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Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 451 records · Page 25Linked to original sources

Effects of acute and chronic administration of MCI-225, a new selective noradrenaline reuptake inhibitor with 5-HT3 receptor blocking action, on extracellular noradrenaline levels in the hypothalamus of stressed rats.

In the present study, we investigated the effects of acute and chronic systemic administration of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride), a newly-developed selective noradrenaline (NA) reuptake inhibitor with 5-HT3-receptor-blocking action, on extracellular NA levels in the hypothalamus of stressed and non-stressed rats by utilizing intracerebral microdialysis. Acute administration of MCI-225 (3 and 10 mg/kg, p.o.) significantly and dose-dependently increased extracellular NA levels in the hypothalamus in non-stressed rats. Footshock for 20 min also significantly increased NA levels in the hypothalamus of both groups of rats pretreated with vehicle and MCI-225. Although chronic administration of MCI-225 (3 or 10 mg/kg, p.o. for 14 days) did not alter the basal extracellular NA levels in the hypothalamus, the stress-induced increases in extracellular NA levels were significantly lower in rats chronically treated with MCI-225 (10 mg/kg) than those of rats pretreated with vehicle for the same period. The increase in extracellular NA levels induced by MCI-225 challenge (3 or 10 mg/kg, p.o.) were not different between rats chronically treated with MCI-225 or vehicle. These results suggest that MCI-225 enhances extracellular NA levels in the hypothalamus in both non-stressed and stressed rats by inhibiting NA uptake and that chronic systemic administration of MCI-225 did not alter basal extracellular NA levels, but reduced the increase in NA release caused by footshock stress. These data suggest the possibility that MCI-225 might possess anxiolytic and/or antidepressant properties.

Adrenergic Uptake Inhibitors↗

Exposure to strong magnetic fields at power frequency potentiates X-ray-induced DNA strand breaks.

We examined the effect of an extremely low-frequency magnetic field (ELFMF) at 5, 50 and 400 mT on DNA strand breaks in human glioma MO54 cells. A DNA damage analysis was performed using the method of alkaline comet assay. The cells were exposed to X-rays alone (5 Gy), ELFMF alone, or X-rays followed by ELFMF at 4 degrees C or on ice. No significant difference in the tail moment was observed between control and ELFMF exposures up to 400 mT. X-ray irradiation increased DNA strand breaks. When cells were exposed to X-rays followed by ELFMF at 50 and 400 mT, the tail moment increased significantly compared with that for X-rays alone. When the exposure of cells was performed at 37 degrees C, no significant change was observed between X-rays alone and X-rays plus 400 mT. We previously observed that exposure to 400 mT ELFMF for 2 h increased X-ray-induced mutations (Miyakoshi et al, Mutat. Res., 349: 109-114, 1996). Additionally, an increase in the mutation by exposure to the ELFMF was observed in cells during DNA-synthesizing phase (Miyakoshi et al., Int. J. Radiat. Biol., 71: 75-79, 1997). From these results, it appears that exposure to the high density ELFMF at more than 50 mT may potentiate X-ray-induced DNA strand breaks.

Cell Death↗

Stability and bioavailability of antioxidants in garland (Chrysanthemum coronarium L.).

The stability and bioavailability of the major antioxidants in garland (Chrysanthemum coronarium L.), chlorogenic acid, 3,5-dicaffeoylquinic acid and 4-succinyl-3,5-dicaffeoylquinic acid, were investigated together with caffeic acid. These compounds were stable in artificial digestive juice, but more than 90% of them disappeared from plasma within 30 min after intravenous injection into rats. When they were orally administered, only caffeic acid could be detected.

Administration, Oral↗

Suppression of integrin alpha(v) expression by endothelin-1 in vascular smooth muscle cells.

