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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 127 records · Page 7Linked to original sources
PubMed2001

Formation of human fibroblast aggregates (spheroids) by rotational culture.

In the current study, we attempted to form aggregates of fibroblasts by rotationally shaking, declining fibroblast-material interactions, and augmenting cell-cell interactions. In addition, to promote cell-cell interactions, the medium was supplemented with insulin, dexamethasone, and basic fibroblast growth. Under such improved culture conditions, normal neonatal human dermal fibroblasts formed spheroidal aggregates within 1 day of rotation on a rotational shaker. The aggregates that formed had irregular shapes and were composed from only several cells after 12 h. However, they became nearly spheroidal after 24 h of shaking. The aggregates were approximately 240 microm in diameter. After 36 h of shaking, their shape became more rounded and their surfaces became smoother. No evidence of necrosis in the center of the aggregates was observed, although a small number of dead cells was scattered throughout the aggregates. After 24-36 h, aggregates of normal human fibroblasts were collected and reinoculated onto a scaffold composed of polyglycolic acid. which is used commercially as a scaffold for artificial skin, coated with collagen. The aggregates were successfully trapped to the mesh of polyglycolic acid and became attached within 24 h. Therefore, the aggregates could provide an alternative method for seeding fibroblasts to scaffold for an artificial skin, such as a mesh of polyglycolic acid.

Cell Aggregation↗
PubMed2001

[Past trends in hepatitis C virus infection and route of transmission in Japan].

In Japan, it is known that the prevalence of hepatitis C virus(HCV) is high among the older people over 60 years of age in sharp contrast to the low prevalence among those under 30. The annual incidence rate of HCV carriers in general population remains quite low to be 1.8-3.4 per 100,000 person-year. On the other hand, HCV prevalence among intravenous drug users(IVDU) is still greater than 60%. Taking into account this epidemiological pattern together with the historical fact that Japan experienced an explosion of drug abuse among young generation of 15 to 25 years old in the period of post World War II turmoil together with the poor sanitary and medical conditions, it is suggested that a great wave of HCV spread in Japan occurred most likely in 1960's to 1970's. The spread then may have gradually fallen to the range today.

Adolescent↗
PubMed2001

[Asterriquinone derivatives as candidates for new orally available anti-diabetics].

Orally available anti-diabetic candidates, reported by Merck researchers, are reviewed. The lead, asterriquinone B1(1a), was discovered in a fungal extract by screening with the cell line CHO.IR. An analog, 2,5-dihydroxy-3-(1-methylindol-3-yl)-6-phenyl-1,4-benzoquinone(2h), was selected by studying structure-activity relationships with various in vitro and in vivo tests. Analog 2h exhibited selective tyrosin kinase activity to an insulin receptor and a glucose-lowering effect by testing on diabetic rodent models. However, on the basis of the results of in vivo tests on streptozotocin-induced and on normal lean mice, the activity of 2h was attributed to a sensitizing effect on insulin together with an insulin mimetic effect in part. These studies shed light on the search for new anti-diabetic agents by targeting insulin receptors.

Administration, Oral↗
PubMed2001

[A case of thymoma with pure red cell aplasia].

A 71-year-old man was admitted to the hospital because of general fatigue. There were few reticulocytes in the peripheral blood and no erythroblasts in the bone marrow. Chest CT revealed an anterior mediastinal tumor. Under a diagnosis of thymoma with PRCA, extended thymothymectomy was performed. Histological diagnosis was mixed type thymoma with no invasive growth beyond the capsule. Administration of predonisolone following surgery was not effective for PRCA. Otherwise, peripheral blood counts were significantly improved following occasional onset of acute bronchitis.

Acute Disease↗
PubMed2000

The immediate early gene 1 product of human cytomegalovirus is sufficient for up-regulation of interleukin-8 gene expression.

We previously observed that human cytomegalovirus (CMV) infection induced a massive production of a chemokine with potent neutrophil chemotactic activity, interleukin-8 (IL-8). Hence, we examined the effect of CMV immediate early (IE) gene products on IL-8 production by the human astrocytoma cell line, U373MG. Transient or stable transfection with a CMV IE1 gene expression vector, but not with a IE2 gene expression vector, significantly augmented IL-8 protein secretion and IL-8 mRNA expression. Luciferase activity was enhanced in U373MG cells when the cells were cotransfected with CMV IE1 and chimeric firefly luciferase reporter genes driven by the transcriptional regulatory region of the human IL-8 gene. Moreover, IE1 gene-mediated enhancement of luciferase activity was abolished by the introduction of mutations into the AP-1 or NF-kappa B factor binding elements in the regulatory region of the IL-8 promoter. Furthermore, electrophoretic mobility shift assays demonstrated that CMV IE1 gene products induced the formation of NF-kappa B or AP-1 complexes. Finally, Western blotting analysis demonstrated that the CMV IE1 gene product increased the amount of NF-kappa B complexes translocated into the nucleus. Collectively, CMV IE1 gene expression may be sufficient to activate AP-1 and NF-kappa B, resulting in IL-8 gene expression.

