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Biomedical subjects

Y Miyashita

Publications and source records attributed to Y Miyashita.

At least 19 recordsLinked to original sources
PubMed2005

Deeply located granule cells and mitral cells undergo apoptosis after transection of the central connections of the main olfactory bulb in the adult rat.

The main olfactory bulb (MOB) is the first relay station of the olfactory system: it receives afferents from sensory neurons and sends efferents to the primary olfactory cortex. The MOB also receives many centrifugal afferents from various regions. Transection of peripheral afferents to the MOB has been reported to induce cell death in granule cells. However, little is known about the effect of transection of these central connections of the MOB in adult rats. Here, we used a unilateral olfactory peduncle transection model in the adult rat to examine neuronal degeneration in the MOB. In the MOB ipsilateral to the surgery, the granule cell layer (GCL) was smaller, and the number of mitral cells was decreased compared with the contralateral MOB at 7 days after surgery. Many degenerating cells were present in both the mitral cell layer (MCL) and GCL in the ipsilateral MOB at 3 days after surgery, although there were no obvious changes in the gross morphology. We also found terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL)-positive cells in the MCL and GCL in the ipsilateral MOB at 3 days after surgery. The majority of the degenerating and TUNEL-positive cells were located in the deep, rather than the superficial, GCL. Immunohistochemistry for activated caspase-9 further supported the occurrence of apoptotic cell death in the mitral and deeply located granule cells. These results indicate that not only axotomized mitral cells, but also deeply located granule cells that were not directly injured, underwent apoptosis after transection of the central connections, and suggest that sensitivities to transection of the central connections differ among granule cells according to their depth in the GCL.

Animals↗
PubMed2005

Effect of weight loss using formula diet on renal function in obese patients with diabetic nephropathy.

OBJECTIVE: To evaluate the effect and safety of treatment with low-calorie formula diet on renal function and proteinuria in obese patients with diabetic nephropathy. DESIGN: Prospective study on safety and efficacy of a 4-week low-calorie (11-19 kcal/kg/day) normal-protein (0.9-1.2 g/kg/day) diet partly supplemented with formula diet. SUBJECTS: In all, 22 obese patients with diabetic nephropathy (BMI: 30.4+/-5.3 kg/m(2), HbA1c: 7.1+/-1.4%, serum creatinine: 172.4+/-57.5 micromol/l, urinary protein: 3.3+/-2.6 g/day). RESULTS: The mean body weight decreased by 6.2+/-3.0 kg. The mean systolic blood pressure, creatinine, blood urea nitrogen, urinary protein, and 8-hydroxydeoxyguanosine decreased significantly by 7.5+/-12.7 mmHg, 41.6+/-23.9 micromol/l, 1.50+/-1.61 mmol/l, 1.8+/-1.7 g/day, and 3.1+/-3.6 ng/mg creatinine, respectively. No patient had increased serum creatinine and urinary protein. Mean creatinine clearance (40.6+/-17.9 to 46.1+/-14.6 ml/s/1.73 m(2)) and serum albumin showed no significant changes. Delta serum creatinine and Delta urinary protein correlated with Delta body weight (r=0.62 and 0.49, respectively) and Delta visceral fat area (r=0.58 and 0.58, respectively), but did not correlate with Delta systolic blood pressure, Delta fasting blood glucose and Delta subcutaneous fat area. CONCLUSION: These results suggested that weight reduction using formula diet might improve renal function and proteinuria safely for a short term in obese patients with diabetic nephropathy.

Adipose Tissue↗
PubMed2005

Clearance rates of cerivastatin metabolites in a patient with cerivastatin-induced rhabdomyolysis.

We report on a patient who developed acute rhabdomyolysis after taking cerivastatin. A 74-year-old hypercholestrerolaemic woman taking cerivastatin (0.15 mg/day) for 22 days complained of general muscle weakness and muscle pain. Her serum creatinine phosphokinase level was 19,190 IU/L. Serum myoglobin was over 3000 ng/mL. Serum concentration of cerivastatin at 6 h after taking the last dose (0.15 mg) was 8062.5 ng/L, which was almost 5.7 times higher than that of normal persons. The serum concentration of cerivastatin showed that the half-life of cerivastatin in this patient was 22.4 h, compared with 2.4 h for normal controls. Cerivastatin is catabolized by cytochrome P450, 3A4 and 2C8 to M-1, and by 2C8 to M-23. The ratio of M-23 to M-1 in her serum was much lower than that of control persons (0.64 vs. 2.08). She had previously taken simvastatin which is metabolized by CYP3A4, without any sign and symptoms of rhabdomyolysis. These results suggest that the slowed clearance of cerivastatin in this patient might have been compounded by cytochrome P450, 2C8 dysfunction.

