Biomedical subjects

N Yamashita

Publications and source records attributed to N Yamashita.

At least 19 recordsLinked to original sources

PubMed1998

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes.

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined: Interleukin-1 beta induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS, L-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2 (0.1 mM, 1 h). Inhibition of iNOS with N omega-nitro-L-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

1-Methyl-3-isobutylxanthine↗

PubMed1998

[Limited operation for stage I lung cancer: a retrospective study].

Although lobectomy is standard therapy for Stage I non-small cell lung cancer, it often cannot be performed in poor-risk patients. In this report, we describe the results of a retrospective study to assess the usefulness of limited operation for stage I lung cancer. Over a 21-year period, 1,286 lung cancers were resected at our center. Among the 497 patients with stage I lung cancer, 36 sublobar resections were performed. There was only one surgery-related death, and the 5-year survival rate was 46% for all patients. At 5 years, survival was 69.2% for patients with squamous cell carcinoma and 33.7% for patients with adenocarcinoma. Survival rates were higher in patients who underwent mediastinoscopy than those who did not, and depended on histological findings and accurate pathological staging.

Adenocarcinoma↗

PubMed1997

Phosphodiesterase type 4 that regulates cAMP level in cortical neurons shows high sensitivity to rolipram.

To characterize the role of phosphodiesterase type 4 (a cAMP-specific and rolipram-sensitive phosphodiesterase) among phosphodiesterases in the regulation of the intracellular cAMP level in cortical neurons, we investigated the effects of phosphodiesterase inhibitors on the intracellular cAMP levels in primary cultured rat cortical neurons. Selective inhibitors of phosphodiesterase type 4 and type 2 significantly enhanced beta-adrenoceptor-mediated cAMP increase. Selective inhibitors of phosphodiesterase type 1, type 3 and type 5/6 had no effect on the cAMP level. Rolipram enhanced the beta-adrenoceptor-mediated cAMP increase in cortical neurons, astrocytes and vascular smooth muscle cells at different minimum effective concentrations (10, 100 and 1000 nM, respectively). These findings indicate that phosphodiesterase type 4, showing a high-sensitivity to rolipram, plays a major role in regulating cAMP in the cortical neurons, and that rolipram at low doses enhances the intracellular cAMP increase in the cortical neurons selectively.

Adenylyl Cyclases↗

PubMed1997

Autoreactive T cell clones from patients with systemic lupus erythematosus support polyclonal autoantibody production.

This work examines the functional properties and TCRbeta gene utilization of 15 autoreactive T cell clones derived from five patients with systemic lupus erythematosus. All these clones proliferated and secreted cytokine when stimulated in vitro by autologous (but not allogenic) B cells. Individual T cell clones used diverse TCRbeta genes and did not show skewing toward the preferential usage of anionically charged receptors. Autoreactive T cell clones supported polyclonal B cell activation, as characterized by the production of anti-DNA, anti-Sjögren syndrome A, and anti-tetanus toxoid (anti-TT) Abs. This T cell help was mediated through the production of immunostimulatory cytokines, especially IL-6. Although stimulation of the autoreactive clones was blocked by anti-HLA class II Abs, the T cell clones did not proliferate, nor did they support polyclonal IgG production by HLA class II-matched normal B cells. Unlike the autoreactive clones, TT-specific clones derived from the same patients provided help selectively to B cells secreting anti-TT Abs. These findings suggest that autoreactive T cells from systemic lupus erythematosus patients are triggered to provide help following cognate interactions with self-peptides presented in the context of HLA class II molecules expressed on autologous B cells regardless of their specificities.

Amino Acid Sequence↗

PubMed1997

The effect of azelastine on acute radiation dermatitis in mice models.

PURPOSE: In our previous report we described the clinical value of azelastine, an oral antiallergic agent, as an inhibitor of radiation dermatitis. Here we studied the effect of azelastine on normal skin and tumor size after irradiation in a mouse model. METHODS AND MATERIALS: The modifying effects of azelastine on both the degree of radiation dermatitis and antitumoral effect of radiation therapy were investigated in the normal skin as well as in SCC VII tumors of C3H/He mice. The right hind legs, with or without tumors, were irradiated with 20-60 Gy at 0.62 Gy/min. Azelastine was administered via the mouse chow, and acute skin reactions and tumor growth curves were compared between the azelastine and control groups. RESULTS: The acute skin reactions of the azelastine group were significantly less prominent than those of the control group (p < 0.01). At a dose of 40 Gy the dose modification factors were 1.19-1.25. The tumor growth curves of the azelastine and control groups were almost identical, indicating that the treatment response of irradiation was not affected by administration of azelastine. CONCLUSIONS: Application of azelastine reduces the degree of acute radiation dermatitis without affecting the antitumoral effect of radiation therapy.

