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Biomedical subjects

M Yasuda

Publications and source records attributed to M Yasuda.

At least 127 records · Page 7Linked to original sources
PubMed1999

Developmental neurotoxicity of phenytoin on granule cells and Purkinje cells in mouse cerebellum.

Phenytoin (PHT) is a primary antiepileptic drug. Cerebellar malformations in human neonates have been described following intrauterine exposure to PHT. The neonatal period of development in the cerebellum in mice corresponds to the last trimester in humans. To examine the neurotoxic effects of PHT in the developing cerebellum, we administered PHT orally to newborn mice once a day during postnatal days 2-4. We observed many apoptotic cells in the external granular layer (EGL) on postnatal day 5, labeled cells in the EGL still remaining 72 h after labeling with 5-bromo-2'-deoxyuridine, and EGL thicker than that in the control on postnatal day 14. These results showed that PHT induced cell death of external granule cells and inhibited migration of granule cells in cerebella. In specimens immunostained with antibody against inositol 1,4,5-trisphosphate receptor type 1, Purkinje cells in the treated group had poor and immature arbors, and partially showed an irregular arrangement. The motor performance of the treated mice in a rotating rod test was impaired, although there were no changes in muscular strength or in walking pattern at the period of maturity. These findings indicate that PHT induces neurotoxic damage to granule cells and Purkinje cells in the developing cerebellum and impairs selected aspects of motor coordination ability.

Animals↗
PubMed1999

Studies on the HLA-DRB1 genotypes in Japanese women with severe pre-eclampsia positive and negative for anticardiolipin antibody using a polymerase chain reaction-restriction fragment length polymorphism method.

The human leukocyte antigen (HLA)-DR genotype was determined in 54 Japanese women with severe pre-eclampsia in order to elucidate the relationship between HLA-DR antigen systems and pre-eclampsia. The patients were divided into two groups according to positivity for the anticardiolipin antibody (ACA), i.e. one patient group negative for ACA (n = 41) and the other patient group positive for ACA (n = 13). The frequency of each HLA-DRB1 allele in both groups was compared with that in 81 normally fertile Japanese women who had not experienced pre-eclampsia. The genotypes of HLA-DR antigens were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of DRB1*04 and DRB1*0403 in the patient group positive for the ACA was significantly higher compared with that in the group of normal fertile women (P< 0.05). The frequency of each HLA-DRB1 allele was not significantly different between patient group with pre-eclampsia negative for ACA and group of normal fertile women. These results suggest a difference in the immunogenetic background between the patient groups with severe pre-eclampsia positive and negative for the ACA.

Adult↗
PubMed1999

Runaway pacemaker caused by a stuck accelerometer.

We report a case of runaway pacemaker with a ventricular pacing rate of 190 beats/min. The runaway occurred when the accelerometer became stuck due to the magnet application during VVIR pacing. Runaways in modern pacemakers are particularly rare, but they do still occur. The best solution for this phenomenon is generator replacement.

Electrocardiography↗
PubMed1999

Possible susceptibility of the HLA-DPB1*0402 and HLA-DPB1*04 alleles to unexplained recurrent abortion: analysis by means of polymerase chain reaction-restricted fragment length polymorphism method.

PROBLEM: To clarify whether HLA-DP antigens are associated with patient population of unexplained recurrent abortion. METHOD OF STUDY: The frequency of HLA-DPB1 alleles in patients with unexplained recurrent abortion, and the compatibility of HLA-DPB1 alleles between patient couples, were studied using a polymerase chain reaction (PCR)-restricted fragment length polymorphism (RFLP) method. Thirty patients who had a history of unexplained primary recurrent abortion, and their husbands, were typed for HLA-DPB1 genotype. Two hundred and ninety-nine base pair fragments from the second exon of HLA-DPB1 genes were selectively amplified using the PCR-primers. After amplification, the DNAs were digested with restriction endonucleases, and subjected to electrophoresis in a 12% polyacrilamide gel to determine HLA-DPB1 genotype. RESULTS: The frequency of HLA-DPB1*0402 and DPB1*04 alleles in the patient group (n = 30) was significantly increased, as compared to that in the normal fertile women (n = 30). The frequency of HLA-DPB1*04 allele in the patient group was significantly increased, as compared to that in the general population (n = 112). No significant compatibility of HLA-DPB1 alleles could be observed between patient couples and normal fertile couples. CONCLUSION: These findings suggest a possible new class II association with patient population of unexplained recurrent abortion.

