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S Harada

Publications and source records attributed to S Harada.

At least 217 records · Page 12Linked to original sources
PubMed1997

Osteogenic protein-1 up-regulation of the collagen X promoter activity is mediated by a MEF-2-like sequence and requires an adjacent AP-1 sequence.

Bone morphogenetic proteins induce chondrogenesis and osteogenesis in vivo. To investigate molecular mechanisms involved in chondrocyte induction, we examined the effect of osteogenic protein (OP)-1/bone morphogenetic protein-7 on the collagen X promoter. In rat calvaria-derived chondrogenic C5.18 cells, OP-1 up-regulates collagen X mRNA levels and its promoter activity in a cell type- specific manner. Deletion analysis localizes the OP-1 response region to 33 bp (-310/-278), which confers OP-1 responsiveness to both the minimal homologous and heterologous Rous sarcoma virus promoter. Transforming growth factor-beta2 or activin, which up-regulates the expression of a transforming growth factor-beta-inducible p3TP-Lux construct, has little effect on collagen X mRNA and on this 33-bp region. Mutational analysis shows that both an AP-1 like sequence (-294/-285, TGAATCATCA) and an A/T-rich myocyte enhancer factor (MEF)-2 like sequence (-310/-298, TTAAAAATAAAAA) in the 33-bp region are necessary for the OP-1 effect. Gel shift assays show interaction of distinct nuclear proteins from C5.18 cells with the AP-1-like and the MEF-2-like sequences. OP-1 rapidly induces nuclear protein interaction with the MEF-2-like sequence but not with the AP-1 like sequence. MEF-2-like binding activity induced by OP-1 is distinct from the MEF-2 family proteins present in C2C12 myoblasts, in which OP-1 does not induce collagen X mRNA or up-regulate its promoter activity. In conclusion, we identified a specific response region for OP-1 in the mouse collagen X promoter. Mutational and gel shift analyses suggest that OP-1 induces nuclear protein interaction with an A/T-rich MEF-2 like sequence, distinct from the MEF-2 present in myoblasts, and up-regulates collagen X promoter activity, which also requires an AP-1 like sequence.

Activins↗
PubMed1997

Idiopathic CD4+ T-lymphocytopenia in a non-Hodgkin's lymphoma patient.

We report a case of idiopathic CD4+ T-lymphocytopenia with malignant lymphoma (diffuse large, B-cell type) for which there was no evidence of human immunodeficiency virus type 1 or type 2 infection and no other known causes of immunodeficiency. She had never suffered from any opportunistic infection until the diagnosis of malignant lymphoma was made, and the CD4+ T-lymphocytopenia persisted after complete remission of the lymphoma. As the clinical features and immune status of the patient differed from those associated with the acquired immunodeficiency syndrome (AIDS)-related syndrome, we conclude that immunodeficiency in this case did not contribute to the opportunistic infection but may have been associated with the genesis of malignant lymphoma.

CD4-Positive T-Lymphocytes↗
PubMed1997

Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes.

Vascular endothelial cells (EC) exhibit organ-to-organ heterogeneity in their functions and morphologies. In particular, brain capillary EC have unique characteristics exemplified by the blood-brain barrier (BBB). The formation and the maintenance of BBB have been ascribed to EC responses to inductive signal(s) or factor(s) from astrocytes that encircle microvessels in the central nervous system. These EC responses were demonstrated in numerous in vivo studies, exemplified by those of Janzer and Raff (Nature 325:253, 1987) and Tout et al. (Neuroscience 55:291, 1993) showing that transplanted astrocytes induced BBB properties in non-neural vascular EC. In this study, we constructed a heterologous co-culture system, in which rat fetal brain astrocytes were cultivated on one surface of a porous membrane and human umbilical vein EC on the opposite surface. Electron microscopic examination revealed that astrocytes passed their endfeet through the pores, making contact with EC. In this system, gamma-glutamyltranspeptidase (gamma-GTP) activity in EC was found to be significantly increased by contacting astrocytes in a density- and time-dependent manner, but not when the astrocyte feeder layer was apart from EC or replaced by COS cells; astrocyte-derived extracellular matrix partially activated gamma-GTP. mRNAs for some of the representative BBB markers, including transferrin receptor, P-glycoprotein, brain-type glucose transporter (GLUT-1), and gamma-GTP were also demonstrated by reverse transcription-polymerase chain reaction to be upregulated in EC co-cultured with astrocytes. Astrocyte inductions of close membrane apposition resembling a zonula occludens and of an increase in the content of mitochondria in EC were also noted in electron micrographs. Furthermore, an increased barrier activity against inulin was conferred on EC when they were lined with astrocytes. The results obtained with this heterologous co-culture system thus indicate that through contact with their feet, astrocytes are capable of transdifferentiating non-neural EC into the brain type, endowing them with the BBB properties.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