Both integrins and endothelins (ETs) are known to play important roles in vascular remodeling via proliferation, apoptosis, and migration of vascular smooth muscle cells (VSMCs), whose dysfunctions have been implicated in the pathogenesis of end-organ damage associated with hypertension and arteriosclerosis. However, whether there is any interaction between endothelin-1 (ET-1) and integrins remains unknown. Therefore, the aim of the present study was to elucidate whether ET-1 regulates the expression of integrin alpha(v) in rat VSMCs. ET-1 dose- and time-dependently suppressed the integrin alpha(v) messenger RNA (mRNA) transcripts, as quantified by a real-time quantitative polymerase chain reaction (PCR) method, and decreased the transcriptional activity of integrin alpha(v) gene, as demonstrated by integrin alpha(v)-luciferase assay. The inhibitory effect of ET-1 on integrin alpha(v) gene expression was abrogated by an ETA receptor antagonist (BQ123) but not by an ET(B) receptor antagonist (BQ788). ET-1 also suppressed the cell surface expression of integrin alpha(v)beta5 and the adhesion to vitronectin, but not to fibronectin. These results demonstrate that the adhesion of vitronectin to rat VSMCs is inhibited by ET-1 via the ET(A) receptors by suppressing integrin alpha(v) gene transcription, suggesting that ET-1 is involved in regulation of vascular integrin alpha(v) gene expression.

Animals↗

Factors predicting mortality in patients after myocardial infarction caused by left main coronary artery occlusion: significance of ST segment elevation in both aVR and aVL leads.

Acute left main coronary artery obstruction is rare and most patients in this clinical setting die of sudden death or cardiogenic shock. During the past 8 years, we encountered 13 patients with acute myocardial infarction caused by total occlusion of the left main coronary artery (LMCA-AMI). Thus, we surveyed these patients, and attempted to elucidate helpful predictors related to the prognosis. Six of 13 patients with LMCA-AMI survived. Successful left coronary artery dilatation was achieved in all survivors (group S), and in 5 (71%) non-survivors (group non-S). The age was not different between the two groups. A past history of angina was confirmed in 83% of group S. while only in 29% of group non-S. Clinical findings such as time of onset of AMI, interval from the AMI onset to admission, elapsed period from the AMI onset to recanalization of LMCA and the value of CK on admission were not different between the two groups. However, cardiogenic shock occurred in only 1 patient (17%) in group S compared with 5 patients (71%) in group non-S. As emphasized in the literature, good collateral circulation to the left anterior descending artery was observed in 5 patients (83%) in group S, while not observed in group non-S. Electro cardiographically, ST elevation in the aVR lead was very characteristic. This finding was confirmed in 69% of the total patients. Noticeably, 5 out of 6 non-survivors (83%) showed ST elevation not only in leads aVR but also in the aVL lead. In addition to the absence of collateral circulation, this electrocardiographic finding, which obviously indicates the presence of extensive myocardial ischemia in the diseased heart, is a simple and important predictor suggesting a poor prognosis in LMCA-AMI patients.

Angioplasty, Balloon, Coronary↗

Differential activation of ERK 1/2 and JNK in normal human fibroblast-like cells in response to UVC radiation under different oxygen tensions.

The mechanisms by which mitogen-activated protein kinases (MAPK) respond to the input of UV-induced signal transduction pathways and the resulting biological functions are not well understood. We investigated whether the level of oxygen tension of culture was responsible for the differential activation of MAPK and different cellular outcomes in UVC-irradiated cells. The intracellular oxidative level of normal human fibroblast-like cells in a normal atmosphere (normoxic, 20% O2) was increased within 30 min after UVC irradiation. When cells were cultured at lower oxygen tension in the presence of an antioxidant N-acetyl-L-cysteine (NAC) or under physiologically hypoxic (5% O2) conditions, the elevation of the oxidative level by UV-irradiation was significantly reduced. Among MAPK, extracellular-signal related kinase (ERK) 1/2 was activated by UV regardless of the oxidative level, while c-Jun N-terminal kinase (JNK) activation was inhibited in NAC-treated and in hypoxic cultures. In addition, in cultures at lower oxygen tension, there was less apoptosis and cell survival was enhanced. These results suggest that UV-induced oxidative stress was responsible for intracellular signaling through the JNK pathway. Furthermore, the balance between ERK1/2 and JNK activities after UV irradiation under different oxygen tensions possibly modified cellular outcome in response to UV.

Apoptosis↗

Prevention of nephrotoxicity of cisplatin by repeated oral administration of ebselen in rats.

