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Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 343 records · Page 19Linked to original sources

[Inhibitory effects of saiboku-to and compornent herbs on the production of peptide leukotrienes (LTs) and LTB4].

We investigated the effects of Saiboku-to, Syoseiryu-to and compornent herbs of these two Kampo-Medicines (Saiko, Hange, Bukuryo, Ogon, Koboku, Taiso, Ninjin, Kanzo, Soyo, Syokyo, Keihi, Gomisi, Saisin, Syakuyaku, Mao and Kankyo) on the production of peptide leukotrienes (LTs) and LTB4 in cultured rat basophilic leukemia (RBL)-1 cells. Cultured RBL-1 cells were stimulated with Ca ionophore, A23187, at 10(-5) M in the absence or presence of various concentrations of these substances, and the production of peptide LTs and LTB4 was measured by reversed phase-high performance liquid chromatography (RP-HPLC). The production of LTs was dose-dependently suppressed by the addition of Saibokuto. Saiboku-to (100 micrograms/ml) showed 35% and 30% inhibition on the production of peptide LTs and LTB4, respectively. These inhibitory actions of Saiboku-to on LT-synthesis were attributable to the effects of its component herbs, Ogon, Koboku and Kanzo. On the other hand, Syoseiryu-to showed no inhibitory action on LT-production. these results indicate that anti-allergic action of Saiboku-to is, at least in part, attributable to its inhibitory action on LT-synthesis.

Animals↗

Clinical experience of percutaneous cardiopulmonary support.

Recently, percutaneous cardiopulmonary support (PCPS) combined with femoro-femoral bypass without reservoir has become valued because of its quick and easy application. We developed a fully preconnected compact integrated cardiopulmonary bypass (CPB) unit (priming volume of 250 ml) with a blind pore membrane oxygenator (Kuraray Menox) for PCPS. From 1990 to 1995, PCPS was performed in 49 patients of whom 26 were weaned from support. In most cases, we applied this CICU in patients with no active bleeding (22 patients); in patients with active bleeding (n = 13), we used Medtronic's heparin-bonded close chest support pack (CCSP). Of these, PCPS was performed uneventfully for 2 h (median) in 8 elective cases; all of these patients were weaned or were switched to a left ventricular assist system (LVAS). In 8 urgent cases, such as those with low cardiac output syndrome, PCPS was performed for 4 days (median), 1 was weaned, and 2 CICU were cases switched to other procedures. In 32 cases of shock, 5 CICU patients were weaned, and 3 of them survived. Eight patients including 5 CICU patients and 1 CCSP patient were switched to operation or LVAS, and 2 CICU patients remain alive. From these data, PCPS has been shown to support the patient's circulation in the acute phase and earn time to switch to operation or LVAS; the quick and easy set-up of the CICU can improve the clinical results. The use of the Medtronic device broadened the indication for PCPS. The CCSP enlarged the indication of PCPS but could not improve the results. To improve the results, a heparin-bonded surface is desired.

Cardiopulmonary Bypass↗

[Gene diagnosis of hemolytic anemia].

Gene analysis in hemolytic anemia has been reported recently. It is now recognized that inherited molecular defects of red blood cell membrane proteins have at least five phenotypes. The recent cloning of the G-6-PD gene has given us an entirely new perspective on the population genetics of G-6-PD deficiency and provided new and useful diagnostic tools. Prenatal diagnosis of thalassemia has been possible. Deficiency of the GPI anchor protein may be caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.

Anemia, Hemolytic, Congenital↗

[Acute myocardial infarction in young Japanese women].