Base Sequence↗
PubMed2000

Improvement of the viability of cultured rat neurons by the non-essential amino acids L-serine and glycine that upregulates expression of the anti-apoptotic gene product Bcl-w.

The non-essential amino acids L-serine (Ser) and glycine (Gly) have recently been shown to exhibit specific actions in the nervous system. In the present study, L-Ser and Gly promoted the survival of cultured rat cerebrocortical neurons in a concentration-dependent manner as revealed by Alamar blue assay and microtubule-associated protein-2 (MAP2) immunoblotting. The maximum effects of the amino acids were detected at the concentrations of 30-100 microM. L-Ser was more effective than Gly. D-Ser failed to promote neuronal survival. L-Ser and Gly upregulated expression of the anti-apoptotic gene product Bcl-w, while they did not affect the expression of Bcl-xL. The promotion of neuronal survival by L-Ser and Gly may be, at least in part, attributable to the upregulated Bcl-w.

Animals↗
PubMed2000

Effects of dopamine and L-DOPA on survival of PC12 cells.

The effects of dopamine and L-DOPA on survival were examined in differentiated PC12 cells. Addition of dopamine to the culture medium at 3-30 microM prevented cell death induced by depletion of serum and nerve growth factor (NGF). At 100 microM, dopamine induced cell death. The cell-protective effect of dopamine was not affected by nomifensine, an inhibitor of dopamine uptake, or pargyline, an inhibitor of monoamine oxidase, suggesting that dopamine is working outside the cell. The cell-protective effect of dopamine was blunted by SCH-23390, a D(1) antagonist, but not sulpiride, a D(2) antagonist, indicating that the cell protective effect of dopamine is mediated by D(1) receptors in PC12 cells. L-DOPA also protected PC12 cells from cell death induced by depletion of serum and NGF at low concentrations and showed toxicity at high concentration. The effect of L-DOPA was unchanged after inhibition of conversion of L-DOPA to dopamine by m-hydroxybenzylhydrazine (NSD-1015), an inhibitor of DOPA decarboxylase, suggesting that L-DOPA itself is working for cell protection. Intracellular Ca(2+) concentration and mitogen-activated protein (MAP) kinase activity were increased by both dopamine and L-DOPA. The effects of dopamine and L-DOPA on cell survival were blunted by nicardipine, a Ca(2+) channel blocker, and PD-98059, an inhibitor of MAP kinase kinase (MEK). These results taken together raised the possibility that dopamine and L-DOPA protect PC12 cells from cell death at low concentrations by activating MAP kinase activity via elevation of intracellular Ca(2+) concentration.

Animals↗
PubMed2000

Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth.

The OX-40 receptor (OX-40R) is a cell surface glycoprotein of the tumor necrosis factor receptor family that is expressed primarily on activated CD4 T cells. Engagement of OX-40R by the OX-40 ligand (OX-40L) is known to costimulate the production of cytokines by activated T lymphocytes and to rescue effector T cells from activation-induced cell death. It was previously reported that in vivo ligation of OX-40R by administration of OX-40L:immunoglobulin fusion protein or OX-40R monoclonal antibody (mAb) resulted in a significant prolongation of survival of tumor-bearing mice in four histologically distinct solid tumors. In this study, we demonstrate that the therapeutic efficacy of OX-40R mAb was influenced by the tumor burden, the intrinsic immunogenicity of the tumor as well as by the histological site of tumor growth. Whereas subdermal and intracranial growth of weakly immunogenic MCA 203 and MCA 205 sarcomas and GL261 glioma were susceptible to the mAb treatment, established pulmonary MCA 205 metastases were refractory to the same regimen of treatment. Furthermore, the mAb administration had no impact on the growth of the poorly immunogenic B16/D5 mela noma. Tumor regression mediated by OX-40R mAb was dependent on the participation of both CD4 and CD8 T cells and as a result of tumor rejection, a long-term tumor-specific immunity was established. Analysis of tumor-infiltrating T cells revealed the presence of a far greater number of OX-40R+ T cells of both CD4 and CD8 phenotypes in the intracranial immunogenic GL261 glioma than that in the poorly immunogenic B16/D5 melanoma. These results suggest that ligation of OX-40R on activated T cells in situ in the tumor may provide a necessary costimulatory signal to augment immune responses leading to tumor regression and immunological memory.

