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Biomedical subjects

H Miyata

Publications and source records attributed to H Miyata.

At least 91 records · Page 5Linked to original sources
PubMed2001

Denervation causes changes in electrophysiological properties in rat phrenic motoneurons.

Thirty-nine male adult rats were divided into a control group and a denervation group that had been subjected to phrenicotomy 4 weeks earlier. Electrophysiological membrane properties (input resistance and rheobase) of phrenic motoneurons were measured from intracellular recordings made with glass microelectrodes. Under anesthetized and artificially ventilated conditions, the recorded motoneurons were divided into recruited (spike discharge) and non-recruited (depolarization only) types. There was a significant inverse relationship between the rheobase and input resistance in the control rats, but not in the denervated rats. In the control rats, the mean value of rheobase in the non-recruited motoneurons was significantly higher than that in the recruited motoneurons. In denervated rats, however, the mean value of rheobase in the recruited motoneurons was identical to that in the non-recruited motoneurons. The results indicated that phrenicotomy induced a de-differentiation of electrophysiological properties of the phrenic motoneurons, and that these changes might be restricted to the motoneurons innervating fast-twitch, low fatigue resistance muscle fibers.

Animals↗
PubMed2001

Observation of Cabibbo suppressed B --> D(*)K- decays at Belle.

We report observations of the Cabibbo suppressed decays B-->D((*))K- using a 10.4 fb(-1) data sample accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB e(+)e(-) storage ring. We find that the ratios of Cabibbo suppressed to Cabibbo favored branching fractions are B(B--->D0K-)/B(B--->D0pi(-)) = 0.079+/-0.009+/-0.006, B(B(0)-->D+K-)/B(B(0)-->D+pi(-)) = 0.068+/-0.015+/-0.007, B(B--->D(*0)K-)/B(B--->D(*0)pi(-)) = 0.078+/-0.019+/-0.009, and B(B(0)-->D(*+)K-)/B(B(0)-->D(*+)pi(-)) = 0.074+/-0.015+/-0.006. These are the first observations of the B-->D+K-, D(*0)K-, and D(*+)K- decay processes.

Journal Article↗
PubMed2001

Clinical significance of CDC25A and CDC25B expression in squamous cell carcinomas of the oesophagus.

CDC25A, CDC25B and CDC25C belong to a family of protein phosphatases which activate the cyclin-dependent kinase at different points of the cell cycle. According to accumulating evidence, CDC25A and CDC25B seem to possess oncogenic properties. We have analysed these expressions by immunohistochemistry, western blot and RT-PCR in a series of 100 patients with squamous cell carcinoma of the oesophagus. When compared with non-cancerous cells, CDC25A and CDC25B were strongly expressed in the cytoplasm of cancer cells, with positive (+) classification in 46% (46 cases) and 48% (48 cases), respectively. There was no significant correlation between CDC25A and CDC25B expression, nor was there any association with the expression of other cell cycle-regulating molecules, including cyclin D1, Rb, p16(INK4), p27(KIP1)and PCNA (proliferating cell nuclear antigen). CDC25A (+), as well as CDC25B (+), was more frequently found in patients with deeper tumour invasion and lymph node metastasis, while tumour size was correlated only with CDC25A expression. Postoperative survival was significantly poorer for CDC25A (+) patients than CDC25A (-) patients, but was not affected by the CDC25B status. Nuclear localization of CDC25A was observed in 51 cases (51%), regardless of its cytoplasmic expression, and was not associated with clinico-pathological factors or prognosis. Multivariate analysis revealed only the CDC25A status to be an independent significant prognostic factor among these biological and clinico-pathological factors. CDC25A but not CDC25B may be a new prognostic factor for squamous cell carcinoma of the oesophagus. Thus, regulation of the G1 checkpoint in the cell cycle may be important in oesophageal carcinogenesis, which may also involve many other oncogenes.

Aged↗
PubMed2001

Discovery of novel N-phenylglycine derivatives as potent and selective beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence.

