Search PubMed⌕ Search

Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 163 records · Page 9Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

L-tryptophan-kynurenine pathway metabolite 3-hydroxyanthranilic acid induces apoptosis in macrophage-derived cells under pathophysiological conditions.

Accumulation of L-kynurenine and 3-hydroxyanthranilic acid (3HAA) occurs in the monocyte-derived cells following immune stimulation, and may derive from L-tryptophan following induction of indoleamine-2,3-dioxygenase. In the present study, we evaluate the possibility that 3HAA acts as an endogenous inducer of monocyte/macrophage apoptosis. Supplementation with 200 microM of 3HAA, but not other L-tryptophan metabolites tested, significantly increased the number of apoptotic cells in both THP-1 and U937 cells. Catalase, superoxide dismutase and manganese ions markedly enhanced apoptosis in the presence of 3HAA in these cells. The present results suggest that 3HAA induces the macrophage/monocyte apoptosis under certain conditions, which may be relevant to pathophysiology of inflammatory conditions.

3-Hydroxyanthranilic Acid↗
PubMed1999

Disease patterns of the homeless in Tokyo.

In recent years, homelessness has been recognized as a growing urban social problem in various countries throughout the world. The health problems of the homeless are considerable. The purpose of this study was to elicit, with sociodemographic profiles, the disease patterns among Tokyo's homeless. The subjects were 1,938 men who stayed at a welfare institution from 1992 to 1996. Diagnosed diseases/injuries and sociodemographic profiles were analyzed. The disease patterns of the homeless were compared to those of the male general population. Of the subjects, 8.3% were admitted to the hospital; 64.0% received outpatient care. Their observed morbidity rates by disease category were greater than those of the male general population in both Japan and Tokyo. Comorbidity of alcoholic psychosis/alcohol-dependent syndrome to both liver disease and pulmonary tuberculosis were greater than the average (P < .01). Construction work brought a higher risk of pulmonary tuberculosis (odds ratio = 2.0) and dorsopathies (odds ratio = 1.4) than did other jobs (P < .05). Disease patterns among the homeless in Tokyo were characterized by alcoholic psychosis/alcohol-dependence syndrome; liver disease; pulmonary tuberculosis; diabetes mellitus; fractures, dislocations, sprains, strains; hypertension; and cerebrovascular disease. Although the sociodemographic backgrounds of Tokyo's homeless have become more diverse, the principal occupation of the homeless was unskilled daily construction work, which underlay the characteristics of their disease patterns.

Adult↗
PubMed1999

The surgical treatment of fixed subaortic stenosis: a clinical experience in Japan.

We report herein the results of a retrospective study conducted on ten consecutive Japanese patients who underwent successful surgical relief of fixed subaortic stenosis between 1972 and 1994 at ages ranging from 8 months to 21 years, and followed for 3.6 years and 26 years. Associated cardiovascular defects were present in six patients, two had a history of infective endocarditis, a discrete fibrous ring was found in nine patients, and a redundant abnormal sheet was found in one. A stenotic structure was removed in nine patients and incised in one, while myotomy was additionally performed in one. There were no early complications or deaths. Cardiac catheterization revealed a significant decrease in the peak systolic pressure gradient from 84+/-22 mm Hg preoperatively to 32+/-22 mm Hg postoperatively (P = 0.0017). Reoperation of an aortic valve replacement with or without valvular annulus enlargement was required in four patients because of a small annulus with aortic insufficiency or infective endocarditis. Infective endocarditis was a major cause of late mortality (n = 1) and morbidity (n = 1), but the remaining eight patients have been asymptomatic. Thus, although this lesion is relatively rare in Japan, the typical discrete type may be more common than previously believed. While a relief operation is associated with low early mortality, the palliative aspect regarding pathology of the aortic valve should not be underestimated, including poor growth of the valve annulus, deterioration of aortic insufficiency, and infective endocarditis. The most appropriate operative procedure for reoperation remains to be evolved.

Adolescent↗
PubMed1999

Mitral valve replacement in patients younger than 6 years of age.

UNLABELLED: We present our experience in mitral valve replacement (including left-sided tricuspid valve in corrected transposition) in patients younger than 6 years of age. The long term results were examined with special focus on re-replacement of the valve. Between 1974 and 1995, we performed mitral valve replacement in 14 patients younger than 6 years of age, with no operative mortality. There were 3 late deaths, caused by endocarditis, valve thrombosis, and congestive heart failure, respectively. The five-year-survival rate after primary replacement was 85%, and the ten-year-survival rate was 75%, using Kaplan-Meier analysis. Ten patients (11 occasions) required repeated mitral valve replacements at 2 months to 17 years after the original replacement. The indication for the second or third mitral valve replacement was paravalvular leakage (2 patients), valve thrombosis (1 patient), degeneration in the porcine prosthesis (3 patients), and patient outgrowth of the original small prosthesis (5 patients). Again there was no operative mortality. One patient who suffered from multiple occasions of valve thrombosis died at two years after the second replacement. All patients who had outgrown the prosthetic valve received larger prosthesis at the second replacement than at the primary replacement. The actuarial percentage of freedom from valve-related events at 3 years, 5 years, and at 10 years, was 50%, 37%, and 8%, respectively. CONCLUSIONS: Mitral valve replacement in patients younger than 6 years of age can be performed relatively safely, but meticulous follow-up and appropriate decision making for re-replacement is mandatory for the long-term survival of these patients.

