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Biomedical subjects

K Ohtani

Publications and source records attributed to K Ohtani.

At least 91 records · Page 5Linked to original sources
PubMed1997

Leptin stimulates insulin secretion and synthesis in HIT-T 15 cells.

Leptin, an ob gene product, corrects hyperinsulinemia in ob/ob mice. The leptin receptor may exist in pancreatic islets. The present studies were undertaken to determine the direct effect of 1-100 ng/ml recombinant leptin on insulin secretion and synthesis in HIT-T 15 cells by using static culture system. The addition of recombinant leptin significantly increased insulin secretion for 20 min at the highest concentration (100 ng/ml). The addition of recombinant leptin dose-dependently increased insulin secretion for 24 h in the 7 mM glucose-containing F-12 K medium. The incubation with recombinant leptin for 24 h increased preproinsulin mRNA expression, assessed with reverse transcription-polymerase chain reaction (RT-PCR) method. It was furthermore demonstrated that HIT-T 15 cells possessed the specific binding site for [125I]-labeled leptin. The present study demonstrated the existence of the leptin-specific binding sites that mediate its stimulatory effect on insulin secretion and synthesis in HIT-T 15 cells.

Actins↗
PubMed1997

Selective depression of the spinal polysynaptic reflex by the NMDA receptor antagonists in an isolated spinal cord in vitro.

1. The effects of N-methyl-D-aspartate (NMDA) receptor glycine-binding site antagonists 7-chlorokynurenate (7-Clkyn) and (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966) on spinal reflexes in an isolated spinal cord that was maintained in Mg(2+)-free medium in vitro were examined. The actions of 7-Clkyn and HA-966 were compared with those of the channel-site antagonist (i.e., dizocilpine) and NMDA-binding site antagonists--that is, 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) and DL-2-amino-5-phosphonovalerate (APV). 2. 7-Clkyn and HA-966 produced a selective depression of the polysynaptic reflex (PSR) while negligibly affecting the activity of the monosynaptic reflex (MSR). The PSR was also differentially suppressed by dizocilpine, CPP and APV. The PSR inhibitory activity of the NMDA antagonists was in the following order: dizocilpine > CPP > APV = 7-Clkyn > HA-966. 3. The inhibitory effects of 7-Clkyn on PSR were markedly antagonized by the simultaneous application of D-serine, an agonist for the NMDA receptor glycine-binding sites. However, PSR inhibition by dizocilpine and CPP was unaffected. 4. Inhibition of the PSR by 7-Clkyn persisted in the presence of strychnine, which markedly increased the PSR activity by itself. 5. These findings suggest that the NMDA receptor glycine-binding sites play a role in generating the NMDA receptor-mediated PSR in the spinal cord in vitro.

Animals↗
PubMed1997

Pontine hypoplasia in a child with sensorineural deafness.

A 2-year-old girl with bilateral sensorineural deafness showed pontine hypoplasia as well as a bulging contour of the pontine tegmentum on magnetic resonance imaging (MRI). There were no bilateral responses of brainstem auditory-evoked potentials (BAEPs). The absent late components of blink reflex (BR) indicated brainstem dysfunction. Chromosomal abnormalities and neurodegenerative or neurometabolic disorders, which might have been the cause of the pontine hypoplasia, were ruled out. The authors describe a rare case with pontine hypoplasia combined with sensorineural deafness and absent blink reflex and suggest that the brainstem in this child may become involved in the early gestation period.

Blinking↗
PubMed1997

Serum leptin concentration is associated with total body fat mass, but not abdominal fat distribution.