Animals↗
PubMed2000

Lipopolysaccharide-induced HIV-1 expression in transgenic mice is mediated by tumor necrosis factor-alpha and interleukin-1, but not by interferon-gamma nor interleukin-6.

BACKGROUND: As serum HIV-1 load correlates well with the prognosis of the disease, it is suggested that the viral load is one of the major determinants of the disease progression of AIDS. Accordingly, HIV-1 activation mechanisms were extensively studied in vitro, and involvement of cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6 and interferon (IFN)-gamma has been suggested in this process. However, so far the roles of these cytokines in the HIV-1 expression in vivo have not been well elucidated because of the lack of appropriate animal disease models. OBJECTIVE: To elucidate the roles of cytokines in HIV-1 activation in vivo. DESIGN AND METHODS: Transgenic mice carrying a defective HIV-1 genome were used as a model for HIV-1 carriers. In order to examine the possible involvement of cytokines in HIV-1 expression, TNF-alpha-, IL-1-, IL-6- and IFN-gamma-deficient HIV-1 transgenic mice, were produced and HIV-1 expression was analyzed after activation with bacterial lipopolysaccharides (LPS). RESULTS: HIV-1 expression in the transgenic mouse spleen was activated 10- to 20-fold by LPS, and the serum p24 Gag protein levels reached 400 pg/ml, which is nearly equal to the levels that occur in AIDS patients. However, this augmentation was suppressed by 60% in TNF-alpha-deficient mice and by 40% in IL-1alpha/beta-deficient mice. In contrast, no suppression was observed in either IL-6-, IFN-gamma-, IL-1alpha, or IL-1beta-deficient mice. CONCLUSIONS: Results suggest that TNF-alpha and IL-1 play important roles in HIV-1 gene activation and selective suppression of these cytokines could improve clinical prognosis and potentially slow progression of the disease.

Animals↗
PubMed2000

Histochemical cytochrome c oxidase activity and caspase-3 in gerbil hippocampal CA1 neurons after transient forebrain ischemia.

We examined the cytochrome c oxidase (COX) activity in gerbil hippocampal CA1 neurons after 5-min ischemia by a histochemical method in the presence or absence of exogenous cytochrome c. In the CA1 neurons, COX activity without exogenous cytochrome c decreased from 1 h after ischemia, but was restored by the addition of exogenous cytochrome c in the following 6 h after ischemia. These results suggest that it is not COX activity but endogenous cytochrome c that is changed in the early phase after ischemia, and that COX activity begins to decrease 9 h after ischemia. We examined caspase-3 in the CA1 region by immunoblotting, as caspase-3 is known to take part in the cell-death cascade downstream from cytochrome c. Although pro-caspase-3 was strongly detected, active caspase-3 was not detected before and until 84 h after 5-min ischemia. Our data suggested that delayed neuronal death is likely to progress via cytochrome c-release but not via caspase-3 activation.

Animals↗
PubMed2000

The Surface Structure of Hydroxyapatite Single Crystal and the Accumulation of Arachidic Acid.

Single crystals of hydroxyapatite (HAp) were grown by a flux method using beta-tricalcium phosphate and Ca(OH)(2) under hot isostatic pressure. After chemical etching by 0.05 N HCl aqueous solution, the HAp crystal surfaces were observed by an atomic force microscope (AFM) and shown dominantly to consist of steps with heights corresponding to a lattice distance d(100) or its 2/3. Arachidic acid films were accumulated on the etched HAp crystal by a Langmuir-Blodgett method. From section analyses by AFM, a distance between the carboxyl groups of arachidic acid and the HAp surface was estimated to be approximately 0.04 nm, sufficiently adjacent for a chemical interaction to take place. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Hepatitis B epidemiology in Latin America.

The available data on prevalence of hepatitis B virus (HBV) infection in Latin America are incomplete and largely based on analysis of blood banks, which are not stratified by age or social class. An epidemiological study was recently undertaken in six countries in Latin America to update the data. The highest seroprevalence of antibody to the HBV core antigen (anti-HBc) was found in the Dominican Republic (21.4%), followed by Brazil (7.9%), Venezuela (3.2%) and Argentina (2.1%). The lowest seroprevalence was found in Mexico (1.4%) and Chile (0.6%). The seroprevalence in different regions of Brazil varied from 21% in Manaus to 1.2% in Fortaleza. There were no differences in seroprevalence of anti-HBc between females and males except in Brazil (significantly higher in males) and in the Dominican Republic (significantly higher in females). In Brazil alone, higher seroprevalence was associated with lower socioeconomic class. In both the Dominican Republic and Brazil, seroprevalence was high in childhood, and in Brazil and Argentina, anti-HBc was detected in 3.0-6.6% of children up to 1 year old, suggesting vertical transmission. Other risk factors included dental and surgical procedures, sexual activity and tattooing. There was an increase in seroprevalence in all countries at or after adolescence, suggesting that sexual activity is a major route of transmission.