Animals↗

PubMed1997

Scanning electron microscopic evaluation of the skin surface after ultrasound exposure.

BACKGROUND: Transdermal drug-delivery systems have become widely accepted clinically for the administration of several systemic drugs. Recently, research on ultrasound irradiation to facilitate the penetration of drugs through the skin have been reported. The present study investigated the morphological changes induced in skin after ultrasound irradiation to hairless mouse skin and human skin. METHODS: Hairless mice and human skin were immersed in an ultrasound irradiation water tank. Ultrasound was delivered for a duration of 5 min. Ultrasound frequency of 48 kHz was generated at an intensity of 0.5 W/cm2. The surface of the skin was observed with scanning electron microscopy for comparison with skin samples unexposed to ultrasound energy. RESULTS: For hairless mouse exposed to ultrasound, the cells of the stratum corneum of the skin surface were almost completely removed. The polygonal cells of the stratum spinosum and basal cells were exposed. In addition, large craterlike pores with a diameter of 100 microns were formed sporadically in some of the skin samples. In contrast, the surface of human skin exposed to ultrasound showed only slight removal of keratinocytes around the hair follicles. CONCLUSION: The removal of the stratum corneum and other alterations in hairless mouse and human skin by ultrasound may explain the enhancement of transdermal drug penetration. The effect on human skin was relatively minor compared with that on hairless mouse skin.

Animals↗

PubMed1997

Heat shock-induced manganese superoxide dismutase enhances the tolerance of cardiac myocytes to hypoxia-reoxygenation injury.

We evaluated the mechanism of the heat shock-induced tolerance to ischemia-reperfusion using a model of hypoxia-reoxygenation tolerance in neonatal rat cardiac myocytes. Myocytes exposed to heat shock (42 degrees C, 1 h) exhibited a 1.8-fold increase in levels of manganese superoxide dismutase (Mn-SOD) mRNA after 40 min v control cells. The concentration of Mn-SOD increased from 0.49+/-0.04 microg/mg protein to 0.68+/-0.05 microg/mg protein after 24 h (P<0. 05). Levels of heat shock protein 72 (hsp72; inducible form) mRNA and protein also increased markedly after heat shock exposure. The release of creatine kinase (CK) from the myocytes and the depletion of ATP level in the myocytes exposed to hypoxia (pO2: 7 mmHg, 3 h) and reoxygenation (pO2: 143 mmHg) were significantly reduced following heat shock pretreatment (CK: 1.18+/-0.14 U/l v 0.62+/-0.13 U/l, ATP: 11.9+/-1.1 nmol/mg protein v 16.2+/-1.0 nmol/mg protein, P<0.05). Treatment with antisense oligodeoxyribonucleotides to Mn-SOD (1.5 micromol/l) completely inhibited the heat shock-associated induction of Mn-SOD (0.47+/-0.05 microg/mg protein), but not hsp72, and abolished the heat shock-induced decrease in CK release (1.04+/-0.15 U/l, P<0.05) and depletion of ATP level (11. 2+/-1.1 nmol/mg protein, P<0.05). Results indicate that Mn-SOD induction, not hsp72 induction, plays a pivotal role in the heat shock-induced acquisition of tolerance to hypoxia-reoxygenation in neonatal rat cardiac myocytes.

Animals↗

PubMed1997

Time course of tolerance to ischemia-reperfusion injury and induction of heat shock protein 72 by heat stress in the rat heart.

We compared the time course of tolerance to myocardial ischemia-reperfusion injury with the time course of heat shock protein 72 (hsp72; inducible form) induction after heat stress in a rat model. The size of the infarct resulting from ischemia-reperfusion was increased 12 h after whole-body hyperthermia (42 degrees C for 15 min), but was significantly decreased 48 and 72 h after hyperthermia, compared with the sham control. The infarct size was decreased as late as 96 h after hyperthermia, although the infarct-limiting effect was smaller at that time. The myocardial content of hsp72 was markedly increased for 3-72 h after hyperthermic treatment, and was decreased after 72 h in association with an increase in the infarct size. The hsp72 content remained elevated during the period of tolerance to ischemia-reperfusion injury, but the infarct size decreased after the hsp72 content peaked. Pretreatment with a protein kinase C (PKC) inhibitor, chelerythrine chloride, immediately before hyperthermia, significantly suppressed the delayed cardioprotective effect of hyperthermia and reduced hsp72 induction. These results suggest that newly synthesized hsp72 through PKC activation after heat stress may have to be post-translationally modified and compartmentalized prior to assuming to the development of the delayed tolerance to ischemia-reperfusion injury in rats.