Women appear to be protected, until the menopause, from the development of coronary artery disease. The incidence of acute myocardial infarction in young women is very low, so there is little information on the etiology, clinical features, and prognosis for such patients. We studied 24 young female patients with acute myocardial infarction (< 50 years) among 2,457 consecutive patients with acute myocardial infarction admitted to the coronary care unit of the National Cardiovascular Center from December 1977 through August 1994. Their clinical features and in-hospital mortality were compared with 100 consecutive young male patients (< 50 years) with acute myocardial infarction. The fraction of patients of age younger than 50 years among all age groups was lower in female than in male acute myocardial infarction patients (5% vs 13%, p < 0.01). The increase of the coronary risk factors, hypercholesterolemia (25% vs 55%, p < 0.05) and cigarette smoking (17% vs 96%, p < 0.05) were less common in women. In female patients, the serum total cholesterol level was lower (195 +/- 50 vs 216 +/- 48 mg/dl, p = 0.06), and the serum high-density lipoprotein cholesterol level was higher (50 +/- 12 vs 39 +/- 12 mg/dl, p < 0.05) than in male patients. Other risk factors did not differ significantly between the two groups. Angiography 1 month after myocardial infarction showed fewer diseased coronary arteries (> 75% stenosis) in female than male patients (0.8 +/- 0.9 vs 1.8 +/- 1.0, p < 0.01), and normal coronary arteries were seen in 35% of female patients (male 6%, p < 0.05). Ten female patients (42%) had obviously non-atherosclerotic causes of acute myocardial infarction: Takayasu aortitis in three patients, coronary embolism in two, acute dissection of the aorta in two, and idiopathic coronary artery dissection, Kawasaki disease, and systemic lupus erythematosus in one each. In contrast, among male patients, only one had coronary embolism (1%). In-hospital mortality was higher in women (17%) than in men (2%, p < 0.05). Young female patients (< 50 years) with acute myocardial infarction have a low incidence of hyperlipidemia and normal coronary arteries or involvement of the left main trunk are more common compared with male patients (< 50 years). Although 42% of female patients had obvious non-atherosclerotic etiology of acute myocardial infarction, the causes varied widely.

Adult↗

Effects of theophylline in p-chlorophenylalanine-treated mice in a light/dark test.

The effects of theophylline were examined in a light/dark test in p-chlorophenylalanine (PCPA)-treated mice to investigate serotonergic contribution to its effects. Three consecutive treatments with PCPA (200 mg/kg once daily) barely affected parameters in the light/ dark test. In vehicle- and PCPA-treated mice, theophylline (100 mg/kg) significantly decreased time spent in the light zone, which suggested its anxiogenic-like activity. In PCPA-treated mice, theophylline (50 mg/kg) also tended to decrease the time spent in the light zone. The effects of theophylline on the contents of monoamines and their metabolites in the brains of vehicle- and PCPA-treated mice were also investigated. Treatment with PCPA significantly decreased the contents of serotonin (5-HT) and its metabolite, as well as the contents of the metabolites of noradrenaline (NA) and dopamine (DA). Theophylline increased the metabolites of 5-HT, NA and DA in the brains of vehicle-treated mice. The increases produced by theophylline in the metabolites of NA and 5-HT were extinguished in PCPA-treated mice. Behavioral and biochemical data in the present study demonstrate that theophylline-induced anxiogenic-like activity was not mediated by serotonergic neuronal systems and that NAergic neuronal systems also might not contribute to the activity.

Animals↗

Early activation signal transduction pathways of Th1 and Th2 cell clones stimulated with anti-CD3. Roles of protein tyrosine kinases in the signal for IL-2 and IL-4 production.

In the present experiments, TCR-CD3-associated early activation signal transduction pathways were examined in Th1 and Th2 clones by the stimulation with soluble monovalent anti-CD3 which resulted in efficient production of IL-2 and IL-4 in Th1 and Th2 cells, respectively. Although protein tyrosine kinases such as Fyn and ZAP-70 were activated in Th1 clones shortly after stimulation, these kinases in Th2 clones were not activated; but, their activity in resting conditions was shown to be decreased by the stimulation. In accordance with these findings, neither phospholipase C-gamma 1 activation nor phosphatidyl inositol-4,5-bisphosphate breakdown was induced in Th2 clones, in contrast to positive responses in Th1 clones. The oscillation of intracellular free Ca2+ concentration ([Ca2+]i) was a common signal for the activation of both Th1 and Th2 clones; however, the [Ca2+]i elevation in Th1 clones was herbimycin A sensitive, whereas that in Th2 was clone resistant, suggesting that the mechanism of the [Ca2+]i elevation in Th2 cells is different from that in Th1 cells in terms of the participation of protein tyrosine kinases. The anti-CD3 stimulation did not cause Lck activation in either the Th1 or Th2 clone, although remarkable activation was induced in both clones following anti-CD4 stimulation, indicating that Lck activation was not required for either IL-2 or IL-4 production of Th cells. Taken together, these results indicate that Th1 and Th2 cells are different from each other in early activation signal transduction pathways, especially in the role of protein tyrosine kinases.

Animals↗

Saiboku-To, a herbal extract mixture, selectively inhibits 5-lipoxygenase activity in leukotriene synthesis in rat basophilic leukemia-1 cells.

