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Biomedical subjects

N Miki

Publications and source records attributed to N Miki.

At least 55 records · Page 3Linked to original sources
PubMed1997

Growth hormone-releasing hormone (GHRH)-GH-somatic growth and luteinizing hormone (LH)RH-LH-ovarian axes in adult female transgenic mice expressing human GH gene.

We have examined alterations in the hypothalamo-pituitary GH-somatic growth axis and the hypothalamo-pituitary LH-ovarian axis in a line of transgenic ICR mice expressing human GH (hGH) under the influence of the whey acid protein promoter. Transgenic female mice weighed twice as much as control females and were infertile. The size of the anterior pituitary (AP) was 1/3 that of the controls. In transgenic mice, acinar cells in the mammary and mandibular glands displayed hGH-immunoreactivity, and plasma hGH was detected by radioimmunoassay. In the medial basal hypothalamus (MBH) of transgenic females, the immunoreactive-GHRH level was decreased (P<0.01). There was a corresponding reduction in the number of GHRH-immunoreactive neurons in the arcuate nucleus (ARC) and in the immunostaining of GHRH nerve terminals in the median eminence. The level of somatostatin (SRIH) in the MBH was increased (P<0.05), and SRIH-immunoreactive neurons in the periventricular nucleus (PeV) were increased in size and number in transgenic mice. The MBH level of LHRH in transgenic animals was greater (P<0.01) than in controls, although there was no apparent difference in the number of LHRH-immunoreactive neurons or in LHRH level in the preoptic area. There are fewer SRIH- and LHRH-immunoreactive neurons in the ARC in transgenic mice. Cells in the AP for GH, PRL, and LH were fewer in transgenic mice. The ovary suffered disturbance of follicular development and of corpora lutea formation. These results demonstrate that chronic overproduction of hGH may profoundly affect the organization of the GHRH/SRIH-GH-somatic growth axis and the LHRH-LH-ovarian axis due to reduction of GHRH-, SRIH- and LHRH-neurons in the ARC and increase of SRIH-neurons in the PeV.

Animals↗
PubMed1997

Cervical spondylotic amyotrophy associated with Hirayama's disease.

A 47-year-old man with Hirayama's disease who developed cervical spondylotic amyotrophy (CSA) is presented. The patient had noted weakness and atrophy of hand and forearm muscles bilaterally at the age of 16. At the age of 40, he developed proximal muscle atrophy and weakness bilaterally after 20 years of a non-progressive state. Myelography and computed tomography (CT)-myelography revealed that ventral cord compression at multiple levels of C4-7 vertebral bodies was increased when the neck was extended. The clinical diagnosis was CSA associated with Hirayama's disease. To our knowledge, this is the first such case to be reported.

Cervical Vertebrae↗
PubMed1997

Cortical field potentials preceding vocalization in monkeys.

Field potentials before vocalization were studied with electrodes chronically implanted on the surface and at a 2.0-3.0 mm depth in various cortical areas in three monkeys. Surface-negative, depth-positive (s-N, d-P) slow potentials prior to vocalization were recorded in the premotor (including the Broca's homolog), motor and somatosensory cortices, and the supplementary motor area (SMA). Such premovement potentials were recorded also in the cingulate and prefrontal cortices when a monkey uttered a sound with intense motivation for reward. Cerebellar hemispherectomy on the right side eliminated the s-N, d-P premovement potentials in the motor cortex and in the posterior bank of inferior limb of the arcuate sulcus (homolog of Broca's area) in the left hemisphere. After the operation, the tone came to have less components of different frequencies, and its duration varied much more than before. These facts suggest that the neocortical area homologous to the human speech area takes part in the generation and control of monkey vocalization together with the cerebellum possibly through cerebro-cerebellar interactions. This is against ideas so far proposed on nonhuman primate vocalization, i.e., it is generally considered that animal vocalization differs fundamentally from human speech.

Animals↗
PubMed1997

[Gicerin].

Explore the source record for details and available documents.

Animals↗
PubMed1996

Characterization of single-stranded cAMP response element binding protein (ssCRE-BP) from mouse cerebellum.

It has been speculated that opiate tolerance and dependence may occur at the level of gene expression. Our previous studies have shown that the binding activity of a nuclear factor (ssCRE-BP) to single-stranded CRE of somatostatin gene is altered by long-term treatment with morphine in the mouse cerebellum. ssCRE-BP was purified from the mouse cerebellum by a combination of chromatography on DNA affinity agarose and Mono Q HR. The native protein exhibited a molecular size of 110-150 kDa by gel filtration, and two polypeptides of about 35-40 kDa were observed on SDS-PAGE. The cloning and sequencing of a cDNA encoding ssCRE-BP showed that the protein possesses a glycine-rich domain and a glutamine-rich domain in the amino terminus and the carboxyl terminus, respectively. To investigate the function of ssCRE-BP in the brain, recombinant glutathione-S-transferase (GST) fusion proteins containing ssCRE-BP were expressed in bacterial systems. Rabbit anti-ssCRE-BP antibodies were raised against a GST-ssCRE-BP fusion protein. Using the antibodies in western blot analysis, a polypeptide of approximately 66 kDa was detected in the brain. These findings indicate that ssCRE-BP is involved in opiate tolerance and dependence.

