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Biomedical subjects

S Ishii

Publications and source records attributed to S Ishii.

At least 73 records · Page 4Linked to original sources
PubMed2001

Role of PML and PML-RARalpha in Mad-mediated transcriptional repression.

Fusion of the promyelocytic leukemia (PML) protein to the retinoic acid receptor-alpha (RARalpha) generates the transforming protein of acute promyelocytic leukemias. PML appears to be involved in multiple functions, including apoptosis and transcriptional activation by RAR, whereas PML-RARalpha blocks these functions of PML. However, the mechanisms of leukemogenesis by PML-RARalpha remain elusive. Here we show that PML interacts with multiple corepressors (c-Ski, N-CoR, and mSin3A) and histone deacetylase 1, and that this interaction is required for transcriptional repression mediated by the tumor suppressor Mad. PML-RARalpha has the two corepressor-interacting sites and inhibits Mad-mediated repression, suggesting that aberrant binding of PML-RARalpha to the corepressor complexes may lead to abrogation of the corepressor function. These mechanisms may contribute to events leading to leukemogenesis.

Animals↗
PubMed2001

Overexpression of the granulocyte colony-stimulating factor gene impairs bone morphogenetic protein responsiveness in mice.

Granulocyte colony-stimulating factor (G-CSF) is the major hematopoietic growth factor regulating the production and differentiation of neutrophils. We previously demonstrated that permanent overexpression of G-CSF in transgenic mice produces a dramatic enlargement of the bone cavity and reduction of bone mass. This phenotype was shown to be associated with an increase of osteoclast-mediated bone resorption. As a way of determining the role of G-CSF in bone formation in vivo, an ectopic bone was induced subcutaneously into G-CSF transgenic mice by bone morphogenetic protein (BMP)-2, a potent initiator of bone and cartilage from undifferentiated mesenchymal cells. A BMP-2/atelocollagen pellet containing recombinant human BMP-2 was implanted into a dorsal subfascial pocket. At one week after implantation, proliferation of mesenchymal cells around the implant was significantly decreased in transgenic mice compared with control mice. At three weeks, an ectopic bone containing bone marrow was formed both in transgenic and control mice. However, the ectopic bones of the transgenic mice were smaller and less consistent than those of control mice, and the calcium contents were reduced to 56.2% of those of controls. The ectopic bone in the G-CSF mice showed poor development of both lamellar and trabecular bone. Semiquantitative reverse transcription-polymerase chain reaction analysis of the ectopic bone at 3 weeks disclosed no significant differences in the mRNA levels of type I collagen, osteopontin, and osteocalcin between G-CSF mice and control mice. Immunohistochemical study in G-CSF mice showed reduced staining of osteocalcin in the bone matrix surrounding the reduced number of osteoblasts. The half-life of BMP in the implants was prolonged to 7 to 9 days in the G-CSF mice, whereas it was 5 days in the control mice. Collectively, the permanent expression of G-CSF may retard the differentiation process of osteoblasts by impairing the initial induction of mesenchymal cells, resulting in reduction of bone mass, suggesting that G-CSF regulates the bone metabolism by modulating both osteoclast and osteoblast function. Furthermore, it is suggested that G-CSF is a potent modulator of the BMP-2 signal pathway in vivo.

Animals↗
PubMed2001

Murine Schnurri-2 is required for positive selection of thymocytes.

A key step in T cell development involves the positive selection of cells that recognize antigen presented by self-major histocompatibility complex. Yet, the signals that are activated by T cell receptor engagement and lead to cell survival remain unclear. We show here that mice lacking the transcription factor Schnurri-2 (Shn-2), a large metal-finger protein, had severely defective positive selection of CD4+ and CD8+ cells. Drosophila Shn acts as a cofactor of Smad homolog and is required for Decapentaplegic signaling. Vertebrates have at least three Shn orthologs (Shn-1, Shn-2 and Shn-3), which are thought to act as nuclear targets in the bone morphogenetic protein-transforming growth factor-beta-activin signaling pathways. These data raised the possibility that the Smad-Shn-2 complex is involved in the thymic selection of T cells.

Activins↗
PubMed2001

Thyroid hormones regulate pituitary growth hormone secretagogue receptor gene expression.

Thyroid hormones regulate growth hormone (GH) secretion by actions both at the hypothalamus and at the pituitary gland. At the level of the pituitary, thyroid hormones increase GH and GH-releasing hormone receptor (GHRH-R) mRNA expression. To test if thyroid hormones might also regulate the pituitary expression of mRNA for the recently identified GH secretagogue (GHS) receptor, GHS-R, primary pituitary cell cultures from adult male rats were treated with triiodothyronine (T3) and GHS-R mRNA levels were assessed by reverse transcriptase-polymerase chain reaction. T3 increased pituitary GHS-R mRNA levels in a dose- and time-dependent manner. The stimulatory action of T3 on GHS-R mRNA levels was also observed in the presence of the RNA synthesis inhibitor, actinomycin D, indicating that gene transcription is not required. Closer examination of the decay rates of GHS-R mRNA in the presence of actinomycin D revealed T3 extended the half-life of the GHS-R mRNA from 8 h (basal) to15 h, demonstrating that T3 increases GHS-R mRNA levels in vitro by increasing message stability.

