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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 523 records · Page 29Linked to original sources
PubMed1993

Expression of platelet-derived growth factor beta receptor on human monocyte-derived macrophages and effects of platelet-derived growth factor BB dimer on the cellular function.

Platelet-derived growth factor (PDGF) plays an important role in the process of atherosclerosis which is characterized by the presence of macrophage-derived foam cells. In the present study, the induction of the mRNA of PDGF-beta receptor was demonstrated during cell differentiation of human monocyte-macrophages, whereas no mRNA was detected in the cells during the early days of culture. Flow cytometry analysis using antibodies specific for PDGF-beta receptor and CD14 showed the presence of both PDGF-beta receptor and CD14 on human monocyte-derived macrophages, whereas no PDGF-beta receptor was detected on human monocytes 4 h after cell adhesion to a culture dish. In the binding assay of PDGF-BB on human monocyte-derived macrophages, a saturable and high affinity binding site with Kd of 27.5 pM and Bmax of 23.3 fmol/mg of cell protein was demonstrated. When human monocytes were cultured in the presence of the protein kinase C inhibitor staurosporine, PDGF-beta receptor induction was inhibited, and tetradecanoylphorbol acetate enhanced PDGF-beta receptor expression in human monocyte-derived macrophages, indicating that PDGF-beta receptor expression is associated with maturation and differentiation of monocyte-macrophages through the activation of protein kinase C. In response to PDGF-BB homodimer, PDGF-beta receptor was phosphorylated, and thymidine uptake and inositol trisphosphate production were stimulated in monocyte-derived macrophages. Furthermore, PDGF-BB suppressed the production of macrophages colony-stimulating factor in macrophages. The expression of PDGF-beta receptor on human monocyte-derived macrophages suggests that PDGF influences the process of atherosclerosis by regulating the function of macrophages as well as smooth muscle cells in the vascular wall.

Animals↗
PubMed1993

Induction of trypsin-induced hyperexcitability in the rat hippocampal slice is blocked by the N-methyl-D-aspartate receptor antagonist, MK-801.

Bath application of trypsin (0.05%, type I) gave rise to epileptiform activities in CA1 of the rat hippocampal slice. A non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, MK-801, blocked the induction of the epileptiform activity, whereas a competitive antagonist, D-APV, showed weak antagonism on the induction of the epileptiform activity. These results may lead us to the understanding of the role of NMDA receptors in the neurotoxic action of trypsin.

2-Amino-5-phosphonovalerate↗
PubMed1993

Overexpression of human lipoprotein lipase in transgenic mice. Resistance to diet-induced hypertriglyceridemia and hypercholesterolemia.

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. To determine the role of LPL in lipoprotein metabolism, we established three transgenic mouse lines overexpressing the human LPL gene; the highest expressor line, which transcribed human LPL mRNA in the heart, skeletal muscles, and adipose tissue, was used in this study. The transgenic mice had 5- and 1.7-fold higher LPL activity in adipose tissue and post-heparin plasma, respectively. Plasma triglyceride levels in transgenic mice were 24.2% of that in control mice, and gel filtration chromatography showed that very low density lipoprotein (VLDL) triglycerides were much reduced in transgenic mice. In the chemical analysis of plasma lipoproteins isolated by ultracentrifugation, we found that LDL particles were cholesterol-rich and HDL2 cholesterol was increased 1.4-fold in transgenic mice as compared to control mice. When we injected 125I-VLDL intravenously into transgenic mice, the clearance of 125I-VLDL and the conversion of VLDL to LDL was markedly enhanced as compared to control mice. Furthermore, the clearance of chylomicrons, estimated by both the fat loading and retinyl palmitate loading tests, was significantly enhanced in transgenic mice. After sucrose feeding, no increase in VLDL was observed in transgenic mice. When fed a high cholesterol diet, the development of hypercholesterolemia was suppressed in transgenic mice. These results suggested that LPL determined not only hydrolysis of triglyceride-rich lipoproteins but also lipolytic conversion, and that overexpression of LPL acted to protect against diet-induced hypertriglyceridemia as well as hypercholesterolemia.

