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Biomedical subjects

A Miyamoto

Publications and source records attributed to A Miyamoto.

At least 73 records · Page 4Linked to original sources
PubMed2000

Captopril increases the affinity of bradykinin receptor binding sites in bovine coronary arterial endothelial cells.

In a radioligand binding study using bovine coronary artery endothelial cell membranes, captopril changed a single bradykinin (BK) binding site (Kd = 1.77 nM, Bmax = 60.2 fmol/mg protein) to high- (Kd = 0.68 pM, Bmax = 17.7 fmol/mg protein) and low- (Kd = 1.00 nM, Bmax = 72.5 fmol/mg protein) affinity binding sites. This effect was reversed by GppNHp. Captopril also enhanced BK-induced endothelium-dependent relaxation in saponin-treated coronary rings, and GppNHp partially suppressed this enhancement. These results suggest that captopril may affect BK receptors that couple to G-proteins.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Illusory recouplings of onsets and terminations of glide tone components.

We present a new auditory illusion, the gap transfer illusion, supported by phenomenological and psychophysical data. In a typical situation, an ascending frequency glide of 2,500 msec with a temporal gap of 100 msec in the middle and a continuously descending frequency glide of 500 msec cross each other at their central positions. These glides move at the same constant speed in logarithmic frequency in opposite directions. The temporal gap in the long glide is perceived as if it were in the short glide. The same kind of subjective transfer of a temporal gap can take place also when the stimulus pattern is reversed in time. This phenomenon suggests that onsets and terminations of glide components behave as if they were independent perceptual elements. We also find that when two long frequency glides are presented successively with a short temporal overlap, a long glide tone covering the whole duration of the pattern and a short tone around the temporal middle can be perceived. To account for these results, we propose an event construction model, in which perceptual onsets and terminations are coupled to construct auditory events and the proximity principle connects these elements.

Adult↗
PubMed2000

Assessment of Stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers.

We assessed Stanniocalcin-1 (STC-1) mRNA expression in human normal tissues, various types of human cancer cell lines, and cancer tissues obtained during surgery. Using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay developed to detect STC-1 mRNA, the transcripts were detected in 20 out of 21 cancer cell lines and in all tumor tissues from various types of cancer. Semi-quantitative analyses with multiplex RT-PCR showed that STC-1 mRNA tended to be enhanced in cancer tissues of hepatocellular carcinoma and colorectal cancer compared to background cancer-free tissues. Analysis of blood samples obtained from 11 patients with hepatocellular carcinoma before, after and during hepatectomy showed STC-1 mRNA expression in 8 out of 11 patients at least one time. Normal donor blood samples (n=31) were all-negative for STC-1 mRNA expression. Our results indicate that STC-1 mRNA might be a useful molecular marker for detection of tumor cells in blood from patients with various types of malignancies.

Aged↗
PubMed2000

Low extracellular Mg2+ concentrations suppress phagocytosis in vitro by alveolar macrophages from rats.

The aim of this study was to assess the effects of extracellular Mg2+ concentrations on phagocytosis in vitro by alveolar macrophages from rats. Phagocytosis was suppressed in the presence of low, but not high, Mg2+ concentrations. Vanadate, a Mg(2+)-ATPase inhibitor, suppressed phagocytosis. In the presence of a low Mg2+ concentration or vanadate, the cytosolic free Ca2+ concentration ([Ca2+]i) increased, but the cytosolic free Mg2+ concentration did not. These results suggest that low extracellular Mg2+ concentrations and vanadate suppress phagocytosis by rat alveolar macrophages by increasing [Ca2+]i.

Animals↗
PubMed2000

Expression of interferon alpha/beta receptor in human hepatocellular carcinoma.