Animals↗
PubMed2001

Length and width of the tendinous portion of the palmaris longus: a cadaver study of adult Japanese.

We examined 72 forearms of 36 cadavers to measure the length and width of the tendinous portion of the palmaris longus in adult Japanese. The palmaris longus muscles were absent in both arms in 1 cadaver and in a unilateral arm in 1 cadaver. Double palmaris longus muscles were found in 1 arm in another cadaver. Most cadavers had a typical palmaris longus muscle and tendon shape. The mean length and width of the tendons were 124.6 +/- 17.0 and 4.5 +/- 0.7 mm, respectively, in male specimens and 108.3 +/- 16.4 and 4.0 +/- 0.7 mm in female specimens, respectively. The mean lengths of the forearms were 240.0 +/- 12.6 mm in male specimens and 218.8 +/- 14.6 mm in female specimens. There was a statistically significant correlation between the lengths of the palmaris longus tendon and forearm. These results indicate that one can estimate the length of palmaris longus tendons before surgical intervention.

Adult↗
PubMed2001

The efficacy of intra-articular analgesia after total knee arthroplasty in patients with rheumatoid arthritis and in patients with osteoarthritis.

The pain relief provided by intra-articular injection of morphine plus bupivacaine after total knee arthroplasty (TKA) plus partial synovectomy in patients with rheumatoid arthritis was compared with pain relief after TKA alone in patients with osteoarthritis. There were lower pain scores, a much smaller requirement for systemic analgesics, longer duration until the first requirement of systemic analgesics, and improvement in the range of motion of the knee joint in the patients who received intra-articular injection of analgesics. There was more pronounced postoperative analgesia in the patients with rheumatoid arthritis than in the patients with osteoarthritis in the study groups that received intra-articular injection of analgesics.

Analgesia↗
PubMed2001

Unrelated cord blood transplantation for an infant with chemotherapy-resistant progressive Langerhans cell histiocytosis.

The authors describe a patient successfully treated with unrelated cord blood transplantation (CBT) for chemotherapy-resistant progressive Langerhans cell histiocytosis (LCH). An 8-month-old boy had LCH diagnosed based on the histologic examination of skin lesions. Despite intensive chemotherapy and immunotherapy, the disease was progressive, with organ dysfunction. He received unrelated CBT after a conditioning regimen consisting of total body irradiation, etoposide, and melphalan. He was in complete remission 12 months after the transplantation. The authors suggest that CBT could be considered in the treatment of patients with chemotherapy-resistant progressive LCH, especially if there are no available human leukocyte antigen-matched family donors.

Combined Modality Therapy↗
PubMed2001

Loss of ErbB2 expression in pulmonary metastatic lesions in osteosarcoma.

OBJECTIVES: The c-erbB2 protooncogene is located on human chromosome 17 and encodes a 185-kilodalton transmembrane glycoprotein (ErbB2). Elevated ErbB2 expression or gene amplification has been shown to be associated with a poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of the ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. To further investigate the role of ErbB2 overexpression in pulmonary metastasis of osteosarcoma, its expression in the primary and metastatic lesions of the same osteosarcoma patients was compared. METHODS: We compared the expression levels of ErbB2 receptor protein between the biopsy samples and pulmonary metastatic lesions in each of 19 patients with osteosarcoma who had not presented with metastasis at diagnosis. All archival materials from patients were retrieved and stained with monoclonal antibody CB11 to detect ErbB2 protein. RESULTS: The rate of overexpression was significantly lower in the pulmonary metastatic tumors than in the biopsy samples (11 versus 42%; p = 0.03). Among 8 patients who had shown increased levels of ErbB2 in the biopsy samples, 7 exhibited complete absence of ErbB2 in the pulmonary metastatic lesions. Overall loss of ErbB2 expression was noted in 14 of 19 patients as the initial tumor became metastatic. CONCLUSIONS: It is suggested that overexpression of ErbB2 decreases within individual osteosarcomas as they become metastatic. Overexpression of ErbB2 may not play an important role in the development of pulmonary metastases of osteosarcoma. Further data are needed before ErbB2 can be used in making clinical decisions for osteosarcoma patients.

Adolescent↗
PubMed2001

Gaussian process approach to spiking neurons for inhomogeneous Poisson inputs.

