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Biomedical subjects

M Yamamura

Publications and source records attributed to M Yamamura.

At least 55 records · Page 3Linked to original sources
PubMed1998

Increased type 2 cytokine expression by both CD4+ CD45RO+ T cells and CD8+ CD45RO+ T cells in blood circulation is associated with high serum IgE but not with atopic dermatitis.

Type 2 cytokines, such as interleukin-4 (IL-4) and IL-13, are associated with immunoglobulin E (IgE) production. This association has also been observed in CD8+ T cells from patients infected with leprosy and human immunodeficiency virus (HIV). Using intracellular cytokine staining and flow cytometry, the cytokine profile [IL-2, IL-4, IL-10, IL-13, and interferon (IFN)-gamma] of both CD4+ and CD8+ memory/effector T cells circulating in atopic dermatitis (AD) patients was investigated at the single cell level. The levels of type 2 cytokines in CD4+ T cells or CD8+ T cells in AD patients with high levels of serum IgE (AD-H), low levels of serum IgE (AD-L), and healthy controls were compared. Increased production of IL-4 and IL-13 in both CD4+ CD45RO+ T cells and CD8+ CD45RO+ T cells after 4 h in vitro stimulation with phorbol 12-myristate 13-acetate and ionomycin, was more prominent in AD-H patients than in AD-L patients or healthy controls, whereas IFN-gamma-producing CD4+ CD45RO+ T cells and CD8+ CD45RO+ T cells were relatively diminished in AD-H patients. CD4+ T cells and CD8 + T cells from AD-H patients, cultured for 48 h with phorbol 12-myristate 13-acetate and ionomycin, released larger amounts of IL-4 and IL-13 but smaller amounts of IFN-gamma than both types of cells from AD-L patients or healthy controls. In addition, when stimulated with immobilized anti-CD3 monoclonal antibody (MoAb) and anti-CD28 MoAb, CD4+ CD45RO+ T cells and CD8+ CD45RO+ T cells from AD-H patients contained more IL-4-producing cells but fewer IFN-gamma-producing cells compared with healthy controls. Finally, spontaneous mRNA expression of IL-4 in blood CD8+ CD45RO+ T cells isolated from AD-H patients was increased, as determined by reverse transcriptase-polymerase chain reaction. Therefore, in AD patients with high IgE levels, type 2 cytokine (IL-4 and IL-13) expression is associated with IgE production, in both CD4+ CD45RO+ T cell and CD8+ CD45RO+ T cell subsets.

Adolescent↗
PubMed1998

Antisense oligonucleotides targeting c-fos mRNA inhibit rheumatoid synovial fibroblast proliferation.

OBJECTIVE: To determine whether antisense oligonucleotides targeting c-fos mRNA have the ability to inhibit the growth of interleukin 1 (IL1) stimulated fibroblast-like cells from the synovium in rheumatoid arthritis (RA). METHODS: Fibroblast-like cells established from RA synovium were stimulated by IL1 with antisense or sense oligonucleotides complementary to c-fos mRNA, and the proliferation of these cells was determined by 3H-thymidine incorporation. Effect of antisense oligonucleotides on expression of activator protein 1 (AP1) activity was evaluated using electrophoretic mobility shift assay. RESULTS: C-fos antisense oligonucleotides inhibited IL1 stimulated synovial fibroblast proliferation. The expression of AP1 activity induced by IL1 was suppressed by treatment with antisense oligonucleotides. CONCLUSION: These results suggest the feasibility of antisense strategies designed to suppress c-fos expression as therapeutic agents for RA.

Arthritis, Rheumatoid↗
PubMed1998

Influences of low intensity exercise on body composition, food intake and aerobic power of sedentary young females.