A hidden immunoglobulin G2 in patients with rheumatoid arthritis detected by nuclear magnetic resonance.

OBJECTIVE: The ratios of immunoglobulin (Ig) G1 and IgG2 in patients with rheumatoid arthritis (RA) were examined by nuclear magnetic resonance (NMR) and the results were compared to data obtained by ELISA. METHODS: The IgG of 11 patients with RA were prepared with a DE-52 column and the specific signals for IgG1 and IgG2 were measured by NMR. The ratios of IgG1 and IgG2 were determined by the intensity of this signal. The samples were also measured by ELISA. RESULTS: The ratios of IgG2 in patients with RA measured by NMR were increased significantly compared to controls. However, there were no significant differences in the data determined by ELISA. Thus, a discrepancy exists in the analysis of IgG2 ratios between NMR and ELISA methods. CONCLUSION: There was a discrepancy in the IgG2 ratios of patients with RA between NMR and ELISA methods, and we attribute this to a conformational difference in IgG2 in patients with RA.

Adult↗
PubMed1997

[The distribution and the characteristics in computed tomography (CT) of the lungs in primary Mycobacterium avium complex (MAC) infection].

We investigated the distribution and the characteristics of the lung lesions of patients with primary Mycobacterium avium complex (MAC) infections mainly by computed tomography (CT). They admitted to our hospital during the period from 1984 to 1995 and none of them had a medical history of tuberculosis or other lung diseases. The subjects consisted of fifty patients: fourteen male (average age +/- SD was 66.4 +/- 14.0 year old) and thirty six female (69.0 +/- 11.9 year old). Of 50 patients 24 were M. intracellulare infection, 10 were M. avium infection and others were not identified. First, by using the ratio of slices with lesions on CT to all CT slices from the apex to the base of the lungs, all the patients were divided into two groups; a slight group with less than 15.0% (n = 19) and a severe group with 15.0% or more (n = 31). Next, the density of abnormal shadows in each segment as divided into 5 grades; none (-), minimal (+/-), slight (+), moderate (+2) and severe (+3). The grading was done by taking into account the grade of distribution, density of lesions and destruction of lung parenchym found mainly on CT, and in addition by a standard roentogenographic and tomographic features supplemental. The characteristics frequently observed findings on CT in primary MAC infection patients were nodular (94%), cavitary (74%), bronchiectatic (62%), infiltrative (74%), atelectatic (56%), and pleural-thickened (36%) shadows. Comparing the incidence of segmental lesions in MAC infection patients by segment, it was higher in right and in left lung, but the difference was statistically not significant. As to the number of segments with lesions graded from (+/-) to (+3), many segments were infected unexpectedly: the mean value was 7.7 +/- 1.5 even in the slight group. The proportion of segments with relatively severe lesions graded from (+2) to (+3) in each segment was observed, and the rate in the slight group was 52.6% in S5, 28.9% in S4, 16.7% in S1 (S1 + 2a, b), and 16.7% in S2 (S1 + 2c). In severe group, it was 54.8% in S5, 45.2% in S4, 46.8% in S1 (S1 + 2a, b) 54% in S2 (S1 + 2c), 27.4% in S3 and 26.2% in S6, respectively. The rate of segments with lesions in the lower lobes were less frequent especially in the slight group while it was slightly higher in the severe group. Speculating the initial lesions in the slight group, it was assumed that there might be two types of foci; the one is relatively localized in the beginning and the other is a diffuse type with lesions in many segments even from its early stage. As to the location of initial lesions, the middle lobe and lingula were the most important sites, and the right upper lobe and the left upper division were the next.