With a novel assay using isolated ferret detrusor to estimate beta(3)-adrenoceptor agonistic activity, we found that a series of glycine derivatives of ritodrine, a beta(2)-adrenoceptor agonist, are potent beta(3)-adrenoceptor agonists, with excellent selectivity versus beta(1) and beta(2) subtypes. Substitution of halogens in the phenyl ring increased potency and selectivity for the beta(3)-adrenoceptor, and this was dependent upon the position of the halogens. The chlorine-substituted derivatives 3f-i exhibited potent beta(3)-adrenoceptor-mediated relaxation of ferret detrusor (EC(50) = 0.93, 11, 14, and 160 nM) and higher potency at beta(3)-adrenoceptors than at beta(1) or beta(2). The intravenous administration of 3h significantly reduced the urinary bladder pressure in anesthetized male rats (ED(50) = 48 microg/kg) without cardiovascular side effects. This article is the first report of structure-activity relationships (SAR) concerning beta(3)-adrenoceptor agonists as agents for the treatment of urinary frequency and incontinence.

Adrenergic beta-Agonists↗
PubMed2001

Overexpression of CDC25B overrides radiation-induced G2-M arrest and results in increased apoptosis in esophageal cancer cells.

CDC25B phosphatase plays a key role in controlling G2-M progression by dephosphorylating two inhibitory residues of CDC2 and also has been suggested to have an oncogenic property. In this study, we investigated the effect of CDC25B overexpression on radiation-induced G2-M arrest and radiation sensitivity in esophageal cancer cells. TE8-CDC25B, in which CDC25B was overexpressed under an inducible system, was more radiosensitive than the vector control (TE8-neo) in a clonogenic survival assay. Without radiation, CDC25B overexpression had little effect on cell cycle fractions or growth rate. After 10-Gy radiation, TE8-CDC25B showed decreased G2-M arrest and increased apoptosis, whereas TE8-neo displayed prolonged G2-M arrest and less apoptosis. During this period, there were no differences in the protein amounts of CDC2 and cyclin B1 between the two cell lines. However, more CDC25B expression, which was reduced immediately by radiation, was sustained in TE8-CDC25B than in TE8-neo. Moreover, induction of tyrosine phosphorylation of CDC2 and reduction of CDC2 kinase activity after irradiation was less significant in TE8-CDC25B than in TE8-neo. These results indicate that cancer cells that overexpress CDC25B override G2-M arrest by retaining CDC2 kinase activity and undergo apoptosis after radiation. This may point to an effective approach toward improving radiotherapy outcomes of various cancers.

Apoptosis↗
PubMed2001

Localization of IQGAP1 is inversely correlated with intercellular adhesion mediated by e-cadherin in gastric cancers.

Down-regulation of E-cadherin function is characteristic of cancer cells and might involve the small G-protein Rho family, including Rac1 and Cdc42. IQGAP1 has been reported to be one of the target proteins of Rac1 and Cdc42. To elucidate the role of IQGAP1 in cancer-cell adhesion, its expression was investigated in 47 cases of human gastric cancer by immunohistochemistry and Western blot upon protein fractionation, especially in comparison with E-cadherin and catenin expression. In the non-cancerous columnar epithelium of the stomach, IQGAP1, as well as E-cadherin/catenin, was expressed at the cell-cell boundary. IQGAP1 was frequently observed diffusely in the cytoplasm in intestinal-type tumors (20/22 cases) but was expressed at the cell membrane in diffuse-type tumors (19/25 cases), thus showing significant association with tumor differentiation (p < 0.01). Interestingly, membranous expression of IQGAP1 was inversely correlated with that of E-cadherin (p < 0.05) or alpha-catenin (p < 0.001). These observations were consistent with the Western blot results following protein fractionation. IQGAP1 was dominantly expressed in the soluble fraction in differentiated tumors; however, in undifferentiated tumors, it was mostly in the insoluble fraction. In contrast, both E-cadherin and alpha-catenin were detected only in the insoluble fraction. Thus, subcellular localization of IQGAP1 from the cytoplasm to the cell membrane was correlated with E-cadherin dysfunction and tumor dedifferentiation in gastric carcinogenesis.

