PubMed Health⌕ Search

Biomedical subjects

T Miyachi

Publications and source records attributed to T Miyachi.

At least 19 recordsLinked to original sources
PubMed2000

Induction of mammalian cell transformation and genotoxicity by 2-methoxyestradiol, an endogenous metabolite of estrogen.

2-methoxyestradiol (2-MeOE(2)) is an endogenous metabolite of 17beta-estradiol and a proposed inhibitor of tumor growth and angiogenesis. However, 2-MeOE(2) is also an inhibitor of microtubule assembly and other microtubule inhibitors, e.g. colcemid and diethylstilbestrol, induce aneuploidy and cell transformation in cultured mammalian cells. To assess the in vitro carcinogenicity and related activity of 2-MeOE(2), the abilities of this metabolite to induce cell transformation and genetic effects were studied simultaneously using Syrian hamster embryo (SHE) fibroblasts. Growth of these cells was reduced by treatment with 2-MeOE(2) at 0.1-1.0 microg/ml in a concentration-dependent manner. Treatment of SHE cells with 2-MeOE(2) at 0.3 or 1.0 microg/ml for 2-48 h also resulted in a concentration- and treatment time-related increase in the mitotic index and the percentage of multinucleated cells. Treatment with 2-MeOE(2) at 0.1-1.0 microg/ml for 48 h induced a statistically significant increase in the frequencies of morphological transformation of SHE cells in a concentration-dependent manner. A statistically significant increase in the frequencies of somatic mutations at the Na(+)/K(+) ATPase or hprt locus was also observed in cells treated with 2-MeOE(2) for 48 h at 0.1 or 0.3 microg/ml, respectively. Treatment of SHE cells with 2-MeOE(2) at 0.3 or 1.0 microg/ml for 24 h induced chromosome aberrations, mainly breaks, exchanges and chromosome pulverization. The incidence of chromosome aberrations was not affected by co-treatment with alpha-naphthoflavone, an inhibitor of 2-hydroxylase that inhibits oxidative conversion of 2-MeOE(2) to 2-hydroxyestradiol, but the incidence was slightly increased by co-treatment with L-ascorbic acid. Numerical chromosomal changes in the near diploid range and in the tetraploid and near tetraploid ranges were also detected in 2-MeOE(2)-treated cells. These findings indicate that 2-MeOE(2) has cell transforming and genotoxic activities in cultured mammalian cells and potential carcinogenic activity.

2-Methoxyestradiol↗
PubMed2000

[Studies on surfactant replacement therapy in pediatric measles pneumonitis].

Measles pneumonitis, as well as encephalitis, is the most important complication associated with mortality in measles. Many medications including steroids and vitamin A have been applied to pediatric measles pneumonitis. However, the efficacy of such medication has not yet been established. This study is aimed at evaluating the effectiveness of surfactant replacement therapy in pediatric measles pneumonitis. Five patients (aged 1-2 years) with measles pneumonitis were transferred to our emergency center. On the transferred day, Surfactant-TA was administered by intratracheal method. After administration of surfactant, PaO2/FIO2 increased from 63.6 +/- 11.0 (mean +/- SE) to 206.2 +/- 54.1 in an hour and to 163.8 +/- 34.8 in 24. At the same time, the CO2 elimination and the dynamic compliance were improved. Because of these effects, the peak inspiratory pressure employed in mechanical ventilation could be reduced. It is concluded that surfactant replacement therapy can prevent the patients with measles pneumonitis from hypoxemia and ventilation-induced lung injury. However, further study is needed to maintain the improved oxygenation. Recently, it is reported that the effect of exogenous surfactant on oxygenation and activity of pulmonary neutrophils is regulated by the amount and/or concentration of administered surfactant. Therefore, it is an urgent issue to find out the optimum amount and concentration of exogenous surfactant used clinically.

Biological Products↗
PubMed1999

Structure and regulation of the human NeuroD (BETA2/BHF1) gene.