Acute Disease↗
PubMed2001

anti-bis(mu-2-ammonioethanethiolato-kappa2S:S)bis[dichloropalladium(II)] dihydrate.

Each of two square-planar Pd(II) ions in the title compound, [Pd2Cl4(mu-Haet-S)2]*2H2O (Haet = 2-ammonioethanethiolate, C2H7NS), which was obtained by rearrangement of [Pd2[Pd(aet-N,S)2]4]4+ in acidic solution, is coordinated by two bridging S atoms from two Haet ligands and by two terminal Cl atoms, forming the dinuclear structure. Since the complex is situated on a center of symmetry, the two monodentate Haet arms are located on opposite sides of the central Pd2S2 square plane, i.e. the present complex is the anti isomer. The S-C-C-N torsion angle is 177.3 (6) degrees and some intermolecular hydrogen bonds are observed.

Journal Article↗
PubMed2001

Ion selectivities of the Ca(2+) sensors for exocytosis in rat phaeochromocytoma cells.

1. The ion selectivities of the Ca(2+) sensors for the two components of exocytosis in rat phaeochromocytoma (PC12) cells were examined by measurement of membrane capacitance and amperometry. The cytosolic concentrations of metal ions were increased by photolysis of caged-Ca(2+) compounds and measured with low-affinity indicators benzothiazole coumarin (BTC) or 5-nitrobenzothiazole coumarin (BTC-5N). 2. The Ca(2+)-induced increases in membrane capacitance comprised two phases with time constants of 30--100 ms and 5 s. Amperometric events reflecting the exocytosis of large dense-core vesicles occurred selectively in the slow phase, even with increases in the cytosolic Ca(2+) concentration of > 0.1 mM. 3. The slow component of exocytosis was activated by all metal ions investigated, including Cd(2+) (median effective concentration, 18 pM), Mn(2+) (500 nM), Co(2+) (900 nM), Ca(2+) (8 microM), Sr(2+) (180 microM), Ba(2+) (280 microM) and Mg(2+) (> 5 mM). In contrast, the fast component of exocytosis was activated by Cd(2+) (26 pM), Mn(2+) (620 nM), Ca(2+) (24 microM) and Sr(2+) (320 microM), but was only slightly increased by Ba(2+) (> 2 mM) and Co(2+) and not at all by Mg(2+). 4. The fast component, but not the slow component, was competitively blocked by Na(+) (median effective concentration, 44 mM) but not by Li(+), K(+) or Cs(+). Thus, the Ca(2+) sensor for the fast component of exocytosis is more selective than is that for the slow component; moreover, this selectivity appears to be based on ionic radius, with cations with radii of 0.84 to 1.13 A (1 A = 0.1 nm) being effective. 5. These data support a role for synaptotagmin--phospholipid as the Ca(2+) sensor for the exocytosis of large dense-core vesicles and they suggest that an additional Ca(2+)-sensing mechanism operates in the synchronous exocytosis of synaptic-like vesicles.

Animals↗
PubMed2001

fac-Trichloro(quinolin-8-ylimido-N,N')(triphenylphosphine-P)rhenium(V).

The Re atom in [Re(C(9)H(6)N(2))Cl(3)(C(18)H(15)P)] is octahedrally coordinated by three Cl atoms in facial positions, two N atoms from 8-imidoquinoline (imq) and one P atom from triphenylphosphine. The Re-N(imido) distance [1.760 (9) and 1.772 (8) A] for imq is very short and implies double-bond character. The trans influence of the P atom is indicated. Intra- and intermolecular pi-pi interactions between the pi-rings in the complex are also observed.

Journal Article↗
PubMed2001

Spatiotemporal dynamics of brain-derived neurotrophic factor mRNA induction in the vestibulo-olivary network during vestibular compensation.