OBJECTIVE: The obese (ob) gene encodes leptin which inhibits appetite and stimulates thermogenesis. Serum leptin concentrations are determined by total body fat mass, but the influence of visceral fat accumulation and other metabolic factors have been clinically determined. METHODS: We determined the correlations between serum leptin concentrations and the total body fat mass, abdominal fat mass, abdominal fat distribution (estimated by ultrasound), and circulating metabolic factors in 104 Japanese healthy subjects (11 men and 93 women). In addition, the effect of food restriction (30 kcal/kg desired body weight/day) for four weeks on serum leptin concentrations were also examined in 30 women. RESULTS: There was a significant correlation between serum concentrations and total body fat mass (r = 0.708, P < 0.0001), the percentage of body fat (r = 0.561, P < 0.001), and the body mass index (BMI, r = 0.630, P < 0.001). Serum leptin concentrations were correlated with abdominal wall preperitoneal and subcutaneous fat pad thickness, but not the abdominal wall fat index (AFI). Serum leptin concentrations were also correlated with serum immunoreactive insulin (IRI), but not glucose, or free fatty acid (FFA) concentrations. The weight loss after food restriction for four weeks significantly (P = 0.016) reduced the serum leptin concentrations with a significant reduction of body fat mass, serum glucose, IRI and FFA concentrations. However, there was no significant correlation of the percentage change in serum leptin concentrations to that in body fat mass after food restriction. CONCLUSION: Serum leptin concentrations are well correlated with total body fat mass in healthy subjects. Differences in abdominal fat distribution do not appear to be related to a difference in the in vivo leptin production from adipose tissue.

Abdomen↗
PubMed1997

Genomic diversity in the pfoA region of the theta-toxin-deficient strains of Clostridium perfringens.

The genomic structure of the pfoA-colA region in six theta-toxin-deficient strains of Clostridium perfringens was examined by Southern hybridization using the pfoR, pfoA, pbg, arcABDC and colA genes, encoding regulator for pfoA, theta-toxin, beta-galactosidase, arginine metabolism enzymes and kappa-toxin, respectively, as gene probes. It is suggested that the productivity of theta-toxin in these strains is diverse because of the multiple genetic backgrounds including single deletion of pfoA, large deletion of the pfoA-colA region and the putative point mutations.

Bacterial Toxins↗
PubMed1997

Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals.

Mammalian cell growth is governed by regulatory activities that include the products of genes such as c-myc and ras that act early in G1, as well as the E2F family of transcription factors that accumulate later in G1 to regulate the expression of genes involved in DNA replication. Previous work has shown that the expression of the E2F1, E2F2, and E2F3 gene products is tightly regulated by cell growth. To further explore the mechanisms controlling accumulation of E2F activity, we have isolated genomic sequences flanking the 5' region of the E2F2 coding sequence. Various assays demonstrate promoter activity in this sequence that reproduces the normal control of E2F2 expression during a growth stimulation. Sequence comparison reveals the presence of a variety of known transcription factor binding sites, including E-box elements that are consensus Myc binding sites, as well as E2F binding sites. We demonstrate that the E-box elements, which we show can function as Myc-responsive sites, contribute in a positive fashion to promoter function. We also find that E2F-dependent negative regulation in quiescent cells plays a significant role in the cell growth-dependent control of the promoter, similar to the regulation of the E2F1 gene promoter.

Base Sequence↗
PubMed1997

Protective effect of green tea extract and tea polyphenols against the cytotoxicity of 1,4-naphthoquinone in isolated rat hepatocytes.

The cytoprotective effect of green tea extract and its phenolic compounds against 1,4-naphthoquinone-induced hepatotoxicity was evaluated in primary cultured rat hepatocytes. After exposure to 1,4-naphthoquinone, lactate dehydrogenase (LDH) leakage and cell viability were both improved by the presence of the tea extract and tea polyphenols. This cytoprotective effect was related to the structure of tea polyphenols, the galloyl group of (-)-epigallocatechin-3-gallate and (-)-epicatechin-3-gallate being particularly effective. The production of liquid peroxidation by 1,4-naphthoquinone was not inhibited by the tea extract nor by tea polyphenol addition. After 2 h of incubation, the protein thiol concentration was reduced by 1,4-naphthoquinone, but this reduction was prevented by the tea extract and tea polyphenols. The reduction in protein thiol content of the cells closely paralleled the LDH leakage and loss of cell viability. These results suggest that the mechanism of protection by tea polyphenols against 1,4-naphthoquinone-induced toxicity to rat hepatocytes was due to the maintenance of protein thiol levels.