Aged↗
PubMed1997

Dual phasic suppression of viral replication following de novo human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes of asymptomatic HIV-1 carriers.

Replication of human immunodeficiency virus type 1 (HIV-1) is suppressed in asymptomatic HIV-1 carriers (ACs). By using an in vitro experimental system, the mechanism of this suppression was investigated. Following in vitro infection of a laboratory HIV-1 strain, the peripheral blood mononuclear cells (PBMC) of ACs transiently supported a low level of viral replication, then the virus production rapidly decreased. PCR analysis revealed that HIV-1 proviral DNA integrated in the PBMC of ACs following infection gradually decreased. Such tapering consequences of in vitro HIV-1 infection in the PBMC of ACs were abrogated by depletion of CD8+ T cells from the culture. Furthermore, the viruses subsequently produced by the PBMC of an AC were less able to replicate than the virus produced by CD8+ cell-depleted PBMC of the same donor. These observations suggested that the CD8+ T cell-mediated suppression of HIV-1 replication in ACs may involve both cytocidal and cytostatic mechanisms: the former kills the cells producing viruses, and the latter inhibits viral spread by reducing viral infectivity.

CD8-Positive T-Lymphocytes↗
PubMed1997

[Influence of low high-density lipoprotein cholesterolemia induced by probucol on the progression of coronary atherosclerosis].

The influence of probucol-induced low high-density lipoprotein (HDL) cholesterolemia on the progression of coronary atherosclerosis was studied in 320 patients with angina pectoris or myocardial infarction, 32 patients with probucol 500 mg/day, 288 patients without probucol, who underwent follow-up angiography at intervals of at least 2 years. The 288 patients were divided into two groups depending on the serum HDL-cholesterol (HDL-C) level at the follow-up angiography: the low HDL-C group had a serum HDL-C level below 40 mg/dl (152 patients) and the control group had 40 mg/dl or above (136 patients). Coronary sclerosis index was defined as the total products of coronary scores (0-6) by segments according to the American Heart Association reporting system in the branches without angioplasty and was compared between the three groups. In the probucol group, serum HDL-C level was significantly reduced from 43.9 +/- 10.6 (at baseline) to 31.1 +/- 7.6 mg/dl (at follow-up, p < 0.01) and was lower than that in the other two groups (low HDL-C group 33.1 +/- 5.0 mg/dl, p < 0.07; control group 52.6 +/- 9.8 mg/dl, p < 0.01). Coronary sclerosis index was most increased in the low HDL-C group (8.3 +/- 5.4-->11.9 +/- 6.1, p < 0.01), whereas there was no significant change in the probucol group (7.2 +/- 5.9-->9.1 +/- 6.8, p = 0.24). Our results showed that treatment with probucol inhibits the progression of coronary atherosclerosis despite the decrease in HDL-C level. One possible reason may be remarkable improvement in the other lipid factors, especially the low-density lipoprotein cholesterol level (165.7 +/- 33.9-->123.7 +/- 29.0 mg/dl, p < 0.01).

Aged↗
PubMed1997

[Clinical efficacy in pediatrics sinusitis infections of cefditoren pivoxil granule therapy and its in vitro antibacterial activity against clinically isolated strains].