Vestibular compensation, which is the behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy (UL), is attributed to functional and structural reorganization of neural networks in the central vestibular system. To assess the possible contribution of brain-derived neurotrophic factor (BDNF) to this recovery process, we investigated changes in mRNA expression levels in the central vestibular system after UL. We evaluated BDNF mRNA expression levels by quantitative reverse transcription-PCR and in situ hybridization. We found that BDNF mRNA is differentially induced in the medial vestibular nucleus ipsilateral to UL and in the prepositus hypoglossi and inferior olive on the contralateral side. The BDNF mRNA induction lasted for at least 24 hr and returned to the basal expression level within 72 hr after UL. In contrast to BDNF mRNA induction, the expression of an immediate-early gene, c-fos, quickly reached the maximum level at 3 hr and decreased to the basal level within 24 hr after UL. Neither BDNF or c-fos induction was observed in sham-operated animals. The persistent induction of BDNF after UL temporally corresponded to early behavioral manifestations of vestibular compensation. We further found that trkB mRNA was expressed in the central vestibular network at high levels, although its expression levels did not change over time after UL. Because BDNF is implicated in regulating synaptic structure and function, these results provide support for the hypothesis that BDNF is involved in neuronal reorganization that allows vestibular compensation.

Adaptation, Physiological↗
PubMed2001

Backward spreading of memory-retrieval signal in the primate temporal cortex.

Bidirectional signaling between neocortex and limbic cortex has been hypothesized to contribute to the retrieval of long-term memory. We tested this hypothesis by comparing the time courses of perceptual and memory-retrieval signals in two neighboring areas in temporal cortex, area TE (TE) and perirhinal cortex (PRh), while monkeys were performing a visual pair-association task. Perceptual signal reached TE before PRh, confirming its forward propagation. In contrast, memory-retrieval signal appeared earlier in PRh, and TE neurons were then gradually recruited to represent the sought target. A reasonable interpretation of this finding is that the rich backward fiber projections from PRh to TE may underlie the activation of TE neurons that represent a visual object retrieved from long-term memory.

Action Potentials↗
PubMed2001

Outcome prediction by molecular detection of minimal residual disease in bone marrow for advanced neuroblastoma.

BACKGROUND: We have determined whether sequential molecular detection of minimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma (NB). PROCEDURE: Bone marrow samples from 19 patients over 12 months of age with stage 4 neuroblastoma were sequentially examined for tumor cell contamination by detecting tyrosine hydroxylase (TH) mRNA using reverse transcription-polymerase chain reaction (RT-PCR). All patients received repetitive multi-drug chemotherapy including cisplatin, cyclophosphamide or ifosphamide, adriamycin, and etoposide or vincristine. Seventeen patients received myeloablative therapy with hematopoietic stem cell transplantation after achieving complete remission. RESULTS: All but one patient were histologically positive for tumor cells in BM samples at diagnosis, and they became negative for tumor cells within 3 months histologically. By the RT-PCR analysis, all patients were positive for TH mRNA in BM samples at diagnosis, and they became negative for TH mRNA 1 to 13 months after the start of chemotherapy. Six patients whose BM samples became negative for TH mRNA within 4 months after the start of chemotherapy remained alive without evidence of disease (median 61 months, range 20-76). In contrast, 12 of 13 patients whose BM samples remained positive at that time developed relapse and 10 of them died of disease (median 24 months, range 13-43). There was a statistically significant difference in survival between the two groups (P < 0.05). No significant difference of clinical characteristics by the MRD positivity at 4 months after the start of chemotherapy. CONCLUSIONS: Persistence of MRD in BM at 4 months after the start of chemotherapy could predict poor prognosis in advanced neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed2001

Characteristics of type 2 diabetic patients responding to voglibose administration as an adjunct to sulfonylurea.

In this study, we characterized type 2 diabetic patients responding well to the alpha-glucosidase inhibitor voglibose administration as an adjunct to sulfonylurea treatment. Thirty-three type 2 diabetic patients were enrolled in an open prospective study. All the patients had been treated for at least 1 year with a sulfonylurea drug, in whom HbA1c level had been stable for at least 12 weeks. The patients were given voglibose at a dose of 0.2 mg t.i.d. for 12 weeks. Voglibose administration significantly decreased the mean HbA1c level in all the patients at 4, 8, and 12 weeks. Twelve (36%) of the study patients were responders, when the responders were defined as patients whose HbA1c level at 12 weeks fell by at least 1.0% from baseline, or those whose HbA1c level at 12 weeks was < or =7.0%, falling by at least 0.5% from baseline. The baseline fasting plasma glucose (FPG) was significantly lower, and the baseline homeostasis model assessment (HOMA) beta-cell function (HOMA-%beta) was significantly higher in the responders than in the non-responders. There were more patients who had FPG <170 mg/dl and/or HOMA-%beta > or =30% in the responders than in the non-responders (P<0.005). None of the patients with both FPG > or =170 mg/dl and HOMA-%beta >30% responded to the adjunct treatment. These results indicate that baseline FPG and HOMA-%beta are useful clinical markers to predict the effectiveness of the adjunct therapy of voglibose in sulfonylurea-treated type 2 diabetic patients.

