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H Nishimura

Publications and source records attributed to H Nishimura.

At least 55 records · Page 3Linked to original sources
PubMed2001

Therapeutic possibilities of long-term roxithromycin treatment for chronic diffuse sclerosing osteomyelitis of the mandible.

The clinical efficacy of long-term roxithromycin treatment was examined objectively in nine patients with chronic diffuse sclerosing osteomyelitis of the mandible. Roxithromycin was administered orally at a dose of 300 mg/day for between 68 days and 66 months. In seven of the nine cases (77.8%), the symptoms disappeared 1-12 months after the start of therapy. Radiography showed that osteolytic changes (evident from 'moth-eaten' appearance of bone) had improved but that osteosclerosis had persisted or become more predominant by the end of therapy. Therefore, the optimum duration of treatment should be decided according to the amelioration of symptoms along with the disappearance of osteolytic findings in radiographs. Diarrhoea and stomach discomfort occurred in one case, and liver dysfunction in another, but these adverse reactions were relatively mild. The mechanism of action of roxithromycin in this study is not yet fully understood, but our results indicate that long-term roxithromycin treatment may be useful for diffuse sclerosing osteomyelitis of the mandible and should be attempted before surgical treatment is considered.

Adult↗
PubMed2001

Mice lacking interleukin-2 (IL-2)/IL-15 receptor beta chain are susceptible to infection with avirulent Salmonella enterica subsp. enterica serovar choleraesuis but mice lacking IL-2 are resistant.

Interleukin-2 (IL-2)/IL-15 receptor beta (IL-15R beta)(-/-) mice were susceptible to infection with avirulent Salmonella enterica subsp. enterica serovar Choleraesuis, whereas IL-2(-/-) mice were resistant. A natural killer cell response was not evident for both types of deficient mice. A Th1 response was detected in IL-2(-/-) but not in IL-2/IL-15R beta(-/-) mice infected with Salmonella, suggesting that IL-2/IL-15R beta signaling is important for the generation of protective Th1 cells.

Animals↗
PubMed2001

Type 2 rhinovirus infection of cultured human tracheal epithelial cells: role of LDL receptor.

To examine the role of the low-density lipoprotein (LDL) receptor on minor group human rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with a minor group (RV2) or a major group (RV14) RV. Viral infection was confirmed by showing with PCR that viral titers in supernatants and lysates from infected cells increased with time. RV2 and RV14 increased expression of mRNA and protein of the LDL receptor on the cells and the cytokine production. RV2 induced activation of transcription factors SP1 and nuclear factor-kappaB (NF-kappaB). An antibody to the LDL receptor inhibited RV2 infection and RV2-induced cytokine production without an effect on RV14 infection and RV14-induced cytokine production. These findings imply that RV2 upregulates LDL receptor expression on airway epithelial cells, thereby increasing susceptibility to minor group RV infection. LDL receptor expression and cytokine production may be mediated, in part, via activation of transcription factors by RV2. These events may be important in airway inflammation after minor group RV infection in asthma.

Aged↗
PubMed2001

Adrenomedullin inhibits angiotensin II-induced expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells.

Adrenomedullin (AM) is a potent vasodilating peptide having a variety of pharmacological properties mainly in respect to vascular pathophysiology. We have previously demonstrated that angiotensin II (Ang II) or natriuretic peptides have influence on the expression of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) in vascular endothelial cells. The aim of this study was to elucidate the effects of AM on TF and PAI-1 mRNA and protein expression in endothelial cells. As a result, AM inhibited Ang II-induced TF and PAI-1 mRNA expression in a dose- and time-dependent manner. Because the expression of TF and PAI-1 mRNA induced by Ang II was attenuated by the increase of intracellular concentrations of cAMP by forskolin and 8-bromo-cAMP and because AM increased the intracellular level of cAMP in rat aortic endothelial cells, it was indicated that the inhibitory effect of AM on the expressions of TF and PAI-1 was mainly mediated by the cAMP-dependent signal transduction. Furthermore, the inhibitory effect of AM on TF and PAI-1 expression was partly attenuated by an NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester. In conclusion, AM is shown to contribute to the regulation of blood coagulation and fibrinolysis by vascular endothelial cells mainly via the cAMP pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for PPARs in L6 myotubes.

