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Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 199 records · Page 11Linked to original sources
PubMed1996

Tuberculous pseudoaneurysm of the descending thoracic aorta: a case report and literature review of surgically treated cases.

Tuberculous aneurysm of the aorta is an extremely rare disease with a high mortality rate. Only 32 patients treated surgically have been reported in the literature. These reports indicate an 84.4% operative survival rate. We present a case of a tuberculous false aneurysm in the descending thoracic aorta that was successfully treated surgically with an extracorporeal circulation. The hole in the aorta within the false aneurysm was closed with a Dacron patch because the aortic wall appeared to be free of active infection as a result of long-term preoperative antituberculous chemotherapy.

Aneurysm, False↗
PubMed1996

Reciprocal action of interferon-gamma and interleukin-4 promotes granulomatous inflammation induced by Rhodococcus aurantiacus in mice.

An intravenous injection of Rhodococcus aurantiacus to mice causes granulomatous inflammation dependent on endogenous interferon-gamma (IFN-gamma). The present study examined the role of endogenous interleukin-4 (IL-4) on granulomatous inflammation. Endogenous IL-4 in the spleen extracts was not detected during the phase of granuloma formation by enzyme-linked immunosorbent assay (ELISA). However, IL-4 protein level was elevated during the phase of granuloma regression. IL-4 mRNA expression in the livers and spleens was also elevated during the phase of granuloma regression. In addition, IL-4 levels during the phase of granuloma formation were increased by treatment with anti-IFN-gamma monoclonal antibody (mAb), suggesting that endogenous IFN-gamma might inhibit IL-4 production during the phase of granuloma formation. Administration of anti-IL-4 mAb on weeks 3 and 4 after the inoculation inhibited the regression of granulomas and augumented IFN-gamma level at 5 weeks. Endogenous IFN-gamma was produced by CD4+ T cells during the phase of granuloma regression and endogenous IL-4 was produced by both CD4+ and CD8+ T cells. These findings suggest that during the phase of granuloma formation endogenous IL-4 might be inhibited by IFN-gamma, while during the phase of granuloma regression endogenous IL-4 might play a crucial role in the reduction of granulomas and IFN-gamma production.

Actinomycetales Infections↗
PubMed1996

Possible mechanism of the potent vasoconstrictor actions of ryanodine on femoral arteries from spontaneously hypertensive rats.

1. The Ca2+ buffering function of sarcoplasmic reticulum (SR) in the resting state of arteries from spontaneously hypertensive rats (SHR) was examined. Differences in the effects of ryanodine that removes the function of SR, on tension and cellular Ca2+ level were assessed in endothelium-denuded strips of femoral arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). 2. The addition of ryanodine to the resting strips caused a concentration-dependent contraction in SHR. This contraction was extremely small in WKY. In the presence of 10(-5) M ryanodine, caffeine (20 mM) failed to cause a further contraction in SHR, but it caused a small contraction in WKY. After washout of the strips with a Krebs solution, the resting tone was greatly elevated in SHR when compared with WKY. 3. The elevated resting tone in SHR strips was abolished by 10(-7) M nifedipine. The ryanodine-induced contraction was also abolished by 10(-7) M nifedipine. Nifedipine itself caused a relaxation from the resting tone of SHR strips, suggesting the maintenance of myogenic tone. 4. In strips preloaded with fura-PE3, the addition of 10(-5) M ryanodine caused a large and moderate elevation of cytosolic Ca2+ level ([Ca2+]i) in SHR and WKY, respectively. After washout, the resting [Ca2+]i was greatly elevated in SHR. The ryanodine-induced elevation of [Ca2+]i was decreased by 5 x 10(-6) M verapamil in SHR. Verapamil itself caused a decrease in resting [Ca2+]i which was significantly greater in SHR than in WKY, and caused a relaxation only in SHR. 5. The resting Ca2+ influx in arteries measured by a 5 min incubation with 45Ca was significantly increased in SHR when compared with WKY. The resting Ca2+ influx was not increased by 10(-5) M ryanodine in both SHR and WKY. The net cellular Ca2+ uptake in arteries measured by a 30 min incubation with 45Ca was decreased by 10(-5) M ryanodine in both strains. 6. The resting Ca2+ influx was decreased by 10(-7) M nifedipine in the SHR artery, but it was unchanged in the WKY artery. 7. These results suggest that (1) the Ca2+ influx via L-type voltage-dependent Ca2+ channels was increased in the resting state of the SHR femoral artery, (2) the greater part of the increased Ca2+ influx was buffered by Ca2+ uptake into the SR and some Ca2+ reached the myofilaments resulting in the maintenance of the myogenic tone, and (3) therefore the functional removal of SR by ryanodine caused a potent contraction in this artery.