Administration, Oral↗
PubMed2001

Differential induction of brain-derived neurotrophic factor mRNA in rat inferior olive subregions following unilateral labyrinthectomy.

Vestibular compensation, the neuronal process underlying behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy, is attributed to functional reorganization of neuronal circuits in the brainstem and cerebellum. Climbing fibers originating from the inferior olive are suggested to play a crucial role in this compensatory process. To assess the possible contribution of brain-derived neurotrophic factor (BDNF) to the function of climbing fibers during vestibular compensation, we investigated the BDNF mRNA expression in the rat inferior olive after unilateral labyrinthectomy by quantitative in situ hybridization. We found several induction patterns depending on the subregions of the inferior olive 6 h after unilateral labyrinthectomy. First, in the dorsal cap and the ventrolateral outgrowth, the expression levels increased on the side contralateral to the lesion and decreased on the ipsilateral side. Second, in the beta nucleus, C subnucleus of the medial accessory olive, and A/B subnuclei of the medial accessory olive, we detected an increase in the mRNA expression level on the side contralateral to the lesion, but no changes in the expression level on the ipsilateral side. In the beta nucleus, where the strongest induction was observed, the mRNA expression level increased nearly five-fold. Third, in the dorsomedial cell column, the mRNA expression levels increased on both sides. Finally, we did not detect significant changes in mRNA expression levels in the other subregions of the inferior olive, the dorsal accessory olive, principal olive and rostral medial accessory olive. The changes in BDNF mRNA expression reverted to control levels by 72 h after the labyrinthectomy. The inferior olive subregions that showed changes in BDNF mRNA expression levels send climbing fibers to the cerebellar cortical regions that, in turn, project to the vestibular nuclei. Therefore, BDNF induced in these subregions could contribute to the functional reorganization of the olivo-cerebellar system for vestibular control.

Animals↗
PubMed2001

A new radiofrequency thermal balloon catheter for pulmonary vein isolation.

OBJECTIVES: We sought to evaluate whether porcine pulmonary vein (PV) isolation (PVI) can be produced by ablation using our novel radiofrequency (RF) thermal balloon catheter (RBC). BACKGROUND: It has been proposed that PVI can prevent focal atrial fibrillation (AF) originating in or close to the PV. METHODS: The RBC is composed of a 12F main shaft, a 4F inner tube and a balloon. Inside the balloon, there is a unipolar coil electrode with a thermocouple sensor mounted along the tube, the former to deliver RF energy (13.56 MHz) and the latter to monitor the temperature. After the presence of a PV potential was confirmed, the RBC was safely inserted into the left atrium (LA) by the trans-septal approach. Once the balloon was inflated and optimally wedged at the junction between the PV and LA, RF energy was applied for 5 min. Radiofrequency catheter ablation (RFA) was repeated up to three times, until elimination of the PV potential or dissociation between the LA and PV was observed. Finally, each heart was examined histologically. RESULTS: In 18 PVs that had PV potentials, PVI was performed, resulting in success in 15 (success rate 83%, 95% confidence interval [CI] 58.0% to 96.3%; failure rate 17%, 95% CI 3.7% to 42.0%). After successful PVI, the PV potentials completely disappeared and the histologic examination revealed circumferential, transmural necrosis around the PV trunks. No major complications, such as PV stenosis or macroscopic thrombosis, were observed. CONCLUSIONS: The RBC was useful for PVI.

Animals↗
PubMed2001

Sequential-replenishment mechanism of exocytosis in pancreatic acini.