In this study, we isolated and characterized the human NeuroD (BETA2/BHF1) gene. This gene was found to consist of two exons and one intron. The promoter regions were well-conserved compared with the mouse NeuroD gene. Two transcription start points (TSPs) were determined by the oligo-capping method. One TATA box was located at -31 bp from the lower TSP. The results of a transient transfection assay using the human neuroblastoma cell line IMR-32 and hamster insulin tumor cell line HIT-T15 suggested that there are at least three positive regulatory regions in the promoter. In these regions, four E boxes (CANNTG), named the E1 to E4 boxes, and two GC boxes were present. Cotransfection of the NeuroD expression vector into IMR-32 cells enhanced the NeuroD promoter activity by about 4-fold. A deletion and mutation analysis revealed that the E1 and E4 boxes, especially the E1 box, are associated with autoactivation and that E2 and E3 boxes are not associated with autoactivation. As mutation analysis of E3 box showed a decrease in the enhancer activity to the basal level, it showed that the E3 box is important to activate the NeuroD transcription. These results raised the possibility that the NeuroD gene expression is positively regulated through the E box sequence, not only by NeuroD itself but also by another E box binding protein.

Animals↗
PubMed1999

Identification and analysis of the promoter region of the human NeuroD-related factor (NDRF)1.

We isolated and characterized the human NeuroD-related factor (NDRF)/NeuroD2/KW8 gene. The NDRF gene consisted of two exons and one intron. NDRF had one transcriptional starting point, and in its 5'-flanking region, no TATA box was detected, but 16 E boxes (CANNTG) were present. RNA blotting analysis revealed that HIT-T15 and D283 cells expressed a 3.3 kb band of the NDRF transcript. Promoter analysis by luciferase assay demonstrated that luciferase activity changed between -120 and -195, and between -451 and -564, both regions wherein a single E box existed. Radiation hybrid mapping showed that NDRF linked the marker SHGC-36242 with a LOD score of 8.53 and was located on 17q12-22.

Animals↗
PubMed1999

Butyrate augments interferon-alpha-induced S phase accumulation and persistent tyrosine phosphorylation of cdc2 in K562 cells.

Interferon-alpha (IFN-alpha) is a clinically useful cytokine for treatment of a variety of cancers, including chronic myelocytic leukaemia (CML). Most CML cells are sensitive to IFN-alpha; however, its biological effects on leukaemic cells are incompletely characterized. Here, we provide evidence that IFN-alpha induces a significant increase in the S phase population in human CML leukaemic cell line, K562, and that the S phase accumulation was augmented by sodium butyrate. In contrast, neither sodium butyrate alone, nor sodium butyrate plus IFN-gamma, affected the cell cycle in K562 cells. These data suggest that the effect of sodium butyrate depended upon IFN-alpha-mediated signalling. The ability of leukaemic cells to exhibit the S phase accumulation after stimulation by IFN-alpha plus sodium butyrate correlated well with persistent tyrosine phosphorylation of cdc2, whereas treatment with IFN-gamma plus sodium butyrate did not affect its phosphorylation levels. Considering that dephosphorylation of cdc2 leads to entry to the M phase, the persistent tyrosine phosphorylation of cdc2 may be associated with the S phase accumulation induced by IFN-alpha and sodium butyrate. In addition, another human CML leukaemic cell line, MEG-01, also showed the S phase accumulation after stimulation with IFN-alpha plus sodium butyrate. Taken together, our studies reveal a novel effect of sodium butyrate on the S phase accumulation and suggest its clinical application for a combination therapy with IFN-alpha, leading to a great improvement of clinical effects of IFN-alpha against CML cells.

Antineoplastic Agents↗
PubMed1998

Quantitative analysis of CSF flow dynamics using MRI in normal pressure hydrocephalus.

