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Biomedical subjects

H Miyata

Publications and source records attributed to H Miyata.

At least 127 records · Page 7Linked to original sources
PubMed2000

CDC25B and p53 are independently implicated in radiation sensitivity for human esophageal cancers.

Ionized radiation leads to G1 arrest and apoptosis by a p53-dependent pathway and G2-M arrest through a p53-independent pathway. In this study, we evaluated the role of cell cycle-regulating molecules in the sensitivity of cancer cells for radiation therapy. Forty-seven patients with squamous cell carcinomas of the esophagus had undergone radiation therapy, followed by surgical resection. They were classified as sensitive to radiation (SR, 14 cases) with no residual tumor in the surgical specimen or as resistant to radiation (RR, 33 cases) with viable residual tumors. Their preradiation biopsy samples were immunohistochemically investigated for the expressions of cell cycle-related molecules, including p53, CDC25A, CDC25B, cyclin D1, cyclin B1, and Ki-67. p53 expression was negative in 71% (10 of 14) of SR and positive in 91% (30 of 33) of RR. The association was strong between high radiation sensitivity and negative p53 expression (P < 0.0001). CDC25B, which is not expressed in normal epithelium but is in the cytoplasm of esophageal cancers, was strongly expressed (2+) in 46% (6 of 14) of SR and in 6% (2 of 23) of RR. Thus, the sensitivity for radiation therapy was significantly correlated with CDC25B overexpression. With respect to CDC25A, cyclin D1, cyclin B1, and Ki-67, no statistically significant differences were found in their expressions between SR and RR tumors. p53 and CDC25B expressions showed no significant associations, and multivariate analysis revealed that both p53 and CDC25B are significant independent markers for predicting radiation sensitivity. CDC25B was revealed to be a novel predictor of radiation sensitivity in esophageal cancers. Because CDC25B is an oncogene, which affects G2-M progression, these results suggest the importance of a p53-independent G2-M checkpoint in radiation therapy.

Antimetabolites, Antineoplastic↗
PubMed2000

[An autopsied case of progressive spinal muscular atrophy showing tremor and choreiform movement].

A 42-year-old man without family history of neurologic disease developed muscle weakness, and wasting associated with tremor and choreiform movement. He died at age 75 with 33 years of total duration of illness. Autopsy revealed neuronal loss and gliosis in the anterior horns of the spinal cord, hypoglossal nuclei, caudate nuclei, putamen, globus pallidus, and substantia nigra. Bunina bodies or Lewy bodies were not seen. Several similar cases with motor neuron disease, dementia and parkinsonism have been reported in the literature. However, this pattern of chronic spinal neostriato-pallido-nigral degeneration has not been reported.

Aged↗
PubMed1999

Segment-specific branching patterns of single vestibulospinal tract axons arising from the lateral vestibular nucleus in the cat: A PHA-L tracing study.

The purpose of the present study was to detail the spinal cord (SC) trajectories and arborization patterns of vestibulospinal axons descending from the lateral vestibular nucleus (LVN). An anterograde neural tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L), was focally injected into the right-side LVN in 8 cats. Their subsequent survival times varied from 4 days to 12 weeks. The labeled axons were found mainly in the brainstem after 4-5 days and in successively more caudal spinal segments after longer survival times: i.e., in C1-T2 after 2-3 weeks, in C3-T11 after 6-7 weeks, and in T7-S1 after 10-12 weeks. The trajectories of 28 single, thick (diameter >/=2.4 microm) lateral vestibulospinal tract (LVST) axons were traced from serial transverse sections of the SC from C1-8 (n = 10), T1-9 (n = 11), and T11-L7 (n = 7). In the cervical segments, the LVST axons gave off collateral fibers, which terminated mainly in Rexed's laminae VII-VIII. The terminal-field patterns of these collaterals differed from one stem axon to another. In the thoracic segments, the terminal-field patterns from a given LVST axon were similar at each segmental level, i.e., a few main branches with or without short side branches. At the L3-5 midlumbar level, the collaterals usually arborized more extensively, such that their terminal fields occupied a much greater region of laminae VII-VIII. In contrast, at the L6-7 lower lumbar level, collaterals arising from thin axons (diameter <1.0 microm) tended to innervate, with even more extensive arborization, the medial part of the lamina VIII. These results revealed common and segment-specific collateral distribution patterns of LVST axons along the full extent of the spinal neuraxis.