Adenocarcinoma↗
PubMed2001

Histopathologic impact of TT virus infection on the liver of type C chronic hepatitis and liver cirrhosis in Japan.

The present investigation compared the histological findings in the liver of chronic hepatitis C patients who were or were not co-infected with TT virus (TTV) to determine the histological and clinical characteristics of TTV infection. One hundred eighty patients with chronic hepatitis or liver cirrhosis type C were included in this study. Serum samples were tested for the presence of TTV DNA by a nested polymerase chain reaction. The liver biopsy specimen of each patient was examined, and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal, and portal areas; fibrous stage; lymphoid reaction in the portal area; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; damage of bile duct; and irregular regeneration of hepatocytes. Sixty-four (34.4%) of the 180 patients were positive for TTV DNA. The histological features of the liver and the blood biochemical parameters of the TTV DNA-positive and TTV DNA-negative patients, did not differ significantly except for the score of irregular regeneration (IR) of hepatocytes. Among those in the F4 stage of fibrosis, the score of IR of the TTV DNA-positive patients was significantly higher than that of the TTV DNA-negative patients. In conclusion, chronic TTV infection does not modify the biochemical features of chronic hepatitis type C patients. TTV may be a risk factor, however, for the development of hepatocellular carcinoma in patients with type C liver disease in the F4 stage.

Adolescent↗
PubMed2001

Intensification of chemotherapy using block therapies as consolidation and reinduction therapies for acute lymphoblastic leukemia during childhood.

Between April 1994 and March 1997, 143 children (age range, 1-15 years) with newly diagnosed acute lymphoblastic leukemia (ALL), except for those patients with t(9;22), were treated according to protocol-94 of the Osaka Childhood Leukemia Study Group. In this trial, the intensity of chemotherapy was enforced in the consolidation and reinduction phases by introducing AML-type block therapies consisting of concentrated administration of 4 to 6 drugs during 5 or 6 days. For patients in the higher risk groups, rotational combination chemotherapy was introduced following the early phase. A total of 124 children with B-cell precursor ALL (B-pre ALL) were classified into 3 groups, the ultrahigh-risk group (UHRG) (15 patients), the high-risk group (HRG) (61 patients), or the standard-risk group (SRG) (48 patients), based on age. leukocyte count, immunophenotype, central nervous system leukemia, response to treatment, and selected chromosomal abnormalities. The complete remission rate was 93%, and the 6-year event-free survival (EFS) rate was 79%+/-4%. EFS rates for the UHRG, HRG, and SRG groups were 67%+/-12%, 80%+/-6%, and 81%+/-6%, respectively. Nineteen patients with T-cell ALL were treated with the protocol for the UHRG. Thirteen patients (68%) attained complete remission, and the 6-year EFS rate was 55%+/-12%. Thus, intensification of chemotherapy improved the EFS rate and AML-type block therapies appeared to be effective as the consolidation and reinduction therapies for B-pre ALL.

Adolescent↗
PubMed2001

Enhancement in fecal excretion of dioxin isomer in mice by several dietary fibers.

The effect of increased nutrients (protein, lipid, vitamins and minerals) on dioxin-induced toxic manifestations such as immune suppression, hepatic hypertrophy, splenic atrophy and enzyme induction was investigated in mice after oral administration of 1,2,3,4,7,8-HxCDD (HxCDD) as one of a representative compound of dioxin isomers. Consequently, it appeared that increased minerals and vitamins in the diet prevented immune suppression by HxCDD. In addition, to clarify the additive effect of nutrients and the ability to hasten the excretion of dioxins by dietary fiber, the adsorbing of dioxins by 16 dietary fibers was investigated by in vitro experiment. Among 16 dietary fibers, locust bean gum, pectin, alginic acid, guar gum, chitin and cellulose were effective in binding dioxin isomers. These dietary fibers also enhanced the fecal excretion of HxCDD in mice.

