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Biomedical subjects

N Miki

Publications and source records attributed to N Miki.

At least 109 records · Page 6Linked to original sources
PubMed1992

Thyroid hormone modulation of the hypothalamic growth hormone (GH)-releasing factor-pituitary GH axis in the rat.

Both thyroid hormone and hypothalamic growth hormone (GH)-releasing factor (GRF) facilitate pituitary somatotroph function. However, the pathophysiological role of thyroid hormone in GRF secretion is less well understood. Thyrotoxicosis, induced by administration of thyroxine (T4) in rats, inhibited both pituitary GH levels and immunoreactive GRF secretion from incubated hypothalamus. At the highest dose of T4 given for 12 d, GRF secretion and pituitary GH decreased by 50 and 39%, respectively. Hypothyroidism induced by thyroidectomy (Tx) enhanced GRF secretion approximately twofold while depleting pituitary GH by greater than 99%. Both of these hypothalamic and pituitary effects were reversed by replacement of T4 but not human GH for 7 or 14 d. Human GH was as potent as T4 in restoring decreased body weight gains or serum insulin-like growth factor-1 levels in Tx rats. These results indicate that at both physiological and pathological concentrations in serum, thyroid hormone acts as an inhibitory modulator of GRF secretion, probably not involving a feedback mechanism through GH. A biphasic effect of thyroid hormone on pituitary GH levels appears to derive from the difference in primary target tissues of hyper- and hypothyroidism, the hypothalamus and the pituitary, respectively.

Animals↗
PubMed1992

Effect of manidipine on balloon catheter-induced arterial smooth muscle cell proliferation in spontaneously diabetic GK rats.

The inhibitory effect of manidipine, a long acting calcium channel blocker, on vascular smooth muscle cell proliferation was investigated in spontaneously diabetic GK rats with balloon catheter-induced denudation of the carotid artery. Treatment with manidipine at doses of 4.6 and 15.1 mg/kg/day inhibited thickening of the neo-intima in the balloon catheter-injured artery without any effect on blood pressure and lowered the ratio of intima to wall areas and wall to total vascular areas in a dose-dependent fashion. These results suggest that manidipine inhibits an abnormal proliferation of the intima in the carotid artery of spontaneously diabetic rats.

Animals↗
PubMed1992

[The acute and chronic effects of bunazosin on exercise capacity estimated by the anaerobic threshold in patients with chronic congestive heart failure].

To study the effect of bunazosin on exercise capacity in patients with congestive heart failure (NYHA II-III), anaerobic thresholds (AT, VO2, ml/min/kg) were measured before (control) and after initial 1 = 2mg administration of bunazosin (acute phase; N = 14) and after two weeks of bunazosin therapy (3mg/day, 1mg t. i. d., chronic phase; N = 6). AT were determined by Wasserman's V-slope method during ergometer exercise test with a ramp loading (10 watt/min). AT increased significantly from control during both acute (14.2 +/- 2.7 to 16.9 +/- 3.6 ml/min/kg p < 0.005) and chronic (13.6 +/- 2.5 to 16.7 +/- 1.0 p < 0.05) phase. Additionally, work (watt) attained at AT increased significantly from control during both acute (33.6 +/- 19.2 to 52.6 +/- 30.2 p < 0.005) and chronic (35.8 +/- 25 to 49.3 +/- 15 p < 0.05) phase. Pressure-rate-products (PRP, x 10(2) mmHg/min) at AT increased significantly from control during the acute phase (119 +/- 35 to 240 +/- 50 p < 0.005) alone. In the chronic phase, PRP decreased significantly at the work level equal to AT during control (from 207 +/- 41 to 187 +/- 39 p < 0.05). These data suggest that bunazosin has favorable acute and chronic effects on exercise capacity in patients with congestive heart failure.

Adult↗
PubMed1991

Effects of chronic exposure of NG108-15 cells to morphine or ethanol on binding of nuclear factors to cAMP-response element.

The gel retardation assay with a single-stranded oligo-DNA of cAMP-response element (CRE) in a somatostatin promoter region was selected to examine the possibility of transcriptional regulation of cAMP-inducible genes by chronic morphine or ethanol treatment of NG108-15 cells. When the nuclear extracts from the cells treated with morphine (50 microM) or ethanol (100 mM) for several days were assayed, the amount of DNA-protein complex was decreased about 30-40% compared to that of the control. The decreased complex was recovered by 1-2 days after withdrawal of the drugs. Treatment of the cells with these drugs for 1 h did not change the amount of the DNA-protein complex. Thus, changes in CRE-binding proteins from the cells treated chronically with morphine or ethanol suggest that these drugs can modulate the expression of cAMP-inducible genes through which tolerance and dependence may develop.

