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Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 127 records · Page 7Linked to original sources

[Xeroderma pigmentosum].

Xeroderma pigmentosum(XP) is an autosomal recessive disease that is characterized by hypersensitivity to sunlight with high incidence of skin cancer and that exhibit variable neurological abnormalities in some groups. There are eight different complementation groups in XP; groups A through G and a variant(XP-V). XP-A through XP-G have a defect in nucleotide excision repair(NER), while XP-V has a defect in translesion DNA synthesis. Almost all of genes for XP have been cloned and their functions in the NER mechanism have been progressively unveiled. In this review, the present knowledge of the pathological features and genetic defects in XP has been discussed.

Animals↗

Placement of interatrial patch suture lines in atrioventricular canal defect repair.

BACKGROUND: The placement of the suture line for interatrial patches in complete and incomplete atrioventricular canal defect repairs varies from surgeon to surgeon despite established anatomic knowledge of the atrioventricular conduction system. This study describes our technique for it and reviews early and long-term outcomes. METHODS: Between 1980 and 1999, 64 infants and children underwent repair of either complete (n=39) or incomplete (n=25) atrioventricular canal defects. Thirty-four of the children (53.1%) had Down's syndrome. The suture line for the interatrial patch originated on either the artificial or native ventricular septal crest and continued leftward above the annulus of the left inferior leaflet of the atrioventricular valve at the posteroinferior corner. All stitches were placed in a horizontal mattress or U-shaped fashion. RESULTS: The operative survival rate was 94% (4 early deaths) and the overall survival rate was 85% (6 late deaths). Atrioventricular heart blocks occurred in none of the patients. Although left-sided atrioventricular function significantly improved with repair, two patients (3.1%) required reoperation for valve replacement because of residual or recurrent insufficiency. CONCLUSIONS: This suture technique for interatrial patches is straightforward and results in a low incidence of heart block and a low re-operation rate for left atrioventricular valve insufficiency.

Cardiac Surgical Procedures↗

[Combined use of ante- and retrograde cardioplegia: limited efficacy in elective coronary artery bypass].

One Hundred and twenty-four patients undergoing elective coronary bypass surgery were retrospectively selected and divided into two groups according to their difference of cardioplegic methods, either antegrade (AC) only (n = 65) or combination of ante- and retrograde (AC + RC) cardioplegic delivery (n = 64). Myocardial blood flow in the right (RV) and left ventricles (LV) was measured during the cardioplegia by a laser Doppler. Peak CPK-MB levels were compared postoperatively between the two groups and more in detail according to extent of coronary obstructive disease. 1) The antegrade administration of cardioplegic solution provided preferential flow to the RV compared to the LV, whereas the retrograde administration resulted in the opposite result (AC; LV 6.9 +/- 4.7, RV: 8.6 +/- 5.3, p < 0.05, RC; LV: 9.0 +/- 4.9, RV: 5.9 +/- 4.6 ml/min/100 g, p < 0.05). This result suggested that the combination of both administrations was meaningful to obtain uniform distribution of cardioplegic solution. 2) The peak CPK-MB, compared in the entire two groups, was slightly low in the combination use (AC; 48 +/- 16, AC + RC; 43 +/- 15 IU/l, p = 0.08), but the clinical meaning did not exist. However, in the severe cases, which involved two of following criteria (left main disease, severe occlusion of left or right coronary), the max CPK-MB level was statistically decreased by the combined use of ante- and retrograde cardioplegia (AC; 50 +/- 16, AC + RC; 40 +/- 12 IU/l, p < 0.05). We concluded that the merit of combined use was limited to the cases with severely extended coronary obstructive disease.

Aged↗

Correlation between the expression of the HNK-1 epitope and cellular invasiveness in prestreak epiblast cells of chick embryos.