Absorption↗
PubMed2001

A Japanese girl with leukoencephalopathy with vanishing white matter.

A Japanese girl with peculiar leukoencephalopathy was reported. Following normal development until 1 year of age, she showed progressive neurological deterioration with ataxia, epilepsy, pyramidal tract signs and choreic movement. Serial brain computed tomographies (CTs) revealed markedly low density and progressive volume loss in whole white matter. In extensive laboratory investigations, the level of glycine in the urine was elevated. She died at the age of 4 years, and the neuropathological findings were comprised of severe extensive changes in cerebral and cerebellar white matter, such as marked rarefaction or cystic degeneration with axonal loss. The pontine central tegmental tracts were also affected. Neuronal loss was seen in the cerebellar cortex. These features were compatible with leukoencephalopathy with vanishing white matter, which was recently established as a clinical entity. To our knowledge, this is the first report of a non-Caucasian patient with this new type of leukoencephalopathy.

Brain↗
PubMed2001

Nicotine, alcohol, methamphetamine, and inhalant dependence: a comparison of clinical features with the use of a new clinical evaluation form.

The purpose of the present study was to develop a new clinical evaluation form to compare the clinical features of nicotine dependence with those associated with alcohol, methamphetamine, and inhalant dependence. The clinical evaluation form consisted of six scoring items: subjective effects, tolerance, liking (of drug), social disturbance, withdrawal syndrome, and acute psychic and acute physical disorders. A preliminary clinical investigation was performed to test the validity of the evaluation form. Study subjects were those showing dependence on nicotine (n = 25), alcohol (n = 36), methamphetamine (n = 11), and inhalants (n = 6). All subjects met the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnostic criteria for drug dependence, as defined by the Work Group for the chapter "Substance-Related Disorders": M. A. Schuckit, J. E. Helzer, L. B. Cottler, T. Crowley, P. E. Nathan, & G. E. Woody. Nicotine produced subjective effects, tolerance, liking, and psychic withdrawal symptoms, all of which were mild in degree. However, nicotine did not produce social disturbance, physical withdrawal symptoms, or acute psychic or acute physical disorders. With alcohol, acute psychic and acute physical disorders were prominent, and alcohol also produced a moderate degree of influence on various other items that were evaluated. Methamphetamine produced the most serious acute psychic and acute physical disorders with intensive subjective effects. Inhalants were characterized by an intensive degree of acute psychic disorders and subjective effects with mild withdrawal syndrome. Our study findings revealed that the clinical features of drug dependence could be evaluated by using the new clinical evaluation form. Further study is required to clarify the clinical features of nicotine dependence compared with those of other drugs of dependence.

Administration, Inhalation↗
PubMed2001

Neurobiological mechanisms of nicotine craving.

Nicotine induces craving, but the degree of craving is believed to be milder than that with other abused drugs. In this article, the neurobiological mechanisms of craving for nicotine and other drugs are reviewed, focusing especially on three factors that can be involved in the development of craving. The first factor is the affective symptoms of withdrawal, the neural basis of which may involve neuroadaptations (desensitization) within the reward systems. Affective symptoms experienced during withdrawal from nicotine are milder than those experienced in withdrawal from other drugs, probably because of its mode of action on the reward systems, which is similar to that of natural rewards. The second factor is the conditioning process, in which environmental stimuli can gain properties of a secondary reinforcer. Nicotine has weak but reliable conditioning effects, and the brain region mediating those effects of nicotine involves the ventral tegmental area. The third factor is a cognitive (memory) process, but little is known about this area.

Animals↗
PubMed2001

Alpha-like activity in terminal stage of Creutzfeldt-Jakob disease.

We report a case of Creutzfeldt-Jakob disease showing various changes in electroencephalogram (EEG) throughout the course of the disease. The patient's EEG patterns showed periodic synchronous discharge in the intermediate stage of the disease, delta activity in the advanced stage and alpha-like activity in the terminal stage. The mechanism generating alpha-like activity may resemble, at least in part, that of an alpha coma.