Uncoupling protein 3 (UCP3), which uncouples electron transport from ATP synthesis, is expressed at high levels in the skeletal muscle, an important organ in glucose and lipid metabolism. Because several reports proposed that fatty acids induced UCP3 gene expression in skeletal muscle in vivo, in the present study we examined the regulation of UCP3 gene expression by various fatty acids using L6 myotubes. UCP3 gene expression was increased in L6 myotubes by various fatty acids or by alpha-bromopalmitate, a nonmetabolized derivative of palmitic acid. Because fatty acids are also known as agonists for PPARs, we examined the involvement of PPARs in the regulation of the UCP3 gene expression. L-165041, a PPAR delta agonist, increased UCP3 gene expression in L6 myotubes, whereas neither Wy 14,643, a PPAR alpha agonist, nor Pioglitazone, a PPAR gamma agonist, increased it. Therefore, we conclude that UCP3 gene expression is increased by the activation of PPAR delta in L6 myotubes and postulate that PPAR delta mediates at least some part of the increased UCP3 gene expression by fatty acids in skeletal muscle in vivo.

Animals↗
PubMed2001

Troglitazone not only increases GLUT4 but also induces its translocation in rat adipocytes.

Thiazolidinediones, insulin-sensitizing agents, have been reported to increase glucose uptake along with the expression of glucose transporters in adipocytes and cardiomyocytes. Recently, we have further suggested that the translocation of GLUT4 is stimulated by thiazolidinediones in L6 myocytes. However, the direct effects of thiazolidinediones on translocation of glucose transporters have not yet been determined. In this study, using hemagglutinin epitope-tagged GLUT4 (GLUT4-HA), we provide direct evidence of the effect of troglitazone on the translocation of GLUT4 in rat epididymal adipocytes. Primary cultures of rat adipocytes were transiently transfected with GLUT4-HA and overexpressed eightfold compared with endogenous GLUT4 in transfected cells. A total of 24 h of treatment with troglitazone (10(-4) mol/l) increased the cell surface level of GLUT4-HA by 1.5 +/- 0.03-fold (P < 0.01) without changing the total amount of GLUT4-HA, whereas it increased the protein level of endogenous GLUT4 (1.4-fold) without changing that of GLUT1. Thus, the direct effect on the translocation can be detected apart from the increase in endogenous GLUT4 content using GLUT4-HA. Troglitazone not only increased the translocation of GLUT4-HA on the cell surface in the basal state but also caused a leftward shift in the dose-response relations between GLUT4-HA translocation and insulin concentration in the medium (ED(50): from approximately 0.1 to 0.03 nmol/l). These effects may partly contribute to the antidiabetic activity of troglitazone in patients with obesity and type 2 diabetes.

Adipocytes↗
PubMed2001

Troglitazone induces GLUT4 translocation in L6 myotubes.

A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10(-5) mol/l) caused a substantial increase in the 2-deoxy-[3H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 micromol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 x 10(-6) mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-lambda, PKC-beta2, and PKC-zeta; or 5'AMP-activated protein kinase activity. a-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.

Animals↗
PubMed2001

[Survey of vaccination for physically-handicapped and epileptic children].

We studied immunization for 128 handicapped patients, from 3 to 15 years of age, in a Seishi Gakuen Hospital, with 8 vaccines: diphtheria-purified acellular pertussis-tetanus combined (DPT), BCG, polio, measles, rubella, mumps, varicella, and Japanese B encephalitis. The rate of vaccination in these patients was lower than in healthy children at 3 years of age in Kanazawa City. There was no significant difference between patients with and without epilepsy. The rate was higher in the hospitalized patients than in the outpatients. More than 90% of the hospitalized patients was immunized against influenza under informed consent in 1997 and 1998. Despite pandemics of influenza in Kanazawa City, where the hospital was located, the period of fever by influenza was significantly shorter in our patients in both 1997 and 1998 than in 1996. Although a half of our patients had epilepsy, they were safely vaccinated with few side effects.

Adolescent↗
PubMed2001

Impaired IL-15 production associated with susceptibility of murine AIDS to mycobacterial infection.