We investigated the clinical efficacy in pediatrics sinusitis infections of cefditoren pivoxil granule therapy and its in vitro antibacterial activity against clinically isolated strains. The results are summarized as follows. The specimens from 343 patients were cultured and 595 strains of bacteria were isolated and identified. Oral doses of 3 and 5 mg/kg of CDTR-PI were clinically effective at high percentages, 85.1% and 89.5%, respectively, of treated patients. CDTR-PI at 3 mg/kg orally was clinically effective in 80.8% of patients with PCG intermediate S. pneumoniae (PISP) infections, 80.0% of those with PCG susceptible S. pneumoniae (PSSP) infections, 81.8% of those with H. influenzae infections and 78.3% of those with M. (B.) catarrhalis infections among the infections by major causative agents. The frequent isolates included S. pneumoniae accounting for 33.1%, H. influenzae accounting for 32.1%, M. (B.) catarrhalis accounting for 17.6% and S. pyogenes accounting 3.7% of all the isolates. PISP accounted for 16.1% of all the isolates and for 49.8% of the isolates of S. pneumoniae, and were isolated from 28.6% of the 343 patients. The isolation of PISP was frequent from children of 4 and under especially, and especially frequent from those below age 2. Of the isolates of S. pneumoniae, the biotype frequencies among PSSP were in the order of type I > type II > type III, while those among PISP were in the order of type I < type II with none of type III. Bacteriologically, an eradication rate of 89.4% was achieved with 3 mg/kg and 93.5% with 5 mg/kg of CDTR-PI.

Administration, Oral↗
PubMed1997

[A case of pulmonary arteriovenous fistula presenting as multiple brain abscesses after a sustained period without treatment].

A 64-year-old man was admitted to our hospital with multiple brain abscesses accompanied by pulmonary arteriovenous fistula (PAVF). He had been diagnosed with PAVF eight years previously, but had refused any treatment despite a developing exertional dyspnea. Rendu-Osler-Weber disease was diagnosed as well because the patient exhibited teleangiectasis of the nasopharyngeal mucosa and persistent gastro-intestinal bleeding. Despite administration of antibiotics and corticosteroids the abscesses perforated into the lateral ventricle. The natural history of this rare disease is still incompletely understood. Thus, the time at which treatment should be commenced remains unclear. However the natural course of PAVF is unsatisfactory, and it appears that treatment by surgery and/or embolization should be considered in all cases.

Arteriovenous Fistula↗
PubMed1997

[Relationship between alcoholism and CYP2E1 genotypes].

The genotype of the CYP2E1 loci in 36 alcoholic and 42 non-alcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphisms of CYP2E1 (C/D) and the susceptibility to alcohol dependence. There was a significant (df = 1, chi 2 = 4.39, p < 0.05) difference in CYP2E1 CD (heterozygote) genotype frequency between alcohol dependents (56%) and controls (33%), suggesting that the CD (heterozygote) genotype of CYP2E1 may have something to the risk of developing alcoholism in Japanese, whereas DD (homozygote) genotype was high among controls.

Adult↗
PubMed1997

Trichogenic trichoblastoma arising on the supraclavicular fossa with an immunohistochemical study of cytokeratin expression.

We report a 52-year-old female with trichogenic trichoblastoma arising on the supraclavicular fossa. Clinical and histological examinations revealed a thumbnail-sized, elastic, hard, subcutaneous nodule which consisted of keratinous cysts and epithelial cords of basaloid cells with focally follicular differentiation. Based on histological observations, a diagnosis of trichogenic trichoblastoma was made. An immunohistochemical study using a panel of monoclonal antibodies against cytokeratins was performed to investigate the nature and differentiation of this tumour. The most characteristic findings of the immunohistochemistry were CK 8 and 19 expression in the epithelial cords and the outer cells of the cystic structures. These immunoreactivities were similar to those of the outermost layer of the outer root sheath between the lower permanent portion and the upper transient portion, and immunostaining with the other antibodies confirmed this similarity. We can speculate that trichogenic trichoblastoma differentiates mainly toward the outermost layer of the outer root sheath between the lower permanent portion and the upper transient portion, and then into follicular structures.

Female↗
PubMed1996

Insulin-induced egr-1 and c-fos expression in 32D cells requires insulin receptor, Shc, and mitogen-activated protein kinase, but not insulin receptor substrate-1 and phosphatidylinositol 3-kinase activation.

