Search PubMed⌕ Search

Biomedical subjects

K Oba

Publications and source records attributed to K Oba.

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

Transcriptional regulation of the human FTZ-F1 gene encoding Ad4BP/SF-1.

Ad4BP, also known as SF-1, is a steroidogenic tissue-specific transcription factor that is also essential for adrenal and gonadal development. Two mechanisms for the transcriptional regulation of the mammalian FTZ-F1 gene encoding Ad4BP in adrenocortical cells have been proposed in the previous studies: the crucial role of a cis-element, an E box for the steroidogenic cell-specific expression of mouse and rat FTZ-F1 genes, and a possible autoregulatory mechanism of the rFTZ-F1 gene by Ad4BP itself through binding to the Ad4 (or SF-1) site in the first intron. In the present study, the transcriptional regulation of the human FTZ-F1 gene in adrenocortical cells was investigated from several angles, including the above two mechanisms. Using a series of deletion analyses of the 5'-flanking region of the hFTZ-F1 gene and site-directed mutagenesis for transient transfection studies, an E box element, CACGTG at -87/-82 from the transcriptional start site, was also found to be essential for the transcription of the hFTZ-F1 gene in mouse or human adrenocortical cell lines as well as in non-steroidogenic CV-1 cells. Despite the presence of a corresponding Ad4 site, CCAAGGCC at +163/+156 in the first intron of the hFTZ-F1 gene, an autoregulatory mechanism through the Ad4 site was found to be unlikely in the hFTZ-F1 gene mainly due to site-directed mutagenesis. In addition, the forced expression of Ad4BP had little effect on hFTZ-F1 gene transcription in non-steroidogenic CV-1 cells. Such Ad4BP-independent regulation of the hFTZ-F1 gene was in striking contrast to the regulation of steroidogenic CYP genes, such as the human CYP11A gene, in which the proximal promoter activity is Ad4BP-dependent and the transactivation by Ad4BP is silenced by DAX-1. Even though the Ad4BP-dependent transcriptional regulation of the DAX-1 gene has been reported, DAX-1 did not affect the transcriptional activity of the hFTZ-F1 gene in our study. Taken together, these observations suggest that the E box is indeed required for the expression of the FTZ-F1 gene, at least in mammalian species, but may not determine the tissue-specific expression of the hFTZ-F1 gene, and that, unlike the steroidogenic CYP gene, the regulation of the hFTZ-F1 gene appears to be independent of both Ad4BP and DAX-1.

Adrenal Cortex↗
PubMed2000

Overexpression of vascular endothelial growth factor is responsible for the hematogenous recurrence of early-stage gastric carcinoma.

Vascular endothelial growth factor (VEGF) is crucial for angiogenesis in various malignant tumors. However, it is still unclear whether VEGF is responsible for hematogenous metastasis after the curative resection of gastric carcinoma. In the present study, we evaluated the relevance of VEGF expression to the hematogenous recurrence of stage 1 or 2 primary gastric adenocarcinoma. Among 530 patients, 11 (2.1%) had hematogenous recurrence. Clinicopathological variables were compared between these 11 patients (group R) and 88 patients without intramucosal carcinoma who survived for more than 5 years (group S). Microvessel density (MVD) was assessed immunohistochemically along with VEGF protein expression in all patients from group R and 21 randomly selected patients from group S. There were significant differences in age, tumor size and VEGF expression in tumor tissue between the groups. Positive staining for VEGF protein was observed in all patients of group R, of whom 6 had strongly positive staining. On the other hand, 11 out of 21 patients in group S had positive staining and it was weak in all cases. Both the positive and strongly positive rate were significantly higher in group R than those in group S. There was no significant difference in MVD between the 2 groups (17.7 +/- 11.09/field in group R vs. 14.8 +/- 10. 27/field in group S) and no significant correlation between VEGF expression, MVD and venous invasion, though a weak correlation between the intensity of VEGF staining and MVD was observed (negative staining 12.1 +/- 10.51; weakly positive 16.67 +/- 10.41; strongly positive 19.7 +/- 9.97). Our results suggest that overexpression of VEGF, and not MVD or venous invasion, plays an important role in the hematogenous recurrence of curatively resected gastric carcinoma.

Adult↗
PubMed2000

Two cases of acute myositis associated with influenza A virus infection in the elderly.

During the influenza epidemic of 1998-1999, we observed two elderly patients with influenza-like symptoms who had evidence of acute myositis with elevated serum enzymes. Influenza A infection was confirmed serologically in either case. The present cases suggest that it is important to distinguish influenzal myositis from other forms of myopathy in the elderly patients.

Acute Disease↗
PubMed2000

A high level of physical fitness during thirties is a negative risk factor for colonic polyps during fifties.