Animals↗

PubMed1997

Immature teratoma producing alpha-fetoprotein without components of yolk sac tumor in the pineal region.

A case of pineal region tumor in a 9-year-old boy with a high serum alpha fetoprotein (AFP) level is reported. The serum levels of beta-human chorionic gonadotropin (HCG) and placental alkaline phosphatase (PLAP) were not elevated. The tumor was composed of radiologically different components and was removed surgically. Postoperative radiation therapy was performed and the serum level of AFP gradually declined to the normal range. The pathological diagnosis was immature teratoma, and no elements of yolk sac tumor or embryonal carcinoma were found. In the immunohistochemical study, AFP was detected in the cytoplasm of gastrointestinal-type epithelium and primitive neuroepithelial element. This is considered a rare case of intracranial immature teratoma in which AFP was detected immunohistochemically in the columnar epithelium and immature neural tissue.

Biomarkers, Tumor↗

PubMed1997

Vascular angiotensin-converting enzyme activity in cholesterol-fed rabbits: effects of enalapril.

Many reports have shown inhibitory effects of angiotensin-converting enzyme (ACE) inhibitors on the progression of atherosclerotic plaque lesions in vascular tissue of experimental models. However, no report has shown alterations of ACE activity in vascular tissue during the process of atherosclerosis. We measured ACE activity in plasma and aortic tissue in rabbits fed a cholesterol-rich (1%) or normal diet for 10 weeks. We also evaluated the blood pressure response to angiotensin (Ang) I and II. These data were compared in untreated rabbits and in rabbits receiving chronic treatment with an ACE inhibitor, enalapril (3 mg/kg/day for 10 weeks). ACE activity in aortic tissue, but not in plasma, in cholesterol-fed rabbits was gradually but significantly increased compared with that in noncholesterol-fed rabbits even after the 4-week feeding period, when no atherosclerotic lesion was observed in the aortic tissue. Treatment with enalapril for 10 weeks, but not 4 weeks, significantly reduced the ACE activity in aortic tissue in association with the reductions in the elevated Ang II level and the atherosclerotic plaque area of the aortic tissue. These results indicated that ACE activity in aortic tissue was increased during the early phase of atherosclerotic process.

Angiotensin I↗

PubMed1997

Soluble E-selectin as a marker of disease activity in atopic dermatitis.

BACKGROUND: Augmentation in the expression of adhesion molecules on endothelial cells can regulate leukocyte migration. These molecules are also shed into the circulation. The level of soluble adhesion molecules in the serum is known to reflect the degree of systemic inflammation, and this level can therefore be used as a marker of inflammation. OBJECTIVE: To elucidate whether soluble adhesion molecules can be used as the marker of disease severity in atopic dermatitis, we examined the levels of soluble E-selectin, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 and compared these levels with the patients' symptom scores and their total serum IgE levels. METHODS: Fifty-three patients with atopic dermatitis were studied. Soluble adhesion molecules were measured by ELISA. RESULTS: The level of soluble E-selectin was higher in patients with atopic dermatitis than in healthy control subjects (p < 0.01). Moreover, soluble E-selectin is correlated with disease severity (p < 0.01). Soluble E-selectin also reflected the changes in symptom scores. In contrast, there were no differences in soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 between the patients and control subjects. CONCLUSION: Soluble E-selectin is a good marker of disease severity and of its activity in atopic dermatitis.

Adult↗

PubMed1997

Characterization of T cells specific for an epitope of human 60-kD heat shock protein (hsp) in patients with Behcet's disease (BD) in Japan.