Actins↗
PubMed1993

Cholesteryl ester transfer protein deficiency caused by a nonsense mutation detected in the patient's macrophage mRNA.

Cholesteryl ester transfer protein (CETP) deficiency causes marked elevation of plasma high-density lipoproteins, termed hyperalphalipoproteinemia. Only one CETP mutation has been found previously, partly because the relative unavailability of CETP mRNA has hampered analysis. We demonstrated CETP mRNA expression in the monocyte-derived macrophages and identified a new CETP mutation by analyzing the macrophage mRNA of a homozygous patient with familial form of hyperalphalipoproteinemia. The nonsense mutation at codon 309 in exon 10 of the CETP gene was thought to delete the carboxy-terminal third and caused a decrease in the level of CETP mRNA. Our findings provide more evidence that CETP mutations may underlie a subset of familial hyperalphalipoproteinemia.

Base Sequence↗
PubMed1993

Inositol trisphosphate receptor and Ca2+ signalling.

Inositol 1,4,5-trisphosphate (InsP3) is a second messenger that releases Ca2+ from the intracellular stores. The InsP3 receptor (InsP3-R) was purified and its cDNA was cloned. We have found that InsP3-R is identical to the P400 protein identified as a protein enriched in the cerebellar Purkinje cells. We generated an L fibroblast cell transfectant that produced cDNA derived InsP3-R. The expressed protein displays high affinity and specificity for InsP3. InsP3 induces Ca2+ release from the membrane vesicles of the transfected cells. Incorporation of purified InsP3-R into a lipid bilayer showed InsP3 induced Ca2+ release. These result suggest that InsP3-R is a Ca2+ release channel. Immunogold method using monoclonal antibodies against the receptor showed that it is highly condensed on the smooth surfaced endoplasmic reticulum (ER) and slightly on the outer nuclear membrane and rough ER. Cross linking experiments show that the InsP3-R forms a homotetramer. The approximately 650 N-terminal amino acids are highly conserved between mouse and Drosophila melanogaster, and this region has the critical sequences for InsP3 binding. We found novel subtypes of the InsP3-R resulting from RNA-splicing that are expressed in a tissue-specific and developmentally specific manner and also resulting from different genes. It is believed that there are two Ca2+ release mechanisms, InsP3-induced Ca2+ release (IICR) and Ca(2+)-induced Ca2+ release (CICR). Eggs are good materials to analyse the machanism of Ca2+ signalling: fertilized hamster eggs exhibit repetitive Ca2+ transients as well as the Ca2+ wave.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells.

Two novel tyrosine kinase cDNAs were obtained from murine mast cells. These kinases, Emb and Emt, constitute a novel tyrosine kinase subfamily which may also include Tec, a kinase preferentially expressed in liver, and Dsrc28, a fruit fly kinase. Both lack hydrophobic stretches characteristic of the transmembrane domains found in growth factor receptor tyrosine kinases and carboxyl-terminal, negative regulatory tyrosine residue found in Src family kinases. In addition to the Src homology region 2 (SH2) and SH3 domains characteristic of the Src family kinases and other signaling molecules, Emb and Emt share a similar amino-terminal domain comprised mainly of two repeat segments. The emb 2.7-kb transcript was expressed in mast cells, myeloid cells and B lymphocytes while the emt 4.6-kb mRNA in mast cells, myeloid cells and T lymphocytes. The evidence for in vitro tyrosine kinase activity of Emb and Emt proteins is also provided.

Amino Acid Sequence↗
PubMed1993

The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis.

The glycosylphosphatidylinositol (GPI) anchor is a membrane attachment structure of many proteins and occurs in a wide variety of eukaryotes from yeasts to mammals. The structure of the core of the GPI anchor is conserved in protozoa and mammals and so is its biosynthetic pathway. A complementary DNA encoding a human protein termed PIG-A (phosphatidylinositol glycan-class A) was cloned. PIG-A was necessary for synthesis of N-acetylglucosaminyl-phosphatidylinositol, the very early intermediate in GPI-anchor biosynthesis.