Interferon-alpha (IFNalpha) plays a crucial role in the antiproliferation and immunoregulatory activity through the specific cell surface receptor, interferon-alpha/beta receptor (IFNalpha/betaR). We examined the immunohistochemical expression of IFNalpha/betaR in 91 hepatocellular carcinoma (HCC), HCV-related chronic hepatitis (n=38) and cirrhosis (n=53), dysplastic nodules (n=5), and normal liver (n=9). The level of IFNalpha/betaR increased in chronic hepatitis and cirrhosis compared with normal liver. All the dysplastic nodules showed moderate or high expression. In HCCs, 26% (24/91) of patients showed high IFNalpha/betaR expression while the remaining 38% (35/91) showed moderate, and 35% (32/91) no or faint expression. Clinicopathological survey demonstrated a significant correlation between IFNalpha/betaR expression and differentiation of carcinoma (P=0.0008) although there was no correlation between IFNalpha/betaR expression in HCC and survival or disease-free survival. Thus, IFNalpha/betaR was expressed not only in chronic hepatitis or liver cirrhosis but in HCC and its expression was significantly correlated with tissue differentiation of carcinoma.

Blotting, Western↗
PubMed2000

Augmentation of antitumor activity of 5-fluorouracil by interferon alpha is associated with up-regulation of p27Kip1 in human hepatocellular carcinoma cells.

Several clinical trials have demonstrated the effectiveness of combination therapy with 5-fluorouracil (5-FU) and IFN-alpha in colon cancer, hepatocellular carcinoma (HCC), and other malignancies. In our preliminary clinical studies, we have observed outstanding effects with this combination therapy in patients with advanced HCC. However, the underlying mechanism by which IFN-alpha modulates the effects of 5-FU is unknown. We, therefore, conducted a mechanistic study using two HCC cell lines, PLC/PRF/5 and HuH7. IFN-alpha significantly enhanced the growth inhibitory effect of 5-FU in PLC/PRF/5 cells but not in HuH7 cells, and the isobolographic analysis indicated that this effect was synergistic. Flow cytometric analysis showed a delay in the progression of G0-G1 to S phase in PLC/PRF/5, and a sustained, induction of the cyclin-dependent kinase inhibitor p27-Kip1 and down-regulation of cyclin D1 was observed. Moreover, increased expression of p27Kip1 was associated with reduced CDK-2-associated kinase activity. Another difference in the two cell types was that PLC/PRF/5 expressed abundant IFN receptors, but HuH7 did not. Apoptosis assays were not helpful in explaining the mechanism. Our results suggest that the synergistic effects of 5-FU and IFN-alpha may in part be attributable to alterations in cell cycle progression via up-regulation of p27Kip1.

Apoptosis↗
PubMed2000

[Longitudinal study of cognitive function in two patients with focal cortical dysplasia].

To clarify the relationship between epileptic attacks and cognitive dysfunction, we examined the serial findings of 123I-IMP single photon emission computed tomography (SPECT) in relation to the intelligence quotient (IQ), assessed by Wechsler Intelligence Scale of Children-Revised, in two female patients with focal cortical dysplasia (FCD) over a 10-year period. The age of patient 1 at the initial assessment was 2 years, and the age of patient 2 was 9 months. They developed complex partial epilepsy in infancy, and were treated with antiepileptic drugs, which remained effective until 11 years of age, when their epileptic attacks recurred. Patient 1, a 14-year-old girl with FCD of the left parietal lobe suffered from dyscalculia, right-left disorientation, and finger agnosia even when she was free of epileptic attacks. Following the recurrence of seizures which occurred every night, she became unable to understand what was said to her. A hypoperfusion area detected by 123I-IMP SPECT was restricted to the left parietal lobe during the seizure-free period, but spread to the temporo-parietal lobes following the recurrence. Her verbal IQ declined from 94 (at 9 years of age) to 63 (at 11 years and 8 months). After her seizures were controlled again (at 14 years and 4 months), the 123I-IMP SPECT findings improved. Patient 2, a 12-year-old girl with FCD of the left frontal lobe, showed cognitive dysfunction. Her verbal IQ declined from 91 (at 7 years and 5 months) to 76 (at 11 years and 8 months) following a recurrence of epileptic attacks. 123I-IMP SPECT showed hypoperfusion in the left frontal lobe, where the accumulation count ratio (left/right ratio) declined from 0.86 (at 3 years) to 0.64 (at 11 years). These findings suggest that epileptic attacks are related to cognitive dysfunction in FCD patients. This cognitive dysfunction appears to correlate with the appearance of hypoperfusion areas, as detected by 123I-IMP SPECT.

