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Biomedical subjects

H Shibata

Publications and source records attributed to H Shibata.

At least 109 records · Page 6Linked to original sources
PubMed2000

Orphan receptors COUP-TF and DAX-1 as targets in disordered CYP17 expression in adrenocortical tumors.

CYP17 gene transcription is activated by SF-1 binding to a cyclic AMP-responsive sequence within the promoter region of the gene, and its transcription is inhibited by COUP-TF binding to the sequence. Another orphan receptor, DAX-1, is shown to act as a suppressor of SF-1-mediated transcription. We examined the expression level of these orphan receptors in adrenocortical tumors and compared the results with CYP17 expression. CYP17 was highly expressed in cortisol-producing adenomas, whereas COUP-TF and DAX-1 expression levels were very low. In deoxycorticosterone-producing adenomas, on the other hand, CYP17 expression was extremely low, whereas DAX-1 was highly expressed and SF-1 expression was slightly decreased. In conclusion, the reciprocal expression of CYP17 and the transcriptional repressors COUP-TF and DAX-1 indicates that these orphan receptors have a pathophysiologic role in the excessive hormone production in cortisol- and deoxycorticosterone-producing adrenocortical tumors.

Adrenal Cortex Neoplasms↗
PubMed2000

[Alcohol consumption and change of activity of daily living among the elderly living in an urban community].

Alcohol consumption has both adverse and beneficial effects on survival. We examined the baseline status of alcohol consumption and the changes of instrumental activity of daily living (I-ADL) by a prospective survey for the elderly living in an urban community who were participants in the "Longitudinal and Interdisciplinary Study on Aging by the Tokyo Metropolitan Institute of Gerontology (TMIG-LISA)". Detailed information on alcohol intake was collected during a structured interview. At a baseline survey in 1991, 1) the frequency of current drinkers decreased lineally by age. 2) the most popular alcohol beverage was beer for both sexes and average ethanol intake per day were 41 (10-45) g in men and 24 (8-28) g in women. Current drinkers had significantly stronger grip strength, higher velocity in maximum walking and higher score on the TMIG Index of Competence, designed to measure the higher-level competence in elderly community residents. After 4 years follow-up, in 1995, 73.3 percent of the participants completed the examination. They were classified into five categories as "current drinkers", "lifetime abstainers", "beginning to drink during follow-up period", "quit drinking during follow-up period" and "quit drinking at baseline". The decline of I-ADL was significantly greater among the elderly who "quit drinking during follow-up period" than "current drinkers". Further "current drinkers" had significantly lower decline of I-ADL than "lifetime abstainers". Our findings show beneficial effects of moderate alcohol intake in the maintenance of a higher level of competence in the elderly living in a community.

Activities of Daily Living↗
PubMed2000

[Behavioral competence among community dwelling older people with disability in basic activities of daily living].

This study observed the status of independence in behavioral competence among older people who have any disability in basic activities of daily living (BADL) living in a rural community in Japan. Study participants (N = 76) who were regarded as bedridden were surveyed by means of a questionnaire in July to August 1996. The independence variables were age, sex, BADL status, hearing impairment, visual impairment, history of stroke, and cognitive impairment. The dependent variable was each item of the Tokyo Metropolitan Institute of Gerontology (TMIG) Index of Competence, which is a multidimensional 13-item index of behavioral competence. Percentages of subjects who were independent in each item of the TMIG Index of Competence varied from 1% to 36%. Multiple logistic regression analyses revealed that BADL status was independently associated with independence in using a telephone, being interested in news stories or programs dealing with health, being called on for advice, and initiating conversations with young people, after adjustment for age, sex, hearing impairment, visual impairment, history of stroke, and cognitive impairment. These findings suggest that programs for preventing decline in behavioral competence of older people with BADL disability might be important as well as physical therapy for them.

Activities of Daily Living↗
PubMed2000

Value of DNA ploidy and S-phase fraction as prognostic factors in stage III cutaneous melanoma.