Aged↗
PubMed2001

Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.

1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle. 2. Rats with pituitary transplants showed increased serum prolactin concentrations and decreased serum concentrations of gonadotropins and increased pituitary concentrations of gonadotropins. Moreover, these rats showed persistent dioestrous and anovulation from 3 to 6 days after transplantation. 3. A single oral administration of cabergoline (at doses between 0.001 and 0.1 mg/kg) dose-dependently inhibited the elevated serum prolactin concentrations in hyperprolactinaemic rats. At 0.1 mg/kg, cabergoline induced a continuous reduction in serum prolactin concentrations for 5 days after administration. Terguride (0.1 mg/kg) and bromocriptine (10 mg/kg) also reduced serum prolactin concentrations at 1 and 3 days after administration. All three dopamine D2 receptor agonists increased serum gonadotropin concentrations and ovarian weight at 3 days after administration. 4. In rats exhibiting anovulation, a single oral administration of any one of the three dopamine D2 receptor agonists dose-dependently restored ovulation and a normal oestrous cycle appeared. Oral administration of cabergoline (0.03 mg/kg) or terguride (0.1 mg/kg) restored ovarian function and abolished the anovulation following a reduction in serum prolactin concentrations. However, bromocriptine (10 mg/kg) did not completely abolish anovulation. Following administration of terguride (0.3 mg/kg) or bromocriptine (30 mg/kg), only one normal oestrous cycle appeared; however, following cabergoline (0.1 mg/kg), two normal oestrous cycles appeared. 5. These results suggest that cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist and, thus, should be a useful drug for the treatment of galactorrhoea and hyperprolactinaemic amenorrhoea and/or anovulation in humans.

Animals↗
PubMed2001

Photochemically induced equilibrium dysfunction in the hamster model with evaluation by means of a new globe rotatory test system.

Thrombosis in the inner ear is regarded as one of the causes of equilibrium dysfunction. We have established an experimental thrombosis model by producing a photochemical reaction between rose bengal and green light, and have evaluated the dysfunction with a new rotatory test system. Hamsters were treated with tissue-type plasminogen activator (tPA) in doses of 0, 0.13, 0.26, and 0.52 mg/kg. The equilibrium dysfunction of the hamsters was evaluated by scoring their behavior according to visual observation and by measuring their time on the rotatory test system. Treatment of animals with sufficient tPA (> or = 0.26 mg/kg) caused a significant amelioration of the behavior and a concomitant significant prolongation of time on the rotating globe. These findings suggest that the equilibrium dysfunction induced by the photochemical reaction was due to the thrombi formed, and that our test system may provide a useful tool for evaluating equilibrium dysfunction in hamsters.

Animals↗
PubMed2001

N-linked oligosaccharides predominantly distribute in rat cerebellar cortex.

The distribution or localization of glycoconjugates in rat cerebellar cortex was investigated with 26 different kinds of lectins observed by light and electron microscopy. In paraffin-embedded tissues, PHA-L, PHA-E, DSA, WGA, ConA, LEA, LCA, PSA, and RCA-I, which mainly recognize N-linked oligosaccharide sugar structures, stained the cerebellar cortex, especially the molecular layer. PHA-L staining showed the highest selectivity for the molecular layer among these lectins. Pretreatment with N-glycanase altered the staining intensities of these lectins, whereas pretreatment with O-glycanase did not alter the intensity. In electron microscopy, the cell membrane and Golgi membranes of Purkinje cell, parallel fibers, and synaptic vesicles exhibited a positive reaction with PHA-L. Nuclear pores and synaptic vesicles were positive for WGA binding. These results suggest that there exist N-glycoside binding oligosaccharides predominantly in the cerebellar cortex, especially in the molecular layer, which sugar chains may be relevant to the synaptic transmission in the molecular layer.

Amidohydrolases↗
PubMed2001

Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma.

PURPOSE: To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. RESULTS: Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. CONCLUSIONS: The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population.

Amino Acid Sequence↗