During avian gastrulation, certain cells present in the epiblast layer ingress through the basement membrane sealing the basal surface of themselves. Previously we reported that chick prestreak epiblast cells show two different behavioral phenotypes upon reconstituted basement membrane and laminin gel in vitro. Half of the dissociated epiblast cells invade the gel substratum after one-day of culture, whereas the others attach to the gel but do not invade. It is expected that such heterogeneity in the behavior of the epiblast cells reflects some mechanism that sorts the cells into those that will ingress into the blastocoelic cavity and those that will remain in the epiblast layer. To test this hypothesis, we dissociated chick prestreak epiblast cells into single cells, cultured them on the laminin gel, and then stained them with anti-HNK-1 antibody. This antibody binds to an epitope present on half of the prestreak epiblast cells which are thought to differentiate into presumptive mesoendodermal cells. We found that 80% of the invasive epiblast cells were HNK-1-positive whereas 77% of the non-invasive cells were HNK-1 negative. In the case of invasive cells, the edges of the proteolytic holes made by the invasive cells were often stained. These results suggest that the cells expressing the HNK-1 carbohydrate chain are preferentially invasive, and this induces selective ingression of the carrier cells for mesoendodermal differentiation in vivo.

Animals↗

AP-2beta represses D(1A) dopamine receptor gene transcription in neuro2a cells.

Expression of the D(1A) dopamine receptor in brain is restricted to specific neuronal populations. To investigate the mechanism of this selective expression, we localized a silencer upstream of the human D(1A) gene and identified its binding transcription factor in the D(1A)-negative neural cell line Neuro2a. Using deletion CAT analysis, we narrowed this silencer to the region between nucleotides -561 and -532 relative to the CAP site. This 30-bp region, designated D1AS1, contains a sequence homologous to the AP-2 binding site and binds to a factor that also interacts with the AP-2 consensus sequence. In gel supershift assays, this factor is recognized by anti-AP-2beta antibody. Co-transfection of Neuro2a cells with an AP-2beta expression vector repressed the basal CAT activity of D(1A) promoter-reporter plasmids in a D1AS1-dependent manner. RT-PCR analysis indicated that, among AP-2 family members, Neuro2a cells express only AP-2beta. Furthermore, co-transfection of these cells with decoy oligonucleotides corresponding to the D1AS1 sequence de-repressed the D(1A) gene promoter. Unlike in Neuro2a cells, AP-2beta could not repress the D(1A) promoter in the D(1A)-positive neural cell line, NS20Y. In addition, the expression of AP-2beta in different brain regions does not inversely correlate with that of D(1A) dopamine receptor. These observations taken together indicate that AP-2beta is a repressive transcription factor that acts on the D1AS1 silencer of the D(1A) dopamine receptor gene via some cell-specific mechanism(s) in Neuro2a.

Animals↗

Identification of three distinct regions of deletion on the long arm of chromosome 11 in childhood acute lymphoblastic leukemia.

Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identified deletions of chromosome arm 11q. These observations led us to analyse the loss of heterozygosity (LOH) of chromosome arm 11q in 113 primary childhood ALL samples using 14 microsatellite markers. LOH was found in 18 (16%) patients. Detailed examination identified three distinct regions of deletion. The first region is flanked by D11S901 and D11S1391 at 11q22-23 containing the ATM gene. Mutational analysis suggested that the altered gene in this region is not the ATM gene. The second region is flanked by D11S614 and D11S924 at 11q23 containing the MLL gene. The third region is flanked by D11S1356 and D11S614 at 11q23 containing the MLL gene. All the cases with LOH at MLL locus lacked detectable MLL gene rearrangements. In addition, 20 children have been studied both at initial diagnosis and relapse; none of the individuals who relapsed acquired LOH of 11q, suggesting that 11q deletions were infrequently involved in the progression of childhood ALL. Children with 11q LOH had a good response to induction chemotherapy (P=0.015). These data suggest that alterations of putative tumor suppressor genes on 11q are important events in development of childhood ALL. Our map provides important information toward cloning putative tumor suppressor genes associated with childhood ALL.

Child↗

Significance of Steroid Sulfatase Expression in Human Breast Cancer.

The sulfatase pathway has been thought to be a primary means of local production of estrone in human breast cancer tissue. We measured steroid sulfatase (STS) mRNA levels in 97 breast cancers and evaluated its association with disease-free survival. High levels of STS mRNA proved to be a significant predictor of reduced relapse-free survival, both as a continuous variable (log STS mRNA; P = 0.028) and as a dichotomous variable with an optimized cutoff point (P=0.002). In multivariate analysis a high level of STS mRNA was an independent factor for predicting relapse-free survival. These results suggest a putative role of STS in breast cancer growth and metastasis, and administration of sulfatase inhibitors to breast cancer patients with high levels of STS mRNA might be an additional treatment option.