OBJECTIVE: To determine the prognostic value of flow cytometric analysis (S-phase fraction and DNA index) performed on lymph-node metastases of patients with stage III melanoma. DESIGN: A retrospective chart review with flow cytometric analysis of paraffin-embedded tissues. SETTING: A university teaching hospital. PATIENTS: Among 332 patients with cutaneous melanoma, 33 with stage III were identified. Distant metastases developed in 16 patients; 17 had no further recurrence. Charts were reviewed to obtain clinicopathologic parameters such as sex, age, location of the primary tumour, histologic features, presence or absence of ulceration, and Clark's and Breslow's levels. INTERVENTION: DNA ploidy and S-phase fraction were determined on the paraffin-embedded nodes. MAIN OUTCOME MEASURES: The groups with or without recurrence were compared in terms of disease-free survival (DFS) and overall survival (OS). These survival parameters were correlated with DNA ploidy and S-phase fraction. RESULTS: By univariate analysis, clinicopathologic factors did not predict OS. A higher Clark's level of invasion and more than 3 positive lymph nodes were associated with shorter DFS (p < 0.05). Tumour thickness and S-phase fraction did not correlate with either DFS or OS. Patients with diploid lymph-node metastases had an 87% 12-month survival compared with 41% for those with aneuploid tumours. CONCLUSIONS: DNA ploidy may be used as a prognostic index in patients with lymph-node metastases. This could be particularly useful in the context of sentinel lymph-node mapping by which more patients are being identified with single microscopic lymph-node involvement.

Analysis of Variance↗
PubMed2000

[Characteristics of dropouts and participants in a twelve-year longitudinal research of Japanese elderly].

PURPOSES: The attrition of respondents in panel studies of the elderly can create bias in data analysis. The purposes of this study are two fold; 1) to examine characteristics of dropouts, from a particular panel lost except due to natural attrition (by death) by comparison with continuing participants in that wave, and 2) to assess representativeness of those actually continuing in a particular panel by comparison with those eligible for inclusion in that wave. Only those who died were excluded from the group of respondents at the baseline survey because they constituted natural attrition in this longitudinal survey. METHOD: At baseline (1987), 2,200 individuals age 60+ from 3,288 national representative sample were interviewed. Non-response status to three contacts (1990, 1993, 1996) with the panel was examined in relation to variables included in the baseline interview. A number of characteristics of demographic background, health, life-style, and social relations obtained in the baseline survey (1987) were compared between those re-interviewed in a particular panel and subjects lost through unnatural attrition until that wave. To study the influence of unnatural attrition on variable distributions and each related factors of two health indicators (self-rated health and depressive symptoms), baseline responses were compared between those re-interviewed in a particular panel and all who were eligible to respond in that wave. RESULTS: 1) Dropouts lost to each wave were significantly older and had a lower level of social participation than persons remaining in that wave. Significant differences in health and life-style variables appeared between dropouts lost and continuing participants until third or later waves. 2) Continuing participants in a particular panel were likely to be younger, to be more physically, mentally, or socially healthy than those eligible to respond in the wave. Each related factors of two health indicators were almost same between those re-interviewed in a particular panel and those eligible to respond in that wave. CONCLUSION: Dropouts in longitudinal research were found to appear nonrandomly. While distributions of age and health indicators in those re-interviewed were influenced by respondent attrition, related factors of health indicators may be free of bias that can be created by it.

Age Factors↗
PubMed2000

Substituted 3-phenylsulfonylquinazoline-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase.

A series of 3-phenylsulfonylquinazoline-2,4-dione derivatives have been synthesized and evaluated for their ability to inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The phenyl moiety of quinazoline participates in a hydrophobic interaction where an optimum size is required. In this moiety, 7-chloroquinazoline is the best moiety for inhibiting chymase, chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrophobic electron-withdrawing groups at the 4-position potentiated the activity. Anthranil moiety also enhanced the activity. Pyridylmethyl and N-pyridylacetamide at the 1-position gave an IC50 in the order of 10(-8)M. Molecular modeling studies on the interaction of 7-chloro-3-(4-chlorophenylsulfonyl) quinazoline-2,4(1H, 3H)-dione (4) with the active site of human heart chymase suggested that the phenyl moiety of quinazoline interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, the moiety at the 1-position locates in the S2-S3 subsites and the 4-carbonyl and 3-sulfonyl group interact with the oxyanion hole and the His57 side-chain of chymase, respectively.