This case-control study examined the relationship between the occurrence of colonic polyps in men in their fifties and the level of their physical fitness while in their thirties. The subjects consisted of 51 male Japan Self-Defense Forces officials in their fifties who had colonic polyps, as diagnosed by colonoscopic examination, and 46 control individuals. As an indicator of physical fitness between 30 and 39, we selected the best time recorded for each individual during that decade of life for the 1,500 meter Physical Fitness Test run. We calculated the odds ratio for polyps according to selected risk factors (including physical fitness), and a logistic regression analysis was used to adjust for possible confounding variables. Odds ratio (95% confidence interval, p value) for colonic polyps with physical fitness in the thirties was 0.36 (0.16-0.82, p < 0.05). With adjustment for the subjects' maximum Body Mass Index in both their thirties and fifties, and serum total cholesterol, the odds ratio was 0.39 (0.15-0.99, p < 0.05). We suggest that the occurrence of colonic polyps in men in their fifties can be reduced by maintaining a high level of physical fitness while in their thirties.

Adult↗
PubMed1999

Cellular proteinases trigger the infectivity of the influenza A and Sendai viruses.

It has been proposed that the pathogenicity of the influenza and Sendai virus is primarily determined by host cellular proteases that activate viral infectivity. We isolated trypsin-type serine proteases from rat lungs, candidates for the processing proteases of viral envelope glycoproteins, such as tryptase Clara localized in the Clara cells of the bronchial epithelium and mini-plasmin. These enzymes specifically cleave the precursor of fusion glycoprotein HA of influenza virus at Arg325, and the F0 of Sendai virus at Arg116 in the consensus cleavage motif, Gln(Glu)-X-Arg, resulting in the induction of infectivity of these viruses. Proteolytic activation of viruses by these enzymes occurs extracellularly, probably on the surface and/or in the lumen of the respiratory tract. On the other hand, we isolated two compounds from human bronchial lavage, which inhibit the activity of tryptase Clara. One was a mucus protease inhibitor and the other was a pulmonary surfactant. These compounds inhibited multiple cycles of virus replication in vitro and in vivo, but did not themselves affect the hemagglutination and the infectivity of the virus. Administration of these compounds in the airway may be useful for preventing and treating infection with influenza virus and Sendai virus.

Animals↗
PubMed1999

The human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai viruses.

Tryptase Clara, a trypsin-like protease localized exclusively in and secreted by Clara cells of the bronchial epithelium, is a prime host factor that processes viral envelope glycoproteins and determines the infectivity of influenza A and Sendai viruses (H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma, The Journal of Biological Chemistry, 1992, Vol. 267, pp. 13573-13579). We report here that human mucus protease inhibitor (MPI), a major inhibitor of granulocyte elastase in the lining fluid of the human respiratory tract, significantly inhibited induction of the infectivity of influenza A and Sendai viruses by tryptase Clara in vitro and multicycles of mouse-adapted influenza A virus replication in rat lungs in vivo. Recombinant MPI and the C- but not the N-terminal domain of MPI inhibited both the activity of tryptase Clara and the induction of virus infection by tryptase Clara. The 50% inhibitory concentrations of MPI and the C-terminal domain peptide (Pro50-Ala107) of MPI for tryptase Clara were 7.4 and 61.6 nM, respectively, with Sendai virus envelope glycoproteins as the substrate. Studies on deletion mutants of the C-terminal domain of MPI revealed that the minimal size of MPI required for the inhibition of tryptase Clara is the peptide Lys60-Ala107. Studies involving site-directed mutagenesis of the C-terminal domain of MPI indicated that the Leu72-Met73 site of MPI is the inhibitory site for tryptase Clara. Substitution of residue Leu72 with a basic amino acid significantly increased in the inhibitory activity of the C-terminal domain of MPI, but further substitution of residue Met73 with various amino acids in these mutants reduced the inhibitory activity. Since there is evidence suggesting that the concentration of MPI in respiratory fluid is insufficient for prevention of virus infection, the administration of MPI, the recombinant C-terminal domain of MPI, and their mutants, with residue Leu72 substituted with residues Arg72 and Lys72, may be useful for treatment of such pneumotropic virus infections.

Animals↗
PubMed1999

Conradi-Hünermann syndrome with ocular anomalies.

We report a Japanese girl with the Conradi-Hünermann form of chondrodysplasia punctata and anterior segment malformations characteristic of Axenfeld-Rieger syndrome. The patient also had cataracts and unilateral optic atrophy. A possible role for homeobox-containing genes in the etiology of this type of chondrodysplasia punctata is suggested as an explanation for the coincidence of these two syndromes.

Anterior Eye Segment↗
PubMed1999

Dax-1 as one of the target genes of Ad4BP/SF-1.