Abortion, Habitual↗
PubMed1999

Induction of transformation and p53-dependent apoptosis by adenovirus type 5 E4orf6/7 cDNA.

Adenovirus (Ad) E4orf6/7, one of the early gene products of human Ads, forms a stable complex with the cellular transcription factor E2F to activate transcription from the Ad E2 promoter. E2F cDNAs have growth-promoting and apoptosis-inducing activities when overexpressed in cells. We cloned Ad5 E4orf6/7 cDNA in both simian virus 40- and human cytomegalovirus-based expression vectors to examine its transforming and apoptotic activities. The cloned E4orf6/7 collaborated with a retinoblastoma protein (RB)-nonbinding and therefore E2F-nonreleasing mutant of Ad5 E1A (dl922/947) to morphologically transform primary rat cells, suggesting that E2F is an important cellular protein functioning downstream of E1A for transformation. In a G418 colony formation assay, E4orf6/7 was shown to suppress growth of untransformed rat cells. Moreover, a recombinant Ad expressing Ad5 E4orf6/7 induced apoptosis in rat cells when coinfected with wild-type p53-expressing Ad. Mutational analysis of E4orf6/7 revealed that both of the domains required for growth inhibition and transformation by E4orf6/7 lay in the C-terminal region, which is essential for transactivation from the upstream sequence of an E2a promoter containing E2F-binding sites. However, the smallest mutant of E4orf6/7, encoding the C-terminal 59 amino acids, failed to complement the RB-nonbinding dl922/947 mutant despite showing growth inhibition and E2F transactivation activities. Thus, it is suggested that a subregion of E4orf6/7 which is required for growth inhibition and transformation in collaboration with dl922/947 overlaps the transactivation domain of E4orf6/7.

Adenovirus E1A Proteins↗
PubMed1999

Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro.

BACKGROUND: Hepatic stellate cells play a key role in the pathogenesis of hepatic fibrosis. AIMS: To examine the inhibitory effect of oestradiol on stellate cell activation. METHODS: In vivo, hepatic fibrosis was induced in rats by dimethylnitrosamine or pig serum. In vitro, rat stellate cells were activated by contact with plastic dishes resulting in their transformation into myofibroblast-like cells. RESULTS: In the dimethylnitrosamine and pig serum models, treatment with oestradiol at gestation related doses resulted in a dose dependent suppression of hepatic fibrosis with restored content of hepatic retinyl palmitate, reduced collagen content, lower areas of stellate cells which express alpha smooth muscle actin (alpha-SMA) and desmin, and lower procollagen type I and III mRNA levels in the liver. In cultured stellate cells, oestradiol inhibited type I collagen production, alpha-SMA expression, and cell proliferation. These findings suggest that oestradiol is a potent inhibitor of stellate cell transformation. CONCLUSION: The antifibrogenic role of oestradiol in the liver may contribute to the sex associated differences in the progression from hepatic fibrosis to cirrhosis

Animals↗
PubMed1999

Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer.