The present study was designed to investigate the influences of aerobic training on the body composition, aerobic power and food intake of sedentary young females in relation to the initial levels of these variables. Thirty one untrained college females (age = 19.8 +/- 0.2 yr, stature = 154.4 +/- 0.8 cm, body mass = 53.3 +/- 1.2 kg, mean +/- SEM) participated in an exercise regimen consisting of 40% of maximum oxygen uptake (VO2max) for 30 minutes per day on a bicycle ergometer 5 times a week in a training period of 12 weeks. Food consumption was ad libitum but the content of daily food intake was recorded accurately throughout the whole training period and analyzed weekly. The average body mass index (BMI) and fat mass relative to body mass (% FM), estimated from the data of skinfold thickness, decreased significantly after the 12 wk training. There were significant negative correlations between the relative changes (% delta s) and initial levels of both body mass (r = -0.447, p < 0.05) and fat mass (r = -0.638, p < 0.05), but the corresponding correlation for lean body mass (LBM) was not significant (r = 0.186, p > 0.05). While the energy intake during the training period did not differ significantly from that during the control period on the average, the % delta value in energy intake between the two periods was negatively correlated to the energy intake during the control period (r = -0.604, p < 0.05). In addition, there were low but significant negative correlations between both the initial levels of BMI and %FM and % delta in energy intake; r = -0.413 (p < 0.05) for BMI and r = -0.393 (p < 0.05) for %FM. However, no significant correlations were found between % delta in energy intake and those in body composition variables (r = 0.116 to 0.237, p > 0.05). On the average VO2max relative to body mass (VO2max/BM) increased significantly, but VO2max relative to LBM (VO2max/LBM) did not. However, not only VO2max/BM but also VO2max/LBM was negatively correlated to the initial level; r = -0.671 (p < 0.05) for VO2max/BM and r = -0.625 for VO2max/LBM. Thus, the present results indicate that whether the body composition, food intake and aerobic power of sedentary young females can be modified by the exercise regimen eliciting 40% of VO2max depends on their initial levels.

Adult↗
PubMed1998

[An evaluation of efficacy of minocycline as an anti-rheumatic drug in patients with active and refractory rheumatoid arthritis].

The efficacy and safety of minocycline was investigated in Japanese patients with rheumatoid arthritis (RA) who had already received more than three disease modifying anti-rheumatic drugs (DMARDs). Minocycline was administered at 100 mg twice a day to fifteen patients with active RA. The drug efficacy was evaluated by the clinical variables including the number of painful and/or swollen joints, the duration of morning stiffness, grip strength, the erythrocyte sedimentation rate, serum concentrations of C-reactive protein, and the titer of rheumatoid factor. Three patients experienced adverse effects such as dizziness and abdominal pain or discomfort, but only one patient with abdominal pain and dizziness was discontinued. Fourteen RA patients, who had taken minocycline for at least 6 months, were subjected to the clinical evaluation. Among them, 8 patients (54%) showed a significant improvement of clinical valuables for disease activity, beginning even at 4 weeks of the therapy. The continued effects were observed in 8 patients with over 1 year-minocycline therapy. Intriguingly, an active patient with a history of multiple DMARDs-resistancy showed a marked favorable response to this drug. The present study indicates that minocycline may be an effective DMARD with highly safe performance for patients with active and refractory RA. This is the first demonstration of the benefit of minocycline in the Japanese patients.

Aged↗
PubMed1998

In vivo characterization of T-794, a novel reversible inhibitor of monoamine oxidase-A, as an antidepressant with a wide safety margin.

T-794 is a new reversible inhibitor of MAO type A. In order to predict its clinical utility as an antidepressant, we examined its pharmacological profile (i.e., MAO inhibitory activity, antidepressant-like activity and safety) in vivo in rodents. The p.o. administration of T-794 potentiated L-5-hydroxytryptophan-induced symptoms with ED50 = 1.01 mg/kg (mice) or 1.15 mg/kg (rats), and L-dopa-induced behavior with ED50 = 5.90 mg/kg (mice), whereas it did not alter the effect of beta-phenylethylamine even at 100 mg/kg (mice). In the L-5-hydroxytryptophan test in rats, the activity of T-794 (at twice the dose of ED50) disappeared by 8 h; the duration of action was similar to that of moclobemide. These results confirm the previous biochemical results that MAO-A inhibition by T-794 is highly selective and of short duration. T-794 was effective in three animal models of depression: reserpine reversal (mice, rats), behavioral despair test (mice) and learned helplessness (rats). In these tests, it had potency similar to or greater than moclobemide, tranylcypromine or imipramine. The p.o. administration of T-794 (30 mg/kg) did not affect the pressor effect of tyramine in anesthetized rats, whereas moclobemide (30 mg/kg) and tranylcypromine (6 mg/kg) potentiated the effect. Acute toxicity of T-794 proved to be very low (maximal tolerated dose > 2 g/kg p.o.) in contrast to brofaromine (maximal tolerated dose = 150 mg/kg p.o.). Unlike tricyclic antidepressants, T-794 did not prevent the oxotremorine-induced tremor even at 100 mg/kg p.o.; in this it demonstrated a lack of the anticholinergic activity. These results suggest that T-794 is an effective and particularly safe antidepressant and that it may make an important contribution in the treatment of depressive disorders.

Animals↗
PubMed1998

Effects of taltirelin hydrate (TA-0910), a novel thyrotropin-releasing hormone analog, on in vivo dopamine release and turnover in rat brain.

