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Biomedical subjects

M Miyamoto

Publications and source records attributed to M Miyamoto.

At least 199 records · Page 11Linked to original sources
PubMed1997

Fourteen-day oral combination dose toxicity study of CGS 16949 A (aromatase inhibitor) with 5-fluorouracil or tamoxifen in rats.

CGS 16949A, an aromatase inhibitor, was administered orally to female rats at doses of 1 and 10 mg/kg/day alone and in combination with tamoxifen (0.5 or 5 mg/kg/day) or 5-fluorouracil (20 mg/kg/day) for 14 days. CGS 16949A and tamoxifen combination: Increased food intake and body weight noted after CGS 16949A treatment were also observed following combination treatment, though to a lesser degree. Most of the clinical pathological features noted following combination treatment were similar to those induced by single compound treatment. Gross pathological and histopathological changes ascribed to the antiestrogenic action of CGS 16949A, such as increased ovarian weight, decreased uterine weight, cystic follicles and atrophied uterus and vaginal epithelium, were alleviated by combination treatment, and were comparable in severity to those caused by tamoxifen alone. No severe toxic changes were induced by combination treatment. CGS 16949A and 5-fluorouracil combination: Increased body weight noted after CGS 16949A treatment was also observed following combination treatment, though to a lesser degree. Most of the changes caused by single compound treatment, including the aforementioned effects of CGS 16949A on the genital organs, were also noted following combination treatment. There was no evidence of enhancement of the effects by combination treatment.

Administration, Oral↗
PubMed1997

Comparison between the single deepest pocket and amniotic fluid index in predicting fetal distress in small-for-gestational age fetuses.

BACKGROUND: The relationship between reduced amniotic fluid volume and increased risk of fetal distress in small-for-gestational age fetuses is not yet clear. Furthermore, the criteria used for the diagnosis of 'oligohydramnios' are different between the single deepest pocket method and amniotic fluid index. We investigated the relationship between the single deepest pocket and amniotic fluid index and their ability in predicting fetal distress in small-for-gestational age fetuses. METHOD: We examined 69 pregnant women with singleton pregnancy, intact membranes, birth weight below the 50% percentile - 1.5 s.d., in whom delivery occurred within seven days of the last estimation of amniotic fluid volume. Amniotic fluid volume was measured in each woman simultaneously by single deepest pocket and amniotic fluid index. Fetal distress was determined by intrapartum monitoring of fetal heart rate. RESULTS: Estimates of amniotic fluid volume measured by the two methods showed a significant correlation at 24 to 41 weeks of gestation. A cut-off value for single deepest pocket of 3.0 cm was associated with the highest accuracy in predicting fetal distress in small-for-gestational age fetuses. The rate of cesarean section among patients with single deepest pocket <3.0 cm was higher than that in amniotic fluid index <8.0 cm. CONCLUSION: Our results demonstrated that a single deepest pocket measurement of <3 cm is the most useful criterion for 'oligohydramnios' in the prediction of fetal distress.

Amniotic Fluid↗
PubMed1997

Neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, in rats.

We examined the neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzaze pin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase (AChE) inhibitor in vitro and in vivo. TAK-147 showed a potent and reversible inhibition of AChE activity in homogenates of the rat cerebral cortex (IC50 = 51.2 nM), and was 3.0- and 2.4-fold more potent than tacrine and physostigmine, respectively. By contrast, TAK-147 was the least potent inhibitor of butyrylcholinesterase activity in rat plasma (IC50 = 23,500 nM). Tacrine and physostigmine inhibited butyrylcholinesterase activity potently and nonselectively. TAK-147 showed a moderate inhibition of muscarinic M1 and M2 receptor binding with K(i) values of 234 and 340 nM, respectively. TAK-147 showed very weak or no inhibition of high-affinity choline uptake, nicotinic receptor binding and choline acetyltransferase activity. In ex vivo experiments, oral administration of TAK-147 at doses ranging from 1 to 10 mg/kg induced a statistically significant and dose-dependent decrease in AChE activity in the cerebral cortex. Of the monoaminergic systems, TAK-147 moderately inhibited uptake of noradrenaline and serotonin with IC50 values of 4020 and 1350 nM, respectively. TAK-147 also inhibited ligand binding at alpha-1, alpha-2 and serotonin 2 receptors with K(i) values of 324, 2330 and 3510 nM, respectively, whereas it showed only weak activities on D1, D2 and serotonin 1A receptor bindings. Oral administration of TAK-147 (3 mg/kg) significantly accelerated the turnover rates of dopamine, noradrenaline and serotonin in the rat brain. These results suggest that TAK-147 activates the central cholinergic system by specific inhibition of AChE activity without affecting peripheral butyrylcholinesterase activity, and that TAK-147 also moderately activates the monoaminergic systems.