Animals↗
PubMed1997

Cytotoxicity of cholestane 3 beta,5 alpha,6 beta-triol on cultured intestinal epithelial crypt cells (IEC-6).

The effects of cholestane 3 beta,5 alpha,6 beta-triol on intestinal epithelial crypt cells were investigated using the IEC-6 cell line. Cholestane 3 beta,5 alpha,6 beta-triol decreased SH groups (glutathione and protein SH) in the cell, and showed cytotoxicity in a time-dependent manner. Although the concentration of cholestane 3 beta,5 alpha,6 beta-triol used in this study (100 microM) was very high compared with that in plasma of experimental animals, cholestane 3 beta,5 alpha,6 beta-triol did not show any cytotoxicity on IEC-6 cells without fetal calf serum (FCS). The level of cytotoxicity was dependent upon the concentration of FCS in the culture medium. Unknown components in FSC (not VLDL or LDL) were suggested to be associated with the cytotoxicity of cholestane 3 beta,5 alpha,6 beta-triol. Moreover, the fact that even heat-treated FCS (100 degrees C for 30 min) still mediated the cytotoxicity suggested the participation of non-protein components.

Animals↗
PubMed1997

Estrogen increases in vivo leptin production in rats and human subjects.

The decrease in estrogen in menopausal women increases body fat. The present studies were undertaken to investigate the involvement of estrogen in leptin production in vivo. In the first study, expression of ob gene mRNA in white adipose tissue was measured at 2 and 8 weeks after ovariectomy in rats. In the second, serum leptin concentration was measured in total body fat of 87 weight-matched human subjects (29 men, 29 premenopausal and 29 postmenopausal women). In the third, changes in serum leptin concentration with the menstrual cycle were determined. ob gene expression decreased in subcutaneous and retroperitoneal white adipose tissue of ovariectomized rats 8 weeks after the operation, while ovariectomy increased ob gene expression in mesenteric white adipose tissue. Serum leptin concentration was decreased by ovariectomy. Estradiol supplement reversed the effect of ovariectomy on ob gene expression and circulating leptin levels. In humans, serum leptin concentration was higher in premenopausal women than in men, and in postmenopausal women it was lower than in premenopausal women, but still higher than in men. In 13 premenopausal women, serum leptin levels were significantly higher in the luteal phase than in the follicular phase. The present studies strongly indicate that estrogen regulates leptin production in rats and human subjects in vivo. Regional variation in the regulation of ob gene expression by estrogen was found.

Adipose Tissue↗
PubMed1997

Interstitial pneumonitis related to granulocyte colony-stimulating factor administration following chemotherapy for elderly patients with non-Hodgkin's lymphoma.

We treated three cases of interstitial pneumonitis (IP) in 26 elderly (> or = 65 years old) patients with non-Hodgkin's lymphoma (NHL) who received the same chemotherapeutic protocol including granulocyte colony-stimulating factor (G-CSF) administration. Fortunately, all three patients recovered from IP spontaneously by discontinuation of G-CSF alone or with administration of corticosteroid. Because the duration and extent of neutrophilia induced by G-CSF administration was not different between the cases complicated by IP and those without IP, underlying pulmonary damage is suggested to be more involved than neutrophil count in the development of IP.

Aged↗
PubMed1997

Epalrestat, an aldose reductase inhibitor, improves an impaired generation of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients.