Effects of taltirelin hydrate (CAS 103300-74-9, TA-0910), a novel thyrotropin-releasing hormone (TRH) analog, on the cerebral monoamine systems, especially the release and turnover of dopamine (DA) in rat brain were compared with those of TRH by intraperitoneal administration. Taltirelin hydrate (1-10 mg/kg) increased the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and corpus striatum for 3 h in a microdialysis study. TRH (30 mg/kg) also increased the levels of these substances, the potency of TRH being the same as that of taltirelin hydrate at doses of 1-3 mg/kg. Taltirelin hydrate (10 mg/kg) also caused an increase in 3-methoxytyramine (3-MT: DA metabolite) until 6 h after the treatment and L-3-dihydroxyphenylalanine (DOPA: precursor of DA and noradrenaline). Taltirelin hydrate also increased the 3-methoxy-4-hydroxyphenylglycol (MHPG: noradrenaline metabolite) level in the frontal cortex and hypothalamus, and 5-hydroxytryptophan (5-HTP: serotonin precursor) accumulation and 5-hydroxyindoleacetic acid (5-HIAA: serotonin metabolite) level in the nucleus accumbens or corpus striatum. These results suggest that taltirelin hydrate possesses not only an enhancing effect on DA release, but also a stimulating effect on the monoamine system. Moreover, these actions were 10-30 times stronger and also longer-lasting than those of TRH. In addition, the mechanisms of DA release induced by these drugs were different from those induced by methamphetamine.

5-Hydroxytryptophan↗
PubMed1997

A new method for evaluation of motor deficits in 3-acetylpyridine-treated rats.

We established a novel method for quantitative evaluation of the motor deficits induced by 3-acetylpyridine (3-AP) in rats. 3-AP (75 mg/kg, i.p.) was injected in a time-controlled manner by a following injection of niacinamide (NIA; 300 mg/kg, i.p.). Changes in the motor function were evaluated by measuring the maximal height of vertical jump (MHVJ) to escape from an electrical shock on the foot, as well as ataxic gait. The MHVJ decreased and reached a minimum value 5-7 days after the 3-AP treatment. The close correlation of the MHVJ and the incidence of ataxic gait indicates that the decrease of MHVJ is a useful quantitative index of motor deficits.

Animals↗
PubMed1997

Depolymerized holothurian glycosaminoglycan (DHG) prevents neointimal formation in balloon-injured rat carotid artery.

The in vivo activity of depolymerized holothurian glycosaminoglycan (DHG), a newly developed polysaccharide anticoagulant, on neointimal formation induced by a balloon catheter in the left common carotid artery of rats was investigated. In every Sprague-Dawley rat weighing approximately 400 g, a Forgaty 2Fr balloon catheter was inserted from the left femoral artery to the left common carotid artery, and was passed through three times in order to denude the endothelium of the artery. These rats were divided into four groups by the following treatment protocols; DHG was given to rats by daily subcutaneous injection into their abdomens at a dose of 3 mg/kg or 10 mg/kg (D3 or D10 group). For controls, 250 microl saline was injected daily (C group). Furthermore, 1 mg/kg of unfractionated heparin was also injected daily as a comparison to DHG (H group). Each treatment was performed in six rats, and the injections were continued for two weeks after the catheterization. The area ratio of thickened intima/media (I/M ratio) treated with DHG decreased in a dose-dependent manner compared to the control. In addition, the ratio in the D10 group was significantly lower than in the control (P < 0.01). However, the ratio in the H group did not decrease. By anti-a smooth muscle actin antibody staining the intimal thickening layers were seen to be completely occupied by proliferated smooth muscle cells, and their amount in these layers was attenuated by the DHG treatment. This indicated that DHG has an inhibitory effect on intimal thickening induced by balloon catheterization, and that this might be due to the inactivation of aberrant smooth muscle cells by this agent.

Angioplasty, Balloon, Coronary↗
PubMed1997

BAYw6228 suppresses accumulation of macrophages in balloon-induced intimal thickening of rabbit carotid artery.

To determine the in vivo activity of BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, we examined its effect on balloon catheterization-induced carotid arterial intimal thickening in Japanese white rabbits. In all rabbits weighing approximately 3.5 kg, a balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta in order to denude the endothelium of the left common carotid artery. At day 12, they were divided into control and BAYw groups. The latter were subcutaneously injected with BAYw, 1 mg/kg/day, for the following 17 days. At day 15, the second balloon catheterization was performed in the same left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and stained with Elastica-Masson (EM) and anti-rabbit macrophage antibody (RAM 11). With RAM 11 staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared with the control group (P < 0.01). Compared with the area ratio of the thickened intima/media layer of the control group, that of the BAYw group was significantly decreased to 45% (P < 0.05). These results indicate that BAYw prevents accumulation of macrophages and consequently contributes to the inhibition of intimal thickening induced by balloon catheterization.