This article presents a new theoretical framework to consider the dynamics of a stochastic spiking neuron model with general membrane response to input spike. We assume that the input spikes obey an inhomogeneous Poisson process. The stochastic process of the membrane potential then becomes a gaussian process. When a general type of the membrane response is assumed, the stochastic process becomes a Markov-gaussian process. We present a calculation method for the membrane potential density and the firing probability density. Our new formulation is the extension of the existing formulation based on diffusion approximation. Although the single Markov assumption of the diffusion approximation simplifies the stochastic process analysis, the calculation is inaccurate when the stochastic process involves a multiple Markov property. We find that the variation of the shape of the membrane response, which has often been ignored in existing stochastic process studies, significantly affects the firing probability. Our approach can consider the reset effect, which has been difficult to deal with by analysis based on the first passage time density.

Action Potentials↗
PubMed2001

Estrogen receptor (ER)alpha, but not ERbeta, gene is expressed in growth hormone-releasing hormone neurons of the male rat hypothalamus.

GH synthesis and release from pituitary somatotropes is controlled by the opposing actions of the hypothalamic neuropeptides, GH-releasing hormone (GHRH), and somatostatin (SS). There is a striking sex difference in the pattern of GH secretion in rats. Early reports indicate that gonadal steroids have important imprinting effects during the neonatal period. Recently, our laboratory and others have reported that the GH secretory pattern is altered by short-term gonadal steroid treatment in adult rat, suggesting that gonadal steroids are also important determinants of the pattern of GH secretion during adult life. However, the site of action of gonadal steroids in the adult rat hypothalamus is still unknown. In this study, we used in situ hybridization in the adult male rat brain to determine whether GHRH neurons and/or SS neurons coexpress estrogen receptor alpha (ERalpha) and ERss genes. In the medial basal hypothalamus of adult male rat, the ERalpha messenger RNA (mRNA) was located in medial preoptic area (MPA) and arcuate nucleus (ARC), whereas ERss mRNA was detected in MPA, supraoptic nucleus, and paraventricular nucleus. From studies using adjacent sections, the distribution of ERalpha mRNA-containing cells appeared to overlap in part with those of GHRH and SS expressing cells only in the ARC. On the other hand, the distribution of ERss mRNA-containing cells does not appear to overlap with GHRH cells or SS cells. The double label in situ hybridization studies showed that in the ARC, 70% of GHRH neurons contain ERalpha mRNA, whereas less than 5% of SS neurons expressed the ERalpha gene. These results indicated that GHRH neurons are direct target cells for estrogens, and estrogens may act directly on GHRH neurons through ERalpha during adult life to modify GH secretory patterns.

Animals↗
PubMed2001

Regulation of the ghrelin gene: growth hormone-releasing hormone upregulates ghrelin mRNA in the pituitary.

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach. Ghrelin specifically releases GH following intravenous administration, and its GH-releasing activity in vivo is dependent on growth hormone-releasing hormone (GHRH). We previously reported that the expression of the GHS-R gene in the pituitary is developmentally regulated and GHRH infusion increases pituitary levels of GHS-R mRNA. Ghrelin mRNA and peptide have recently been detected in rat and human pituitaries. However, the regulation of the ghrelin gene in the pituitary is unknown. In this study, pituitary levels of ghrelin mRNA were measured with the reverse transcriptase-polymerase chain reaction in male rats at embryonic day (e)18 and postnatal days 1, 10, 30, and 75. The highest concentrations of ghrelin mRNA in the pituitary were observed at e18 and then they declined with age. The infusion of GHRH (10 microg/h, 4h) in freely-moving adult male rats resulted in a 1.9-fold increase in ghrelin mRNA levels relative to control rats (P < 0.05). These data indicated that the expression of the ghrelin gene in the pituitary is developmentally regulated and the pituitary ghrelin/GHS-R signaling system could modulate the regulation of GH secretion by GHRH.

Aging↗
PubMed2001

Phase-independent inhibition by retinoic acid of mineralization correlated with loss of tetranectin expression in a human osteoblastic cell line.

We have recently reported that retinoic acid inhibits dexamethasone-induced alkaline phosphatase activity and mineralization in human osteoblastic cell line SV-HFO. In this study, we show that this inhibitory effect on alkaline phosphatase activity depends on the stage of cell differentiation; however, expression of tetranectin, which is a recently reported bone matrix protein, was completely inhibited by treatment with retinoic acid, irrespective of the stage of cell differentiation. Similarly, mineral deposit formation in SV-HFO cells was phase-independently inhibited by retinoic acid. To our knowledge, this is the first report that retinoic acid downregulates the tetranectin expression in human osteoblastic cells independent of the stage of cell differentiation, and is correlated with inhibition of mineralization.