The DAX-1 (also known as AHC) gene encodes an unusual member of the nuclear hormone receptor superfamily. DAX-1 plays a critical role during gonadal and adrenal differentiation since mutations of the human DAX-1 gene cause X-linked adrenal hypoplasia congenita associated with hypogonadotropic hypogonadism. In recent studies, DAX-1 was reported to function as a transcriptional suppressor of Ad4BP/SF-1, a critical transcription factor in gonadal and adrenal differentiation. With respect to implication of Ad4BP/SF-1 in the transcriptional regulation of the DAX-1 gene, inconsistent findings have been previously reported. We investigated the upstream region of the mouse Dax-1 (also known as Ahch) gene and identified a novel Ad4/SF-1 site by transient transfection and electrophoretic mobility shift assays. In addition, immunohistochemical analyses with a specific antibody to Dax-1 indicated the presence of immunoreactive cells in steroidogenic tissues, pituitary gland, and hypothalamus. Although the distributions of Dax-1 and Ad4BP/SF-1 were very similar, they were not completely identical. The expression of Dax-1 was significantly impaired in knock-out mice of the Ftz-f1 gene, which encodes Ad4BP/ SF-1. Taken together, our findings indicate that Ad4BP/SF-1 controls the transcription of the Dax-1 gene.

Adrenal Cortex Neoplasms↗
PubMed1999

Effect of age on urinary excretion of N-acetyl-beta-D-glucosaminidase.

To examine the relationship between the concentrations of urinary NAG and age, we measured ratios of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (NAG index) in 137 healthy subjects, aged from 19 to 88 years. The study is also designed to evaluate the relationship between urinary NAG and blood pressure. The subjects were divided into 7 subgroups, according to their age (< 30, 30-39, 40-49, 50-59, 60-69, 70-79, 80 or more years). There was a positive correlation between NAG index and age (r = 0.36; P < 0.001). The regression equation relating NAG index (y) to age (x) was y = 0.065x + 0.97. The mean NAG indexes for the 7 subgroups divided by age were significantly different (P < 0.01). There was a positive correlation between NAG index and systolic blood pressure (r = 0.18; P < 0.05), but was not between diastolic blood pressure and NAG index. In multiple regression analysis, age and BUN significantly correlated with NAG index (r = 0.32; P < 0.01, r = 3.3; P = 0.07, respectively), although there was no correlation between systolic blood pressure and NAG index. This cross-sectional study showed a clear elevation in NAG index with age. The rate of elevation was 0.65 per decade. Urinary excretion of NAG may be unrelated to blood pressure.

Acetylglucosaminidase↗
PubMed1999

[An elderly case of giant infected liver cyst that decreased dramatically without percutaneous aspiration].

A 70-year-old woman was referred to our hospital for treatment of cholelithiasis. A giant liver cyst (6 cm in diameter) had been diagnosed three years earlier. On admission, she had low grade fever and hepatomegaly. High values were observed for WBC (9900/microliter), CRP (8.9 mg/dl), GPT (45 IU/l), ALP (1399 IU/l), gamma-GTP (333 IU/l) and LAP (249 IU/l). The diagnosis of infected liver cyst (8 cm in diameter) was made based on contrast-enhanced CT scan. Endoscopic retrograde cholangiopancreaticography showed no communication between the cyst and the intrahepatic bile duct. She was successfully managed with antibiotics and discharged without percutaneous aspiration the cyst. On abdominal CT scan 4 months after the discharge, the liver cyst had decreased dramatically in size (1 cm in diameter). The patient remains healthy without symptoms.

Aged↗
PubMed1999

[Sulfonylureas and daily blood glucose profiles in elderly diabetics].

The aim of this study is to clarify the relationship between the efficacy of sulfonylureas and duration of diabetes in elderly diabetics. Daily blood glucose profiles were measured in 87 Type 2 elderly diabetic patients on sulfonylureas (tolbutamide, gliclazide or glibenclamide). Plasma glucose concentrations were determined at 08.00 (before breakfast), 10.00, 12.00 (before lunch), 14.00, 18.00 (before dinner), 20.00, 24.00, 03.00, 06.00, 08.00 hours. The subjects were divided into 4 sub-groups, according to their duration of the diabetes (< 10, 10-14, 15-19, 20 or more years). Mean plasma glucose values at 08.00, 10.00, 20.00, 03.00 and 06.00 hours were not significantly different among the four groups. However, mean plasma glucose values at 12.00, 14.00, 18.00, 00.00 hours and mean total blood glucose area under the daily profile (total BG) were significantly different among the four groups and the values in patients with a history of diabetes of 15 years or more increased. Duration of diabetes positively correlated with blood glucose values at 12.00, 14.00, 18.00, 00.00, 03.00 hours and total BG, and the dose of sulfonylureas positively correlated with blood glucose values at 12.00, 14.00, 18.00, 00.00 hours and total BG in multiple regression analysis. These results suggest that duration of diabetes and dose of sulfonylureas are important determinants of blood glucose control with sulfonylureas in elderly diabetic patients.