Animals↗
PubMed1996

Zebrafish elav/HuC homologue as a very early neuronal marker.

Drosophila ELAV, a neuron-specific RNA binding protein, is expressed in all neurons right after their birth. This specific pattern of expression has led to its use as a pan-neuronal marker. At least three members of the elav family, HuD, HuC/ple21 and Hel-N1, have been reported to be neuron-specific in vertebrates, although it is unknown which member of this family is expressed at the time of early neuronal determination. We have isolated a zebrafish elav/HuC homologue (zHuC) which has 89% homology to human HuC protein. It is first expressed in the neuronal precursor cells in the neural plate immediately after gastrulation, and then high expression levels persist in most regions of the nervous system. HuC, like elav in Drosophila, may be one of the earliest neuronal markers in zebrafish.

Animals↗
PubMed1996

Involvement of a single-stranded DNA binding protein, ssCRE-BP/Pur alpha, in morphine dependence.

We have purified a nuclear protein from mouse cerebella that binds to single-stranded oligo-DNA of cAMP response element and is modulated by morphine treatment. Isolation of the cDNA clone showed that the nuclear protein (ssCRE-BP) was identical to Pur alpha, a DNA binding protein for single-stranded purine-rich sequences that was originally isolated as a replication factor. ssCRE-BP/Pur alpha and mRNA were abundant in the brain. The levels of ssCRE-BP/Pur alpha and the transcript were not changed by chronic morphine treatment, however, the levels of an activator of ssCRE-BP/Pur alpha, which is necessary for the DNA binding, may be modulated by the treatment.

3T3 Cells↗
PubMed1996

Regulation of pituitary growth hormone-releasing factor (GRF) receptor gene expression by GRF.

We examined how growth hormone-releasing factor (GRF) regulated pituitary GRF receptor gene expression in the conscious rat. GRF receptor mRNA levels were significantly increased by immunoneutralization of endogenous GRF with its specific antiserum. This effect was dose dependent and the maximum level was 3.8-fold higher than that in control rats. A similar rise in GRF receptor gene expression was obtained by the depletion of noradrenaline, a neurotransmitter thought to stimulate GRF release, and was reversed by 87% by the repeated administration of synthetic GRF. These results indicate that pituitary GRF receptor gene expression was up- or down-regulated in vivo in the absence or presence of GRF, respectively.

Analysis of Variance↗
PubMed1996

MEKA/phosducin attenuates hydrophobicity of transducin beta gamma subunits without binding to farnesyl moiety.

Hydrophobic modifications of transducin (T) gamma, such as farnesyl-and carboxyl-methylation, are essential for the association of T beta gamma with the photoreceptor disc membrane, and MEKA/phosducin is known to inhibit the association. In this study, we examined the effect of MEKA on the hydrophobicity of T beta gamma. MEKA could bind to T beta gamma without farnesyl/carboxyl-methyl moieties as well as native T beta gamma. In the Triton X-114 phase separation assay, T beta gamma-MEKA complex was recovered in the aqueous phase, whereas T beta gamma was recover in the detergent phase. N-terminal portion of MEKA which includes T beta gamma-binding domain was not sufficient to reduce the hydrophobicity of T beta gamma or to dissociate T beta gamma from the membrane. The data suggest that MEKA attenuates the hydrophobicity of T beta gamma to result in the dissociation of T beta gamma from the membrane without directly binding to farnesyl/carboxyl-methyl moieties.

Animals↗
PubMed1996

Neuron-specific expression of a chicken gicerin cDNA in transient transgenic zebrafish.

Gicerin, a novel cell adhesion molecule which belongs to the immunoglobulin superfamily, is expressed temporally and spatially in the developing chick brain and retina. The previous in vitro experiments using transfected cells showed that gicerin can function as a cell adhesion molecule which has both homophilic and heterophilic binding activities. For the in vivo analyses of gicerin in neural development, we tried to utilize a zebrafish system, a vertebrate suitable for studying early development. We generated transient transgenic animals by microinjecting DNA constructs into zebrafish embryos. Chicken gicerin, under control of the neurofilament gene promoter, was preferentially expressed in neuronal cells and gicerin-expressing neurons exhibited a fasciculation formation with neighboring gicerin-positive axons, which may be partly due to homophilic cell adhesion activity of gicerin. These experimental results suggest that this fast and efficient transgenic animal system is useful for studying the functional roles of neuron-specific genes during the development.

Animals↗
PubMed1996

Ca2+/calmodulin-dependent transcriptional activation of neuropeptide Y gene induced by membrane depolarization: determination of Ca(2+)- and cyclic AMP/phorbol 12-myristate 13-acetate-responsive elements.