BACKGROUND: Helicobacter pylori affects gastric epithelium integrity by acceleration of apoptosis. However, it remains unclear what product of the bacteria causes apoptosis, or whether or not the apoptosis is involved in the development of ulcers. AIMS: To elucidate the factor from H pylori that causes acceleration of apoptosis and the role of apoptosis in the development of duodenal ulcer in H pylori infection. PATIENTS: Five H pylori negative healthy volunteers, 47 H pylori positive patients with duodenal ulcer, and 35 H pylori positive patients with gastric ulcer. METHODS: An endoscopic examination was carried out to diagnose ulcers and determine their clinical stage. To analyse apoptosis, a cell cycle analysis was performed using biopsy specimens. RESULTS: There was a significant correlation between the urease activity of the H pylori strain and the level of apoptosis induced by this bacterial strain. Moreover, in duodenal ulcer patients infected with H pylori, the patients with an active ulcer exhibited a significantly higher level of apoptosis than those with ulcers at both the healing and scarring stages. CONCLUSION: These findings suggest that acceleration of apoptosis in the antral mucosa caused by the urease of H pylori plays a crucial role in the development of ulcers in the duodenum.

Adolescent↗
PubMed1999

Case-control study of presenilin-1 intronic polymorphism in sporadic early and late onset Alzheimer's disease.

OBJECTIVE: Presenilin-1 is a major causative gene for early onset familial Alzheimer's disease, and the apolipoprotein E epsilon4 allele is a major genetic risk factor known to influence late onset and sporadic early onset Alzheimer's disease. The presenilin-1 1/1 genotype has recently been reported to be associated with sporadic Alzheimer's disease. The purpose of this study is to determine whether Alzheimer's disease is associated with presenilin-1 gene polymorphism and the apolipoprotein E genotype in an extended case-control study. METHODS: An examination was conducted on 217 patients with Alzheimer's disease, along with an equal number of age and sex matched controls derived from the same community in a Japanese population, by using a chi2 test for homogeneity and a logistic regression analysis. A meta-analysis of data from the literature on allele frequencies in Alzheimer's disease and control populations was used for comparison with the Japanese allele frequencies obtained in this study. RESULTS: The presenilin-1 allele-1 frequencies were similar in patients with early onset Alzheimer's disease (0.61) and younger controls (0.61), and in those with late onset Alzheimer's disease (0.63) and elderly controls (0. 63). We found no evidence for a possible association between the presenilin-1 polymorphism and the apolipoprotein E epsilon4 allele. However, the meta-analysis showed that the association between the presenilin-1 1/1 genotype and Alzheimer's disease was significant (Peto odds ratio=1.16, 95% confidence interval=1.04-1.31). CONCLUSIONS: These results suggest a subtle but positive association of presenilin-1 gene polymorphism with Alzheimer's disease, although Japanese data in this study which failed to support such a relation would indicate an ethnic variation.

Adult↗
PubMed1999

Failure to confirm a synergistic effect between the K-variant of the butyrylcholinesterase gene and the epsilon4 allele of the apolipoprotein gene in Japanese patients with Alzheimer's disease.

To confirm a synergistic effect between the polymorphic K variant of the butyrylcholinesterase (BChE-K) gene and the epsilon4 allele of the apolipoprotein E (APOE) gene in Alzheimer's disease, the frequency of the BChE-K allele was re-examined in a large series of Japanese patients with Alzheimer's disease and controls. Two hundred and three patients with Alzheimer's disease and 288 age and sex matched controls were genotyped by polymerase chain reaction and restriction fragment length polymorphism for BChE-K and APOE. No changes were found in the frequency of BChE-K, either in the Alzheimer's disease group as a whole (0.17 v 0.14; p=0.36) or in early (0.16 v 0.16; p=0.98) or late (0.17 v 0.13; p=0.24) onset patients compared with age matched controls. The study failed to confirm the findings of a previous study which found a significantly higher incidence of BChE-K in patients with Alzheimer's disease with APOE epsilon4 allele than in controls. In the Japanese population studied here, there was no association between BChE-K and Alzheimer's disease, nor an interaction between BChE-K and APOE epsilon4 allele.

Aged↗
PubMed1999

Lack of effect of apolipoprotein E E4 allele on neuropsychiatric manifestations in Alzheimer's disease.

The association between the apolipoprotein E epsilon 4 (APOE E4) allele and a wide spectrum of behavioral symptoms of Alzheimer's disease (AD) was investigated. Neither the severity nor the presence of any behavioral changes was associated with the number of APOE E4 alleles, even after controlling for the effects of age at onset, sex, education level, duration of illness, and severity of dementia. The findings do not support the hypothesis that neuropsychiatric manifestations of AD are different in patients with the APOE E4 allele.