Adolescent↗
PubMed1999

Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex.

Endogenous serotonin (5-hydroxytryptamine, 5-HT)-mediated regulation of dopamine release in the rat prefrontal cortex was pharmacologically characterized using in vivo microdialysis. To increase synaptic 5-HT availability, a selective 5-HT uptake inhibitor fluoxetine was applied via the dialysis probe. Local perfusion of fluoxetine (30 and 100 microM) increased dopamine levels in a concentration-dependent manner. The fluoxetine (100 microM)-induced increases in dopamine release were abolished by pretreatment with the 5-HT(1B/1D) receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5- methyl-1,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-carboxamide] ) (10 and 100 microM). The facilitation of dopamine release was also prevented by selective inactivation of the mRNA encoding 5-HT(6) receptors using antisense oligonucleotides techniques. These findings suggest that not only 5-HT(1B) receptors but also 5-HT(6) receptors are associated with the endogenous 5-HT-mediated facilitation of dopamine release. In other words, 5-HT(6) receptors may play, in part, a significant role in the functional interaction between the dopaminergic and serotonergic neuronal system in the rat prefrontal cortex.

Animals↗
PubMed1999

Prostaglandin E2, prostaglandin F2 alpha and endothelin-1 production by cow oviductal epithelial cell monolayers: effect of progesterone, estradiol 17 beta, oxytocin and luteinizing hormone.

The optimal oviductal environment, including contractile activity for gamete transport, fertilization and early embryonic development, is mediated by physiological and anatomical changes in the oviduct during the estrous cycle. Oviductal epithelial cell culture was utilized to investigate the effect of ovarian steroids (progesterone [P4] and estradiol 17 beta [E2]), oxytocin (OT) and luteinizing hormone (LH) on the local production of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and endothelin-1 (ET-1) in the cow oviduct. Epithelial cells isolated from oviducts collected during the follicular phase were cultured in M199 under standard culture conditions until monolayer formation. Then the cells were trypsinized and plated at a density of 3 x 10(4)/mL/well and cultured again until subconfluency, at which time the cells were incubated for 4 or 24 h with M199 only (control), high P4 (H-P4; 1 microgram/mL), low P4 (L-P4; 10 ng/mL), E2 (1 ng/mL), LH (10 ng/mL), OT (10(-9) M) ET-1 (10(-9) M), PGE2 (10(-8) M) PGF2 alpha (10(-9) M) or their combination (H-P4 + E2, L-P4 + E2, LH + E2, ET-1 + E2, L-P4 + E2 + LH and H-P4 + E2 + LH). The production of both PG and ET-1 was increased by E2 + low P4 and LH + E2 + low P4 (P < 0.05), while LH + E2 enhanced the production of PGF2 alpha and ET-1 (P < 0.05). Moreover, E2 + ET-1 stimulated PG production (P < 0.05). However, OT had no effect on the production of any of these substances. These results suggest that the preovulatory LH surge, together with locally re-circulated high levels of E2 from the Graafian follicle and basal P4 from regressing corpus luteum (CL), induces the maximum stimulatory effect on oviductal PGE2, PGF2 alpha and ET-1 production during the periovulatory period. Consequently, the elevated local ET-1 concentration during periovulatory period may induce the high contractile activity of the oviduct and, at the same time, the stimulation of PG production. Thus, ET-1 may act as a local amplifier for oviductal PG production stimulated by LH and ovarian steroids.

Animals↗
PubMed1999

Kabuki make-up syndrome is not caused by microdeletion close to the van der Woude syndrome critical region at 1q32-q41.

We reported on a 5-year-old Japanese girl with clinical manifestations of Kabuki make-up syndrome (KMS) and van der Woude syndrome (VWS). Since the concurrence of the two syndromes is known in four patients, including ours, it suggests a common cause. Assuming that the association of the two syndromes was caused by a microdeletion involving the putative KMS/VWS genes, we carried out fluorescence in situ hybridization and microsatellite analyses using PAC clones and dinucleotide repeat markers spanning the VWS1 critical region at 1q32-q41. No deletion was detected at the VWS1 critical region.