OBJECTIVE: To study the in vivo effect of epalrestat (Epa), an aldose reductase inhibitor, on the generation of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients (HbA1c > 10%). RESEARCH DESIGN AND METHODS: A total of 31 diabetic patients were randomly divided into two groups: an Epa(+) group of 16 patients treated with 150 mg/day epalrestat and an Epa(-) group of 15 patients treated without epalrestat. A control group of 20 age- and sex-matched normal healthy subjects also participated. HbA1c, postprandial plasma glucose (PPG), and neutrophil bactericidal function were measured before and at the end of the drug treatment period (4 weeks). Neutrophil bactericidal function was measured as chemilu-minescence amplified by a Cypridina luciferin analog (CLA), which is dependent on O2- generation, and by luminol (L), which is highly dependent on OCl- generation, in response to formyl-methonyl-leucyl-phenylalanine (fMLP). RESULTS: At the start of the experiment, both CLA-dependent chemiluminescence (CLA-DCL) and L-dependent chemiluminescence (L-DCL) were clearly decreased in diabetic subjects (64 and 54%, respectively; P < 0.05) compared with control subjects (2,182 +/- 144 and 3,221 +/- 173 kc.min-1.10(-6) cells, respectively). At the end of the experiment, CLA-DCL and L-DCL in the Epa(+) group were significantly improved by 44 and 46%, respectively; however, these values were still lower than the corresponding results in the control group. HbA1c and PPG in both the Epa(+) and Epa (-) groups were significantly higher than in the control group, and treatment had no effect on either HbA1c or PPG. CONCLUSIONS: These data suggest that epalrestat may be a useful drug to prevent infection by improving the impaired O2- and OCl- generation by neutrophils from poorly controlled NIDDM patients.

Aldehyde Reductase↗
PubMed1997

HTLV-I Tax trans-activation and cell growth signaling.

We have cloned two genes for cell surface molecules, capable of delivering the intracellular signals, which are modulated for their expression by Tax. One is the gamma chain of the interleukin-2 (IL-2) receptor which is suggested to be critical for IL-2-dependent growth of human T-cell leukemia virus type I (HTLV-I) infected cells. The gamma chain is upregulated by Tax, like the IL-2 receptor alpha chain. This upregulation may compensate the gamma chain downregulation after IL-2 binding, presumably resulting in more frequent growth of HTLV-I infected T cells. The other is gp34 that was initially identified as a molecule specifically expressed on HTLV-I-infected T cells. gp34 has been demonstrated to bind OX40 which belongs to the tumor necrosis factor (TNF) receptor family. We found that HTLV-I Tax induces expression of gp34 and OX40, and that normal T cell transiently express both gp34 and OX40 upon antigenic stimulation. Collectively, it may be possible that HTLV-I-infected T cells are in a predisposition to growth due to modulated expression by HTLV-I Tax of gp34/OX40 and the gamma chain.

Cell Division↗
PubMed1996

Recombinant bovine conglutinin, lacking the N-terminal and collagenous domains, has less conglutination activity but is able to inhibit haemagglutination by influenza A virus.

Conglutinin is a bovine serum protein which was first described as a vertebrate lectin. This protein belongs to the family of C-type lectins. These lectins are composed of four characteristic domains: (1) an N-terminal cysteine-rich domain, (2) a collagen-like domain, (3) a neck domain and (4) a carbohydrate recognition domain (CRD). Recently lectins have been shown to function as immunoglobulin-independent defence molecules due to a complement-mediated mechanism or opsonization. Our previous study showed that bovine conglutinin can inhibit haemagglutination by influenza A viruses and act by directly neutralizing them due to its lectin properties. In order to elucidate the biological role of the collagen-like domain, a recombinant partial conglutinin lacking this collagen-like domain was produced in an Escherichia coli system and its biological activities were examined. A 497 bp sequence, consisting of a short collagen region (two repeats of G-X-Y amino acid sequences), the neck domain, and the CRD of conglutinin cDNA, was amplified by the reverse-transcriptase PCR technique. The cDNA was transferred to a bacterial expression vector system (pRSET-A) and stable transfectants with a high level of conglutinin production were obtained. SDS/PAGE and Western blotting analyses showed a recombinant fusion protein of 27 kDa. Results of a cross-linking study and gel-filtration assay indicated that the recombinant conglutinin can form a trimeric structure and that it has sugar binding activity and specificity similar to that of native conglutinin. The recombinant conglutinin was also found to inhibit haemagglutination caused by influenza A virus as well as to possess less conglutination activity. These results suggest that in order for conglutinin to inhibit haemagglutination caused by the influenza virus, as well as to have sugar binding activity or to form trimers, it does not require the N-terminal and collagenous domains; however, they are essential for full conglutination activity.

