the comparative genomic hybridization method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy and 14 tumors from patients who had complete response to the chemotherapy. We found gains in chromosomal regions 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators, and regulators of the apoptotic pathway are located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance to cisplatin-based chemotherapy in ovarian cancer patients based on the comparative genomic hybridization analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients before cisplatin-based chemotherapy.

Antineoplastic Agents↗
PubMed1999

Effectiveness of a stress management program for family caregivers of the elderly at home.

The aim of this study is to investigate the efficacy of a structured intervention program in emotional and physical states of family caregivers for elderly. This program is a series of five weekly 90-minute sessions including psycho-education, problem-solving techniques, and relaxation training. Subjects were 56 primary caregivers looking after relatives with dementia or disability at home. Psychological inventories, i.e., Profile of Mood States (POMS) and General Health Questionnaire30 (GHQ-30) were administered at the period of 4 weeks before, pre-, post-intervention, and 2 months after intervention. They were taken a blood sample to measure natural killer (NK) cell activity at the 4 weeks before, pre-, and post-intervention. In the waiting list control group, there was no change in the POMS, the GHQ-30 and NK cell activity. The scores for depression, anger-hostility, tension-anxiety, confusion (POMS), and general illness, social dysfunction, anxiety and dysphoria, suicidal depression (GHQ-30) at the post-intervention decreased significantly when compared with pre-intervention scores. Moreover, there was persistence of the improvement during two months after intervention. Post-intervention NK cell activity was significantly higher than the pre-intervention. These results indicated that our program was effective in managing the stress of family caregivers.

Affect↗
PubMed1998

[Effects of closed-circuit breathing apparatus on respiration and metabolism].

The purpose of the study was to evaluate the influence of hyperoxia and hypercapnia on respiration and metabolism during a steady-state exercise. Thirteen healthy subjects were examined during bicycle-ergometer rides at approximately 50% VO2max under four different breathing gas conditions: 1) room air (control); 2) 40% oxygen; 3) 3% carbon dioxide; 4) 40% oxygen and 3% carbon dioxide. Hyperoxia, with or without hypercapnia, decreased respiratory ventilation and carbon dioxide elimination significantly. On the other hand, oxygen uptake in hyperoxia was not significantly different from that of normoxia. Hypercapnia increased respiratory ventilation more than 30% compared to normocapnia, but it did not change oxygen uptake and carbon dioxide elimination significantly.

Adult↗
PubMed1998

Biochemical and pharmacological characterization of YM-60828, a newly synthesized and orally active inhibitor of human factor Xa.

YM-60828 was found to potently inhibit human factor Xa following oral administration. YM-60828 showed high affinity for factor Xa (Ki = 1.3 nM), but did not affect thrombin (Ki > 100 microM). YM-60828 doubled factor Xa clotting time, prothrombin time (PT) and activated partial thromboplastin time (APTT) at 0.10, 0.21, 0.24 microM, respectively. Importantly, it did not prolong thrombin time at 100 microM. YM-60828 also inhibited factor Xa in the prothrombinase complex with an IC50 value of 7.7 nM. In addition to its anticoagulant activity, YM-60828 inhibited platelet aggregation induced by various agonists (IC50 = 3 to 23 microM). Squirrel monkeys were used to study the ex vivo anticoagulant activity and pharmacokinetic properties of YM-60828. One hour after oral administration at 3 mg/kg, YM-60828 strongly prolonged PT and APTT by 4.8- and 1.9-fold, respectively, and plasma concentration reached 788 +/- 167 ng/ml. Bioavailability was calculated to be 20.3%. These results strongly suggest that YM-60828 will be a valuable orally active and potent anticoagulant agent showing potential antithrombotic activity.

Administration, Oral↗
PubMed1997

Physical effects of negative air ions in a wet sauna.

The physical effects of negative air ions on humans were determined in an experimental sauna room equipped with an ionizer. Thirteen healthy persons took a wet sauna bath (dry bulb temperature 42 degrees C, relative humidity 100%, 10 min exposure) with or without negative air ions. The subjects were not told when they were being exposed to negative air ions. There were no differences in the moods of these persons or changes in their blood pressures between the two saunas. The surface temperatures of the foreheads, hands, and legs in the sauna with negative ions were significantly higher than those in the sauna without ions. The pulse rates and sweat produced in the sauna with ions were significantly higher than those in the sauna without ions. The results suggest that negative ions may amplify the effects on humans of the sauna.

Adult↗
PubMed1997

Kinetic analysis of the disposition of MRK16, an anti-P-glycoprotein monoclonal antibody, in tumors: comparison between in vitro and in vivo disposition.

The kinetics of the disposition of MRK16, an anti-P-glycoprotein monoclonal antibody, was studied in two human colorectal tumor cell lines, HCT-15 and COLO205, whose P-glycoprotein expression is extensive and poor, respectively. In a series of in vitro binding studies, the amount of MRK16 associated with HCT-15 cells at steady state was approximately 40 times greater than that associated with COLO205 cells. In in vivo studies, the disposition of MRK16 was determined in tumor-bearing mice after intravenous administration. The difference in the tumor-to-plasma concentration ratio between the two cell lines was only 2.3-fold at 72 hr after injection. To explain the large difference observed between the in vitro and in vivo results, a series of kinetic simulation studies were performed. By considering the physiological parameters specific for MRK16 (such as permeability-surface area product and the kinetic parameters determined in vitro), the time profiles for the tumor concentration were predicted. The predicted difference in the tumor-to-plasma concentration ratio at 72 hr was calculated to be 2.6-fold, although the permeability-surface area product across the tumor capillary and other physiological parameters were comparable between the two tumor cell lines. The discrepancy between the in vitro and in vivo results was accounted for by the fact that the tumor extracellular fluid concentration at this time point was 13-fold lower in HCT-15 tumors than in COLO205 tumors because of the restricted penetration of MRK16 through the tumor capillaries. This finding suggests that this factor accounts for the in vitro and in vivo difference in the tumor disposition of MRK16.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Effect of tumor necrosis factor alpha on intrahepatic bile duct epithelial cell of rat liver.

Tumor necrosis factor alpha (TNF-alpha), which is primarily produced by macrophages, is a cytokine with various biological activities. Macrophage infiltration often accompanies experimental cholangitis in rats, and chronic cholangitis in humans. The pathophysiologic significance of TNF-alpha in cholangitis is not known. We used cultured, polarized intrahepatic bile duct epithelial cells (IBDECs) from rat liver to determine whether TNF-alpha directly affects the organization of IBDEC monolayers. The addition of recombinant TNF-alpha (rTNF-alpha) to culture media at concentrations from 10 to 200 U/mL lacked cytotoxicity to the IBDECs as judged by trypan blue exclusion and lactate dehydrogenase (LDH) release. rTNF-alpha transiently reduced transepithelial electrical resistance in a dose-dependent manner. During this decrease in resistance, the cellular tight junctions became leaky, allowing horseradish peroxidase (HRP) penetration. rTNF-alpha, at concentrations up to 200 U/mL, did not detach IBDECs from Matrigel, an artificial basement membrane. Electron microscopy and immunohistochemistry for F-actin showed a well-preserved cell structure and organization of IBDECs. Results suggest that TNF-alpha is nontoxic to IBDECs, and that it increases the permeability of tight junctions. TNF-alpha may thus disturb the barrier function of the bile duct.

Animals↗