Animals↗
PubMed1999

CD4+ and/or gammadelta+ T cells in the liver spontaneously produce IL-4 in vitro during the early phase of Leishmania major infection in susceptible BALB/c mice.

Numerous studies on the cytokine production profile in Leishmania major infected susceptible and resistant mice have been carried out to elucidate the mechanisms of healing or non-healing of this infection. However, many methods may have failed to detect the actual cytokine production in the inflammatory foci. To overcome this problems, the ELISPOT assay was used to examine the spontaneous production of IL-4 and IFN-gamma in vitro by mononuclear cells from the spleen, lymph nodes and liver in L. major-infected susceptible BALB/c and resistant C57BL/6 mice. None of these mononuclear cells spontaneously produced IFN-gamma in either mouse strains in vitro in the absence of the corresponding antigen(s). However, liver mononuclear cells from infected BALB/c mice spontaneously produced IL-4 in vitro in as early as 2 weeks after the infection, but this was not observed in C57BL/6 mice. The IL-4 producing liver lymphocytes consisted of CD4+ and/or gammadelta+ T cells and uncharacterized cells. These results suggest that liver lymphocytes play some role in the establishment of Th2 prevalence in susceptible BALB/c mice, based on the importance of IL.4 production in the early phase of L. major infection in establishing Th2 dominance in this parasite susceptible mouse.

Animals↗
PubMed1999

Tying a molecular knot with optical tweezers.

Filamentous structures are abundant in cells. Relatively rigid filaments, such as microtubules and actin, serve as intracellular scaffolds that support movement and force, and their mechanical properties are crucial to their function in the cell. Some aspects of the behaviour of DNA, meanwhile, depend critically on its flexibility-for example, DNA-binding proteins can induce sharp bends in the helix. The mechanical characterization of such filaments has generally been conducted without controlling the filament shape, by the observation of thermal motions or of the response to external forces or flows. Controlled buckling of a microtubule has been reported, but the analysis of the buckled shape was complicated. Here we report the continuous control of the radius of curvature of a molecular strand by tying a knot in it, using optical tweezers to manipulate the strand's ends. We find that actin filaments break at the knot when the knot diameter falls below 0.4 microm. The pulling force at breakage is around 1 pN, two orders of magnitude smaller than the tensile stress of a straight filament. The flexural rigidity of the filament remained unchanged down to this diameter. We have also knotted a single DNA molecule, opening up the possibility of studying curvature-dependent interactions with associated proteins. We find that the knotted DNA is stronger than actin.

Actins↗
PubMed1999

Increased expression of phospholipase D1 mRNA during cAMP- or NGF-induced differentiation in PC12 cells.

The rat pheochromocytoma PC12 cells have been employed as a useful model to study neuronal differentiation. To gain insight into the molecular events involved in extension of neurites, the differential expression of phospholipase D (PLD) isozymes were examined in cyclic AMP- or nerve growth factor (NGF)-treated PC12 cells. When the cells were incubated with dibutyryl cyclic AMP (dbcAMP), almost all the cells displayed prominent neurite outgrowth at 24 h. The neurites developed in NGF-treated cells at 24 h were shorter than those in the cells treated with dbcAMP. However, most of the NGF-treated cells extended long neurites at day 5. The rPLD1b mRNA increased within 6 h following dbcAMP treatment and maintained a high level up to 24 h. In contrast, the levels of rPLD1a and rPLD2 mRNAs were rather consistent throughout the time course examined. However, when the cells were treated with NGF, rPLD1a and rPLD1b mRNAs, but not rPLD2 mRNA, increased within 2 days and remained elevated up to 5 days. These results suggest the possible implication of PLD1 in PC12 cell differentiation.

Animals↗
PubMed1999

Protrusive growth from giant liposomes driven by actin polymerization.