Chymases↗
PubMed2000

Functional evaluation of p53 and PTEN gene mutations in gliomas.

We screened mutations of two major tumor suppressor genes, p53 and PTEN, in 66 human brain tumors using a yeast-based functional assay and cDNA-based direct sequencing, respectively. The frequency of p53 mutations was 28.8% (19 of 66) and was higher in anaplastic astrocytoma (9 of 14, 64.3%,) than in glioblastoma multiforme (GBM; 7 of 27, 25.9%,), supporting previous speculation that there are at least two genetic pathways leading to GBM, a de novo pathway without p53 mutation and a "progressive" pathway with p53 mutation. PTEN mutation was observed in 8 of 64 tumors (12.5%), mainly GBMs (7 of 26, 26.9%), both with and without p53 mutation. These results suggest that mutation of the PTEN gene is a later event than that of the p53 gene in glioma progression and is associated with both the genetic pathways. All of the detected PTEN missense mutations and an in-frame small deletion inactivated PTEN phosphoinositide phosphatase activity in vitro. Because the tumors containing PTEN mutations also showed loss of heterozygosity in the chromosome 10q23 region flanking the PTEN gene, our data clearly indicate that inactivation of both PTEN alleles occurs in a subset of high-grade gliomas, therefore confirming the previous idea that PTEN acts as a tumor suppressor gene.

Adolescent↗
PubMed2000

[Characteristics of the elderly transferees in a resort area from metropolitan areas: comparison to the elderly in a rural non-resort area and in a metropolitan area].

PURPOSES: This study examines characteristics of elderly transferees in a resort area who moved from metropolitan areas, comparing them to two groups: elderly living in a rural non-resort area and elderly living in a metropolitan area. METHODS: Both the resort area and the non-resort area were located in Ito, Shizuoka Prefecture. The metropolitan area was in Nerima ward, Tokyo. From each area, 400, 400 and 600 random samples aged 65 and over were selected for face-to-face interview surveys separately. The number of the effective samples in each of the three groups was 176 (excluding transferees from rural area), 267, and 423, respectively. Characteristics were measured from five aspects; demographic aspects, health status, health habits, social networks, and social support. RESULTS: Almost indicators of health status did not show significant differences between respondents living in the resort area and each of the remaining two groups. Respondents living in the resort area were significantly less likely to attend community groups than those living in non-resort rural areas, and they also were less likely to have a home physician or persons who provided care. CONCLUSIONS: Transferees living in a resort area who moved from metropolitan areas may have extra health and welfare needs, compared to the elderly living in non-resort rural areas or the elderly living in metropolitan areas. Possible reasons for these extra needs may be relate to their urbanized life style, lower amount of medical resources in a rural area, or lower level of informal support possessed within a household.

Aged↗
PubMed2000

[Influence of estrogen replacement therapies such as premarin for the measurement of estradiol].

To investigate problems associated with the measurement of estradiol 17 beta(E2) in hormone replacement therapy(HRT), five commercial immunoassay methods(Coat-A-Count E2 as the conventional method; Immulyze E2, Immuno 1 E2, Vitros E2, and HRT-E2 as the comparative methods) were used to assay E2 concentrations. Samples were obtained from 21 women who had been receiving HRT, 99 nonmedicated women, and 10 healthy men volunteers. No significant difference between the Coat-A-Count E2 and the comparative method was observed in the nonmedicated women. However, we found that the serum E2 concentration from patients taking Premarin showed a large discrepancy between the Coat-A-Count E2 method, which showed considerably higher values, and the other four methods. The reason for our conflicting results from patients with HRT was probably because the Coat-A-Count E2 detected circulating estrogen conjugates. The experimental addition of Premarin for the in vitro cross-reactivity was done. The cross-reactivity was low because a similar E2 steroid exists independently. However, the E2 serum value of the ten male volunteers after taking Premarin was elevated. The reason for this result was due to the high cross-reactivity between anti E2 polyclonal antibody and the various metabolic products of Premarin. In conclusion, the influence of Premarin should be taken into consideration when measuring estradiol concentration to monitor HRT.

Biomarkers↗
PubMed2000

[The impact of relocation on well-being of the elderly].