LP-BM5 murine leukemia virus (MuLV) injection causes murine AIDS (MAIDS), a disease characterized by many functional abnormalities of immunocompetent cells. We show that MAIDS mice are susceptible to Mycobacterium bovis Bacille Calmette-Guérin (BCG) infection as assessed by survival rate and bacterial counts. The peritoneal exudate macrophages from MAIDS mice produced a significant level of interleukin (IL)-12 soon after inoculation with BCG, whereas IL-15 and tumor necrosis factor (TNF) production were severely impaired in BCG-infected MAIDS mice. The appearance of natural killer (NK) and CD4+ T helper type 1 (Th1) cells specific for mycobacterial antigen were depressed in MAIDS mice after BCG infection. Thus, it appeared that impaired production of IL-15, besides other inflammatory cytokines, in MAIDS mice may be involved in the poor responses of the NK and Th1 cells, resulting in an increased susceptibility to BCG.

Animals↗
PubMed2001

[Human obesity and point mutations of leptin and leptin receptor].

Obesity-related genes were isolated and identified in these several years. Development of transgenic mice has clarified the molecular mechanisms of obesity. There have been reported point mutations of the genes correspond to leptin(ob-gene) and leptin receptor(db-gene). Thereby leptin is considered to be one of the most important regulators of energy metabolism also in human.

Animals↗
PubMed2001

[Diagnosis of soft tissue tumors: 10 checkpoints].

This review, presents 10 checkpoints for the diagnosis of soft tissue tumors and the MRI reporting method for the general radiologists. The 10 checkpoints consist of the following, (1) clinical information, (2) calcification, (3) characteristic shape, (4) multiplicity, (5) lymph node enlargement, (6) characteristic sign and appearance, (7) internal morphology (fatty component, myxoid matrix, collagenous tissue), (8) flow void, (9) early, strong enhancement, and (10) malignant lymphoma and inflammatory masses for differential diagnosis. A combination of these individual points yields higher sensitivity and specificity for tissue-specific diagnosis and differentiation between benign and malignant lesions. Although pathology will always remain the gold standard in the diagnosis of soft tissue tumors, prediction of a specific histologic diagnosis remains one of the ultimate goals of each imaging technique. Moreover, decisions regarding biopsy and treatment could be simplified if a specific diagnosis or a limited differential diagnosis could be provided on the basis of imaging.

Adipose Tissue↗
PubMed2001

Relations of the c-myc gene and chromosome 8 in non-small cell lung cancer: analysis by fluorescence in situ hybridization.

BACKGROUND: Amplification of the c-myc gene has been reported in non-small cell lung cancer (NSCLC). We investigated the c-myc gene amplification and the numerical aberration of chromosome 8 by dual color fluorescence in situ hybridization (FISH) to evaluate the relation between possible genetic abnormalities, pathological factors and prognosis. METHODS: Tumor tissue samples were obtained from 31 patients with NSCLC who underwent lobectomy with mediastinal lymph node dissection. Samples were analyzed by FISH using 8 alpha satellite DNA probe and c-myc gene cosmid probe. The relation between genetic abnormalities, pathological factors (T factor, tumor size, and N factor), and prognostic factors was evaluated by univariate and multivariate analysis, and by the Kaplan-Meier method and log-rank analysis. RESULTS: Chromosome 8 aberrations were T1 (n=3), 44.0%; T2 (n=18), 35.7%; T3 (n=7), 40.0%; T4 (n=3), 39.7% (p=NS). The c-myc gene amplifications were T1, 54.3%; T2, 51.1%; T3, 51.0%; T4, 66.3% (p=NS). There was no difference between patients whose tumor was more than 5 cm (n=16), and 5 cm or less (n=15) in the rate of chromosome 8 aberration (39.3%: 36.3%), or the rate of the c-myc gene amplification (52.1%: 53.7%). N factors for chromosome 8 aberrations were N0 (n=18), 35.9%; and N2 (n=11), 44.9% (p=NS). In the c-myc gene amplification, there was a significant difference between N0 and N2 (48.6%, 61.3%, p=0.040). In univariate and multivariate analysis, chromosome 8 aberrations correlated with a poor prognosis (p=0.037 and p=0.041). The 5-year survival rate was 15.4% in patients whose rate of chromosome 8 aberrations was 40% or more (n=13), which was significantly less than that in patients with an aberration rate of less than 40% (n=19, 57.9%, p=0.014). CONCLUSION: The c-myc gene amplification correlates with lymph node metastasis. Although there was no significant link between the amplification of the c-myc gene and clinical outcome, the numerical chromosome 8 aberrations was considered to be a factor for survival.

Adult↗
PubMed2001

[The relation between the severity of bronchial asthma and the treatment points in children].