Development of protrusions in the cell is indispensable in the process of cell motility. Membrane protrusion has long been suggested to occur as a result of actin polymerization immediately beneath the cell membrane at the leading edge, but elucidation of the mechanism is insufficient because of the complexity of the cell. To study the mechanism, we prepared giant liposomes containing monomeric actin (100 or 200 microM) and introduced KCl into individual liposomes by an electroporation technique. On the electroporation, the giant liposomes deformed. Most importantly, protrusive structure grew from the liposomes containing 200 microM actin at rates (ranging from 0.3 to 0.7 micrometer/s) similar to those obtained in the cell. The deformation occurred in a time range (30 approximately 100 s) similar to that of actin polymerization monitored in a cuvette (ca. 50 s). Concomitant with deformation, Brownian motion of micron-sized particles entrapped in the liposomes almost ceased. From these observations, we conclude that actin polymerization in the liposomes caused the protrusive formation.

Actins↗
PubMed1999

New hyperprolactinemia and anovulation model in common marmoset (Callithrix jacchus) and effect of cabergoline.

We aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in common marmosets. The serum prolactin level gradually increased during the twice-daily administration of sulpiride and reached a plateau after 4 days. Sulpiride produced as big a response at 10 mg kg(-1) as at 50 mg kg(-1). In this study, the length of the ovarian cycle was approximately 30 days in normal common marmosets. Serum progesterone and estradiol levels showed no consistent change during the first 2 months of treatment with sulpiride. When treatment with sulpiride had been continued for more than 2 months, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle and absence of ovulation was recognized by laparoscopy. A single oral administration of cabergoline (at doses between 0.01 and 0.1 mg kg(-1)) dose dependently reduced the elevated serum prolactin level. Bromocriptine (at an oral dose of 10 mg kg(-1)) also reduced the serum prolactin level at 4 and 8 h after its administration. With bromocriptine, the prolactin level had recovered at 24 h, but with cabergoline at doses of 0.05 mg kg(-1) or more, it had still not recovered at 48 h. In anovulatory common marmosets, oral administration of cabergoline at a daily dose of 0.05 mg kg(-1) restored ovarian function and resulted in ovulation in 100% of the group (following a reduction in the serum prolactin level). Bromocriptine at a daily oral dose of 10 mg kg(-1) resulted in ovulation in 67% of the group, but this dose was about 200 times higher than the dose of cabergoline. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. It is suggested that, in this anovulatory model in common marmosets, cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist, and thus could be a useful drug for the treatment of galactorrhea and hyperprolactinemic amenorrhea and/or anovulation.

Animals↗
PubMed1999

A study of motor dysfunction associated with schizophrenia based on analyses of movement-related cerebral potentials and motor conduction time.

BACKGROUND: Several reports have shown that schizophrenics have motor dysfunction. The aim of this study was to identify the site of the nerve damage responsible for the motor dysfunction in schizophrenics by measuring both movement-related cerebral potentials (MRCPs) and motor conduction times. METHODS: The subjects were 27 patients and 31 controls. There was no significant difference in age, nor in the length of the subjects' arms between the two groups. MRCPs were recorded during voluntary self-paced index movements of the thumb. The motor nerve conduction time was determined by magnetically stimulating the motor cortex and the spinal root. RESULTS: Six of 27 schizophrenics had normal MRCPs, but the remaining 21 showed abnormal MRCPs. Of the 31 controls, 27 were normal, whereas 4 showed abnormal MRCPs. The difference between the two groups was significant; however, no significant differences were found in the motor conduction times, the motor root conduction times, or the central motor conduction times between the two groups. CONCLUSIONS: Our results suggest that the responsible focus of motor nerve disorder in schizophrenia lies in the motor-integrating system in frontal lobe, and not in the nervous conduction system from the brain to the muscles.

Adult↗
PubMed1999

Vasopressin stimulates the induction of heat shock protein 27 and alphaB-crystallin via protein kinase C activation in vascular smooth muscle cells.