Saiboku-To, a mixture of extracts from 10 medicinal herbs, has been used for the treatment of bronchial asthma in Japan. Inhibitory action of this drug on arachidonate 5-lipoxygenase (5-LO) metabolism in rat basophilic leukemia cells (RBL-1 cells) was examined. Saiboku-To significantly inhibited calcium ionophore-stimulated synthesis of cysteinyl leukotrienes (cLTs) and leukotriene B4 (LTB4). Inhibition appeared 10 min after addition of the substance and reached a maximal value after 3 h. Saiboku-To did not inhibit the release of [3H]arachidonic acid (AA) from cell membrane by calcium ionophore stimulation, or the production of cLTs and LTB4 when LTA4-free acid was used as the substrate. However, it significantly inhibited the production of cLTs and LTB4 when free AA was used as the substrate. The production of thromboxane A2 (TXA2). a cyclooxygenase metabolite, was not inhibited when AA was used as the substrate in cell free study. These results indicate that Saiboku-To selectively inhibits 5-LO activity in the metabolic pathway of AA.

Animals↗

Eicosanoids are produced by microglia, not by astrocytes, in rat glial cell cultures.

To determine principal sources of eicosanoid production in glial cells, we analyzed the metabolites of arachidonic acid in cultured rat glial cells by use of reversed-phase, high-performance liquid chromatography and an on-line radioisotope detector. Prostaglandin D2, leukotriene B4, leukotriene C4, and 5-hydroxyeicosatetraenoic acid were present in cultures in which microglia appeared on a monolayer astrocytes. None were detected in culture dishes that contained only astrocytes, although astrocytes have been believed to be a main source of eicosanoid production in brain.

Animals↗

The chromosomal location of the mouse mammary tumor gene Int6 and related pseudogenes in the mouse genome.

The Int6 gene is a common insertion site for the mouse mammary tumor virus (MMTV) in mouse mammary tumors. We have determined that this gene is located centromeric of the Myc protooncogene on mouse chromosome 15. In the mouse genome there are several other Int6-reactive restriction fragments that are located on mouse chromosomes 6, 11, 14, 17, and 18. Nucleotide sequence analysis of four of six of these additional Int6 fragments showed that they contain processed Int6 pseudogenes. Comparisons between the Int6 genes of the inbred mouse laboratory strains and the wild mouse species Mus spretus and Mus mus musculus indicate that some pseudogenes were present before divergence of these species and others were acquired since their separation.

Animals↗

Gadolinium-enhanced magnetic resonance imaging in acute myocardial infarction.

To investigate the clinical application of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) in the management of acute myocardial infarction (AMI), we examined 44 patients with AMI within 1 month after onset. Enhanced images were classified into 4 types: nontransmural (type 1), transmural and homogeneous (type 2), transmural and marginal (type 3), and no enhancement (type 4). Each enhancement pattern was correlated with angiographic and thallium-201 imaging results. The redistribution images of thallium were graded on a 4-point scale from 0 (normal) to 3 (markedly reduced or absent activity). The percentage of the perimeter affected by asynergy was obtained from the left ventriculogram. Peak creatine kinase and the percentage of asynergic perimeter were significantly higher in type 3 than in other type patients. End-diastolic volume index was significantly higher in type 3 than in type 2 patients. Left ventricular ejection fraction was lowest, and end-systolic volume index, thallium-201 score, and incidence of wall thinning on MRI were highest in type 3 patients. Therefore, the transmural and marginal enhancement pattern (type 3) was compatible with extensive myocardial infarction with infarct expansion and less viable myocardium. In the other types, the infarction was small to moderate in size and left ventricular function was well preserved. Thus, Gd-DTPA-enhanced MRI may be useful in the evaluation of left ventricular function and myocardial viability of the infarct region after AMI.

Aged↗

Angioscopic prediction of successful dilatation and of restenosis in percutaneous transluminal coronary angioplasty. Significance of yellow plaque.