Animals↗
PubMed1997

Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease.

We examined human T-lymphotropic virus type I (HTLV-I) DNA integration in 68 patients with adult T-cell leukemia/ lymphoma (ATL) by Southern blotting using EcoRI, which does not cut within the 9 kb of the genome and probes for pX and gag-pol region of HTLV-I. We detected defective proviral integration as a monoclonal band of various sizes with the pX but not with the gag-pol probe, or a monoclonal band of less than 9 kb with the pX probe, in 20 patients (29.4%). These were designated defective (D) type. With both probes, a single band greater than 9 kb was detected in 34 (50.0%), designated complete (C) type, and two or more bands greater than 9 kb, were designated multiple (M) type, in 14 (20.6%). Advanced age, a high LDH value, and hypercalcemia were more frequent in D type patients. The median survival time (MST) was 6.8, 24.4, and 33.3 months, for D, C, and M types, respectively (log rank P = .006). Among 52 sequentially examined patients, the HTLV-I integration patterns changed in 4 (7.5%). In three of these four, the rearrangements of the T-cell receptor (TCR)b gene concomitantly changed, suggesting the appearance of a new ATL clone. Another patient had the same rearrangement of the TCRb gene, indicating clonal evolution. The HTLV-I integration pattern changed at crisis from indolent to aggressive ATL in three patients. These findings suggested that the HTLV-I integration patterns have clinical implications in ATL pathophysiology. In contrast to the clonal evolution characteristic of the multistep carcinogenesis of most human malignancies, the frequent clonal change of ATL at crisis is a peculiar phenomenon, probably reflecting the emergence of multiple premalignant clones in viral leukemogenesis as suggested in Epstein-Barr virus associated lymphomagenesis in the immunocompromised host.

Aged↗
PubMed1997

Inhibition of rheumatoid synovial fibroblast proliferation by antisense oligonucleotides targeting proliferating cell nuclear antigen messenger RNA.

OBJECTIVE: To evaluate the feasibility of antisense oligonucleotides as therapeutic agents to inhibit synovial cell growth in rheumatoid arthritis (RA). METHODS: Fibroblast-like cells established from RA synovium were stimulated with interleukin-1beta (IL-1beta) and treated with antisense or sense oligonucleotides targeting proliferating cell nuclear antigen (PCNA) messenger RNA (mRNA). Proliferation of these cells was determined by 3H-thymidine incorporation. Effects of antisense oligonucleotides on the expression of mRNA and protein were evaluated by reverse transcriptase-polymerase chain reaction and immunohistochemical staining, respectively. RESULTS: Antisense oligonucleotides targeting PCNA inhibited IL-1-stimulated fibroblast proliferation, whereas sense oligonucleotides had no effect. Both mRNA and protein levels of PCNA were suppressed in the cells treated with antisense oligonucleotides, indicating that the antiproliferative effect was occurring through an antisense mechanism. CONCLUSION: These results suggest that antisense strategies designed to suppress PCNA expression have potential use as therapeutic agents for RA.

Arthritis, Rheumatoid↗
PubMed1997

The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis.

OBJECTIVE: To determine the expression of interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and their major cellular sources in the joints of rheumatoid arthritis (RA) patients, as well as the correlation of circulating levels of these IL-6-type cytokines and C-reactive protein (CRP). METHODS: Messenger RNA (mRNA) and protein levels for IL-6, IL-11, LIF, and OSM were determined by using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Cells isolated from the synovium of RA patients expressed mRNA for IL-6, IL-11, LIF, and OSM at higher levels than did synovial cells from osteoarthritis (OA) patients, and spontaneously released greater quantities of these proteins in culture. Fibroblast cell lines derived from RA synovium were able to produce IL-6, IL-11, and LIF, but not OSM, when stimulated with IL-1 and tumor necrosis factor alpha. OSM was found to be produced spontaneously by synovial tissue macrophages. IL-6, IL-11, LIF, and OSM were present in synovial fluid from the RA patients; levels of IL-6, LIF, and OSM were present in significantly greater quantities in RA patients than in OA patients. However, only IL-6 was significantly elevated in the serum of RA patients and correlated with the serum CRP level, while other IL-6-type cytokines were not detected. CONCLUSION: IL-6, IL-11, LIF, and OSM are all produced in large amounts at the site of disease activity, but IL-6 derived from synovial fibroblasts may be the major hormone-like mediator that induces the hepatic synthesis of acute-phase proteins in RA.