OBJECTIVE: This study examined direct and indirect effects, mediated by social contact, of residential relocation on well-being of the elderly. METHODS: We used longitudinal data of a national representative sample of individual aged 60 years and over (N = 1,474). The initial survey was conducted in 1987, and the follow-up survey was conducted three years later. Well-being was measured with the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Life Satisfaction Index A (LSIA). Social contacts were measured in terms of frequency of contacts with relatives, friends and neighbors, as well as frequency of social participation. RESULTS: Relocation had a positive direct effect on well-being, assessed by both CES-D and LSIA, but a negative indirect effect mediated by decline of social contacts. CONCLUSION: Our results suggest that residential relocation indirectly has a detrimental effect on well-being of the elderly through decline in social contacts, though it may directly improve well-being of the elderly.

Aged↗
PubMed2000

[Factors related to attitudes toward medical facility choice by the elderly why do the elderly favor large hospitals?].

PURPOSE: Factors associated with large hospital choice by the elderly were examined. Possible factors were divided among three domains; predisposing factors, need factors, and enabling or restraining factors. Both direct effects and interactive effects of those factors on choice attitudes were examined. METHODS: The data were obtained from a face-to-face interview survey with a national sample aged 60 and over. The survey was conducted in 1996, and 2,447 elderly were interviewed. Choice attitudes were measured in two ways: 1) preference to use a large hospital regardless of disease, and 2) complaint of not being able to use a large hospital without an referral system by a clinic. Predisposing factors were age, sex and educational attainment. Need factors were assessed in terms of activities of daily living (ADL) and number of illnesses. Enabling or restraining factors included attitudes toward medical care, accessibility of medical facilities, home doctor existence at a clinic, and labor force participation. RESULTS: 18.5 percent of respondents reported a preference for large hospitals regardless of disease, and 51.3 percent had complaints about the referral system. Respondents with a higher number of illnesses were more likely to report a preference for use of a large hospital, regardless of the type of disease, and respondents with low ADL had more complaints about the referral system than those with higt ADL. The group who employed high technology as a criteria in choosing medical facilities, did not have a home doctor at a clinic, and had good access only to a large hospital, reported a strong preference for use of a large hospital regardless of disease type, and they also complained about the referral system. Regarding preference, an interactive effect between the number of illnesses and the existence of home doctor at a clinic was observed. CONCLUSION: Existence of a home doctor in a clinic, attitudes toward medical care, and accessibility to medical facilities might have direct effects on choice of a large hospital, and only the existence of a home doctor at a clinic might have a strong influence decreasing this preference among the elderly with a higher number of illnesses.

Aged↗
PubMed1999

Interaction of PKN with a neuron-specific basic helix-loop-helix transcription factor, NDRF/NeuroD2.

By the yeast two-hybrid screening of a human brain cDNA library with the amino-terminal regulatory region of PKN as a bait, a clone encoding a neuron-specific basic Helix-Loop-Helix (bHLH) transcription factor, NDRF/NeuroD2 was isolated. NDRF/NeuroD2 was co-precipitated with PKN from the lysate of COS-7 cells transfected with both expression constructs for NDRF/NeuroD2 and PKN. In vitro binding studies using the deletion mutants of NDRF/NeuroD2 synthesized in a rabbit reticulocyte lysate indicated that the internal region containing the bHLH domain of NDRF/NeuroD2 was necessary and sufficient for the interaction with PKN. In addition, recombinant NDRF/NeuroD2 purified from Escherichia coli could bind PKN, suggesting the direct interaction between NDRF/NeuroD2 and PKN. Transient transfection assays using P19 cells revealed that expression of NDRF/NeuroD2 increased the transactivation of the rat insulin promoter element 3 (RIPE3) enhancer up to approximately 12-fold and that co-expression of catalytically active form of PKN, but not kinase-deficient derivative, resulted in a further threefold increase of NDRF/NeuroD2-mediated transcription. These findings suggest that PKN may contribute to transcriptional responses through the post-translational modification of the NDRF/NeuroD2-dependent transcriptional machinery.

Animals↗
PubMed1999

Recurrent cerebral infarctions and del(10)(p14p15.1) de novo in HDR (hypoparathyroidism, sensorineural deafness, renal dysplasia) syndrome.