In order to clarify the flow dynamics of cerebrospinal fluid (CSF) in normal pressure hydrocephalus (NPH), a phase-contrast cine magnetic resonance (MR) imaging technique with retrospective cardiac gating was used to measure the quantitative flow velocity of CSF in the aqueduct in patients with NPH after subarachnoid hemorrhage (SAH-NPH group, n = 17), idiopathic NPH (1-NPH group, n = 2), asymptomatic ventricular dilatation or brain atrophy (VD group, n = 7) and healthy volunteers (control group, n = 19). Intracranial pressure (ICP) and pressure volume response (PVR) were also measured during the shunt operation in six of the SAH- NPH group. The maximum CSF flow velocity (Vmax) in the aqueduct was significantly larger in the SAH-NPH group (9.21 +/- 4.12 cm/sec, mean +/- SD) than in the control group (5.27 +/- 1.77, p < 0.001) and the VD group (4.06 +/- 1.81, p < 0.005). Vmax was not different between the control and VD groups. There was a positive correlation between the PVR and the peak CSF flow velocity in the SAH-NPH group. These findings suggest that the changes of CSF flow velocity in the SAH-NPH group might be caused by a moderate decrease of intracranial compliance. The CSF flow study using MRI is useful to differentiate NPH from brain atrophy or asymptomatic ventricular dilatation and also to estimate the intracranial compliance.

Adult↗
PubMed1998

[A case of polymyositis with anti-Jo-1 antibody preceded by BOOP].

A 56-year-old man experienced dyspnea since August 1995 and the chest X-ray film showed abnormal shadow. The diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) was established based on the histological findings of transbronchial lung biopsy. The patient was treated with prednisolone and symptoms improved. Myalgia and muscle weakness developed associated with relapse of BOOP after withdrawal of prednisolone. Patient was admitted to our department on December 1995 for further examination. An increased level of serum CPK, histological findings of muscle biopsy consistent with myositis, and positive anti-Jo-1 antibody were identified. Those findings supported a diagnosis of polymyositis (PM), and BOOP was considered as a pulmonary complication of PM. Myositis and pulmonary lesion improved after second course of steroid therapy and patient was discharged on May 1996. Both chronic pulmonary fibrosis and acute progressive interstital pneumonia are well known as pulmonary lesion associated with PM. The former is frequently recognized in cases of PM with anti-Jo-1 antibody and the latter is often observed in cases without autoantibodies. The association of PM and BOOP, however, has rarely been reported. The findings that BOOP frequently preceded PM and anti-Jo-1 antibody was positive in half of the cases were observed in the literature.

Antibodies, Antinuclear↗
PubMed1997

Raised plasma concentrations of parathyroid hormone related peptide in hypercalcemic multiple myeloma.

In order to clarify the pathogenesis of hypercalcemia in multiple myeloma, we measured plasma levels of parathyroid hormone related peptide (PTHrP), tumor necrosis factor alpha (TNF-alpha), tumor necrosis factor beta (TNF-beta), intact PTH and, serum 1,25-dihydroxyvitamin D in fifteen patients of multiple myeloma. We also measured serum levels of inorganic phosphorus (iP) and alkalinephosphatase activity (ALP). No significant differences in iP (3.2 +/- 0.4 vs. 4.0 +/- 2.2 mg/dl), ALP (150 +/- 28 vs. 335 +/- 305 IU/l) 1,25(OH)2 D (31.5 +/- 17.0 vs. 23.3 +/- 11.2 pg/ml) or TNF-alpha (7.8 +/- 2.1 vs. 8.0 +/- 2.0 pg/ml) were observed between normocalcemic and hypercalcemic patients. Plasma iPTH levels in hypercalcemic patients were significantly lower than those in normocalcemic patients (28.5 +/- 9.4 vs. 16.3 +/- 5.6 pg/ml, p = 0.01). Plasma levels of TNF-beta were less than 15.6 pg/ml in all subjects. On the other hand, the frequency of patients with abnormally high plasma levels of PTHrP was significantly greater (2/9 for normocalcemia vs 5/6 for hypercalcemia, chi 2 = 5.20, p = 0.02) in patients with hypercalcemia than in normocalcemic patients. Furthermore, a significant positive relationship between plasma PTHrP levels and corrected serum calcium levels (cCa) was observed using Spearman's correlation analysis by rank in fifteen myeloma cases (rs = 0.66, p = 0.013). These results suggest that PTHrP might be involved in the elevation of serum calcium levels in hypercalcemic myeloma patients. However, a few cases exhibit normocalcemia despite elevated plasma PTHrP levels or hypercalcemia without high plasma PTHrP levels. Therefore, further studies are necessary to elucidate the pathogenesis of hypercalcemia in multiple myeloma.

Aged↗
PubMed1997

[Lipoprotein(a) as a risk factor for cardiovascular disease in elderly patients with diabetes].