Amino Acid Sequence↗
PubMed1993

A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylamide).

Poly(N-isopropyl acrylamide) (PIPAAm) demonstrated a fully expanded chain conformation below 32 degrees C and a collapsed, compact conformation at high temperatures. This unique temperature responsive polymer was grafted onto surfaces of commercial polystyrene dishes and used as temperature switches for creating hydrophilic surfaces below 32 degrees C and hydrophobic surfaces above 32 degrees C. Cell attachment and the growth of bovine endothelial cells and rat hepatocytes on PIPAAm-grafted surfaces at 37 degrees C demonstrated similar behavior to the commercialized culture dishes. Both cell types were observed to detach from the PIPAAm-grafted surface simply by reducing the temperature below the polymer transition temperature (collapse). Cells recovered by this method maintained substrate adhesivity, growth, and secretion activities nearly identical to those found in primary cultured cells in contrast to the compromised function found in cultured cells damaged by trypsinization. These results provide strong evidence that PIPAAm-grafted surfaces, as thermal switches are very effective for reversing cell attachment and detachment without cell damage. Properties of cell culture surfaces can be readily transformed by this technique reversibly into hydrophilic and hydrophobic coatings of PIPAAm-grafted polymers.

Acrylic Resins↗
PubMed1993

Effects of two substituted hydrazine monoamine oxidase (MAO) inhibitors on neurotransmitter amines, gamma-aminobutyric acid, and alanine in rat brain.

Time- and dose-response analyses were undertaken to investigate the effects of the substituted hydrazine monoamine oxidase (MAO) inhibitors iproniazid and nialamide on the following: MAO-A and -B activity; levels of gamma-aminobutyric acid (GABA), alanine (ALA), and the neurotransmitter amines dopamine, noradrenaline, and 5-hydroxytryptamine (serotonin) and their acid metabolites; and the activity of GABA-transaminase and ALA-transaminase. The results showed that these drugs are relatively potent MAO inhibitors but, unlike the unsubstituted hydrazine MAO inhibitor phenelzine, they do not produce increased GABA and ALA levels in brain. These experiments suggest that a free hydrazine group is necessary for MAO inhibitors to also have marked effects on GABA and ALA.

Alanine↗
PubMed1993

Antiepileptogenic action of 7-chlorokynurenic acid on amygdala kindling of rats.

To investigate the role of strychnine-insensitive glycine receptors in epilepsy, we studied the effects of 7-chlorokynurenic acid (7-CK), a selective strychnine-insensitive glycine receptor antagonist, on amygdala kindling development and previously amygdala-kindled seizures in rats. ICV administration of 7-CK (10 or 20 micrograms) suppressed amygdala kindling development, according to the motor seizure stage and afterdischarge development, in a dose-dependent manner. However, 7-CK had no significant effect on previously kindled seizures at either of these doses nor did 20 micrograms at any time (15 min, 30 min, 2 h, and 24 h) after injection studied. These results demonstrate that this selective strychnine-insensitive glycine receptor antagonist has antiepileptogenic activity and suggest a role for the glycine receptors in the contribution of the NMDA receptor complex to epileptogenic events.

Amygdala↗
PubMed1993

Magnetic resonance imaging of pericardial malignant mesothelioma.

Magnetic resonance imaging of pericardial malignant mesothelioma in two patients is reported. Magnetic resonance imaging clearly depicted the tumor location and expansion, and was useful in delineating the anatomic extent of pericardial malignant mesothelioma.

Adult↗
PubMed1993

Difference in 201Tl accumulation on single photon emission computed tomography in benign and malignant thoracic lesions.