Animals↗
PubMed1991

Purification and characterization of an 82-kD membrane protein as a neurite outgrowth factor binding protein: possible involvement of NOF binding protein in axonal outgrowth in developing retina.

Neurite outgrowth factor (NOF) is a glycoprotein isolated from an extract of gizzard that induces neurite outgrowth from cultured retinal or ciliary ganglionic (CG) neurons. We have reported that a glycoprotein of approximately 82 kD solubilized from gizzard muscles binds to NOF (ligand blotting) and inhibits the neurite promoting activity of NOF (inhibition assay). The 82-kD protein (NOF binding protein) was purified from gizzard muscle membranes as a doublet band on SDS-PAGE and a polyclonal antibody was raised against it. An NOF binding protein in developing retina exhibited the same physicochemical properties as that of the gizzard muscle. Quantitative decrease in NOF binding protein in embryonic retinas was observed after day 11 by the inhibition assay, ligand blotting, and immunoblotting, its decrease being parallel with reduction of NOF-induced neurite outgrowth of embryonic retinas. In an immunohistochemical study, the antibody stained only the optic fiber layers of the retinas of 8-d embryos, and this staining was no longer detectable in retinas of 18-d embryos. These results suggest that the 82-kD protein is a novel membrane protein that behaves as an NOF receptor and that the loss of neuritic response of the retinal neurons to NOF reflects a decrease in NOF receptor molecules.

Animals↗
PubMed1991

Age-dependent increase in neuropeptide Y gene expression in rat adrenal gland and specific brain areas.

Age-dependent changes in the expression of neuropeptide Y (NPY) peptides and prepro-NPY mRNA (NPY mRNA) were studied in rat adrenal gland and brain areas by means of radioimmunoassay, immunohistochemistry, and northern blot analysis. In the adrenal gland, NPY immunoreactivity (NPY-I) increased by 80-fold, mainly in the chromaffin cells, during aging (from 7 to 33 weeks old). The increase in NPY-I was accompanied by a concomitant increase in the content of NPY mRNA (800 bases in size, by 16-fold) and putative NPY pre-mRNA, a result suggesting that this increase results from that in NPY gene expression, probably at the level of transcription. In contrast, in some brain areas, such as striatum and medulla oblongata plus pons, NPY-I decreased in an age-dependent manner, whereas NPY mRNA abundances in these areas increased by twofold with age (from 7 to 33 weeks old). The opposite changes between NPY and NPY mRNA content in specific brain areas suggested the accelerated turnover/degradation of NPY peptide in the brain areas. Furthermore, beta-actin mRNA abundance did not change in rat adrenal gland and brain areas during aging. Thus, the characteristic age-related increase in NPY gene expression in rat adrenal gland and some brain areas seems to be important for physiological regulation of some neuronal functions, such as blood pressure, in aged animals.

Adrenal Glands↗
PubMed1991

Rapid decrease in neuropeptide Y gene expression in rat adrenal gland induced by the alpha 2-adrenoceptor agonist, clonidine.

1 The mechanism of regulation of the neuropeptide Y (NPY) gene by pharmacological treatment with the alpha 2-adrenenoceptor agonist, clonidine, was investigated by quantitative Northern blot analysis of the effects of this drug on the NPY mRNA levels in rat adrenal gland and medulla oblongata/pons. 2 In the adrenal gland, clonidine-treatment (50 microgram kg-1, s.c., once daily) resulted in decrease in the amount of NPY mRNA to 44 +/- 10% of the control level in 24 h and then its increase to 162 +/- 16% of the control level after 5 days. Concomitant changes in putative NPY pre-mRNA species (7.0 and 3.3 kb) were observed, probably due to changes at the level of NPY gene transcription. 3 The short-term (24 h) effect of clonidine was blocked by yohimbine (5 mg kg-1, i.p., once daily). Yohimbine alone tended to increase the NPY mRNA level after 24h. 4 The recovery/increase in the NPY mRNA level in the adrenal gland after 5 days treatment with clonidine was similar to its increase after treatment with reserpine (0.5 mg kg-1, i.p., once daily). 5 NPY gene expression in the medulla oblongata/pons was not changed by short- or long-term treatment with clonidine. 6 These results suggest that clonidine suppresses NPY gene expression in the adrenal gland, probably at the level of transcription, by activation of the alpha 2-adrenoceptor.

Adrenal Glands↗
PubMed1991

Effect of antiserum to rat growth hormone (GH)-releasing factor on physiological GH secretion in the female rat.