We report on a Japanese boy with HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia) and recurrent cerebral infarctions in the basal ganglia. The patient experienced cerebral infarctions four times between age 7 months and age 20 months. Chromosome analysis of the patient demonstrated a 46,XY, del(10)(p14p15.1) de novo. This suggests that the putative gene responsible for HDR syndrome is located at 10p14-p15.1.

Adult↗
PubMed1999

Detection and cloning of an X-linked locus associated with a NotI site that is not methylated on mouse inactivated X chromosome by the RLGS-M method.

In looking for genes that escape X chromosome inactivation, we scanned the methylation status of genomic DNA from XX, X0, and XY mice using the method of restriction landmark genomic scanning using methylation-sensitive endonuclease. We detected and cloned a candidate locus and identified the Orf1 gene. Orf1 has sequence similarities to the B2 repetitive element and human CXORF4 (formerly called EXLM1), which escapes X inactivation. The B2 element spans the 3' terminus of the ORF and the 3' UTR of Orf1. The Orf1 gene encompasses 18.5 kb of genomic DNA including 11 exons and 10 introns. Taking advantage of genomic polymorphisms present between MSM and C3H/He, we showed that murine Orf1 is mapped to the proximal region of the X chromosome. Despite the unmethylation of the NotI site, Orf1 is subject to X inactivation.

Amino Acid Sequence↗
PubMed1999

Identification and characterization of PKNbeta, a novel isoform of protein kinase PKN: expression and arachidonic acid dependency are different from those of PKNalpha.

The cDNA clone encoding a novel isoform of protein kinase PKN, termed PKNbeta, was isolated from a HeLa cDNA library. PKNbeta had high sequence homology with PKNalpha, originally isolated PKN, especially in the repeats of charged amino acid-rich region with leucine-zipper like sequences (CZ region/HR1), in the carboxyl-terminal catalytic domain, and in approximately 130 amino acid stretch (D region/HR2), located between CZ region/HR1 and the catalytic domain. However, the amino acid sequence of PKNbeta differed from that of PKNalpha in the region immediately amino-terminal to the catalytic domain, which contained two distinct proline-rich sequences consistent with the class II consensus sequence, PXXPXR, for binding to SH3 domain. Distribution of PKNbeta differed from that of PKNalpha in the following two respects: (1) Northern blotting indicated that PKNbeta mRNA could not be detected in human adult tissues, but was expressed abundantly in human cancer cell lines; (2) immunochemical analysis indicated that PKNbeta localized in nucleus and perinuclear Golgi apparatus, and was almost absent in cytoplasmic region in NIH3T3 cells. Recombinant PKNbeta expressed in COS7 cells displayed autophosphorylation and peptide kinase activity, but was found to be significantly less responsive to arachidonic acid than PKNalpha. The identification of this novel isoform underscores the diversity of PKN signaling pathway.

Adenosine Triphosphate↗
PubMed1999

Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus.

A novel 450-kDa coiled-coil protein, CG-NAP (centrosome and Golgi localized PKN-associated protein), was identified as a protein that interacted with the regulatory region of the protein kinase PKN, having a catalytic domain homologous to that of protein kinase C. CG-NAP contains two sets of putative RII (regulatory subunit of protein kinase A)-binding motif. Indeed, CG-NAP tightly bound to RIIalpha in HeLa cells. Furthermore, CG-NAP was coimmunoprecipitated with the catalytic subunit of protein phosphatase 2A (PP2A), when one of the B subunit of PP2A (PR130) was exogenously expressed in COS7 cells. CG-NAP also interacted with the catalytic subunit of protein phosphatase 1 in HeLa cells. Immunofluorescence analysis of HeLa cells revealed that CG-NAP was localized to centrosome throughout the cell cycle, the midbody at telophase, and the Golgi apparatus at interphase, where a certain population of PKN and RIIalpha were found to be accumulated. These data indicate that CG-NAP serves as a novel scaffolding protein that assembles several protein kinases and phosphatases on centrosome and the Golgi apparatus, where physiological events, such as cell cycle progression and intracellular membrane traffic, may be regulated by phosphorylation state of specific protein substrates.

A Kinase Anchor Proteins↗