Acetylcholinesterase↗
PubMed1997

Suppression of tumour necrosis factor-alpha expression in leprosy skin lesions during treatment for leprosy.

The expression of tumour necrosis factor (TNF)-alpha in leprosy skin lesions was examined before and during successful treatment in a patient with borderline lepromatous leprosy. Before treatment, immunohistochemical staining of a skin biopsy specimen showed diffuse TNF-alpha deposits in granulomas and significant TNF-alpha deposits on infiltrated mononuclear cells. After 1 year's treatment, the skin lesions exhibited a reduction in granulomas, and a concomitant reduction in deposits of TNF-alpha. Furthermore, the level of expression of TNF-alpha messenger RNA, as examined using a reverse transcriptase-polymerase chain reaction method, was reduced markedly after treatment. These findings provide evidence for a correlation between the expression of TNF-alpha and disease activity suggesting that TNF-alpha is a useful prognostic indicator for inflammation in leprosy.

Aged↗
PubMed1997

[A case of recurrent IgA nephropathy following renal transplantation under tacrolimus (FK506)].

We report a case of recurrent IgA nephropathy following renal transplantation under tacrolimus (FK506). A 23-year-old female who had been diagnosed with IgA nephropathy was transplanted from her HLA two-mismatched mother under tacrolimus, prednisolone and azathioprine. Two years after transplantation, suddenly she noticed macroscopic hematuria. At that time, functional renal deterioration (serum creatinine: 2.3 mg/dl) and mild proteinuria were observed. Allograft biopsy disclosed acute cellular rejection. She was administered a bolus injection of methylprednisolone, 15-deoxyspergualin and anti-lymphocyte globulin. However, the response to the treatment was poor. A transplant biopsy revealed focal segmental glomerulosclerosis by PAS staining and granular IgA and C3 deposits on immunofluorescence examination. There was no sign of acute rejection and toxicity by tacrolimus. We diagnosed recurrent IgA nephropathy. At the present time, she has normal urinalysis and renal function is stable (serum creatinine: 1.9 mg/dl). No proteinuria was observed after total dosage of immunosuppressants was increased. Although recurrence of IgA nephropathy in renal allograft is frequent, allograft dysfunction is rare. However, IgA nephropathy has several types with different prognosis. For functional renal deterioration after renal transplantation, we should consider not only an acute rejection or the toxicity of immunosuppressants but also recurrent nephropathy.

Adult↗
PubMed1997

[Cerebral infarction due to stenosis of the bilateral internal carotid artery in Turner's syndrome].

A 43-year-old woman was admitted into our hospital because of aphasia and right hemiparesis. Computed tomographic scan demonstrated border zone infarction in the anterior and middle cerebral artery. Magnetic resonance imaging scans showed the borderline area between the terminal branches of the lenticulostriate arteries and the perforating branches of the middle cerebral artery. Digital subtraction ICA angiogram showed severe narrowing of the distal portion of the right and left ICA. A pattern analysis of ambulatory blood pressure monitoring (ABPM) was carried out in this patient, and it was showed "dipper type". Laboratory data was elevated excretion of pituitary gonadotropines and low estrogen excretion. Chromosome analysis revealed the 45, X/46, XX. She was diagnosed with mosaic type of Turner's syndrome. The cerebrovascular abnormality might be due to congenital hypoplasia of arteries, and declining of blood pressure during sleep was possible significant factors in the pathogenesis of cerebral infarction in this patient.

Adult↗
PubMed1997

Molecular cloning and characterization of the gene encoding 53 kD outer membrane protein of Porphyromonas gingivalis.