Aged↗
PubMed1999

A kinetic study of protein binding to ecabet sodium using quartz-crystal microbalance.

To define the mechanism of the protection by ecabet sodium of the gastric mucosa, the characteristics of protein binding of this drug were investigated using a quartz-crystal microbalance (QCM) method. The binding rate constants (kb) and the binding amounts (delta m) were obtained from time courses of the frequency decrease (mass increase) of the QCM. The binding constants to proteins of two ecabet analogues (G1, ecabet type and G2, non-ionic ecabet type) were dependent on the pH, leading to large kb values at the acidic region. Furthermore, the kb values of G1 with the addition of bovine serum albumin (BSA) and bovine serum fibrinogen (BSF) at the acid region were larger than those of G2. The difference in kb values between G1 and G2 for porcine gastric mucin (PGM) is hardly discernible. Ecabet seems to be more heavily distributed in the ulcerous areas than in the intact mucosa, judging from the large binding constants of this drug to BSA and BSF compared with those to PGM. It is suggested that ecabet is bound to proteins by hydrophobic interaction, moreover, the electrostatic interaction between this drug and proteins (BSA and BSF) occurs at acidic pH region. On account of these interactions, ecabet sodium seems to have a more protective effect on an ulcer at intraluminal acidity than sucralfate. Finally, QCM was found to be a useful technique for detecting quantitatively the time course of binding proteins with drug.

Abietanes↗
PubMed1999

Analysis of heart rate variability during head-up tilt testing in a patient with idiopathic postural orthostatic tachycardia syndrome (POTS).

A 16-year-old boy was diagnosed with idiopathic postural orthostatic tachycardia syndrome (POTS) during head-up tilt testing. During a passive tilt, the patient's heart rate (HR) increased by 30 beats/min within 5 min. After 25 min of tilting, his HR further increased to 133 beats/min and he began to complain of lightheadedness and weakness without hypotension. Power spectral analysis of HR variability during the tilt test revealed that the ratio of low and high frequency powers increased with the onset of orthostatic intolerance. Propranolol (10mg every morning) dramatically alleviated his clinical symptoms, and he has been asymptomatic with gaining weight after discontinuing his crowded train commuting.

Adolescent↗
PubMed1999

Acute performance of steroid-eluting screw-in leads for atrial free wall pacing.

The aim of this study was to clarify the acute performance of steroid-eluting screw-in leads in comparison with that of nonsteroid screw-in leads for atrial free wall pacing. In 114 cases (68 males, 46 females, average age 70 years) with atrial free wall pacing by screw-in leads, pacing thresholds and P-wave amplitudes were compared at the time of implantation and 1 week later between 68 cases of nonsteroid and 46 cases of steroid-eluting screw-in leads. No significant differences were seen between the 2 groups at implantation in either voltage or current thresholds measured at pulse widths of 0.1, 0.3, 0.6, 1.0, 2.0 ms, or P-wave amplitudes. Pulse width thresholds at outputs of 2.5 V and 5.0 V were significantly lower for steroid leads 1 week after implantation (2.5 V: 0.34+/-0.27 ms nonsteroid vs. 0.12+/-0.08 ms steroid, p<0.001; 5.0 V: 0.12+/-0.08 ms nonsteroid vs. 0.06+/-0.02 ms steroid, p<0.01). P-wave amplitudes after 1 week were significantly higher for steroid leads (2.6+/-0.7 mV nonsteroid vs 3.0+/-1.2 mV steroid, p<0.001). Threshold rise, including pacing failure, was observed in 15 (22%) of the non-steroid leads, but in only 1 (2%) of the steroid leads. In conclusion, steroid-eluting screw-in leads suppress the acute rise of pacing thresholds in the right atrial free wall and their acute performance is better than that of non-steroid leads. These results suggest that appropriate low-output atrial pacing is feasible immediately after implantation.