Animals↗
PubMed1996

Effect of YM934, a novel potassium-channel opener, in various experimental asthma models in guinea-pigs.

YM934 is a novel synthetic potassium-channel opener. We have investigated its anti-asthma effect after intravenous (i.v.) and oral (p.o.) administration in various experimental asthma models in the guinea-pig, and compared the results with those for lemakalim, theophylline and salbutamol. In an ovalbumin-active sensitization anaphylaxis asthma model, YM934, lemakalim, theophylline and salbutamol dose-dependently prolonged the time before the occurrence of asthma attacks and reduced the mortality rate. The respective ED50 values (dose required to prolong by 50% the time before the occurrence of attacks) of the anti-asthma effects of YM934, lemakalim, theophylline and salbutamol were 6, 340, 30000, and 45 micrograms kg-1 (i.v.); the efficacy ratios were YM934 (1) > salbutamol (1/9) > lemakalim (1/57) > > theophylline (1/5000). YM934 also prolonged the period before the occurrence of attacks in the anti-BSA (bovine serum albumin) serum-passive sensitization anaphylaxis, histamine-induced and methacho-line-induced asthma models, with respective ED50 values for these models of 15, 22 and 20 micrograms kg-1 (i.v.). Among these models a reduction in mortality rate was seen in the histamine- and methacholine-induced asthma models. After oral administration, YM934 showed an anti-asthma effect in the ovalbumin-active sensitization anaphylaxis, histamine-induced and methacholine-induced asthma models, with respective ED50 values of 38, 44 and 193 micrograms kg-1. YM934 was 5-6 times more potent than salbutamol. These results indicate that YM934 has potent anti-asthma activity, and that this activity is mainly attributable to bronchodilation, most likely mediated through its potassium-channel opening activity.

Administration, Oral↗
PubMed1996

Endogenous interleukin-4, but not interleukin-10, is involved in suppression of host resistance against Listeria monocytogenes infection in interferon-depleted mice.

The production and roles of endogenous interleukin-4 (IL-4) and IL-10 in a sublethal infection with Listeria monocytogenes were studies in normal mice and anti-gamma interferon (IFN-gamma) monoclonal antibody (MAb)-pretreated mice. In normal mice, the expression of mRNAs for IL-4 and IL-10, which was amplified by reverse transcription-PCR, was induced in the spleens and livers either early or late in infection, although the serum IL-4 and IL-10 were not detectable by enzyme-linked immunosorbent assays. In vivo administration of anti-IL-4 MAb showed no effect on antilisterial resistance, whereas anti-IL-10 MAb partially diminished the defense. In anti-IFN-gamma MAb-pretreated mice, a delay in the bacterial elimination from the spleens and livers was observed and high titers of serum IL-4 and IL-10 were induced late in infection. Production of endogenous IL-4 and IL-10 was suppressed in both CD4+ cell-and CD8+ cell depleted mice. The suppression of antilisterial resistance in anti-IFN-gamma MAb-pretreated mice was canceled when anti-IL-4 MAb was injected late in infection, whereas anti-IL-10 MAb showed no effect. These results suggest that the host immune responses were polarized into the T-helper 2 phenotype in anti-IFN-gamma MAb-pretreated mice and that inhibition of host resistance against L. monocytogenes by depletion of IFN-gamma might be attributable to IL-4 produced by T cells polarized into the T-helper 2 phenotype as well as the inhibition of the IFN-gamma effects.

Animals↗
PubMed1996

Transforming growth factor beta is protective in host resistance against Listeria monocytogenes infection in mice.

The role of transforming growth factor beta (TGF-beta) in host resistance against Listeria monocytogenes infection was studied with mice. The constitutive expression of TGF-beta 1 mRNA was observed in the spleens and livers of mice before and after infection. Injecting the mice with anti-TGF-beta 1 peptide serum resulted in diminished antilisterial resistance, whereas the administration of human platelet-derived TGF-beta 1 enhanced the resistance. Moreover, mice were protected against lethal infection when treated with TGF-beta 1. These results suggest the TGF-beta 1 might be involved in antilisterial resistance. On the other hand, injecting the mice with TGF-beta 1 resulted in a decrease in the titers of endogenous gamma interferon, tumor necrosis factor alpha, and interleukin-6, which are crucial in antilisterial resistance, in sera and in extracts of spleen and liver. Thus, a complicated mechanism might be involved in the role of TGF-beta 1 in host resistance against L. monocytogenes infection.