Membrane depolarization stimuli (high potassium concentration and veratridine) increased neuropeptide Y (NPY) mRNA abundance time-dependently, without a change in beta-actin mRNA level, in NG108-15 and PC12 cells. Although the induction by veratridine was blocked completely by tetrodotoxin, the induction by potassium was suppressed minimally. Voltage-dependent Ca channel blockers and calmodulin antagonists inhibited the increases by both depolarization stimuli completely, suggesting involvement of Ca2+/calmodulin-dependent kinases (CaM kinases). Transient assay using chloramphenicol acetyltransferase reporter genes containing the rat NPY gene promoter indicated that membrane depolarization and Ca entry stimulate transcription of the NPY gene. The depolarization-induced transactivation was also blocked by CaM kinase inhibitors. The 200-bp 5'-upstream region (-344/-145) was localized as a Ca2+/ calmodulin-responsive element (CaMRE), which confers depolarization-induced transactivation. It is interesting that this CaMRE did not contain the canonical Ca-responsive elements such as CRE, SRE, NF-AT, or the C/EBP beta-binding site and was separated from a 64-bp cyclic AMP/ phorbol 12-myristate 13-acetate-responsive element (-144/-81). These findings suggested that membrane depolarization regulates the NPY gene transcription positively through the unique CaMRE by activation of CaM kinases following Ca entry through L-type Ca channels.

Animals↗
PubMed1996

Involvement of gicerin, a cell adhesion molecule, in tracheal development and regeneration.

Gicerin is a novel cell adhesion protein that belongs to the immunoglobulin superfamily. Gicerin protein adheres to neurite outgrowth factor, an extracellular matrix protein in the laminin family, and also exhibits homophilic adhesion. In the present study, we investigated the involvement of gicerin and neurite outgrowth factor in tracheal development and regeneration. In an early embryonic stage, gicerin protein was highly expressed in tracheal epithelial cells, but not in loosely arranged mesenchymal cells. During development, mesenchymal cells become condensed around the tracheal epithelium and then differentiate into muscle and cartilage; high levels of gicerin expression were observed in these cells. In the later embryonic and posthatching stages, no gicerin expression was detected in tracheal epithelium or cartilage. In addition, expression of gicerin increased transiently in the tracheal epithelium during the regeneration after tracheitis induced by the infectious bronchitis virus. Furthermore, a polyclonal antibody against gicerin inhibited the epithelial regeneration in tracheal organ cultures. These findings suggest that glcerin plays an important role in both tracheal development and regeneration.

Animals↗
PubMed1995

Thyroid hormone regulation of gene expression of the pituitary growth hormone-releasing factor receptor.

To examine thyroid hormone regulation of the pituitary receptor for hypothalamic growth hormone (GH)-releasing factor (GRF), we studied effects of hypothyroidism on the pituitary GRF receptor (GRF-R) mRNA and its related parameters in rats. Thyroidectomy (Tx) induced a 61-65% reduction in GRF-R mRNA levels, which was significantly reversed with thyroxine (T4) replacement for 5 days at a dose of 1 microgram/100 g/day. Pituitary GH contents changed parallel to GRF-R mRNA levels following the Tx and T4 replacement. In contrast, Tx enhanced GRF release > 2 fold, which was not reversed with the regime of T4 replacement. These results indicate that thyroid hormone promotes pituitary GRF-R gene expression, not by modulating GRF secretion, but by acting on the pituitary directly. The decline in GRF receptor expression would contribute to somatotroph failure by rendering the pituitary refractory to the increased GRF signal in hypothyroidism.

Animals↗
PubMed1995

Expression and functional analysis of a novel isoform of gicerin, an immunoglobulin superfamily cell adhesion molecule.

We have cloned a novel cDNA of gicerin, a cell adhesion molecule belonging to the immunoglobulin superfamily. Both gicerin isoforms share the same extracellular domain, which has five immunoglobulin-like loop structures and a transmembrane domain as s-gicerin, but differ in the cytoplasmic tail domain. As the newly identified form has a larger cytoplasmic domain than the previously reported form, we refer to them as l-gicerin and s-gicerin, respectively. l-gicerin is transcribed from a distinct mRNA containing an inserted sequence not found in s-gicerin mRNA which caused a frameshift for the coding region for a cytoplasmic domain. Previous studies demonstrated that gicerin showed a doublet band of 82 and 90 kDa in chicken gizzard smooth muscle. We report that the 82-kDa protein corresponds to s-gicerin and the 90-kDa protein to l-gicerin. We also found that the two gicerin isoforms are expressed differentially in the developing nervous system. Functional analysis of these gicerin isoforms in stable transfectants revealed that they had differ in their homophilic adhesion properties, as well as in heterophilic cell adhesion assayed with neurite outgrowth factor. In addition, these isoforms have neurite-promoting activity by their homophilic adhesion, but differ in their ability to promote neurite outgrowth.

Amino Acid Sequence↗