Lipoprotein(a) (Lp(a)) is an independent risk factor for cardiovascular diseases in non-diabetic people, but few studies have been done in diabetic patients. To investigate whether Lp(a) is a risk factor for cardiovascular disease in elderly people with diabetes, we examined the association of Lp(a) and serum lipid levels (total cholesterol: TC; triglycerides: TG; and high-density lipoprotein cholesterol: HDL-c) with the incidence of coronary artery disease and cerebrovascular disease. We studied 354 outpatients(131 men and 223 women, 60-97 years of age) with non-insulin-dependent diabetes mellitus. The mean concentration of Lp(a) was 21.1 +/- 19.6 mg/dl and the median was 14.0 mg/dl. The Lp(a) concentration did not correlate significantly with age or with sex, but it did correlate significantly with TC (r = 0.152, p < 0.05) and with the level of apoprotein B (r = 0.168, p < 0.05). The incidence of cerebrovascular disease was significantly higher in patients with high concentrations of Lp(a) (> or = 30 mg/ dl) than in those with low concentrations (< 30 mg/ dl). Multivariate logistic regression analysis revealed that male sex, hypertension, a high level of HbA1c, a low level of HDL, and a high level of Lp(a) were independent risk factors for cerebrovascular disease. The incidence of coronary artery disease tended to the higher in those with high concentrations of Lp(a) (> or = 30 mg/dl). However, multivariate logistic regression analysis revealed no significant correlation between Lp(a) concentration and the incidence of coronary artery disease. We conclude that a high concentration of Lp(a) is an independent risk factor for cerebrovascular disease in elderly patients with diabetes.

Aged↗
PubMed1997

[Sjögren's syndrome with presenting as aseptic meningoencephaloradiculopathy in an elderly woman].

A 76-year-old woman was found to have acute aseptic meningoencephalitis with meningial irritation, disturbance of consciousness, elevation of cell counts in cerebrospinal fluid, and swelling of a right temporal-lobe lesion on a CT scan of the head. Muscle weakness in the lower extremities and urinary dysfunction developed and progressed gradually. The protein content of cerebrospinal fluid was high, and the distal latencies of F waves were prolonged, which suggested that the inflammation extended to the nerve roots. Sjögren's syndrome was diagnosed on the basis of atrophy of the labial salivary glands; invasions of lymphocytes and plasma cells to the intercellular space; and elevation of the titers of serum antinuclear antibody, anti-SS-A antibody, and anti-SS-B antibody. The patient had no xerosis. Aseptic meningoencephalitis was the first manifestation of Sjögren's syndrome. In recent years, several cases in which Sjögren's syndrome was associated with aseptic meningitis have been reported. However, we know of no previous report of such a case in a patient of this age. Aseptic meningoencephalitis can be the first manifestation of Sjögren's syndrome.

Acute Disease↗
PubMed1997

[Chronic neuropathy, a high level of protein in cerebrospinal fluid, and vitamin B1 and folate deficiency in a patient with normal-pressure hydrocephalus].

A 67-year-old woman presented with a 1-year history of gradual weight loss, reduced mental activity, muscle weakness, and urinary dysfunction. Neurological examination revealed mild lethargy, severe muscular atrophy, and diminished deep tendon reflexes in the extremities. The levels of vitamin B1 and folate in blood were low: 1.9 micrograms/dl (normal range 2.0-7.2) and 0.7 ng/ml (normal range 4.0-12.0). respectively. A lumbar puncture was done. The pressure of the cerebrospinal fluid was within normal limits, the level of protein was very high (467 mg/dl), and only a few lymphocytes were seen. A nerve-conduction study showed low amplitudes of action potentials and slow conduction velocities in both the motor and sensory nerves. Myelin irregularity, "onion bulb formation", and axonal atrophy were seen in a specimen obtained by sural nerve biopsy. A T2-weighted magnetic resonance image of the brain showed ventricular dilatation, high-intensity signals around the lateral ventricles, and a flow-void sign of the cerebral aqueduct. Radioisotope cisternography (111In-DTPA) disclosed ventricular reflux and slow clearance of the tracer from the ventricles. These findings indicated the presence of chronic inflammatory demyelinating polyneuropathy, nutritional polyneuropathy, vitamin B1 deficiency, folate deficiency, and normal pressure hydrocephalus. In this patient, the high level of protein in the cerebrospinal fluid may have caused the hydrocephalus.