The pga53 gene which encoded the antigenic 53 kD outer membrane protein (Ag53) was isolated from a genomic DNA library of Porphyromonas gingivalis FDC381 by using an Ag53-immunized rabbit serum. Determination of its complete nucleotide sequence revealed that the precursor of Ag53 had a 50 amino-acid putative signal sequence and the mature protein of 448 amino acids. The deduced amino acid sequence after a 50 amino-acid putative signal sequence was in complete agreement with the first 20 N-terminal amino acids of purified Ag53. Analysis of the deduced amino acid sequence revealed the presence of a highly hydrophilic proline-rich region at the C-terminal of Ag53. The deduced amino acid sequence showed 29.9% homology with that of a 72 kD cell-surface protein in P. gingivalis. Southern hybridization revealed that pga53 was specific to several P. gingivalis strains and that P. gingivalis strains which did not possess Ag53 had genes homologous to pga53.

Amino Acid Sequence↗
PubMed1996

Relationship of impaired brain glucose metabolism to learning deficit in the senescence-accelerated mouse.

The relationship between brain glucose metabolism and learning deficit was examined in the senescence-accelerated-prone mouse (SAMP) 8, which has been proven to be a useful murine model of age-related behavioral disorders. SAMP8, 7 months old, exhibited marked learning impairment in the passive avoidance task, as compared with the control strain, senescence-accelerated-resistant mice (SAMR) 1. SAMP8 also exhibited a reduction in brain glucose metabolism, as indicated by a reduction in [14C]2-deoxyglucose accumulation in the brain following the intravenous injection impaired glucose metabolism correlated significantly with the learning impairment in all brain regions in SAMR1 and SAMP8. In the SAMP8, a significant correlation was observed in the posterior half of the cerebral cortex. These results suggest that the SAMP8 strain is a useful model of not only age-related behavioral disorders, but also glucose hypometabolism observed in aging and dementias.

Aging↗
PubMed1996

Contribution of sustained Ca2+ elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca2+ transient in vascular smooth muscle cells in coculture.

To elucidate the intracellular Ca2+ (Ca2+i ) transient responsible for nitric oxide (NO) production in endothelial cells (ECs) and the subsequent Ca2+i reduction in vascular smooth muscle cells (VSMCs), we administrated four agonists with different Ca2+i-mobilizing mechanisms for both cells in iso- or coculture. We monitored the Ca2+i of both cells by two-dimensional fura-2 imaging, simultaneously measuring NO production as NO2-. The order of potency of the agonists in terms of the peak Ca2+i in ECs was bradykinin (100 nM) > ATP (10 microM) > ionomycin (50 nM) > thapsigargin (1 microM). In contrast, the order in reference to both the extent of Ca2+i reduction in cocultured VSMCs and the elevation in NO production over the level of basal release in ECs completely matched and was ranked as thapsigargin > ionomycin > ATP > bradykinin. Treatment by NG-monomethyl-L-arginine monoacetate but not indomethacin or glybenclamide restored the Ca2+i response in cocultured VSMCs to the isoculture level. In ECs, when the Ca2+ influx was blocked by Ni2+ or by chelating extracellular Ca2+, all four agonists markedly decreased NO production, the half decay time of the Ca2+i degenerating phase, and the area under the Ca2+i curve. The amount of produced NO hyperbolically correlated to the half decay time and the area under the Ca2+i curve but not to the Ca2+i peak level. Thus, the sustained elevation of Ca2+i in ECs, mainly a result of Ca2+ influx, determines the active NO production and subsequent Ca2+i reduction in adjacent VSMCs. Furthermore, L-arginine but not D-arginine or L-lysine at high dose (5 mM) without agonist enhanced the NO production, weakly reduced the Ca2+i in ECs, and markedly decreased the Ca2+i in VSMCs, demonstrating the autocrine and paracrine effects of NO (Shin, W. S., Sasaki, T., Kato, M., Hara, K., Seko, A., Yang, W. D., Shimamoto, N., Sugimoto, T., and Toyo-oka, T. (1992) J. Biol. Chem. 267, 20377-20382).

Animals↗
PubMed1996

Inflammatory cytokine production induced by an analogue of muramyl dipeptide MDP-Lys(L18) in rat macrophage cultures and dog synovial fluid.