Journal Article↗

Presenilin 1 suppresses the function of c-Jun homodimers via interaction with QM/Jif-1.

Presenilin 1 (PS1) is the causative gene for an autosomal dominant familial Alzheimer's disease (AD) mapped to chromosome 14. Here we show that QM/Jun-interacting factor (Jif)-1, a negative regulator of c-Jun, is a candidate to mediate the function of PS1 in the cell. We screened for proteins that bind to PS1 from a human embryonic brain cDNA library using the two-hybrid method and isolated one clone encoding the QM/Jif-1 gene. The binding of QM/Jif-1 to full-length PS1 was confirmed in vitro by pull-down assay, and in vivo by immunoprecipitation assays with human samples, including AD brains. Immunoelectronmicroscopic analysis showed that QM/Jif-1 and PS1 are colocalized at the endoplasmic reticulum, and the nuclear matrix in human brain neurons. Chloramphenicol acetyltransferase assays in F9 cells showed that PS1 suppresses transactivation by c-Jun/c-Jun but not by c-Jun/c-Fos heterodimers, consistent with the reported function of QM/Jif-1. By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13- acetate (TPA)-responsive element (TRE). PS1 suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1. Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis.

Adult↗

Molecular cloning and characterization of the chicken pro-opiomelanocortin (POMC) gene.

The gene for pro-opiomelanocortin (POMC), a common precursor of melanocortins, lipotropins and beta-endorphin, was isolated in the chicken first among avian species. The chicken POMC gene was found to be a single copy gene and appeared to show the same structural organization as that of other species of different classes. The predicted POMC displayed the highest identity to Xenopus POMC(A) (60. 1%), and consisted of 251 amino acid residues with nine proteolytic cleavage sites, suggesting that it could be processed to give rise to all members of the melanocortin family, including adrenocorticotropic hormone and alpha-, beta- and gamma-melanocyte-stimulating hormones, as well as the other POMC-derived peptides. RT-PCR analysis detected the POMC mRNA in the brain, adrenal gland, gonads, kidney, uropygial gland and adipose tissues, each of which has been demonstrated to express melanocortin receptors. These results suggest that melanocortins act in a paracrine and/or autocrine manner to control a variety of functions both in the brain and in the peripheral tissues in the chicken.

Adrenal Glands↗

Purification and characterization of protease produced by Staphylococcus aureus isolated from a diseased chicken.

A protease produced by Staphylococcus aureus, isolated from a chicken suffering from dermatitis, was purified by successive precipitation with ammonium sulfate, ion-exchange chromatography on Q-Sepharose FF, Sp-Sepharose FF and Mono-Q columns. By Mono-Q column chromatography, two proteases (protease 1 and 2) were obtained. The molecular weights of protease 1 and 2 were estimated at 23.1 and 22.7 kDa, respectively, by SDS-polyacrylamide gel electrophoresis. Their isoelectric points were 5.85 and 5.55, respectively, and they possessed antigenic similarity when examined by the immunoblotting. The N-terminal amino acid sequences of both the proteases were identical (RAQYVNQLKNFKIRETQ). The activities of both the proteases were strongly increased by reducing agents such as L-cysteine and sodium thioglycolate. Their activity was inhibited by thiol protease inhibitors, but was not inhibited by metalloprotease or serine protease inhibitors. From the results, it seems likely that these proteases, produced by S. aureus from diseased chickens, might belong to the thiol protease group.

Amino Acid Sequence↗

Breast Cancer in Two Patients with Poland's Syndrome.