The ability of ebselen, which exhibits glutathione peroxidase (GSH-Px)-like activity, to prevent cisplatin (CDDP)-induced nephrotoxicity was examined in rats. CDDP (6 mg/kg [20 micromol/kg] body weight) was injected intraperitoneally. In subgroups, daily ebselen doses of 2.75 (10 micromol), 5.5 (20 micromol), or 11.0 mg (40 micromol)/kg body weight were administrated orally 1 hour prior to CDDP treatment. Treatment with CDDP alone resulted in significantly increased plasma creatinine (Cr) and blood urea nitrogen (BUN) levels. Repeated administration of 5.5 and 11.0 mg/kg ebselen prevented the CDDP-induced elevation of plasma Cr and BUN levels and protected against kidney damage. Relative to controls, rat that received CDDP treatment displayed a decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), an indicator directly related to oxidative stress, and elevated malondialdehyde (MDA) levels in the kidney. In comparison with controls, activity of GSH-Px activity, which antioxidant enzyme, was also reduced in the kidney of rats treated with CDDP. Repeated administration of 5.5 or 11.0 mg/kg ebselen prevented CDDP-induced alteration of GSH/GSSG ratios, MDA levels, and GSH-Px activity; however, no protection against CDDP was observed with administration of 2.75 mg/kg ebselen. Effective protection of CDDP-induced nephrotoxicity with ebselen was observed only when the molar amount of each daily ebselen treatment equaled or exceeded

Administration, Oral↗

Auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration: short-term results.

Autologous iris pigment epithelial cell transplantation was performed on patients with exudative age-related macular degeneration (AMD). Autologous IPE cell culture was performed using autologous serum after iridectomy in 7 patients with AMD. The cell suspensions (2 approximately 20 x 10(4) cells) were transplanted into the submacular lesion of individuals after removal of neovascular membranes. Subsequent ophthalmological examinations, including best corrected visual acuity and fluorescein or indocyanine green angiography, were performed. In addition, 15 patients with AMD, who underwent removal of neovascular membrane without transplantation, were evaluated as non randomized controls. Varying degrees of atrophy or defects of choriocapillaris and retinal pigment epithelium were observed in all of the patients. No cystoid macular edema or fluorescein leakage was observed after treatment, but window defects were present. No patient had decreased visual acuity. One treated patient developed mild subretinal fibrosis and an other patient developed mild preretinal fibrosis, however no difference was significant when compared with the control. In conclusion, the treatment resulted in no significant improvement in macular function, as compared with the control; however, no rejection or deterioration in visual acuity occurred up to the 13 month follow up.

Aged↗

[Woody plant and gravity].

In this review, we attempted to summarize the effect of gravity on growth of woody plants, broad leaved trees, on earth. It is well known that in tilted broad leaved trees, tension wood formed in the secondary xylem causes negative gravitropism. Gibberellin has been shown to induce tension wood in weeping branch, causing its upright growth. Recent study has shown that seedling of Japanese cherry tree grown on three dimensional clinostat, a device that simulates microgravity, grew at random angles, and that the formation of secondary xylem, as supporting tissue for upright growth, decreased. In the decreased xylem formation, the inhibition of the differentiation and development of fiber cell was clearly observed. These results suggest that in attitude control and morphogenesis of stem in woody plant, secondary xylem formation seriously relates to gravity on earth. In woody plant, the mechanism of gravity perception and the following signal transduction have not yet been elucidated, although the recent study reported the possibility that endodermal starch sheath cells and plant hormones may play some role in the mechanism. Space experiment for woody plant is expected to study these problem.

Biomechanical Phenomena↗

An anomalous case of the hepato-spleno-mesenteric and the gastro-phrenic trunks independently arising from the abdominal aorta.

This report describes an arterial anomaly case in the celiaco-mesenteric region, which was encountered in a Japanese male cadaver in the dissecting room at Kurume University School of Medicine in 1999. In this case, the usual celiac trunk was not identified, and the hepato-spleno-mesenteric and the gastro-phrenic trunks were independently arising from the abdominal aorta. In addition, the common hepatic artery divided into the left hepatic, the right hepatic, and the gastroduodenal arteries simultaneously, then, the accessory gastric artery arose from the left hepatic artery. This type of arteral anomaly belongs to the Type III of Adachi's classification and the Type II of Morita's classification.