The difference in 201Tl-chloride (201Tl) accumulation on single photon emission computed tomography (SPECT) between 58 benign (58 cases) and 48 malignant (46 cases) thoracic lesions, each of more than 20 mm in diameter was investigated. In the 34 benign and 48 malignant lesions depicted in both early (15 min) and delayed (3 h) images there was no significant difference in the mean early and delayed uptake ratios of lesion to normal contralateral lung between benign and malignant. However, the retention index in the lesion derived from (delayed ratio--early ratio)/(early ratio) x 100% showed a significant difference (benign -4.30 +/- 13.6% versus malignant 23.3 +/- 18.9%, P < 0.01), indicating the poor 201Tl retention in the benign lesions. Using the criteria of nondepiction in the delayed image or a negative retention index, 81.1% accuracy and 95.2% predictive value for diagnosis of benign lesions were obtained. Thus, 201Tl SPECT appears to have potential usefulness in the diagnosis of benign thoracic lesions.

Adenocarcinoma↗
PubMed1993

Effects of emergency coronary angioplasty on left ventricular volume after acute myocardial infarction compared with intracoronary thrombolysis.

BACKGROUND: The effects of emergency coronary angioplasty on left ventricular remodeling have not been fully evaluated. We compared the effects of emergency coronary angioplasty on left ventricular volume with those of intracoronary thrombolysis in patients suffering from their first acute myocardial infarction (AMI). METHODS: A total of 51 patients who had a culprit lesion at site No 6 of the American Heart Association (AHA) classification were analyzed. Patients with re-obstruction of the culprit lesion after reperfusion were excluded from the study. The coronary angioplasty and the thrombolysis groups consisted of 28 and 23 patients, respectively. Left ventricular volume was measured by left ventriculography at 4 weeks after infarction. RESULTS: Clinical and angiographic background factors showed no significant differences between these two groups. The left ventricular end-systolic volume index was significantly smaller in the angioplasty group than in the thrombolysis group (31 +/- 14 versus 45 +/- 14 ml/m2, P < 0.01). Similarly, the left ventricular end-diastolic volume index was significantly smaller in the angioplasty group (64 +/- 13 versus 82 +/- 13 ml/m2, P < 0.01). Conversely, the left ventricular ejection fraction was larger in the angioplasty group than in the thrombolysis group (54 +/- 13 versus 45 +/- 13%, P < 0.05). Multivariate analysis revealed that the selection of coronary angioplasty was one of the factors significantly associated with a decrease in left ventricular end-systolic and end-diastolic volume. CONCLUSION: These results suggest that emergency coronary angioplasty produces better left ventricular remodeling than intracoronary thrombolysis after AMI.

Adult↗
PubMed1993

Changes in the frequency distribution pattern of body weight in patients with major depression.

To compare the frequency distribution of body weight of the depressed patients with that of a standard group and to evaluate the change in distribution during treatment, body weight was measured in 106 depressed inpatients with major depressive disorder as defined by DSM-III criteria both on admission and on discharge. The body weight distribution in the depressed patients skewed towards a high frequency of lower weights on admission but shifted to the normal pattern on discharge. In women, this tendency was more obvious and was statistically significant. The body weight distribution in the depressed patients with melancholia maintained high frequencies of lower body weight on discharge, while that in those without melancholia did not, suggesting that there could be a difference in the pattern of body weight distributions between those with endogenous and nonendogenous depression. Three tricyclic antidepressants examined (imipramine, clomipramine and desipramine) did not seem to have the side effect of pathological weight gain in the frequency distribution pattern.

Adult↗
PubMed1993

Repirinast inhibits antigen-induced early and late pulmonary responses and airway hyperresponsiveness in guinea pigs.

The antiallergic drug repirinast (30 mg/kg i.p.) significantly inhibited antigen-induced early and late pulmonary responses in guinea pigs. The same dose of repirinast significantly inhibited bronchoalveolar lavage eosinophilia and neutrophilia 5 h after antigen challenge (at the peak of the late response). Histologic examination revealed that repirinast markedly inhibited leukocyte (predominantly eosinophils) infiltration into bronchial tissue. Repirinast also blocked antigen-induced airway hyperresponsiveness to inhaled acetylcholine. The inhibitory effect of repirinast on the infiltration of eosinophils and/or neutrophils into the airway may reflect the inhibition of late pulmonary response and airway hyperresponsiveness.

Airway Resistance↗