Aged↗
PubMed1996

Turbo spin-echo magnetic resonance imaging depiction of facial nerve compression by a vertebral artery in a patient with hemifacial spasm--technical note.

Turbo spin-echo magnetic resonance (MR) imaging of a patient with hemifacial spasm clearly demonstrated vascular compression of the facial nerve by the vertebral artery. The high resolution images of this method may be an appropriate alternative to preoperative cerebral angiography. Turbo spin-echo MR imaging is a diagnostic procedure of choice for patients with hemifacial spasm and possibly trigeminal neuralgia.

Adult↗
PubMed1994

Structure of the human LC-PTP (HePTP) gene: similarity in genomic organization within protein-tyrosine phosphatase genes.

Recently, various cDNA sequences coding protein-tyrosine phosphatases (PTPs) have been reported and their extensive similarities in the catalytic domains clarified, but knowledge of the structures and organizations of their genes is still limited. In this study, a detailed structure and organization of the human intracellular LC-PTP (also called HePTP) gene is reported. The 13 to 18.5 kb genomic clones encoding human LC-PTP have been isolated. The LC-PTP gene is organized into 11 exons, including the 5'-noncoding first exon and the 3'-noncoding exon. Splicing sites for exons 4 to 10, which encode the conserved catalytic PTP domain, arise almost at the same position as for the CD45 gene. This elucidation of the LC-PTP gene structure provides insight into the domain evolution of intracellular LC-PTP and transmembrane CD45, which may be generated by gene duplications of an ancestral gene.

Amino Acid Sequence↗
PubMed1993

Phase II study of carboplatin, cisplatin, and vindesine in advanced non-small-cell lung cancer.

Cisplatin in combination with vindesine has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC), producing an overall response rate of 32%. We conducted a phase II study to examine whether the addition of carboplatin to the combination of cisplatin and vindesine would improve the antitumor activity of the two platinum agents in advanced NSCLC without increasing their toxicity. Carboplatin (240 mg/m2) and vindesine (3 mg/m2) were given intravenously on day 1 and cisplatin (60 mg/m2) and vindesine (3 mg/m2), on day 8. Of the 40 evaluable patients with advanced NSCLC, 12 showed a partial response, for an overall response rate of 30% (95% confidence interval, 17%-47%). The median duration of response was 12 weeks, and the median survival duration for all patients was 38 weeks. The major toxicity was hematologic: leukopenia (WHO grade > or = 3) was observed in 21 patients (53%) and anemia (WHO grade > or = 3), in 13 patients (33%). However, thrombocytopenia was mild and WHO grade 3 toxicity was observed in only 4 patients (10%). Nonhematologic toxicities consisted mainly of WHO grade > or = 2 nausea and vomiting in 16 patients (40%) and WHO grade > or = 2 alopecia in 11 patients (28%). No significant nephrotoxicity or neurotoxicity was seen. Our findings indicate that the addition of carboplatin to the combination of cisplatin and vindesine does not improve antitumor activity in patients with advanced NSCLC.

Adult↗
PubMed1992

Molecular cloning of a novel protein-tyrosine phosphatase SH-PTP3 with sequence similarity to the src-homology region 2.

Protein-tyrosine phosphorylation and dephosphorylation are directly associated with cellular growth, signal transduction, and neoplastic transformation. Here we report the isolation of a complementary DNA (cDNA) clone encoding a novel protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 68-kDa protein composed of 593 amino acids which contains two src-homology region 2's (SH2 domains) at the N terminus; this PTP is designated as SH-PTP3. Northern blot analysis revealed that SH-PTP3 mRNA was expressed throughout many tissues and the transcriptional size was consistent at about 6.0 kb. As with other SH2 domains in src-family kinases, the SH2 domains of SH-PTP3 may play a crucial role in interactions with tyrosine phosphorylated signaling proteins, including itself and protein tyrosine kinases (PTKs), to regulate targets' enzyme activity.

Amino Acid Sequence↗