Animals↗
PubMed1996

Novel potassium channel activators: synthesis and structure-activity relationship studies of 3,4-dihydro-2H-1,4-benzoxazine derivatives.

Strong potassium channel-activating effects were found among a series of novel 4-substituted 3,4-dihydro-2H-1,4-benzoxazine derivatives. The key step in preparation was the nucleophilic substitution of 3,4-dihydro-2H-1,4-benzoxazine (3) with activated halogenopyridines, such as halogenopyridine N-oxides (15a--c) and the borane adduct (15d) of 4-bromopyridine. Structure-activity relationship studies identified 2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridin e-1-oxide (16a: YM934) as the optimal compound. This compound (16a) showed a more potent oral antihypertensive effect than cromakalim in conscious spontaneously hypertensive rats.

Animals↗
PubMed1996

Effect of tamsulosin, a novel alpha 1-adrenoceptor antagonist, on urethral pressure profile in anaesthetized dogs.

1. The effect of tamsulosin (YM617, (R) (-)-S-[2-[[2-(o-ethoxyphenoxy)ethyl]amino] propyl]-2-methoxybenzenesulfonamide HCl), a potent and selective alpha 1-adrenoceptor antagonist, was examined on urethral pressure profile (UPP) and mean arterial blood pressure (MBP) in pentobarbital anaesthetized male dogs. 2. Selective alpha 1-adrenoceptor antagonists tamsulosin (1-100 micrograms kg-1 i.v.), prazosin (1-100 micrograms kg-1 i.v.) and bunazosin (1-100 micrograms kg-1 i.v.) produced a dose dependent reduction in prostatic pressure in the UPP. Doses required to reduce prostatic pressure in UPP by 30% were 3.6 +/- 0.8 (n = 8), 6.9 +/- 1.5 (n = 8) and 4.6 +/- 0.9 (n = 8) micrograms kg-1 i.v., respectively. At the highest dose, tamsulosin exerted less hypotensive effect than prazosin and bunazosin. 3. The calcium antagonist nicardipine (0.1-10 micrograms kg-1 i.v.) and angiotensin converting enzyme inhibitor captopril (10-1,000 micrograms kg-1 i.v.) reduced MBP in a dose dependent manner, but exerted no effect on prostatic pressure in the UPP. The diuretic trichloromethiazide (1-100 micrograms kg-1 i.v.) exerted no effect on UPP or MBP. Treatment with nicardipine (3 micrograms kg-1 i.v.), captopril (100 micrograms kg-1 i.v.) or trichlormethiazide (100 micrograms kg-1 i.v.) did not affect relaxant effect of tamsulosin on prostatic pressure in UPP, or potentiate its hypotensive effect. 4. These results suggest that the alpha 1-adrenoceptor regulates urethral pressure as well as blood pressure in anaesthetized dogs, and that alpha 1-adrenoceptor antagonists may be useful in the treatment of micturition disorders associated with benign prostatic hyperplasia. In addition, as tamsulosin decreased urethral pressure with less hypotension, and as its effect was not influenced by treatment with hypotensive drugs, it may be a useful drug for the treatment of micturition disorders with few cardiovascular side effects.

Adrenergic alpha-Antagonists↗
PubMed1996

[Molecular aspects of secretory IgA (S-IgA) in gut-associated lymphoid tissues].

Secretory IgA, which plays an important role in the defense of the exocrine tissue, is composed of a polymeric IgA, joining (J) chain and secretory component (SC). Polymeric IgA and J chain are produced by plasma cells and SC by glandular epithelial cells. We here described the molecular aspects of J chain and SC. Study of the J chain has been confined to vertebrates which produce immunoglobulin (Ig) because the function of J chain is considered to be a polymerization of Ig. Recent molecular studies indicate that the role of J chain has been questioned. The J chain is expressed in invertebrates, as well as, representative species of vertebrates and that J chain is a primitive polypeptide that arose before the evolution of Ig molecules. SC is a 80 kDa glycoprotein functioning as a receptor for J chain-containing polymeric Ig. The expression of SC is regulated by various inflammatory cytokines such as, IL-1, IL-4, IL-6, IL-8, IFN-gamma and TNF-alpha, suggesting SC upregulation in vivo in inflammatory conditions. The human SC cDNA analysis reveals that it consisted of 11 exons with no functional TATA-box or CCAAT-box in the putative promoter region. Further upstream, there are several interesting motifs such as NF-kB and IFN-gamma response element, suggesting possible regulation of SC by cytokines through cellular signal transduction pathways.