In the present study, we examined the effect of vasopressin on the induction of the low-molecular-weight heat shock proteins heat shock protein 27 (HSP27) and alphaB-crystallin in an aortic smooth muscle cell line, A10 cells. Vasopressin induced a time-dependent accumulation of HSP27 and alphaB-crystallin. The stimulatory effects of vasopressin were dose-dependent over the range 0.1 nmol/L to 0.1 micromol/L. The EC50 values for vasopressin were 2 (HSP27) and 4 nmol/L (alphaB-crystallin). Vasopressin induced increases in the levels of the mRNAs for HSP27 and alphaB-crystallin. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, induced an accumulation of HSP27 (EC50, 20 nmol/L) and alphaB-crystallin (EC50, 2 nmol/L). In contrast, 4alpha-phorbol 12,13-didecanoate, a non-PKC-activating phorbol ester, had no such effect. Staurosporine and calphostin C, inhibitors of PKC, significantly reduced the vasopressin-induced accumulation of HSP27 and alphaB-crystallin as well as that induced by TPA. BAPTA/AM and TMB-8, inhibitors of intracellular Ca2+ mobilization, significantly reduced the vasopressin-induced accumulation of HSP27 and alphaB-crystallin. These results strongly suggest that vasopressin stimulates the induction of HSP27 and alphaB-crystallin via PKC activation in vascular smooth muscle cells and that this effect of vasopressin is dependent on intracellular Ca2+ mobilization.

Animals↗
PubMed1999

Inactivity-induced remodeling of neuromuscular junctions in rat diaphragmatic muscle.

We hypothesized that inactivity-induced remodeling of neuromuscular junctions (NMJs) depends on fiber type and the match between muscle fiber and motoneuron (MN) activities. Two inactivity models were studied in rat diaphragmatic muscle: spinal hemisection at C2 (SH), where both diaphragmatic muscle fibers and phrenic MNs were inactive, and tetrodotoxin (TTX) nerve blockade, where only muscle fibers were inactive. After 2 weeks of inactivity, there was increased number of pre- and postsynaptic branches (fragmentation) of NMJs at type IIx/b fibers in both models. In addition, planar NMJ areas at type IIx/b fibers in the SH model were enlarged. In contrast, NMJs at type I and IIa fibers were unaffected in both SH and TTX models. Functionally, neuromuscular transmission in diaphragmatic muscle fibers improved in the SH model, but worsened in the TTX model, compared to controls. These results suggest that NMJ remodeling depends on the level of MN activity. The relative preservation of NMJs at type I and IIa fibers suggests a potential for recovery from diaphragmatic paralysis in the clinical setting, at least for respiratory behaviors.

Animals↗
PubMed1999

Medial prefrontal cortex is involved in the discriminative stimulus effects of nicotine in rats.

RATIONALE: Central nicotinic receptors have been reported to be involved in the discriminative stimulus (DS) effects of nicotine. OBJECTIVES: The purpose of the present study was to investigate the role of the medial prefrontal cortex (mPFC) and the medial habenular nucleus (mHb) in the DS effects of nicotine. METHODS: Substitution tests with nicotine administered into mPFC and mHb were conducted in rats trained to discriminate nicotine (0.5 mg/kg, SC) from saline in a two-lever, food reinforced, operant task. RESULTS: Nicotine (40 microg) administered into mPFC substituted for nicotine (0.5 mg/kg, SC), whereas nicotine administered into mHb did not. CONCLUSIONS: Together with our previous study indicating that the nucleus accumbens and the ventral tegmental area are partially involved in the DS effects of nicotine, the present study suggests that mPFC is primarily involved in the DS effects of nicotine.

Animals↗
PubMed1999

Development of Purkinje cells in humans: an immunohistochemical study using a monoclonal antibody against the inositol 1,4,5-triphosphate type 1 receptor (IP3R1).

Immunohistochemical analyses were carried out on the Purkinje cells from 21 autopsied fetal and early postnatal normal cerebella using a monoclonal antibody against the inositol 1, 4, 5-triphosphate type 1 receptor (IP3R1) as a cytochemical marker of Purkinje cells. In normal adult cerebella used as positive controls, the cell bodies, axons, and dendrites, including spiny branchlets of the Purkinje cells, were specifically stained by the antibody. In the fetal cerebella examined, the IP3R1 immunoreactivity was first detected in the soma of multilayered cells just beneath the molecular layer at 16 weeks of gestation. The IP3R1 immunoreactivity gradually increased in area of positive staining from soma to dendrites and spiny branchlets, and the dendritic outgrowth rapidly progressed during 6 months after birth. The Purkinje cell maturation was more advanced in the vermis than in the hemisphere, more in the posterior lobe than in the anterior lobe, and more at the bottom of the folia than at the top. Partial absence of the Purkinje cells in the cerebellar cortex was observed in three cases. Heterotopias including Purkinje cells were often noted in the cerebellar white matter in five cases.

Antibodies, Monoclonal↗