Aged↗

Two anomalous cases of the hepato-mesenteric and the gastro-splenic trunks independently arising from the abdominal aorta.

This report describes two arterial anomaly cases in the celiaco-mesenteric region, which were encountered in two Japanese male cadavers in the dissecting room at Kurume University School of Medicine in 1999. In these cases, the usual celiac trunks were not identified, and the hepato-mesenteric and the gastro-splenic trunks were independently arising from the abdominal aorta. Moreover, in the first case, the common hepatic artery passed ventral side of the portal vein and divided into the hepatic proper and the gastroduodenal arteries. This type of arterial anomaly belongs to the Type V of Adachi's classification and the Type IV' of Morita's classification. In the second case, the common hepatic artery passed dorsal side of the portal vein and divided into the hepatic proper and the gastroduodenal arteries. This type of arterial anomaly belongs to the Type VI of Adachi's classification and the Type IV' of Morita's classification.

Aged↗

Detection of anti-neutrophil cytoplasmic antibodies in MRL/Mp-lpr/lpr mice and analysis of their target antigens.

Anti-neutrophil cytoplasmic antibodies (ANCA) have been widely studied and recognized to be clinically very important for some human diseases including systemic rheumatic diseases. We analyzed ANCA response and their target antigens in MRL/Mp-lpr/lpr (MRL-lpr) mice, an animal model of systemic rheumatic disease. P-ANCA was detected in 57% of the mice. Antibodies to the known P-ANCA target antigens at the same age were examined. Among these, antibodies to high mobility group (HMG) proteins HMG1 and HMG2 were detected in 57% of the mice, 75% of which were also positive for P-ANCA. These anti-HMG1/HMG2 activities were absorbed by preincubation with a mixture of HMG1 and HMG2. In contrast, antibodies to myeloperoxidase and cathepsin G were detected in 14% and 7%, respectively, but these activities were not inhibited by preincubation with corresponding antigens. In addition, the titers of P-ANCA and anti-HMG1/HMG2 antibodies in MRL-lpr mice were significantly correlated with each other. Thus, HMG1 and HMG2 were considered to be significant target antigens of P-ANCA in MRL-lpr mice.

Animals↗

Autologous peripheral blood stem cell transplantation for adults with B-lineage acute lymphoblastic leukemia: a pilot study.

We conducted a pilot study on autologous peripheral blood stem cell transplantation (PBSCT) for 11 adults with B-lineage acute lymphoblastic leukemia (ALL) in first complete remission (CR) or even in those with more advanced stages. All patients achieved CR by induction therapy, of whom 10 were treated with anthracycline, vincristine and prednisolone-based regimens. After consolidation therapy, all patients except one received high-dose cytarabine followed by granulocyte colony-stimulating factor (G-CSF) administration to collect PBSCs. Ten patients received busulfan 4 mg/kg for 4 days, etoposide 20 mg/kg for 3 days and ranimustine 200 mg/m2 for 2 days as a conditioning regimen. One received a regimen consisting of etoposide, cyclophosphamide and total body irradiation. From day 1, G-CSF was given intravenously, and no additional chemotherapy was administered. At the median follow-up time of 30.8 months, four of six patients with standard-risk B-lineage ALL survived within the range of 19.7 to 85.4 months without relapse. In contrast, only one of five with high-risk B-lineage ALL survived for 36.3 months without relapse. Autologous PBSCT as post-remission therapy may prolong CR in adults with standard-risk B-lineage ALL.

Adolescent↗

Influence of anteroposterior and mediolateral instability on range of motion after total knee arthroplasty: an ultrasonographic study.

Ultrasonographically, the femoral component and the tibial plate of total knee prostheses are strongly echogenic, while the high-density polyethylene insert is hypoechoic. This study evaluated the influence of mediolateral and anteroposterior stability after total knee arthroplasty (TKA) on range of motion using real-time monitoring with ultrasound. Mediolateral stress translation, which is increased by horizontal resection of more bone at the ends of the femur or tibia for easy prosthesis implantation, was examined on coronal scans at the level of the collateral ligaments. Anteroposterior drawer was examined on sagittal scans at the level of the patellar tendon. Mediolateral translation (0-10 mm; mean 2.24 mm) did not correlate with range of motion, while anteroposterior drawer (2-10 mm, mean 5.05 mm) correlated well with range of motion. These ultrasonographic findings suggest that horizontal over-resection of the ends of the femur and tibia contributed to joint laxity, which would not result in better ROM. Rollback and sliding of the femoral component on the tibia, which is believed to be correlated with anteroposterior drawer, may be important in achieving better range of motion and obtaining excellent results in TKA.