Many studies suggest that insulin utilizes multiple signal transduction pathways. Insulin's effects are initiated by insulin binding to the insulin receptor, resulting in tyrosine phosphorylation of insulin receptor and intracellular substrates, such as insulin receptor substrate-1 (IRS-1), IRS-2, or Shc. We recently demonstrated that immediate-early gene egr-1 transcription was fully induced without phosphorylation of IRS-1 in Chinese hamster ovary cells (Harada, S., Smith, R. M., Smith, J. A., Shah, N. , Hu, D.-Q. & Jarett, L. (1995) J. Biol. Chem. 270, 26632-26638). In the present study, we examined the effects of insulin on immediate-early gene egr-1 and c-fos expression in 32D cells overexpressing the insulin receptor (32D/IR), IRS-1 (32D/IRS), or both (32D/IR+IRS) and compared these effects with insulin-induced tyrosine phosphorylation. Insulin (17 nM) increased egr-1 and c-fos expression in 32D/IR and 32D/IR+IRS cells, but not in parental cells or 32D/IRS cells, as determined by Northern blot analysis. Insulin treatment (5 min at 37 degrees C) markedly increased tyrosine phosphorylation of several proteins, including the insulin receptor, IRS-1, and Shc, in 32D/IR+IRS cells as determined by immunoprecipitation and Western blot analysis with anti-phosphotyrosine antibody. In contrast, only two tyrosine-phosphorylated proteins, i.e. insulin receptor and Shc, were detected in 32D/IR cells. These data suggest that insulin receptor and Shc phosphorylation is necessary for insulin-induced egr-1 and c-fos expression, but IRS-1 phosphorylation is not necessary or sufficient for the expression of these genes. Furthermore, the effect of specific inhibitors on insulin-induced egr-1 expression was examined. Wortmannin (25 nM), a phosphatidylinositol 3-kinase inhibitor, had no effect on insulin-induced egr-1 expression. In contrast, PD 98059 (30 microM), a mitogen-activated protein kinase kinase inhibitor, totally blocked egr-1 expression induced by insulin. These data indicate that mitogen-activated protein kinase activation, but not phosphatidylinositol 3-kinase activation, is involved in insulin-induced egr-1 expression. Taken together, insulin receptor tyrosine phosphorylation, Shc tyrosine phosphorylation, and mitogen-activated protein kinase activation appear to be the signal transduction pathway responsible for insulin-induced egr-1 expression in 32D cells. These data demonstrate that insulin has multiple signal transduction pathways that vary from cell to cell.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Polymorphism of the apolipoprotein B gene and blood lipid concentrations in Japanese and Caucasian population samples.

To examine whether a racial difference in apolipoprotein B (Apo B) gene polymorphism between Japanese and American Caucasians corresponds with the lower blood cholesterol concentrations in Japanese than in Americans, we examined the EcoRI polymorphism of the Apo B gene for 271 nonsmoking men and women aged 47-69 years in two population-based samples: rural Japanese living in Akita and Caucasians living in Minneapolis-St. Paul, Minnesota, USA. Mean values of serum cholesterol concentrations were significantly lower in Japanese than in Caucasians for both men and women (difference = 25-26 mg/dl). An allele-specific polymerase chain reaction was conducted to examine the Eco RI cutting site at the 12669 cDNA position of the Apo B gene. The allele R2 (absence of the cutting site) has been associated with lower cholesterol concentrations in two previous studies. The frequency of the R2 allele was 6% for Japanese and 17% for Caucasians (P < 0.001), and this race difference in allele frequency was identical for men and women. After controlling for age, body mass index, alcohol intake, and for women, menopausal status and hormone replacement therapy, the adjusted mean (SE) cholesterol level among Japanese was 204 (3) mg/dl for genotype R1R1 and 185 (7) mg/dl for genotype R1R2 or R2R2 combined (P = 0.01). The respective mean values among Caucasians were 224(5) mg/dl and 232(7) mg/dl (P = 0.36). The polymorphism had a similar effect on total cholesterol concentrations for both men and women. The observed lower prevalence of the R2 allele in Japanese than in Caucasians indicates that this variation in the Apo B gene does not explain the racial difference in blood cholesterol concentrations.

Aged↗