The treatment points and score for definition of the asthma severity were initially introduced in the guideline for pediatric asthma treatment and management on 1998. We studied the relationship between the severity of clinical symptoms for children with bronchial asthma and the treatment points from July 1998 to November 1999 in our hospital. One hundred twenty five patients (one to 15 years of age, 77 boys and 48 girls) were retrospectively investigated. The treatment points and scores were associated with the clinical symptom score. However, there was no relationship in some patients. In order to define the severity of bronchial asthma, we should investigate not only the severity in terms of the clinical symptoms; the number and degree of asthma attacks, but also the treatment points and score. Furthermore, we should pay attention to the seasonal variation of the treatment points.

Adolescent↗
PubMed2000

Reciprocal modulation of transcriptional activities between HIV-1 Tat and MHC class II transactivator CIITA.

HIV-1 is the etiologic agent of acquired immune deficiency syndrome (AIDS). Functional loss of antigen-presenting cells (APC) in HIV-1 infection is considered to be involved in AIDS pathogenesis. We found that actions of the viral transactivator Tat and the transactivator of MHC class II genes, CIITA, are mutually inhibitory. While Tat inhibited expression of MHC class II genes in APC, overexpression of CIITA inhibited Tat and subsequently HIV-1 replication. This action of Tat appears to be mediated by sequestering the common cofactor, cyclin T1, but not p300 and CBP. These reciprocal actions between Tat and CIITA not only explains the functional impairment of APC in HIV-1 infection but also rationalizes the suppression of HIV-1 virus load by induction of CIITA such as IFN-gamma.

Cell Line↗
PubMed2000

Memory-type CD8+ T cells protect IL-2 receptor alpha-deficient mice from systemic infection with herpes simplex virus type 2.

IL-2Ralpha-deficient (IL-2Ralpha(-/-)) mice exhibit an impaired activation-induced cell death for T cells and develop abnormal T cell activation with age. In our study, we found that IL-2Ralpha(-/-) mice at the age of 5 wk contained an increased number of CD44(+)CD69(-)CD8(+) T cells in lymph nodes, which expressed a high intensity of IL-2Rbeta and vigorously proliferated in response to a high dose of IL-15 or IL-2. The T cells produced a large amount of IFN-gamma in response to IL-15 plus IL-12 in a TCR-independent bystander manner. When IL-2Ralpha(-/-) mice were inoculated i.p. with HSV type 2 (HSV-2) 186 strain, they showed resistance to the infection accompanied by an increased level of serum IL-15. The depletion of CD8(+) T cells by in vivo administration of anti-CD8 mAb rendered IL-2Ralpha(-/-) mice susceptible to HSV-2-induced lethality. These results suggest that memory-type CD8(+) T cells play a novel role in the protection against HSV-2 infection in IL-2Ralpha(-/-) mice.

Animals↗
PubMed2000

Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.

PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell receptor-mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon gamma, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation.

Amino Acid Sequence↗
PubMed2000

A protective role of interleukin-15 in a mouse model for systemic infection with herpes simplex virus.

To define the role of cytokine binding to the IL-2/IL-15R beta chain in protective immunity against systemic infection with herpes simplex virus type 2 (HSV-2), IL-2/IL-15 receptor(R)beta knock-out mice were inoculated intraperitoneally with HSV-2 strain 186. IL-2/IL-15R beta-deficient mice were susceptible to systemic HSV-2 infection compared with their heterozygous littermates. The emergence of natural killer (NK) cells was impaired in IL-2/IL-15R beta knock-out mice, but CD4(+) T cell receptor (TCR) alpha beta(+) T cells were normally detected in the peritoneal cavity after infection with HSV-2. However, the generation of HSV-2-specific CD4(+) T helper (Th) 1 cells producing interferon-gamma was impaired in IL-2/IL-15R beta knock-out mice following HSV-2 infection. The serum IL-15 level in control mice was increased in the early stage after HSV-2 infection but was not detectable in IL-2/IL-15R beta knock-out mice. In vivo administration of recombinant IL-15 protected normal mice from HSV-2-induced lethality, accompanied by increases in numbers of NK cells and HSV-2-specific Th1 cells. Taken together, these results suggest that IL-15, using the IL-2/IL15R beta chain, plays an important role in mounting protective immunity during the course of systemic HSV-2 infection.

Animals↗