Abnormalities, Multiple↗
PubMed1999

Tooth-specific expression conferred by the regulatory sequences of rat dentin sialoprotein gene in transgenic mice.

We have isolated a 3.8-kb DNA fragment containing the 5' flanking region, 1st exon, and 1st intron of the rat dentin sialoprotein (rDsp) gene and produced transgenic mice carrying a LacZ reporter gene under the control of this fragment. Expression of the transgene transcript and beta-galactosidase activity were restricted to dentin and odontoblasts with spatial and temporal patterns comparable to those of the endogenous mouse Dsp transcript, although beta-galactosidase activity could not be detected visually during embryonal stages. Other tissues tested, such as alveolar bones, ameloblasts and dental pulps, did not express the transgene. This indicates that the regulatory elements necessary for tooth-specific expression are present in the fragment, which contains a TATA box and several consensus sequences for binding sites of transcription factors related to tooth development, such as TCF-1/LEF-1, MSX-1 and Dlx-1. The regulatory sequences and the transgenic mice described here provide useful information for the study of tooth development.

Amino Acid Sequence↗
PubMed1999

Effect of ovarian steroids and oxytocin on the production of prostaglandin E2, prostaglandin F2alpha and endothelin-1 from cow oviductal epithelial cell monolayers in vitro.

Cyclic physio-anatomical variation in the oviducts is mediated by the local countercurrent transfer of ovarian products. Thus, in this study cow oviductal epithelial cells (COEC) culture were utilized to investigate the effects of ovarian products such as progesterone (P4), estradiol 17beta (E2) and oxytocin (OT) on local oviductal prostaglandin E2 (PGE2), F2alpha (PGF2alpha) and endothelin-1 (ET-1) production. COEC were collected from non-pregnant Holstein cows (n = 8) during the follicular phase and cultured in M199 under standard culture conditions until monolayer formation. Cells in first passage were incubated for 24 or 48 h with P4 (500 ng/ml), E2 (1 ng/ml), OT (10(-9) M) or combination of E2 + P4. Administration of E2 significantly increased the production of PGE2, PGF2alpha and ET-1. However, simultaneous administration of P4 blocked the effect of E2. OT did not show any effect on oviductal productions of either PGs or ET-1. The results of this study show that E2 stimulates PG and ET-1 production by COEC in vitro. Thus, it can be suggested that locally transferred E2 from the ovarian follicles may be important for oviductal contraction and gamete/zygote transport during the peri-ovulatory period.

Animals↗
PubMed1999

Activation of guanine nucleotide-binding proteins and induction of endothelial tissue-type plasminogen activator gene transcription by alcohol.

The mechanism by which moderate alcohol ingestion lowers the risk of cardiovascular disease is unknown but may be due, in part, to the ability of alcohol to increase the level of tissue-type plasminogen activator (t-PA). Human endothelial cells were treated with low concentrations of ethanol (0.25-25 mM, 0-24 h), which are associated with moderate alcohol consumption. Although treatment with ethanol alone did not affect t-PA gene transcription or mRNA expression, it augmented isoproterenol (ISO)-stimulated t-PA gene transcription and mRNA levels by 3.4- and 2.8-fold, respectively, and decreased plasminogen activator inhibitor-1 mRNA levels by 65%. These effects of ethanol correlated with 2.5- and 6.9-fold increases in ISO-stimulated cyclic AMP levels and 4x-cyclic AMP response element heterologous promoter activity, respectively. To determine whether alcohol-induced changes in agonist-stimulated cyclic AMP levels were because of modulation of guanine nucleotide-binding proteins (G proteins), we assessed the effects of ethanol on Galphas and Galphai2. Although ethanol did not affect the expression of Galphas or Galphai2, it increased ISO-stimulated Galphas GTPase and GTP binding activity by 2.2- and 2.9-fold and decreased UK14304-stimulated Galphai2 GTPase and GTP binding activity by 38 and 80%. These results indicate that treatment with relatively low concentrations of ethanol enhances agonist-stimulated cyclic AMP-dependent t-PA gene transcription in vascular endothelial cells through differential modulation of G protein.