Animals↗
PubMed1996

Superficial sarcoplasmic reticulum calcium buffering of resting, voltage-dependent Ca++ influx in rat femoral arterial smooth muscle.

To determine the Ca(+2)-buffering function of sarcoplasmic reticulum (SR) in the resting state of arterial smooth muscle, the effects of cyclopiazonic acid (CPA) and thapsigargin, which inhibit the Ca(+20-ATPase of SR, on tension and cytosolic Ca+2 level ¿[Ca+2]¿ were examined in endothelium-denuded strips of rat femoral artery. In resting strips preloaded with fura-PE3, the addition of CPA (10 microM) or thapsigargin (100 nM) caused an elevation of [Ca+2]i and a contraction. These responses were inhibited by blockers of L-type voltage-dependent Ca+2 channels (verapamil, nifedipine and diltiazem). The inhibition by verapamil was much greater for contraction than for [Ca+2]i Verapamil itself decreased the resting [Ca+2]i without affecting the resting tone. In a Ca(+2)-free solution, CPA caused a small elevation of [Ca+2]i that was not accompanied by a contraction. In the presence of CPA or thapsigargin, the effects of caffeine (20 mM) on [Ca+2]i and tension were greatly inhibited. In strips where the SR Ca+2 was depleted by the addition of caffeine and a Ca(+2)-free solution, the Ca+2 influx from the extracellular space was completely taken up into the SR. This process was inhibited by CPA or thapsigargin, which resulted in a contraction. This contraction was also inhibited by verapamil. However, the basal Ca+2 influx measured by a 5-min incubation of the artery with 45Ca+2 was not increased by CPA or thapsigargin. The net Ca+2 entry measured in a 30-min incubation of the artery with 45Ca+2 was decreased by CPA or thapsigargin. The basal 45Ca+2 efflux from the artery was increased during the addition of CPA. These results suggested that the basal Ca+2 influx was completely buffered by Ca+2 uptake into the SR in the resting state of rat femoral artery and therefore the inhibition of SR Ca+2 uptake by CPA or thapsigargin caused an elevation of [Ca+2]i and a contraction. During this process, the basal Ca+2 influx via L-type voltage-dependent Ca+2 channels mainly contributed to the contraction. The present study also showed the existence of a relatively large compartment of cytosolic Ca+2 that does not contribute to contraction during the addition of CPA or thapsigargin.

Animals↗
PubMed1995

Selectivity of action of staurosporine on Ca2+ movements and contractions in vascular smooth muscles.

We examined the effects of staurosporine, a protein kinase inhibitor, on Ca2+ movements and contractions due to KCl and 12-deoxyphorbol 13-isobutyrate (DPB), which are thought to activate myosin light chain kinase and protein kinase C, respectively. In rabbit aortae, staurosporine inhibited contractions due to KCl (65.4 mM) and DPB (1 mu M) with IC50 values of 140.5 +/- 1.3 nM and 13.3 +/- 1.3 nM, respectively. Calphostin C, a putative inhibitor of protein kinase C, inhibited DPB-induced contraction with much less effect on the KCl-induced one. On the other hand, wortmannin, an inhibitor of myosin light chain kinase, was 4 times more potent on KCl-induced contraction than the DPB-induced one. Staurosporine at 100 nM decreased the rise in cytosolic Ca2+ due to KCl, whereas wortmannin did not affect it. In rabbit cerebral arteries permeabilized with beta-escin, staurosporine at 100 nM, but not 30 nM, inhibited Ca2+ -induced contraction in the presence of 1 mM ATP. The results indicate that staurosporine preferentially inhibits a contraction dependent on protein kinase C than that dependent on myosin light chain kinase in vascular smooth muscles. Its ability to inhibit KCl-induced contraction involves inhibition of voltage-dependent Ca2+ channels.

Alkaloids↗
PubMed1995

Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death.

Typical programmed cell death requires de novo macromolecular synthesis and shares common morphological changes referred to as apoptosis. To elucidate the molecular mechanism of apoptosis, we isolated cDNA clones that are induced in various types of apoptosis by the differential display method. Among such clones, the MA-3 mRNA was induced in all apoptosis-inducible cell lines tested so far, including thymocytes, T cells, B cells and pheochromocytoma. The nucleotide sequence of the MA-3 cDNA predicted an amino acid (aa) sequence of 469 aa, which did not reveal significant similarity to any known proteins and functional aa motifs in databases. The MA-3 mRNA was strongly expressed in the thymus although small amounts of the MA-3 mRNA were ubiquitously expressed in mouse adult tissues. The MA-3 gene was highly conserved during evolution and cross-hybridization bands were found not only in vertebrates but also in Drosophila melanogaster.