Alkaline Phosphatase↗
PubMed2001

Influence of the vitamin D receptor alleles on human osteoblast-like cells.

We investigated the effect of vitamin D receptor gene (VDRG) polymorphism on the responsiveness to 1,25(OH)2D3 in human osteoblast-like cells. The cells were obtained from the femoral heads of 18 women with osteoarthritis of the hip. Three different restriction enzymes, BsmI, ApaI, and TaqI, were used to analyse the polymorphism. The genotypes of the 18 patients were bbAaTT (8), bbaaTT (6), BbAaTt (3), and BbAATt (1). Our findings showed that there were no differences according to the VDR genotype, but there was a statistically significant difference in the production of osteocalcin between BbAaTt and bbAaTT, and between BbAaTt and bbaaTT. Northern blot analysis of osteocalcin and VDR mRNA showed no significant differences among the three VDR genotypes. These findings suggest that VDR gene polymorphism affects the individual responsiveness of 1,25(OH)2D3.

Aged↗
PubMed2001

Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee.

We studied 99 patients who were undergoing total knee arthroplasty (TKA) to determine the optimum protocol for the administration of tranexamic acid (TNA) in order to reduce blood loss. It decreased by more than 40% after the administration of TNA. The haemostatic effect was greatest when TNA was given preoperatively and on deflation of the tourniquet. There was no increase in the incidence of adverse affects in the patients receiving TNA, compared with a control group. We conclude that two injections of TNA, one given preoperatively and one on deflation of the tourniquet, significantly reduce blood loss without increasing the risk of thromboembolic complications.

Aged↗
PubMed2001

Kudo total elbow arthroplasty in patients with rheumatoid arthritis: a long-term follow-up study.

BACKGROUND: Improvements in the design of total elbow prostheses over the last two decades have led to better and more consistent results. The type-3 Kudo total elbow prosthesis was developed in 1980. The long-term results of use of this implant have not been reported. Because it is an unlinked prosthesis, it is not known whether preservation of the anterior oblique component of the ulnar collateral ligament at the time of implantation is important. METHODS: A type-3 Kudo total elbow arthroplasty with cement was performed in forty-seven patients (fifty elbows) with rheumatoid arthritis. Revision rates, clinical symptoms, postoperative complications, and radiographic changes were assessed eleven to sixteen years (mean, thirteen years) postoperatively. RESULTS: The overall survival rate of the prosthesis was 90% at sixteen years. The mean Mayo elbow performance scores were all poor (mean overall score, 43 points) initially. The overall score was substantially improved at both the intermediate follow-up examination (four to six years after the operation) and the late follow-up examination (eleven to sixteen years after the operation), to 81 and 77 points, respectively. The overall rate of radiolucency about the humeral component was 45% at the intermediate follow-up examination and 100% at the long-term follow-up examination. The rate of radiolucency about the ulnar component at the intermediate and late follow-up examinations was 4.3% and 8.9%, respectively. No great differences in results were found with preservation of the anterior oblique component of the ulnar collateral ligament. CONCLUSIONS: This long-term follow-up study showed acceptable results of the type-3 Kudo total elbow arthroplasty in patients with rheumatoid arthritis. Preservation of the ulnar collateral ligament does not seem to be necessary when performing this procedure.

Arthritis, Rheumatoid↗
PubMed2001

Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats.

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach. Like the synthetic growth hormone secretagogues (GHSs), ghrelin specifically releases growth hormone (GH) after intravenous administration. Also consistent with the central actions of GHSs, ghrelin-immunoreactive cells were shown to be located in the hypothalamic arcuate nucleus as well as the stomach. Recently, we showed that a single central administration of ghrelin increased food intake and hypothalamic agouti-related protein (AGRP) gene expression in rodents, and the orexigenic effect of this peptide seems to be independent of its GH-releasing activity. However, the effect of chronic infusion of ghrelin on food consumption and body weight and their possible mechanisms have not been elucidated. In this study, we determined the effects of chronic intracerebroventricular treatment with ghrelin on metabolic factors and on neuropeptide genes that are expressed in hypothalamic neurons that have been previously shown to express the GHS-R and to regulate food consumption. Chronic central administration of rat ghrelin (1 microg/rat every 12 h for 72 h) significantly increased food intake and body weight. However, it did not affect plasma insulin, glucose, leptin, or GH concentrations. We also found that chronic central administration of ghrelin increased both neuropeptide Y (NPY) mRNA levels (151.0 +/- 10.1% of saline-treated controls; P < 0.05) and AGRP mRNA levels (160.0 +/- 22.5% of saline-treated controls; P < 0.05) in the arcuate nucleus. Thus, the primary hypothalamic targets of ghrelin are NPY/AGRP-containing neurons, and ghrelin is a newly discovered orexigenic peptide in the brain and stomach.

Agouti-Related Protein↗