BACKGROUND: Coronary angiography has been used to assess the anatomy of coronary artery and intraluminal pathological changes. However, it has several limitations in its diagnostic quality and sensitivity in the detection of intraluminal details. Angioscopy has enabled coronary artery lumens to be visualized directly and fine intraluminal morphological changes to be detected. The information obtained by angioscopy is expected to provide new insights into the mechanisms and pathophysiology of transluminal coronary angioplasty. METHODS AND RESULTS: Forty-seven patients (39 men and 8 women) with stable angina were enrolled in the present study. Angioscopy was performed before and after angioplasty with a 0.68-mm angioscope with a double-guiding catheter system. The patients who were successfully evaluated by angioscopy were divided into two groups according to the color of the lesion: group 1, mainly yellow; and group 2, white. Angiographic, angioscopic, and clinical parameters in the two groups were compared. Detailed angioscopic findings were obtained in 36 of the 47 patients (77%) before percutaneous transluminal coronary angioplasty (PTCA) and in 24 of the 47 (51%) after PTCA. Yellow plaque were found in 13 of 36 (36%). Age, sex, presence of coronary risk factors, serum cholesterol level, and duration of angina showed no correlation with plaque color. The incidence rates of dissection and thrombi after angioplasty also were not different. Successful dilatation was achieved in 13 of 13 patients (100%) in group 1 and in 21 of 23 (91%) in group 2. The restenosis rate of group 1 was significantly lower than that in group 2 (16.7% versus 57.9%, P < .05). Cox proportional hazards model revealed that plaque color was the independent variable associated with restenosis after PTCA (P = .03). CONCLUSIONS: The restenosis rate after successful balloon angioplasty differs, with the color of the target lesion being significantly higher in patients with solely white plaque. Therefore, angioscopic findings are highly predictive of restenosis.

Angina Pectoris↗

Fas antigen-mediated DNA fragmentation and apoptotic morphologic changes are regulated by elevated cytosolic Ca2+ level.

More than 80% of cells of the human B cell line FMO, which expresses the Fas Ag, underwent apoptosis within 2 h after addition of an anti-Fas mAb. Rises in cytosolic Ca2+ concentration ([Ca2+]i) and their effects were investigated by imaging individual cells continuously and introducing Ca2+ chelators to the outside and/or inside of the cell. The typical Ca2+ response consisted of 1) an early [Ca2+]i rise (basal [Ca2+]i, 85 to 110 nM; peak, 140 to 200 nM; duration, 15 to 20 min), 2) sustained elevation of [Ca2+]i at 140 to 150 nM, 3) a second Ca2+ rise (200 to 500 nM, 15 to 30 min) between 1.5 and 2 h, and 4) a large [Ca2+]i rise (1.2 to 2.0 microM) between 2 and 4 h after addition of mAb. Responses 1, 3, and 4 were mainly caused by Ca2+ entry, and response 2 involved intracellular Ca2+ release from stores. Apoptosis could be induced by mAb even in Ca(2+)-deprived external medium. Chelating cytosolic Ca2+ revealed that the [Ca2+]i rise is a prerequisite for fragmentation of DNA and chromatin, and is also necessary for fragmentation of cells. The critical [Ca2+]i was 140 to 150 nM and a sustained [Ca2+]i rise was more effective. A [Ca2+]i rise itself (without mAb) was ineffective. About 20% of mAb-treated cells showed chromatin condensation at the periphery of the nucleus (possibly an earlier stage of nuclear change) and a bubble-like cell shape even when [Ca2+]i was held below 100 nM. Thus, Ca2+ is mobilized immediately after Fas stimulation and functions as a key factor causing advanced apoptotic changes. Response 4 was related to secondary necrosis.

Antibodies, Monoclonal↗

Calcium signalling during mammalian fertilization.

The fertilized mammalian egg is a nice model system for analysing spatiotemporal Ca2+ signalling in the intact cell. Hamster eggs show repetitive Ca2+ transients, associated in the initial response with Ca2+ waves which begin from the site of sperm attachment and are propagated across the deep cytoplasm to the opposite pole. In unfertilized eggs, a regenerative Ca2+ wave is induced by injection of either inositol 1,4,5-trisphosphate (InsP3) or Ca2+, and Ca2+ oscillations are produced by continuous injection of InsP3. These Ca2+ waves and oscillations in both fertilized and unfertilized eggs are inhibited in a dose-dependent manner by a monoclonal antibody to the type 1 InsP3 receptor. Ryanodine receptors (both skeletal and cardiac types) are not detected by physiological or immunoblot analyses. Positive and negative feedback between cytosolic Ca2+ and Ca2+ release from InsP3-sensitive pools accounts for the spatiotemporal Ca2+ signalling. In addition to intracellular Ca2+ release, Ca2+ entry from outside the egg is necessary to refill the Ca2+ pools and maintain Ca2+ oscillations. Evidence suggests that inositol 1,3,4,5-tetrakisphosphate activates the Ca2+ influx. The signal transduction process leading to the production of InsP3 and the mechanism of egg activation following the Ca2+ response still remain to be elucidated.