To further study the physiological role of GH-releasing factor (GRF), we examined the effect of antiserum to rat hypothalamic GRF on spontaneous GH secretion in the normal female rat. Two groups of six conscious female rats were passively immunized with either nonimmune rabbit serum (NRS) or antirat GRF serum via a chronic indwelling atrial catheter. The secretory profiles of GH were observed by collecting blood samples at 15-min intervals for 1 h before and 4 h after administration. The NRS-treated rats showed a characteristic female pattern of spontaneous GH secretion. GH pulses were of low amplitude (mean +/- SEM, 26.8 +/- 2.4 ng/ml) and occurred irregularly at a frequency of 4.2 +/- 0.2/5 h, while interpeak through levels of GH were relatively high, with nadir values of 8.6 +/- 0.7 ng/ml. Synthetic rat GRF, given iv at a dose of 1 microgram/kg BW after the last blood sampling, stimulated GH release to a peak level of 153 +/- 37 ng/ml in the control rats. Administration of GRF antiserum caused a profound suppression of both pulse and trough components of GH secretion. This effect occurred rapidly, within 15 min after injection of antiserum, and GH secretion decreased uniformly to very low levels (3.4 +/- 0.1 ng/ml), with little or no fluctuation throughout the observation period. GRF antiserum also abolished the synthetic rat GRF-induced GH release, indicating sufficient potency of immunoneutralization. These results demonstrate that both GH pulses and troughs are dependent upon hypothalamic GRF in normal female rats, thereby substantiating earlier observations in male rats which demonstrated the physiological role of GRF in GH secretion.

Animals↗
PubMed1991

[Molecular mechanism of drug tolerance and dependence].

Morphine and ethanol drugs known to develop tolerance and dependence, induce changes in the adenylate cyclase system. Morphine inhibits the adenylate cyclase activity in NG108-15 cells and causes increases in adenylate cyclase synthesis and the down-regulation of opiate receptors in cells treated for several days. Chronic exposure of NG108-15 cells to ethanol also causes a decrease in the mRNA of the GTP-binding protein (Gs). These observations suggest the possibility that a group of genes is expressed in response to morphine or ethanol during the acquisition of tolerance and dependence. Recently, it has been reported that cAMP regulates a number of genes through a cAMP response element (CRE) in their promotor regions and that nuclear CRE-binding proteins bind specifically to the CRE to stimulate the transcription of cAMP-responsive genes. The gel shift assay with a single stranded oligo-DNA of CRE in a somatostatin promotor region was employed to examine the possibility of transcriptional regulation of cAMP-inducible genes by chronic morphine or ethanol treatment of NG108-15 cells. When the nuclear proteins from the cells treated with morphine or ethanol for several days were provided for the assay, the amounts of DNA-protein complex were decreased. The decreased complexes were recovered by 1-2 days after morphine withdrawal. The nuclear proteins were purified partially by a combination of chromatography on Q-Sepharose, Sephacryl S-300 and DNA affinity-Sepharose. Changes in CRE-binding proteins from the cells treated chronically with morphine or ethanol suggest that these drugs can modulate the expression of cAMP-inducible genes through which tolerance and dependence may develop.

Base Sequence↗
PubMed1991

Mechanism of anti-inflammatory action of etodolac.

The effect of etodolac (CAS 41340-25-4) on the inflammatory reactions induced by histamine and bradykinin was compared with that of indomethacin and other nonsteroidal anti-inflammatory drugs. Etodolac (50 mg/kg p.o.), indomethacin (20 mg/kg p.o.), diclofenac Na (20 mg/kg p.o.) and acetylsalicylic acid (200 mg/kg p.o.) had no effect on the increase of vascular permeability induced by histamine or bradykinin and on passive cutaneous anaphylaxis in rats. Etodolac (5, 10 and 20 mg/kg p.o.) suppressed concanavalin A-induced paw edema in rats. Etodolac (10 mg/kg p.o.) and bromelain (10 mg/kg i.v.) significantly suppressed the heat-induced elevation of bradykinin in perfusates of rat paws, but indomethacin (20 mg/kg p.o.) and diclofenac Na (20 mg/kg p.o.) did not. Etodolac inhibited bradykinin-forming enzyme activity in a concentration-dependent manner (IC50 = 1.5 x 10[-4) mol/l). These results suggest that etodolac is a unique nonsteroidal anti-inflammatory drug which can inhibit bradykinin formation, unlike indomethacin or diclofenac Na.

Animals↗
PubMed1991

[The molecular genetics of color blindness].

The gene structures of three color pigments have been reported by Nathans et al. in 1985. One copy of red gene and 1 to 3 copies of green genes are tandemly repeated on X chromosome. As the structures of red and green genes are highly homologous (96%) and tandemly repeated, they cross-over on chromosome during meiosis and hybrid genes were produced. The function of these hybrid genes exhibits abnormal spectrum for red and green light. The 5' portion of the gene determines which cone cell type express the gene and the 3' portion of the gene determines the type of spectrum. In the 3' portion, exon 4 are associated with a small shift of spectrum and exon 5 determines a large shift of spectrum. For example, a hybrid gene with 5' region of red and 3' region of green is expressed in the red cones and exhibits green spectrum. Abnormality of color perception depends on the hybrid ratio of red and green genes.