BD is prevalent in the area of the Silk Route. It has been shown that hsp are involved in the T cell activation in patients with BD in the UK, where this disease has developed sporadically. We have thus examined whether the T cell response to the hsp-derived peptides may be induced in patients with BD in Japan, an east pole of the Silk Route. As with patients in the UK, the human 60-kD hsp peptide 336-351 also yielded vigorous proliferation of T cells in Japanese patients with BD, but neither in normal subjects nor in patients with rheumatoid arthritis (RA); there was significant association between proliferation by this peptide and the presence of ocular lesion, but not any other symptoms of BD. To clarify whether the peptide stimulates T cells as a polyclonal activator, a specific antigen or a superantigen-like substance, we analysed T cell receptor (TCR) usage of responding T cells by means of MoAbs specific for TCR Vbeta subfamily and polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP)-based technique. We found that T cells with certain TCR Vbeta subfamilies (including Vbeta5.2-3, 8, 13.6, 18, 21.3) were increased in circulation and responded to the hsp peptide in an antigen-specific fashion. In addition, TCR Vbeta gene-amplified products of freshly isolated T cells of patients with BD formed several bands in the PCR-SSCP analysis; some of them became prominent after stimulation with the peptide. This suggests that T cells in patients with this disease have already been expanded oligoclonally in vivo, which may be a result of stimulation by triggering antigens, including the hsp peptide. In addition, hsp peptide stimulation induced proinflammatory cytokine mRNA expression in peripheral blood mononuclear cells, including IL-8, tumour necrosis factor-alpha (TNF-alpha) and TNF-beta in eight out of eight patients studied. Taken together, the results suggest that hsp antigen may play a role in the pathogenesis of BD, not only in the area of the Silk Route, but also outside the Silk Route area.

Adult↗

PubMed1997

Therapeutic effects of preferential induction of mite-specific T helper 0 clones.

The predominance of Th2 cytokine-secreting pattern in allergic asthma has been known as a cause and an accelerating factor, and Th1 suppresses these allergic phenomena, but the role of Th0 clones is obscure. Because Th1/Th2 differentiation has been determined by cytokine environment, we investigated how mite-specific helper T cells stimulated in different cytokine environments actually influenced IgE and IgG4 synthesis, which are known to be regulatory immunoglobulins for allergic response. Th0 clones, which were mainly established in the presence of IL-12, provided a great deal of help for IgG4 and IgG1 synthesis, but did not provide help for IgE synthesis, whereas Th2 clones helped IgE synthesis prominently, and IgG4 and IgG1 synthesis marginally. These characteristics of Th0 clones were also true for Th0 clones obtained from patients who were successfully treated with desensitization therapy. Furthermore, the differences in helper activity between Th0 and Th2 clones were not ascribed solely to soluble factors. These data indicate that IgE and IgG4 synthesis is differentially regulated by antigen-specific T cells, and that conversion or selection from Th2 to Th0 by the addition of IL-12 may exhibit therapeutic effects.

Adult↗

PubMed1997

Role of gammadelta T lymphocytes in the development of Behçet's disease.

Phenotypic and functional properties of gammadelta T cells, which play an important role in mucocutaneous immunity, were examined to elucidate whether immunological abnormality in Behcet's disease may be related to a specific T cell population. We found that CD45RA+ Vgamma9+ Vdelta2+ gammadelta T cells, which constitute a minor population of gammadelta T cells in healthy individuals, were increased in number in Behçet's disease irrespective of disease activity. This CD45RA+ subset of gammadelta T cells in the active, but not inactive, phase of this disease expressed IL-2Rbeta and HLA-DR, suggesting that they are activated in vivo in active Behçet's disease. In addition, the CD45RA+ gammadelta T cells produced extreme amounts of tumour necrosis factor and contained perforin granules. These data indicate that a phenotypically distinct subset of gammadelta T cells, CD45RA+ CD45RO- Vgamma9+ Vdelta2+, may contribute to immunological abnormalities which may lead to complexity of pathophysiology in Behçet's disease.

Adult↗

PubMed1997

Long-term probucol treatment reverses the severity of myocardial injury in watanabe heritable hyperlipidemic rabbits.