Poland fs syndrome is characterized by a congenital defect of the pectoralis major associated with various types of anomalies of the ipsilateral upper extremity. Furthermore, there have been reports of Poland fs syndrome associated with malignancies such as leukemia, malignant lymphoma, and leiomyosarcoma. We describe two cases of Poland fs syndrome associated with breast cancer. The first patient developed right breast cancer associated with ipsilateral breast hypoplasia, defects of the pectoralis major and minor, and syndactyly. She underwent mastectomy and dissection of the axillary nodes. The second patient had left breast cancer associated with ipsilateral breast hypoplasia, defects of the pectoralis major and minor, and syndactyly. She underwent breast-conserving surgery and dissection of the axillary nodes without irradiation of the breast. Both patients are currently alive and free of disease. Although previously there has been no evidence that links Poland fs syndrome and breast cancer, elucidating the molecularmechanism that causes Poland fs syndrome may further clarify the relationship between Poland fs syndrome and malignancies.

Journal Article↗

Steroid sulfatase expression is an independent predictor of recurrence in human breast cancer.

Steroid sulfatase (STS) hydrolyzes several sulfated steroids such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate. In the present study, we have measured STS mRNA levels in 97 breast cancers by reverse transcription-PCR using a fluorescent primer in the presence of an internal standard RNA and evaluated its association with disease-free and overall survival. The median value was 728.0 amol/ng RNA (range, 0-11,778 amol/ng RNA). Levels were significantly higher in tumors demonstrating lymph node metastasis than in those without nodal involvement (P = 0.033) and in patients who experienced a recurrence during the follow-up period (mean, 40.8 months; median, 39 months) compared with those with no evidence of further disease (mean, 49.2 months; median, 48 months; P = 0.029). No significant associations were found between STS mRNA expression and age, menopausal status, tumor size, histological grade, estrogen receptor status, or postoperative adjuvant therapy. High levels of STS mRNA proved to be a significant predictor of reduced relapse-free survival as a continuous variable (log STS mRNA; P = 0.028). As a dichotomous variable with an optimized cutoff point of 1,240 amol/ng RNA, expression was also associated with a significantly shorter relapse-free survival rate (P = 0.002), but no significant correlation was found between the STS mRNA level and overall survival. Expression was found to be an independent factor for predicting relapse-free survival on multivariate analysis. The results thus support a putative role of STS in breast cancer growth and metastasis.

Adult↗

A possible involvement of melanocortin 3 receptor in the regulation of adrenal gland function in the chicken.

The melanocortin 3 receptor (MC3-R) in the melanocortin receptor family has been identified as a neural receptor subtype mainly expressed in the brain in mammals. We report here the isolation of the chicken gene for MC3-R, CMC3, displaying different tissue distribution from mammalian counterparts. The CMC3 gene was found to be a single copy gene encoding a 325 amino acid protein, sharing 75.3-76.8% identity with mammalian counterparts. When assessed by RT-PCR, the CMC3 mRNA was not detected in the brain but was exclusively expressed in adrenal glands, where Agouti-related protein/Agouti-related transcript (AGRP/ART), a newly identified endogenous antagonist of MC3-R, is expressed in mammals, raising the possibility that the CMC3 plays a role in complicated regulation of the gland function by melanocortins and AGRP/ART in the chicken. Noteworthy, MC1-R gene was found to be a quite unique member of the chicken MC-R family with regard to GC content and codon usage. It may reflect as yet unidentified evolutionary pressure operating specifically on the gene.

Adrenal Glands↗

Four new genotypes of adenovirus type 3 isolated from patients with conjunctivitis in Japan.

Adenovirus type 3 (Ad3) was the most frequently isolated serotype from patients with conjunctivitis during the period from 1989 to 1991 in Japan. All Ad3 strains isolated in 1990 had an identical genotype, Ad3f. However, in 1992, the predominant serotype was replaced by Ad4. The genome type was examined to determine whether genetic changes existed in Ad3 isolates in 1992. Ad3 isolated from 55 patients with acute conjunctivitis during the period from June 1992 to February 1993 in Japan was assessed by genome typing with restriction endonucleases BamH I, Bgl II, Hind III, and Sma I recognizing 6-base-pair sequences. The emergence of four new genotypes of Ad3 was identified; one with a new Bam HI site (one isolate), one with a new Bgl II site (two isolates), one with a new Hind III site (three isolates) and one with a new Sma I site (two isolates). This study demonstrates that the emergence of a new genotype of Ad3 may contribute to the replacement of the predominant serotype associated with adenovirus conjunctivitis in Japan.

Adenovirus Infections, Human↗