Here we report exocytosis of zymogen granules, as examined by multiphoton excitation imaging in intact pancreatic acini. Cholecystokinin induces Ca 2+ oscillations that trigger exocytosis when the cytosolic Ca 2+ concentration exceeds 1 microM. Zymogen granules fused with the plasma membrane maintain their Omega-shaped profile for an average of 220 s and serve as targets for sequential fusion of granules that are located within deeper layers of the cell. This secondary exocytosis occurs as rapidly as the primary exocytosis and accounts for most exocytotic events. Granule-granule fusion does not seem to precede primary exocytosis, indicating that secondary fusion events may require a plasma-membrane factor. This sequential-replenishment mechanism of exocytosis allows the cell to take advantage of a large supply of fusion-ready granules without needing to transport them to the plasma membrane.

Animals↗
PubMed2001

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons.

Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.

Animals↗
PubMed2001

Expression of opsin molecule in cultured murine melanocyte.

Recently, we demonstrated the expression of rhodopsin in the tail fin of the Xenopus tadpole, in which photosensitive melanophores exist (Miyashita et al, The photoreceptor molecules in Xenopus tadpole tail fin, in which melanophores exist. Zool Sci 18:671-674, 2001). The presence of opsin molecules in pigment cells of lower vertebrates raises the possibility that pigment cells in animal skin function as photosensors generally. To explore this possibility in higher vertebrates, we tried to detect photoreception molecules in mammalian melanocytes. We extracted total RNA from Melan a2, a cell line of immortal murine melanocyte, which is derived from C57BL mice. The DNA sequence obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification was homologous to the corresponding portion of the sequence of ocular rhodopsin of mice. Western blotting and fluorescent immunocytochemistry showed the existence of the opsin protein in the melanocytes. Another cell line, EL4, which is derived from lymphoma of C57BL/6N, scarcely expresses opsin mRNA, as judged by RT-PCR. Thus expression of the opsin gene is not ubiquitous among immortal cell lines. Detection of rhodopsin mRNA in murine tissues of C57BL/6N by RT-PCR showed its presence in the eye and skin but not in the liver. The role of the opsin molecule in melanocyte is not known at present, but this will provide additional insight into photoreception systems in animal skin.

Animals↗
PubMed2001

Disease outcome may be predicted by molecular detection of minimal residual disease in bone marrow in advanced neuroblastoma: a pilot study.

PURPOSE: This pilot study focussed on whether sequential molecular detection of minimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma. PATIENTS AND METHODS: Bone marrow samples from 21 patients older than age 12 months with stage IV neuroblastoma were sequentially examined for tumor cell contamination by detecting tyrosine hydroxylase (TH) messenger ribonucleic acid (mRNA) using reverse transcription-polymerase chain reaction (RT-PCR). Twenty patients received myeloablative therapy with hematopoietic stem cell transplantation after achieving complete remission. RESULTS: All BM samples of patients except that of one patient was cytologically positive for neuroblastoma cells at diagnosis, and they became negative for neuroblastoma cells within 3 months by cytologic examination. By RT-PCR analysis, BM samples of all patients were positive for TH mRNA at diagnosis, and samples of 19 patients became negative for TH mRNA 1 to 13 months after the start of chemotherapy. Six patients whose BM samples became negative for TH mRNA within 4 months after the start of chemotherapy remained alive without evidence of disease (median 76 mos, range 36-91). In contrast, out of 15 patients whose BM samples remained positive, 10 patients had relapse develop and 9 patients died from disease (median 15 mos, range 10-25). There was a statistically significant difference in disease-free survival between the two groups (P < 0.05). CONCLUSION: Persistence of MRD in BM may predict poor prognosis in advanced neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed2001

Reconstructing spatio-temporal activities of neural sources using an MEG vector beamformer technique.

We have developed a method suitable for reconstructing spatio-temporal activities of neural sources by using magnetoencephalogram (MEG) data. The method extends the adaptive beamformer technique originally proposed by Borgiotti and Kaplan to incorporate the vector beamformer formulation in which a set of three weight vectors are used to detect the source activity in three orthogonal directions. The weight vectors of the vector-extended version of the Borgiotti-Kaplan beamformer are then projected onto the signal subspace of the measurement covariance matrix to obtain the final form of the proposed beamformer's weight vectors. Our numerical experiments show that both spatial resolution and output signal-to-noise ratio of the proposed beamformer are significantly higher than those of the minimum-variance-based vector beamformer used in previous investigations. We also applied the proposed beamformer to two sets of auditory-evoked MEG data, and the results clearly demonstrated the method's capability of reconstructing spatio-temporal activities of neural sources.

Brain Mapping↗