Adenylyl Cyclases↗
PubMed1999

Role of nitric oxide production in carbachol-induced negative chronotropy in cultured rat ventricular myocytes.

It has been reported that nitric oxide (NO) plays a physiological role in mediating the effect of vagal stimulation in the autonomic regulation of the heart. In this study, the changes in NO production induced by carbachol were investigated by measuring the NO metabolites, nitrite (NO2-) and nitrate (NO3-), with a high-performance liquid chromatography-Griess reaction system, and the carbachol-induced chronotropic response was simultaneously investigated. Cultured rat ventricular myocytes exhibited a dose-dependent negative chronotropic response and NO metabolite production in response to carbachol. The negative chronotropy and the enhancement of NO metabolite production induced by 10(-4) M carbachol were completely abolished by 10(-6) M atropine. Both of these effects of carbachol were completely abolished by NO synthase inhibitors such as 3 X 10(-4) M NG-monomethyl-L-arginine acetate and 10(-5) M methylene blue. Furthermore, the negative chronotropic effect induced by 10(-4) M carbachol was also abolished by 10(-6) M 1 H-[1,2,4]oxadiazolo[4,3-alpha]quanoxalin-1-one, a selective guanylyl cyclase inhibitor. In addition, 10(-4) M 8-bromoguanosine 3':5'-cyclic monophosphate, a cell-permeable analogue of guanosine 3':5'-cyclic monophosphate, caused a negative chronotropic effect. These results suggest that the NO-signaling pathway may play an important role in the muscarinic cholinergic regulation of myocardial function.

Animals↗
PubMed1999

Encephalopathy associated with haemophagocytic lymphohistiocytosis following rotavirus infection.

UNLABELLED: A 2-year-old Japanese boy with a haemophagocytic lymphohistiocytosis (HLH) associated encephalopathy which developed after rotavirus infection is described. The neurological symptoms consisted of coma, seizures and spastic quadriplegia. On therapy with steroids, etoposide and cyclosporin A, the patient recovered without any neurological deficits. The interferon-gamma levels in serum and CSF were elevated at onset of the disease but had returned to normal at the time of clinical remission. Brain MRI revealed diffuse white matter abnormalities and parenchymal volume loss. Proton magnetic resonance spectroscopy revealed elevated lactate in the abnormal lesions observed on MRI, indicating that macrophages not exhibiting aerobic metabolism had infiltrated the CNS. At the time of clinical remission, the white matter abnormalities and brain lactate had disappeared. These findings suggested that the neurological symptoms resulted from the overproduction of cytokines by activated T-cells and macrophages. The pathophysiology of a HLH associated encephalopathy was considered to be a local immune response within the CNS, because interferon-gamma can induce the expression of major histocompatibility complex class I and II antigens on glial cells in the CNS. CONCLUSION: Haemophagocytic lymphohistiocytosis associated encephalopathy should be considered early in the differential diagnosis of cases with acute onset neuropathy.

Brain Diseases↗
PubMed1999

Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome.

We studied the circadian rhythm of serum melatonin levels in two patients with classical Rett syndrome having severe sleep disorders; serum melatonin levels were measured before and during melatonin treatment using radioimmunoassay. Patient 1 had a free-running rhythm of sleep-wake cycle from 3 years of age. At the age of 4 years, the peak time of melatonin was delayed 6 h compared to normal control and the peak value was at the lower limit. Patient 2 had a fragmented sleep pattern accompanied by night screaming from 1 year and 6 months of age. At the age of 10 years, the peak time of melatonin secretion was normal but the peak value was at the lower limit. These patients were given 5 mg melatonin orally prior to bedtime. Exogenous melatonin dramatically improved the sleep-wake cycle in patient 1. In patient 2, exogenous melatonin showed a hypnotic effect but early morning awakenings occurred occasionally. When melatonin treatment was stopped, the sleep disorders recurred and re-administration of 3 mg melatonin was effective in both patients. The effect was maintained over 2 years without any adverse effects. These findings suggests that sleep disorders in patients with Rett syndrome may relate with an impaired secretion of melatonin.

Adolescent↗