We previously reported that administration of NO donors ameliorates the severity of myocardial injury in cholesterol-fed rabbits. We now evaluated the effects of probucol, a lipid-lowering antioxidant that can preserve endothelium-dependent relaxation (EDR), in the aortas of cholesterol-fed rabbits. We examined the effects of short-term (7 days) or long-term (24 weeks) administration of 1% probucol on the size of infarcts resulting from 30 minutes of coronary occlusion followed by reperfusion (for 48 hours) in Watanabe heritable hyperlipidemic (WHHL) rabbits. Infarcts in untreated WHHL rabbits were significantly larger than those in the rabbits receiving the long-term but not the short-term treatment with probucol (72.2 +/- 5.4%, 37.6 +/- 6.4%, and 66.7 +/- 3.5%, respectively). Long-term probucol treatment also significantly reduced myeloperoxidase activity in both ischemic and nonischemic myocardium and suppressed P-selectin expression in the coronary vasculature. No significant differences were observed in hemodynamic parameters during myocardial ischemia/reperfusion. Long-term probucol treatment significantly reduced the surface area of atherosclerotic plaque lesions in the aorta (24.4 +/- 3.8% vs 46.3 +/- 6.3, P < .05). Moreover, long-term probucol treatment restored acetylcholine-induced EDR in aortic rings but did not affect sodium nitroprusside-induced relaxation. Finally, long-term probucol treatment resulted in significantly elevated cGMP levels in the aorta. These results indicate that long-term probucol treatment significantly ameliorates myocardial injury in heritable atherosclerotic rabbits, perhaps by reducing the accumulation of leukocytes in the myocardium and atherosclerotic vascular lesions. Thus, long-term administration appears to suppress the progression of atherosclerotic vascular disease in this animal model.

Administration, Oral↗

PubMed1997

Regulation of K+ channels by cell contact in a cloned folliculo-stellate cell (TtT/GF).

Membrane currents in a folliculo-stellate cell line (TtT/GF) were examined using the whole-cell clamp technique. The cultured cells were morphologically categorized as isolated spread cells, isolated round cells, contact spread cells, and contact round cells. A distinct outward current was observed in isolated spread cells, contact round cells, and contact spread cells, whereas the outward current detected in isolated round cells was barely perceivable. The reversal potentials of the outward tail current obeyed the Nernst equation, indicating that the outward current was carried by K+ ions. The activation and deactivation processes of the K+ current could be fitted by single exponential curves. 4-aminopyridine, tetraethylammonium, and Ba2+ inhibited the K+ current. The concentrations for half-maximal inhibition of these agents to block the K+ current were 0.2 mM, 0.8 mM, and 8 mM, respectively. The biophysical and pharmacological characteristics of the K+ current in TtT/GF cells were similar to those of the K+ current in glial and Schwann cells. According to the results of the present study, it was concluded that TtT/GF cells possessed outward K+ channels, characteristics of which were similar to those of the K+ channels in glial and Schwann cells, and that the amplitude of the K+ current in TtT/GF cells seemed to be regulated by the condition of the cell contact.

4-Aminopyridine↗

PubMed1997

Rolipram, a phosphodiesterase-4-selective inhibitor, promotes the survival of cultured rat dopaminergic neurons.

We evaluated the effects of rolipram, a selective inhibitor of phosphodiesterase (PDE) 4, on the survival of dopaminergic neurons in 13-day culture. Rolipram did not affect the survival of dopaminergic neurons in the absence of forskolin, but significantly enhanced the survival of dopaminergic neurons in the presence of 10(-5) M forskolin in a concentration-dependent manner (10(-8) - 10(-5) M). Rolipram also enhanced the neurotrophic effect of forskolin on total neurons including dopaminergic and non-dopaminergic neurons at a high concentration (10(-5) M), but did not affect the survival of cells containing glutamate or gamma-aminobutylic acid. A non-selective PDE inhibitor, 1-isobutyl-3-methylxanthine, caused a marked increase of dopaminergic neurons, whereas selective inhibitors of PDE2 and PDE3 showed far weaker effects. A PDE1 inhibitor, on the other hand, caused non-specific cell death in the presence or absence of forskolin. These findings suggest that rolipram has a potential to enhance the survival of dopaminergic neurons selectively by way of PDE4 inhibition.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1997

Rolipram, a selective inhibitor of phosphodiesterase type 4, pronouncedly enhanced the forskolin-induced promotion of dopamine biosynthesis in primary cultured rat mesencephalic neurons.

A selective inhibitor of cyclic nucleotide phosphodiesterase (PDE) 4, rolipram, markedly enhanced the forskolin-induced increase of intracellular dopamine and dihydroxyphenylacetate (DOPAC, a metabolite of dopamine) levels in primary cultured rat mesencephalic neurons and the forskolin-induced increase of dopamine and DOPAC in extracellular medium. Selective inhibitors of PDE2, PDE3, PDE5 and PDE6 did not have such a promoting effect, and the PDE1 inhibitor vinpocetine and W-7 caused dopamine depletion in the neurons. These findings suggested that PDE4 plays a major role in regulating the intracellular cAMP level to control the dopamine biosynthesis in mesencephalic neurons, whereas PDE1 regulates dopamine release instead.

3',5'-Cyclic-AMP Phosphodiesterases↗