Adolescent↗
PubMed2000

Hepatitis A shifting epidemiology in Latin America.

In the past, Latin America was considered to be an area of high endemicity for hepatitis A virus (HAV) infection, with most people infected in early childhood. A seroepidemiological study was recently undertaken in six countries to determine whether this pattern has changed. The highest seroprevalence of antibodies to HAV (anti-HAV) was found in Mexico and the Dominican Republic. Analysis of the different age groups showed that at age 6-10 years, 30% of children in Chile and 54-55% in Brazil, Venezuela and Argentina had been infected, compared with almost 70% in Mexico and 80% in the Dominican Republic. At age 11-15 years, nearly 90% in Mexico and 91% in the Dominican Republic had been infected, compared with 54% in Argentina, 62% in Venezuela, 60% in Brazil and 70% in Chile. By age 31-40 years, over 80% of the populations in all six countries had been exposed to HAV. In all of the countries except Brazil and Venezuela, the seroprevalence of anti-HAV was significantly higher in females than in males. In Mexico, Argentina and Brazil, anti-HAV seroprevalence was significantly higher in the low socioeconomic groups than in the middle/high socioeconomic groups. The results show that there has been a shift from high to medium endemicity of HAV infection throughout Latin America, which may result in more clinical cases in adolescents and adults and a greater potential for outbreaks. The vaccination strategy for hepatitis A should thus be reviewed.

Adolescent↗
PubMed2000

Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils.

Cytochrome c was detected by immunoblotting in the cytosolic fraction 3 h after 5-min ischemia in the non-ischemia-tolerant CA1 region in which about 96% of neurons had developed delayed neuronal death, while less cytosolic cytochrome c was detected in the ischemia-tolerance-induced CA1 region where many more neurons survived. In the immunohistochemical study using anti-non-native cytochrome c monoclonal antibody, immunoreactivity was observed throughout the cytoplasm in the non-ischemia-tolerant CA1 neurons, but not in the normal and ischemia-tolerant CA1 neurons. Then we determined whether Bcl-2, Bax, Bcl-xL and Bcl-xS, which regulate the release of cytochrome c from mitochondria, were altered in the ischemia-tolerant CA1 region. Bcl-2 and Bax were up-regulated in the ischemia-tolerant group, but Bcl-xL and Bcl-xS showed no apparent difference in their expression. These results suggest that cytochrome c release is prevented in CA1 neurons in gerbils in which ischemia-tolerance had been induced and that the altered ratio of Bcl-2 to Bax may play a part in this mechanism.

Animals↗
PubMed2000

Apatite formation on organic monolayers in simulated body environment.

Organic monolayer films with the same functional groups as collagen were prepared by a Langmuir-Blodgett (LB) method and the LB monolayers were soaked in a simulated body fluid. Nucleation of hydroxyapatite (HA) took place on the monolayers of the carboxyl group, while no nucleation occurred on the monolayers of amino groups. From IR spectra analyses it was found that an interfacial interaction between carboxyl groups and Ca ions was important for the HA nucleation, causing the formation of HA crystals from the simulated body environment.

Amines↗
PubMed2000

Fatal cerebral hemorrhage associated with cyclosporin-A/FK506-related encephalopathy after allogeneic bone marrow transplantation.

We report a case of cerebral hemorrhage associated with cyclosporin A (CsA)/FK506-related encephalopathy that developed in a 16-year-old woman after allogeneic bone marrow transplantation. Hematopoietic engraftment occurred on day 15, and the patient developed systemic convulsions after CsA was replaced by FK506 for the treatment of acute graft-versus-host disease (GVHD). Based on magnetic resonance imaging, laboratory findings and cerebrospinal fluid studies, she was diagnosed as having CsA/FK506-related encephalopathy with cerebral hemorrhagic infarction. Although she recovered completely after discontinuation of FK506, she developed convulsions again 15 days after re-administration of FK506. A computed tomography scan showed cerebral hemorrhage. She died of respiratory failure. Vascular damage induced by immunosuppressive drugs and enhanced by acute GVHD seemed to be the cause of the cerebral hemorrhage. Since hypertension, which was present during both of the central nervous system events, seemed to have contributed to the development of the cerebral hemorrhage, it is proposed that CsA and FK506 should be reduced or discontinued when patients who have risk factors of hypertension become hypertensive even if they have no symptoms of neurotoxicity.

Adolescent↗