Amino Acid Sequence↗
PubMed1995

Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor121.

We elucidated the relationship between vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), which is a potent angiogenic factor, and the growth of primary and metastatic tumors using an immunoneutralizing monoclonal antibody against human VEGF/VPF121. The monoclonal antibody, MV303, suppressed the growth of human umbilical vein endothelial cells (HUVEC) induced by VEGF/VPF121 or VEGF/VPF165 but did not inhibit its growth induced by basic fibroblast growth factor. MV303 inhibited the binding of 125I-VEGF/VPF121 to HUVEC. We examined the effects of MV303 on tumor angiogenesis using a membrane chamber packed with the human fibrosarcoma cell line HT-1080 and implanted s.c. into BALB/c mice. The neovascularization induced by HT-1080 was inhibited by the i.v. injection of MV303 at a dose of 100 micrograms/mouse. Furthermore, the growth of solid tumors of s.c. implanted HT-1080 in BALB/c nude mice was almost completely inhibited by the i.v. and s.c. administration of MV303 ten times from day 1 at a dose of 100 micrograms/mouse (T/C values of tumor volume at day 18 were 0.20 and 0.18, respectively). Tumor growth was suppressed when MV303 was administered, even from eight days after tumor inoculation. MV303 suppressed the increase in lung weight caused by experimental metastasis with i.v. inoculation of cultured HT-1080 cells to BALB/c nude mice. The life spans of the mice treated with MV303 were significantly prolonged. These results indicated that VEGF/VPF played an important role in both primary and metastatic tumor growth as a tumor angiogenesis factor. MV303, an immunoneutralizing monoclonal antibody against VEGF/VPF, potently inhibited both primary and metastatic tumor growth with no marked side effects.

Animals↗
PubMed1995

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.

Approximately 10% of peripheral CD4+ cells and less than 1% of CD8+ cells in normal unimmunized adult mice express the IL-2 receptor alpha-chain (CD25) molecules. When CD4+ cell suspensions prepared from BALB/c nu/+ mice lymph nodes and spleens were depleted of CD25+ cells by specific mAb and C, and then inoculated into BALB/c athymic nude (nu/nu) mice, all recipients spontaneously developed histologically and serologically evident autoimmune diseases (such as thyroiditis, gastritis, insulitis, sialoadenitis, adrenalitis, oophoritis, glomerulonephritis, and polyarthritis); some mice also developed graft-vs-host-like wasting disease. Reconstitution of CD4+CD25+ cells within a limited period after transfer of CD4+CD25- cells prevented these autoimmune developments in a dose-dependent fashion, whereas the reconstitution several days later, or inoculation of an equivalent dose of CD8+ cells, was far less efficient for the prevention. When nu/nu mice were transplanted with allogeneic skins or immunized with xenogeneic proteins at the time of CD25- cell inoculation, they showed significantly heightened immune responses to the skins or proteins, and reconstitution of CD4+CD25+ cells normalized the responses. Taken together, these results indicate that CD4+CD25+ cells contribute to maintaining self-tolerance by down-regulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage; elimination/reduction of CD4+CD25+ cells relieves this general suppression, thereby not only enhancing immune responses to non-self Ags, but also eliciting autoimmune responses to certain self-Ags. Abnormality of this T cell-mediated mechanism of peripheral tolerance can be a possible cause of various autoimmune diseases.

Animals↗
PubMed1995

Autoimmunity induction by human T cell leukemia virus type 1 in transgenic mice that develop chronic inflammatory arthropathy resembling rheumatoid arthritis in humans.

We recently reported on an inflammatory arthropathy resembling rheumatoid arthritis that develops in high incidence among transgenic mice that carry the env-pX region of the human T cell leukemia virus type 1 genome. In an effort to elucidate the pathogenesis of this disease, we found that genes for inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, transforming growth factor-beta 1, IFN-gamma, and IL-2, as well as MHC genes were activated in transgenic joints. Serum levels of IL-1 beta and IL-6 were also elevated. Interestingly, these mice produced Ab against IgG, type II collagen (IIC), and heat shock proteins accompanied by IgG hypergammaglobulinemia. The cellular immune response to IIC as well as that to heat shock proteins were activated. Moreover, these mice became immunologically responsive to exogenously administered IIC and developed arthritis, in contrast to their nontransgenic littermates, which showed little response to IIC. Taken together, the results suggest that human T cell leukemia virus type 1 can cause immune system hyperreactivity and induce autoimmunity. The possibility that elevated cytokine and/or MHC gene expression are involved in the development of autoimmunity and arthropathy are discussed.

Animals↗