To examine the involvement of cytokines in the mechanisms of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18)-induced arthritis, we analyzed interleukin-1 (IL-1), tumor necrosis factor (TNF), colony-stimulating factor (CSF), and neutrophil chemotactic factor (NCF) by bioassays in the rat macrophage-conditioned medium (Mluminal diameter-CM) stimulated by MDP-Lys(L18) in vitro and the synovial fluid from dogs treated subcutaneously with MDP-Lys(L18) for 14 days in vivo. The dog showed arthritis characterized by swelling of the knee joint, increased synovial fluid and thickened synovial membrane, and a single subcutaneous injection of MDP-Lys(L18) was previously shown to induced synovitis in rat tarsal joint. IL-1, TNF, CSF, and NCF activities in Mluminal diameter-CM were increased by MDP-Lys(L18), while only NCF activity was detected in the dog synovial fluid. Partial purification procedures revealed that NCF in Mluminal diameter-CM was not leukotriene B4 but a protein having heparin-affinity, and, in addition, immuno-reactive IL-8 was evident to be in Mluminal diameter-CM. The NCF activity in the dog synovial fluid was not inhibited by dialysis, showing that NCF is a protein substance, possibly a chemokine. These results suggest that MDP-Lys(L18) produces a chemokine, such as IL-8, which recruits neutrophils to the synovial membrane for subsequent development of synovitis in rats and dogs.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

Identification of peptides mimicking the antigenicity and immunogenicity of conformational epitopes on Japanese encephalitis virus protein using synthetic peptide libraries.

Monoclonal antibodies (mAbs) N.03 and N.08 that recognize conformational epitopes on the prM protein of Japanese encephalitis virus (JEV) were analyzed to identify their peptide ligands by using a novel approach that combined two different synthetic peptide libraries. Immunoscreening of a library containing 20(5) sequences of pentapeptides revealed that the ligands for N.03 and N.08 had motif sequences, (Y/W/F)GG(I/L/M) and (N/Q)WY(D/E), respectively. To select higher-affinity ligands, we synthesized and screened another type of library with 20 peptide mixtures that were based on the identified motif, where only one amino acid position was defined; and the process was reiterated for the remaining undefined positions. Consequently, the peptides YGGIYMNG and QWYDDR were identified as peptide ligands of N.03 and N.08, respectively. These peptides bound specifically to the antigen-combining sites of the mAbs as confirmed by competitive binding assays. Mouse antisera directed against the peptide YGGIYMNG specifically recognized JEV, while those against QWYDDR did not. These data demonstrated that peptide ligands which reproduce or mimic the immunogenicity as well as the antigenicity of conformational epitopes can be at least partly identified using this approach. This approach may be useful for analyzing conformational epitopes, which are generally difficult to characterize, and might provide a step toward vaccine development when applied to protective mAbs.

Antigens, Viral↗
PubMed1996

EM523L, a nonpeptide motilin agonist, stimulates gastric emptying and pancreatic polypeptide secretion.

We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

Adult↗
PubMed1996

Neurotoxicity of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine, a potent agonist for class II metabotropic glutamate receptors, in the rat.

Neurotoxicity of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), a potent agonist for metabotropic glutamate receptors negatively coupled to adenylyl cyclase, was investigated in vivo by the intraventricular administration in the rat, compared with that of (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I) and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]. Neither L-CCG-I nor (1S,3R)-ACPD caused any apparent pathological change in the brain at an intraventricular dose of 1 mumol, whereas DCG-IV induced selective neuronal damage in some rats at higher doses than 3 nmol. The neurotoxicity was intensified in a dose-dependent manner, and at a dose of 50 nmol DCG-IV caused repetitive seizures and selective neuronal damage in all cases. Neuronal damage was pronounced in the cingulate cortex, lateral septum and hippocampus, and a few degenerating neurons were observed also in other brain areas, such as the striatum, thalamus or neocortex. Since DCG-IV activates N-methyl-D-aspartate-type receptors as well at relatively high concentrations, the protective effect of a competitive antagonist for N-methyl-D-aspartate receptors, 3-[(RS)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP), was examined on the neurotoxicity of DCG-IV. Although a combined treatment with CPP (0.1 nmol) completely blocked the neurotoxicity of N-methyl-D-aspartate (100 nmol), at least 3 nmol of CPP was necessary to decrease the neurotoxicity of DCG-IV (50 nmol) to a considerable extent. The synergistic activation of metabotropic glutamate receptors and N-methyl-D-aspartate receptors is suggested as a possible mechanism underlying the selective neuronal damage induced by DCG-IV, although a direct participation of metabotropic glutamate receptors in glutamate neurotoxicity is not deniable.