Aged↗
PubMed1999

[Effect of age, gender, and body fat distribution on serum leptin concentrations].

The aim of this study was to clarify the relationship between serum leptin concentration and age, gender and body fat distribution. Serum leptin concentrations were determined 267 subjects (138 men and 129 women), aged 30 to 91. The thicknesses of the preperitoneal fat layer (Pmax) and subcutaneous fat layer (Smin) in the abdomen were measured by ultrasonography. Fat mass and percent fat were measured by the bioelectrical impedance analysis method. Women had higher leptin and leptin/fat mass values than men in all BMI groups (BMI < 20, 20-23.9, 24-25.9, > or = 26). The leptin concentration correlated significantly with BMI, fat mass, percent fat, waist, hip, waist/hip ratio (W/H), Pmax, Smin and serum Cr in both men and women. The leptin concentration correlated significantly with age in men only and P/S in female only. Leptin/fat mass values significantly correlated with age, fat mass, and percent fat, but not with BMI, waist, hip, W/H, Pmax, Smin and P/S in men. In women, leptin/fat mass values significantly correlated with BMI, fat mass, percent fat, waist, hip, Pmax, Smin and P/S, but not with age or W/H. Multiple regression analysis showed that fat mass and serum creatinine were significant determinants of the leptin and leptin/fat mass values both in men and women, but that age was a significant determinant of these values only in men. These results suggest that the influence of aging on serum leptin concentration exists only in men.

Adipose Tissue↗
PubMed1998

L-galactono-gamma-lactone dehydrogenase from sweet potato: purification and cDNA sequence analysis.

L-Galactono-gamma-lactone dehydrogenase (EC 1.3.2.3, GLDHase) was partially purified from mitochondria of sweet potato tuberous roots over 600-fold on a specific activity basis, followed by purification of the enzyme protein of 56 kDa by a preparative SDS-PAGE. The absorption spectrum of the hydroxylapatite column-purified GLDH-ase showed peaks at 448 and 373 nm, suggesting the presence of flavin as a prosthetic group. The activity of GLDH-ase was inhibited by lycorine, an alkaloid which inhibits ascorbic acid biosynthesis in vivo. N-terminal partial sequences of four internal polypeptides generated by partial digestion of GLDHase with V8 protease were determined. The deduced nucleotide sequences were used to amplify a cDNA fragment of the GLDHase gene. The clone encoded a polypeptide of 581 amino acid residues with a molecular mass of 66 kDa. The deduced amino acid sequence showed 77% identity with that of cauliflower GLDHase, and significant homology to those of L-gulono-gamma-lactone oxidase (22% identity) from rat and L-galactono-gamma-lactone oxidase from yeast (17% identity), which are enzymes involved in L-ascorbic acid biosynthesis in these organisms. The absorption spectrum and cDNA sequence suggested that the flavin group bound noncovalently. We conclude that GLDHase, L-gulono-gamma-lactone oxidase and L-galactono-gamma-lactone oxidase are homologous in spite of the difference in substrates and electron acceptors. Genomic Southern analysis suggested that GLDHase gene exists as a single copy in the genome of sweet potato.

Amaryllidaceae Alkaloids↗
PubMed1997

[Phe21]big endothelin-1(18-34) and [Ala31]big endothelin-1(18-34) inhibit the human endothelin-converting enzyme-1 (ECE-1) expressed in CHO-K1 cells in a different fashion.

Endothelin-converting enzyme-1 (ECE-1) is one of the most important enzymes to convert big endothelin-1 (big ET-1) to ET-1. To identify the inhibitors of ECE-1, we examined the effects of variously substituted analogues of big ET-1 on ECE-1 activity using solubilized membranes prepared from human ECE-1-expressed CHO-K1 cells. Among the big ET-1 analogues tested, [Phe21]big ET-1(18-34) and [Ala31]big ET-1(18-34) exhibited a significant inhibition of ECE-1. A kinetic analysis revealed [Phe21]big ET-1(18-34) to be a competitive inhibitor (Ki=20.6 microM) and [Ala31]big ET-1(18-34) to be a noncompetitive inhibitor (Ki=35.6 microM). These results not only support the concept that ECE-1 recognizes big ET-1 both at the P1 position and at the C-terminal region but also revealed that these two regions are recognized by this enzyme in a different manner.

Animals↗