Amino Acid Sequence↗
PubMed1996

Withdrawal of [corrected] estrogen increases hypothalamic neuropeptide Y (NPY) mRNA expression in ovariectomized obese rat .

We determined the changes in neuropeptide Y (NPY) mRNA expression of the arcuate nucleus (ARC) in sham-operated (SHAM) and bilaterally ovariectomized (OVX) rats with estradiol (E2) supplement. Ovariectomy increases body weight gain for 3 weeks, accompanied by an increase of daily food intake. Ovariectomy significantly reduced serum corticosterone levels. E2 supplement reversed the effects of ovariectomy on body weight gain, food intake and serum corticosterone levels. Ovariectomy significantly increased NPY mRNA expression in the ARC. E2 supplement decreased NPY mRNA expression in the ARC of OVX rats. The present findings indicated that hypothalamic NPY mRNA expression, which involves the regulation of feeding behavior, are in parallel with circulating estrogen levels. Hypothalamic NPY mRNA expression may be important in the induction of hyperphagia after the withdrawal of estrogen by bilateral ovariectomy.

Animals↗
PubMed1996

An analysis of mandibular bone complications in radiotherapy for T1 and T2 carcinoma of the oral tongue.

PURPOSE: To examine the incidence of mandibular bone complication in patients who underwent radiotherapy for T1 and T2 carcinomas of the oral tongue and to analyze the factors contributing to its occurrence. METHODS AND MATERIALS: The clinical records of 148 patients with T1 and T2 carcinoma of the oral tongue treated with radiotherapy alone between 1978 and 1989 were examined retrospectively. Interstitial brachytherapy, used as the major treatment modality, was performed using cobalt needles, radium needles, or iridium hairpins. The prescribed dose at the plane 5 mm from the plane of the radioactive sources was 65-70 Gy in interstitial brachytherapy alone, and 50-60 Gy in the combined treatment with external irradiation. An external irradiation dose of 30 Gy was usually used. RESULTS: Eleven of the patients showed radiation-induced mandibular bone complication. Two (1 T1, 1 T2) had been treated with interstitial brachytherapy alone, and nine (2 T1, 7 T2) with the combination of external irradiation and interstitial brachytherapy. The incidence of radiation complication of bone was significantly higher in the patients with T2 tumors (p = 0.04) and in those who received the combined treatment (p < 0.01). Multivariate analysis revealed that the total dose (p = 0.04) and dose rate of interstitial brachytherapy (p = 0.03) were significant factors contributing to radiation bone complication. A significant difference in the incidence of bone complication was also seen between patients who received a total dose of 90 Gy or more and those who received less than 90 Gy (p < 0.01), as well as between patients who were treated with 0.55 Gy/h or higher and those who were treated with less than 0.55 Gy/h (p = 0.03). CONCLUSION: A significant increase in the incidence of bone complication was found at the total dose of 90 Gy or more and at the dose rate of 0.55 Gy/h or higher. In combined treatment with external irradiation and interstitial brachytherapy, the interstitial brachytherapy dose of 60 Gy appears to be the threshold at which mandibular bone complication is induced when the external irradiation dose is 30 Gy.

Adult↗
PubMed1996

Furanoid diterpene glucosides from Tinospora rumphii.

The stems of Tinospora rumphii yielded clerodane type furanoid diterpene glucosides: the new rumphioside I, the known borapetosides C and F and three other compounds. Their structures were established on the basis of various spectroscopic techniques. The three compounds have physical and spectral data identical to those of the reported compounds borapetosides E, D and B, respectively. However, the positions of the lactone rings of the first two compounds and the configuration of the bond attaching the glucose moiety to C-6 of the third differ from the reported ones.

Diterpenes↗