Animals↗
PubMed1996

HLA-DM gene polymorphisms in atopic dermatitis.

HLA-DM molecules are involved in the antigen-processing pathway of HLA class II-restricted antigen presentation. We investigated polymorphisms of HLA-DM genes in atopic dermatitis by using the polymerase chain reaction-restriction-fragment length polymorphism method to examine a possible contribution of these genes to the pathogenesis of atopic dermatitis. Genomic DNA was extracted from 37 Japanese patients with atopic dermatitis and 52 control subjects. After polymerase chain reaction amplification of the polymorphic third exon of DMA and DMB genes, amplified products were digested with restriction endonucleases to determine HLA-DM alleles. FokI, HinfI, AciI and SfaNI were used for DMA; HhaI, BsrI, ApaLI, and Bsp1286I for the DMB gene. We identified three DMA alleles and also three DMB alleles. One of 37 patients possessed the DMA*0103 allele, which has been reported as a rare allele in Caucasian populations. Any DMA and DMB alleles were not increased in the patients. The DMA*0102 allele was estimated to constitute a haplotype with DRB1*1201/DQB1*0301 and DRB1*0901/DQB1*0301 in a Japanese population. HLA-DM genes are not considered to contribute primarily to the susceptibility of atopic dermatitis. Further investigation of the functional roles of HLA-DM gene polymorphisms will be useful for a better understanding of susceptibility loci in HLA class II-associated disease.

Adolescent↗
PubMed1996

CCK-4-induced calcium mobilization in T cells is enhanced in panic disorder.

We investigated the effects of brain cholecystokinin (CCK) receptors on the intracellular calcium concentration and protein kinase C in human T cells. CCK-4 produced a transient increase in calcium in the absence of extracellular calcium. CCK-B agonists stimulated calcium mobilization in a dose-dependent manner in T cells. CCK-B antagonists suppressed CCK-4-induced calcium mobilization more potently than CCK-A antagonist. The recovery of desensitization of the CCK-4-induced response was delayed by phosphoserine/phosphothreonine phosphatase inhibitor, calyculin A. The responsiveness to CCK-4 was also reduced by phorbol 12,13-dibutyrate (PDBu), and this effect of PDBu was abolished completely by preincubation with staurosporine. CCK-4-induced calcium mobilization was too small to attribute the desensitization to the protein kinase C transduction pathway. T cells from patients with untreated panic disorder exhibited significantly higher cholecystokinin-4-induced calcium mobilization than those from healthy controls or patients with treated panic disorder. These results suggest that cholecystokinin-B receptor function in T cells of patients with panic disorder is enhanced. Cholecystokinin-4-induced calcium mobilization in T cells may be state dependent and useful as a biological marker of panic disorder.

Adult↗
PubMed1996

Routine low and high resolution typing of the HLA-DRB gene using the PCR-MPH (microtitre plate hybridization) method.

We describe HLA-DRB1 typing using polymerase chain reaction-based microtitre plate hybridization (PCR-MPH), which can process large numbers of samples. MPH typing is similar to an enzyme-linked immunosorbent assay (ELISA), in which a tandemly ligated sequence-specific oligonucleotide is immobilized on microtitre wells. The typing procedure consisted of two steps. In the first, PCR-MPH with 16 probes was performed to determine the specificities of the serological levels (DR1, DR2, DR3, DR4, DR11, DR12, DR13, DR14, DR7, DR8, DR9 and DR10) after generic amplification ("low resolution typing'). In the second step, DR1, DR2, DR4, DR12/8 and DR3/11/13/14 were group-specifically amplified based on the results of the first PCR-MPH, and microtitre plate hybridization proceeded in a similar manner to the first step ("high resolution typing'). Low resolution typing was completed within 2 h after generic amplification, and the results of high resolution typing were obtained in another 3.5 h after amplification. The allelic types classified using PCR-MPH were completely concordant with those obtained by PCR-single-strand conformation polymorphism or PCR-restriction fragment length polymorphism.

HLA-DR Antigens↗