Aged↗
PubMed1999

Stimulation of in vitro angiogenesis by tetrahydrobiopterin in bovine aortic endothelial cells.

This study examined whether tetrahydrobiopterin (BH4) stimulates angiogenesis by measuring the formation of tube-like structures in vascular endothelial cells. Bovine aortic endothelial cells that were cultured between two layers of collagen type I gel formed tube-like networks. Addition of BH4 or sepiapterin, a precursor of BH4 synthesis, stimulated the formation of tube-like structures. The sepiapterin-stimulated tube formation was completely inhibited by co-treatment with N-acetylserotonin, an inhibitor of sepiapterin reductase. These findings show that BH4 stimulates in vitro angiogenesis in vascular endothelial cells.

Animals↗
PubMed1999

[A case of metastatic liposarcoma originating in the retroperitoneum successfully treated with combination chemotherapy].

We reported a 36-year-old woman with metastatic liposarcoma originating in the retroperitoneum, which responded well to adjuvant chemotherapy. The primary tumor was removed by surgery. Two months later, the patient developed metastasis to the brain, and to the lung four months later. Metastatic liposarcomas to the brain generally are extremely rare. The patient was treated with combination chemotherapy using cyclophosphamide, vincristine, adriamycin, and dacarbazine (CYVADIC). After she was examined, the former two drugs were alternated with vindesine and ifosfamide, and another regimen with cisplatin and etoposide was given after a three-week interval. As a result, both of the metastases totally disappeared. No recurrent lesion has been noted for two years. Although the role of chemotherapy for liposarcoma has not been well defined and little data support its use in an adjuvant setting, this combination chemotherapy seemed to be effective for advanced liposarcoma.

Adult↗
PubMed1999

[Intra-arterial chemotherapy via reservoir system for advanced bladder cancer and prostate cancer].

A clinical study was performed on the efficacy of intra-arterial chemotherapy using a reservoir system for advanced urological malignancies. The reservoir system was indwelted in the femoral subcutaneous layer by Seldinger's method. Fifteen cases of inoperable complicated advanced bladder cancer and 10 cases of postoperative local recurrent bladder cancer were administered intra-arterial chemotherapy using a reservoir system. Then, 23 cases of local relapsed prostate cancer and two cases of endpocrine-resistant prostate cancer were administered the chemotherapy. The administered anti-cancerous agents were methotraxate, cis-platinum and adriamycin, then 5-FU or carboplatin was administered as maintenance therapy. The mean number of courses of chemotherapy was six for bladder cancer and four for prostate cancer. During stabilization of the local lesion, no distant deterioration was recognized. The overall clinical efficacy was a positive response (PR) and no change (NC): for 18 and 7 cases of bladder cancer, and 11 and 14 cases of prostate cancer, respectively. The median duration of stabilization was 23 months for bladder cancer and 12 months for prostate cancer. The adverse effects were fever than those with systemic chemotherapy.

Adult↗
PubMed1999

[The current status of molecular detection of micrometastatic prostate cancer cells].

We summarized and reviewed published reports, including our studies, on the reverse transcription-polymerase chain reaction (RT-PCR) detection of micrometastatic prostate cancer cells in lymph nodes, bone marrow and peripheral blood. Some published data preliminarily suggest that the RT-PCR assay of micrometastatic prostate cancer cells may allow a more accurate assessment of lymph node and bone metastases of prostate cancer, and offer a presurgical prediction of the pathological stage of clinically localized disease. In addition, the RT-PCR assay may have a unique prognostic value in prostate cancer. However, controversy remains over the clinical significance of the RT-PCR assay. This assay could potentially develop into a diagnostic procedure for the clinical decision making in patients with prostate cancer. To establish the clinical significance of the RT-PCR assay, further optimized and standardized RT-PCR assay studies are needed, investigating large populations and involving long-term follow-up for the determination of any association between the results of the RT-PCR assay and specific clinical outcome.

Humans↗