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Biomedical subjects

Y Mano

Publications and source records attributed to Y Mano.

At least 19 recordsLinked to original sources
PubMed2001

Splenomegaly induced by recombinant human granulocyte-colony stimulating factor in rats.

Spontaneous ruptures of the spleen have been observed in donors and patients with malignancy during mobilization of peripheral blood stem cells. Thus, we investigated the morphological and histological alteration of the spleen, and mRNA expression levels and activities of the DNA-synthesizing enzymes thymidylate synthase (TS) and thymidine kinase (TK) in the splenic cells, of rats treated with recombinant human granulocyte-colony stimulating factor (rhG-CSF). Daily injections of rhG-CSF for 5 or 7 days slightly enhanced the splenic weight. Single or 3-day treatment with rhG-CSF markedly enhanced the number of granulocytes in peripheral blood. Expression levels of TS and TK mRNA in the splenic cells were significantly increased 6 hours after rhG-CSF treatment. Early expression of TS and TK mRNA in the splenic cells may indicate a reseeding of hematopoietic cells from the bone marrow. Daily injections with rhG-CSF enhanced the TS and TK activities in the splenic cells. As continuous elevations of DNA-synthesizing enzyme activity and spleno-megaly are suggestive of a possible splenic rupture, the monitoring of peripheral granulocytes and splenic size is necessary during the rhG-CSF treatment.

Animals↗
PubMed2001

Primary biliary cirrhosis with antibody against carbonic anhydrase II associates with distinct immunological backgrounds.

Objective: a part of patients with primary biliary cirrhosis (PBC) has anti-human carbonic anhydrase II (CA II) autoantibodies, although several contradictional reports followed. Since immunization of mice with CA II results in cholangitis in a susceptible strain, PBC with anti-CA II antibody may have distinct clinical features. Thus, we tested the sera of patients with PBC for anti-CA II antibodies and compared clinical characteristics of PBC patients with and without anti-CA II antibodies in Japanese patients. Methods: anti-CA II antibodies were detected in nine of 50 (18%) PBC patients by immunoblotting. The evaluation of these patients included various clinical parameters, autoantibodies, and immunological backgrounds. Results: the levels of serum liver tests and the prevalence of serum anti-mitochondrial antibody (77.8 vs. 92.7%) were not different between the patients with and without anti-CA II antibody. However, the prevalence of anti-nuclear antibody (ANA) was significantly higher in the patients with anti-CA II antibody than that in the patients without anti-CA II antibody (66.7 vs. 25.6%, P=0.044), although their mean titers were not statistically different. Association of Sjøgren's syndrome tended to be more frequent in the patients with anti-CA II antibody than those without it (33.3 vs. 14.6%, P=0.327). Studies of HLA class I allotype revealed that three of five (60.0%) patients with anti-CA II antibodies and one patients from 34 (3.0%) patients without anti-CA II antibodies had HLA B51 allotype; the difference in the prevalence of this allotype was significant (P=0.004, Pc=0.01), and the prevalence of other HLA class I and HLA DR allotypes was similar between the patients with and those without anti-CA II antibody. Administration of ursodeoxycholic acid (600 mg per day) was accompanied by change in liver tests in a similar way between the two patient groups. Conclusions: These results suggest that, although clinical features are not distinctive, PBC patients with anti-CA II antibody may have a genetic background, which may contribute to a susceptibility to immune-mediated cholangitis.

Journal Article↗
PubMed2001

A mitochondrial encephalo-myo-neuropathy with a nucleotide position 3271 (T-C) point mutation in the mitochondrial DNA.

We report three members of a family, who exhibited a phenotype similar to 'myoclonus epilepsy with ragged-red fibers' but had a genotype usually associated with 'mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes'. The patients, a 48-year-old female, and her two sons, aged 21 and 19 respectively, presented with photo-reactive syncopal episodes, disturbances of gait and writing, dysarthria and finger tremor since the 3rd and 2nd decade of life, respectively, that were accompanied also by numbness and weakness of the extremities. Subsequently, cerebellar ataxia and myoclonus were also noted. Electromyography revealed both myogenic and neurogenic muscular changes, and nerve conduction studies demonstrated a sensory-motor neuropathy. Biopsy showed ragged-red fibers with strongly stained SDH-positive vessels in skeletal muscles, and a marked loss of myelinated fibers of the sural nerves. Mitochondrial (mt) DNA analyses of peripheral blood, muscles and nerves revealed that all members had a heteroplasmic np3271 (T-C) point mutation in the mitochondrial tRNA-Leu gene (UUR). This family is unique, in that all patients presented with a myoclonus epilepsy with ragged-red fibers-like phenotype and had a distinctive peripheral neuropathy, while the detected mtDNA 327l (T-C) mutation has been reported to date only in rare cases of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes

Adult↗
PubMed2001

Cerebral palsy in adults: Independent effects of muscle strength and muscle tone.

OBJECTIVE: To investigate clinical characteristics and their contribution to activities of daily living (ADLs) in adults with cerebral palsy (CP). DESIGN: Descriptions of the clinical features of medical disorders; survey. SETTING: Rehabilitation counseling center in Japan. PATIENTS: A case series of 256 patients (140 men, 116 women; mean age, 31.6yr; range, 17-83yr) admitted to a rehabilitation center from January 1995 to December 1997. MAIN OUTCOME MEASURES: Characteristics investigated included severity of mental retardation, topography of motor deficits, motor power by manual muscle testing, muscle tone rated by using the muscle tone scale, deformity, sensory disturbance, and pain. ADLs were evaluated with the Barthel Index. RESULTS: Patients showed severe impairment in terms of the Ashworth scale for grading spasticity and deformity, and moderate impairment on manual muscle testing. ADLs were influenced significantly by topography of motor deficits, manual muscle test scores, and muscle tone scale assessment (p <.0001). The muscle tone scale findings showed a significant correlation with deformity (p <.0001), but did not correlate with manual muscle testing. ADLs were affected by muscle power and muscle tone independently. CONCLUSION: Adults with CP showed markedly increased muscle tone and moderate muscle weakness. These 2 factors did not correlate with each other, and were independently responsible for worse ADLs.

Activities of Daily Living↗
PubMed2001

Construction of a genetic map of barley (Hordeum vulgare L.) cross 'Azumamugi' x 'Kanto Nakate Gold' using a simple and efficient amplified fragment-length polymorphism system.

We have devised a simple and efficient amplified fragment-length polymorphism (AFLP) system consisting of small slab gels, a discontinuous buffer system, and silver staining. Using this system, a single worker developed a barley map with 227 polymorphic fragments in 2 months. As a mapping population, 99 recombinant inbred lines of barley cultivars 'Azumamugi' x 'Kanto Nakate Gold' were used. Most of the 227 AFLP fragments showed a Mendelian segregation ratio of 1:1, and all were assigned to the seven barley chromosomes. Thus, these fragments are useful as molecular markers. They were integrated with 40 previously characterized sequence-tagged sites, 3 isozymes, and 2 morphological markers to construct an integrated map. The resulting map covered 925.6 cM with 272 markers (detecting 150 loci) at an average interval of 6.5 cM/locus. This system greatly simplifies map construction.

Chromosome Mapping↗
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↗