Adult↗
PubMed1997

Mucosal blood flow and generation of superoxide in rat experimental colitis induced by succinic acid.

As we consider succinic acid to be an exacerbating factor in ulcerative colitis, we investigated its influence on rat colonic mucosa in terms of mucosal blood flow and superoxide generation. We measured mucosal blood flow by the hydrogen gas clearance method and superoxide generation by the chemiluminescence method, and observed histopathological findings to determine the effects of succinic acid. After the instillation of succinic acid of any concentration tested to the colon, mucosal blood flow decreased. Histopathologically, the higher the concentration of succinic acid, the greater was the erosion formation in the colonic mucosa, while significant polymorpho-nuclear cell infiltration superoxide generation from colon tissue were observed with 0.01% succinic acid compared with higher or lower concentrations. Succinic acid, at fecal concentrations found in active stage ulcerative colitis, appears to be implicated in mucosal injury, mediated by a decrease in colonic mucosal blood flow and infiltration of superoxide-generating polymorpho-nuclear cells into the mucosa.

Animals↗
PubMed1997

Glucose metabolism and protective biochemical mechanisms in a rat brain affected by kaolin-induced hydrocephalus.

To clarify glucose metabolism in a hydrocephalic rat brain, substances related to glycolytic metabolism were biochemically measured. Kaolin-induced hydrocephalic rats were sacrificed and lactate dehydrogenase (LDH), LDH isozyme, lactate, adenosine triphosphate (ATP), and isocitrate dehydrogenase (ICDH) were measured in the following regions: cortex, thalamus, midbrain, hippocampus, cerebellum, and pons with medulla. During the development of hydrocephalus, lactate and LDH increased in most regions, the LDH M-subunit increased in the cortex, and ICDH decreased in most regions. However, ATP levels did not change. The increases in lactate, LDH and M-subunit suggested an anaerobic environment in the cell leading to activation of the anaerobic glycolysis. The decrease in ICDH represented a diminution of the tricarboxylic acid cycle. Through these alterations, the ATP level can be kept constant during the course of hydrocephalus, allowing the brain to create a better biochemical milieu.

Adenosine Triphosphate↗
PubMed1997

Suppression of neointimal thickening by a newly developed HMG-CoA reductase inhibitor, BAYw6228, and its inhibitory effect on vascular smooth muscle cell growth.

1. The aim of this study was to determine whether BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, could suppress an atherogenic process such as intimal thickening by a mechanism other than lowering the level of serum cholesterol. 2. First, we evaluated the in vitro effect of BAYw on the proliferation of vascular smooth muscle cells (SMC) from various species: Sprague-Dawley (SD) rats. New Zealand (NZ) white rabbits, intimal cells from Watanabe hereditary hyperlipidemic (WHHL) rabbit and SMC from the new-born human aorta. The increasing rate of total protein content of these cells was inhibited by the addition of BAYw in a dose-dependent fashion. In the presence of 2% foetal calf serum (FCS), the value of IC50 was 1.0 microM in SD rats, 2.1 microM in NZ white rabbits, and 0.3 microM in WHHL rabbits. With human SMC, the value was 0.02 microM in the presence of 10% FCS and 0.2 microM with a mixture of growth factors. 3. Based on these above in vitro findings, we next examined the in vivo effect of the agent to determine whether it could suppress rabbit intimal thickening induced by balloon catheterization. A balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta to denude the endothelium of the left common carotid artery in Japanese white rabbits. After 12 days they were divided into control and BAYw groups. The former were subcutaneously injected with saline and the latter with BAYw 1 mg kg-1 day-1. Two days after the beginning of treatment, a second balloon injury was performed to the previously injured left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and variously stained. Although the total serum cholesterol in the BAYw group was significantly lower than in the control (P < 0.05), the difference was not enough to affect intimal thickening. In addition, the BAYw group had a smaller intima/media ratio than the control group, decreasing to 45% of control (P < 0.05). By anti-alpha smooth muscle actin antibody staining, these intimal thickening areas were entirely occupied by SMCs, and their amount was attenuated by BAYw. By anti-rabbit macrophage antibody (RAM 11) staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared to control (P < 0.01). 4. These results indicate that BAYw has an inhibitory effect on intimal thickening by attenuating intimal SMC proliferation and infiltration of macrophages, suggesting that BAYw could be effective in the prevention of the progression of atherosclerotic plaque-like restenosis after angioplasty.

Animals↗