Hip Prosthesis↗

[The effects of sleep position change in sleep apnea syndrome].

Changing the sleep position from supine to non-supine is a simple but effective treatment for some patients with sleep apnea syndrome. In the present study, we compared the clinical data for good responders (GRs), those who responded well to the sleep position change, with those for poor responders (PRs), and also evaluated the effect of surgical treatment on the positional improvement of ventilation in the PR group. Forty-one adult patients with sleep apnea syndrome (mean age: 47.1 years, mean obesity index: 125.8%) were divided into two groups based on their polysomnographic responses to sleep position change. Thirty-two patients were classified as the GR group, whose apnea-hypopnea index (AHI) in the non-supine position declined to less than half of their AHI in the supine position, and nine whose non-supine AHI remained greater than half of their supine AHI were classified as the PR group. The AHI and the desaturation index (DI) for the PR group were significantly higher than those for the GR group, and the obesity index was also higher in the PR group. For the eight PRs who had surgical therapy, their polysomnographic data improved much more in the non-supine position than in the supine position. Of six patients whose total AHI was still 10 or more after surgery, four changed into GRs. The combination of surgery and sleep position change seemed to be an effective treatment even for patients with a little improvement before surgery.

Female↗

Atypical Cogan's syndrome successfully treated with corticosteroids and pulse cyclophosphamide therapy.

An 18-year-old woman was admitted to the medical center near her home with complaints of high fever and severe headache in June 1995. A diagnosis of adult-onset Still's disease was suspected and 50 mg/day of prednisolone was orally administered. In early April 1997, the patient suffered from sudden bilateral hearing loss and high fever. Pure tone audiogram taken at the same time showed an asymmetric bilateral neurosensorial hearing loss. A diagnosis of Cogan's syndrome was made. Administration of 60 mg prednisolone daily improved fever. Audiogram taken one month after administration of prednisolone showed improvement in the right ear. Monthly cyclophosphamide pulse therapy 700 mg combined with oral prednisolone was instituted. This combination therapy enabled the successful tapering of prednisolone without recurrence of hearing loss. Combined corticosteroid and pulse cyclophosphamide therapy would appear to be one effective regimen for Cogan's syndrome.

Adolescent↗

Mechanism of cell cycle arrest caused by histone deacetylase inhibitors in human carcinoma cells.

Inhibitors of histone deacetylase (HDAC) block cell cycle progression at G1 in many cell types. We investigated the mechanism by which trichostatin A (TSA), a specific inhibitor of HDAC, induces G1 arrest in human cervix carcinoma HeLa cells. TSA treatment induced histone hyperacetylation followed by growth arrest in G as well as hypophosphorylation of pRb. The Cdk4 kinase activity was essentially unchanged during the TSA-induced G1 arrest. On the other hand, the arrest was accompanied by down-regulation of kinase activity of Cdk2, although the total protein levels of Cdk2 and its activator Cdc25A were unaffected. Upon TSA treatment, amounts of cyclin E and the CDK inhibitor p21WAF1/Cip1 were markedly increased, while that of cyclin A was reduced. The induction of p21 and down-regulation of cyclin A correlated well with the decreased Cdk2 activity and cell cycle arrest. Furthermore, gel filtration chromatography showed the association of p21 with the cyclin E-Cdk2 complex, suggesting that the activation of Cdk2 by the enhanced expression of cyclin E is blocked by the increased p21. The elevated expression of p2 is also observed in cells treated with trapoxin and FR901228, structurally unrelated histone deacetylase inhibitors. A human colorectal carcinoma cell line lacking both alleles of the p21 gene (p21-/-) was resistant to TSA several times more than the parental line (p21+/+). These results suggest that the suppression of Cdk2 kinase activity due to p21 overexpression play a critical role in HDAC inhibitor-induced growth inhibition.

Antibiotics, Antineoplastic↗