Child↗
PubMed1999

Intrathoracic retroesophageal goiter causing tracheal stenosis.

A 65-year-old woman presented with stridor revealed a mass on a chest X-ray on physical examination. A huge goiter arising in the left lobe of the thyroid had extended retroesophageally and across the midline to the right side of the posterior mediastinum far caudally down to the level of the carina. The trachea was remarkably compressed. Surgery was performed via a combined thoracic and cervical approach, and the tumor was completely removed with resultant relief from stridor. The patient is presently doing well at 1 year after the operation.

Aged↗
PubMed1999

Analysis of Th1 and Th2 cytokine production by peripheral blood mononuclear cells as a parameter of immunological dysfunction in advanced cancer patients.

PURPOSE: The presence of immunological dysfunction has not been well demonstrated in cancer patients. Recent studies have revealed that the immune response can be classified into types 1 and 2, and in the present work the immunological function of patients was studied from the perspective of these two types of response. METHODS: Types 1 and 2 immune response were evaluated by monitoring the production of various cytokines by peripheral blood mononuclear cells from 38 patients with advanced cancer of various organs and 20 healthy subjects. The usual immunological parameters, differential cell leukocyte counts, the level of T cell subsets (CD4 and CD8) and natural killer activity were also examined. RESULTS: The production of interleukin-2 (IL-2), interferon gamma, IL-10, IL-12 and tumor necrosis factor alpha was found to be significantly lower in the patients (75 +/- 57, 171 +/- 205, 40 +/- 34, 8 +/- 8, 1450 +/- 1010 pg/ml) than in healthy subjects (143 +/- 99, 422 +/- 296, 64 +/- 34, 16 +/- 10, 2550 +/- 950 pg/ml); however, the mean level of IL-4 in the patients seemed to be higher. The correlations between different cytokine levels suggested that they were produced differently. Lymphocyte counts were significantly lower in patients, but there was no difference in the other usual immunological parameters. CONCLUSIONS: Patients with advanced cancer are deficient in monocytes and the type 1 immune response. The measurement of various cytokines reported in this study provides a more sensitive and valuable tool for evaluating the function of cell-mediated immunity in cancer patients than do the usual tests.

Adult↗
PubMed1999

Elongated pericyte-like cells connect discrete capillaries in the cochlear stria vascularis of gerbils and rats.

Bridging structures between discrete capillaries in the stria vascularis of the cochlea were studied morphologically in gerbils and rats. Serial thin sections for transmission electron microscopy revealed (1) that elongated cells surrounded by the basal lamina provided the structural basis for the bridging structure, (2) that the basal lamina surrounding the elongated cell extended to the basal lamina around the capillary endothelial cell, (3) that the electron density of the cytoplasm was similar to that of the pericytes around the capillaries, and (4) that the cell was attached to the capillaries at both ends only. Visualization of the basal lamina by immunofluorescent methods revealed (1) that capillaries were often bent at the site of attachment of the bridging cell, (2) that the bridging cell bifurcated occasionally, and (3) that the density of the bridging cell was much higher in the stria vascularis than in the underlying spiral ligament. Filamentous actin visualized by fluorescent phalloidin was not apparent in the bridging cell. We propose that the bridging cell provides mechanical strength to the tortuous capillary network in the stria vascularis and participates in the specific function of the stria vascularis in cooperation with other types of cells.

Animals↗
PubMed1999

Immunological identification of an inward rectifier K+ channel (Kir4.1) in the intermediate cell (melanocyte) of the cochlear stria vascularis of gerbils and rats.

The cochlear stria vascularis produces the positive endocochlear potential (EP) and the endolymph. Both the EP and the endolymph are essential for the physiological function of hair cells. The intermediate cell is one of several cell types constituting the stria vascularis. It is known that inward rectifier K+ channels can play a constitutive role in the determination of the resting membrane potential. Localization of a member of the inward rectifier K+ channel family, Kir4.1, in the stria vascularis of gerbils and rats was investigated by immunological methods. A polyclonal antibody specific to the C-terminus of the rat Kir4.1 channel was raised in rabbits. Immunostaining of dissociated cells revealed that the Kir4.1 channel was localized to the intermediate cell, but not to the epithelial marginal cell. Subcellular localization of the Kir4.1 channel to the plasma membrane of the intermediate cell was confirmed by immunoelectron microscopy. Immunostaining of whole-tissue preparations revealed a network-like structure composed of intermediate cells. It seems likely that the Kir4.1 channel mediates the inwardly rectifying K+ current in the intermediate cell as shown previously by electrophysiological methods, and that this channel plays key roles in the production of the EP and K+ transport in the stria vascularis.

Amino Acid Sequence↗