Base Sequence↗
PubMed1990

Isolation and analysis of the human MEKA gene encoding a retina-specific protein.

We have isolated and sequenced a human gene encoding photoreceptor cell-specific MEKA protein. The protein coding region was separated into three exons, which encoded 246 amino acid residues with a molecular weight of 28,311. The coding region of the human gene exhibited the homologies of 90.7% nucleotides and 88.5% amino acids with those of the bovine cDNA. Southern blot analysis revealed that the human MEKA gene has a single copy number. However, the anti-bovine MEKA stained both rod and cone photoreceptor cells in the human retina.

Amino Acid Sequence↗
PubMed1990

Direct photosensitivity of chick pinealocytes as demonstrated by visinin immunoreactivity.

Visinin, a calcium-binding protein isolated from the soluble fraction of homogenized chick retinae, has been recognized immunocytochemically in the pinealocytes of various submammals. In the chick pineal organ, continuous environmental light induced an increase in population density of visinin-immunoreactive pinealocytes. In semi-quantitative, dot-immunoblotting analysis, the amount of visinin in the pineal organs of chicks kept under continuous light for 3 days was 4-8 fold more abundant than that under continuous darkness for the same duration. Eye-enucleation and organ culture experiments clarified that this lighting effect was exerted directly on the pineal organ through the skull, and not via the neural pathway including the retinohypothalamic projection. These data suggest the existence of direct photosensitivity in the chick pinealocyte itself and the possible involvement of visinin in photoreception of the pineal organ as well as the retina of chicks.

Animals↗
PubMed1990

Visinin: a novel calcium binding protein expressed in retinal cone cells.

Visinin is a retinal cone cell-specific protein (molecular weight 24,000, pI 5.1). To investigate its function, visinin cDNA was isolated from a chick retinal lambda gt11 cDNA library, using anti-visinin serum. The beta-galactosidase-visinin fusion protein was used for purifying epitope-selected antibody. The purified visinin antibody reacted only with a 24 kd protein in retinal cone cells. Visinin mRNA was expressed only in the retinal photoreceptor layer. The nucleotide sequence of the cDNA revealed that visinin has three E-F hand structures and is a Ca2+ binding protein. Visinin protein expressed in E. coli exhibited Ca2+ binding activity. These results suggest that visinin is a photoreceptor-specific Ca2+ binding protein and may be involved in phototransduction in the cone cells.

Amino Acid Sequence↗
PubMed1990

Possible involvement of neurite outgrowth factor (NOF) receptor in axonal outgrowth from developing chick retina.

We report that an 82-kDa membrane protein from chicken gizzard muscles is a neurite outgrowth factor (NOF)-receptor interacting with a domain for neurite-promoting activity of NOF. We found that an 82-kDa membrane protein in the developing chicken retina exhibited the same properties as those of gizzard muscles. The neuritic response of the retinal neurons to NOF increased in 6- and 8-day embryos, reaching a maximum level on the 8th-day and then rapidly decreased with aging. In parallel with this, the amount of NOF receptor in the retinas was maximal in 8- and 11-day embryos and thereafter decreased with aging. The results suggest that the failure in the neuritic response of the retinal neurons to NOF with aging is due to the decrease in NOF receptor.

Animals↗
PubMed1990

Long lasting increase in neuropeptide Y gene expression in rat adrenal gland with reserpine treatment: positive regulation of transsynaptic activation and membrane depolarization.

To elucidate how the neuropeptide Y (NPY) gene is regulated by physiological/pharmacological changes in neural functions, the expression and regulation of the NPY gene were studied by measuring changes in the abundances of NPY and NPY mRNA in the adrenal gland and brain regions of rats in vivo and in PC12 rat pheochromocytoma cells after reserpine treatment. Long term treatment with reserpine in vivo, which causes hypotension and increased splanchnic nerve activity, induced prolonged increases in the abundance of NPY mRNA and putative NPY pre-mRNA, with concomitant increases in NPY, in the adrenal gland in a tissue-dependent manner but caused no changes in the abundance of beta-actin mRNA. Transection of the splanchnic nerves almost completely (76%) prevented the reserpine-induced increases in the abundance of NPY mRNA and NPY pre-mRNA, but denervation alone did not affect their steady state levels. These results suggested that increased activity of the splanchnic nerves regulates NPY gene expression positively in the adrenal gland, probably at the level of transcription. In PC12 cells, reserpine decreased the abundance of NPY mRNA directly, but nicotinic receptor activation increased its abundance transiently and the persistent membrane depolarization increased its abundance markedly. Thus, NPY gene expression is positively regulated by membrane depolarization via increased transsynaptic activation with reserpine.

Actins↗