Animals↗

Developmental changes in the distribution of the endoplasmic reticulum and inositol 1,4,5-trisphosphate receptors and the spatial pattern of Ca2+ release during maturation of hamster oocytes.

During maturation of hamster oocytes, the distribution of the endoplasmic reticulum (ER) and inositol 1,4,5-trisphosphate receptors (InsP3Rs) was found to change dramatically, as observed using confocal microscopy with DiI and electron microscopy for the ER and immunohistochemistry for InsP3Rs. In immature oocytes at the germinal vesicle (GV) stage, ER and InsP3Rs were located predominantly in several large masses near the surface and also in the perinuclear region near the surface. In contrast, fine ER networks and low-density InsP3Rs were present in the inner cytoplasm. The ER appeared to be formed as vesicles from annulate lamellae (AL) in the subcortical area. Rises in Ca2+ concentration occurred in the cytoplasm and the GV when immature oocytes were inseminated, but clear Ca2+ waves did not occur. Ca2+ rises began preferentially from the perinuclear region in response to low doses of serotonin or to uniform stimulation of InsP3Rs with photocleavage of caged InsP3. Serum also induced inhomogeneous Ca2+ release, shown by nonpropagating Ca2+ rises at multiple surface sites. Between the GV stage and prometaphase I the number and size of the surface ER masses increased, and the AL disappeared. This quantitative ER maturation was followed by a second step, spatial maturation. After prometaphase I, surface ER masses gradually dispersed to a number of much smaller ER clusters near the surface and, together with the perinuclear mass, were incorporated into thicker ER networks, resulting in a reticular pattern of the ER with small patches of InsP3Rs throughout the mature egg. The ER shifted to the peripheral surface with apposition to cortical granules. These developmental changes in ER Ca2+ stores may account, at least partly, for the acquisition of the ability of an egg to undergo normal fertilization.

Animals↗

Dermoid cyst of the frontal bone away from the anterior fontanel.

A case with a midline dermoid cyst of the frontal bone away from the anterior fontanel is reported. Although a few such cases have been reported, detailed descriptions are not given. Possible intracranial extension of these lesions is discussed with review of the pertinent literature.

Craniotomy↗

Cerebellar ataxia in patients with Leber's hereditary optic neuropathy.

We report the cases of a mother and son with Leber's hereditary optic neuropathy (LHON), where a point mutation of mitochondria DNA from guanine to adenine on nucleotide position 11778 was verified. Both also had cerebellar ataxia and dysarthria and in both cases cerebellar atrophies were detected by computed tomography or magnetic resonance imaging. It was not possible to elucidate the relationship between LHON and the cerebellar atrophy, but it should be kept in mind that various neurological complications may occur in LHON.

Adult↗

Neuroblastoma in infants aged less than 6 months: is more aggressive treatment necessary? A report from the Pediatric Oncology Study Group of the Kyushu area.

Infants with neuroblastoma are known to have a better prognosis than older children. In Japan in 1985, mass screening for neuroblastoma in infants aged 6 months was introduced. With this policy, there has been an increase in the number of patients seen with neuroblastoma between 6 and 11 months of age. In a previous report the authors described the management and prognosis of infants with disease detected by mass screening, but there is still little information regarding the strategies of management for infants with neuroblastoma aged less than 6 months. The authors analyzed the data regarding 27 patients aged less than 6 months registered in their region (population 15 million) from 1985 to 1992, and compared it with that of the previous 8-year period. In the younger age group, there was a significantly higher rate of advanced disease stages (III and IV). In spite of the variation in treatment related to the choice of individual institutions, infants with stages I, II, and III disease had a good outcome, suggesting that aggressive chemotherapy is not necessary unless poor prognostic factors are present. One patient with stage IV disease died of disseminated disease and one with stage IVs and 22 copies of N-myc oncogene also died of tumor relapse in spite of aggressive chemotherapy. It is therefore concluded that the prognosis in infants with stage IV and IVs neuroblastoma under the age of 6 months is not as good as had previously been believed, and that such patients, therefore, require special consideration.

Antineoplastic Combined Chemotherapy Protocols↗