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M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 253 records · Page 14Linked to original sources
PubMed1998

[An autopsy case of poisoning by neuropsychopharmaceuticals including zopiclone].

We report here a suicide case involving neuropsychopharmaceuticals. The deceased was a 30-year-old housewife, 151 cm in height and 46.0 kg in weight. Macroscopically, slight lung congestion and edema and slight brain edema were noted. The stomach contained approximately 200 ml of a greenish-brown material with many solid granules. Toxicological analysis demonstrated 44.9 micrograms/ml of zopiclone (ZP), 12.8 micrograms/ml of phenobarbital (PB), 10.9 micrograms/ml of chlorpromazine (CPZ), and 4.8 micrograms/ml of promethazine (PM) in the gastric contents; 0.5 microgram/ml of ZP, 8.6 micrograms/ml of PB, 0.2 microgram/ml of CPZ, and 0.3 microgram/ml of PM in the serum; and 43.0 micrograms/ml of ZP, 8.1 micrograms/ml of PB, 1.3 micrograms/ml of CPZ, and 1.3 micrograms/ml of PM in the urine. On the basis of these findings, the cause of death was considered to be neuropsychopharmaceutical poisoning; ZP was most probably responsible for her death.

Adult↗
PubMed1997

A Humanized Anti-c-erbB-2 Monoclonal Antibody for the Treatment of Breast Cancer.

The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers that overxpress the c-erbB-2 gene. Its overexpression is also speculated to be correlated with chemoresistance to doxorubicin. The in vitro and in vivo anti-tumor effects of a humanized antibody directed against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 had direct antiproliferative activity against the SK-BR-3 cell line which overexpresses c-erbB-2. The in vivo treatment, using rhu4D5, of SCID mice carrying xenografts of 4-1ST human gastric carcinoma, which overexpresses c-erbB-2, revealed that the recombinant protein had potent anti-tumor activity. Furthermore, the cytotoxic action of human peripheral blood mononuclear cells against the SK-BR-3 cell line was significantly augmented with the administration of rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might be a more efficacious treatment than previously predicted by preclinical studies.

Journal Article↗
PubMed1997

Remodeling of glycoconjugates on CD44 enhances cell adhesion to hyaluronate, tumor growth and metastasis in B16 melanoma cells expressing beta1,4-N-acetylglucosaminyltransferase III.

Beta1-4 N-acetylglucosaminyltransferase III (GnT-III) synthesizes bisecting N-acetylglucosamine structures on asparagine-linked oligosaccharides. Using B16-hm mouse melanoma cells stably expressing GnT-III activity as positive transfectants, the effect of bisecting N-acetylglucosamine on the function of CD44 was analyzed in association with adhesion to hyaluronate and tumor spread in mice. Transfection of GnT-III caused increased affinity of immunoprecipitated CD44 to erythro-agglutinating phytohemagglutinin, that preferentially recognizes bisecting N-acetylglucosamine, without affecting the surface CD44 amount, indicating an increase in bisecting N-acetylglucosamine residues on CD44 in positive transfectants. CD44-mediated adhesion to immobilized hyaluronate and the binding of fluorescence-labeled hyaluronate to the cell surface were increased in positive transfectants. The enhanced adhesion in positive transfectants was suppressed by the treatment with beta-N-acetylhexosaminidase, indicating that N-acetylglucosamine residues were responsible for the enhanced adhesion. Positive transfectants showed promoted CD44-mediated tumor growth and metastatic development in the spleen after subcutaneous inoculation into mice. These results indicate that glycosylation of CD44 due to GnT-III causes enhanced adhesion to hyaluronate, local tumor growth and metastatic growth in spleen, suggesting that the CD44-mediated adhesion and tumor spread can be modified through introduction of a glycosyltransferase gene.

Acetylglucosamine↗
PubMed1997

Detection of Borna disease virus genome in normal human brain tissue.

Borna disease virus (BDV), a neurotropic virus naturally infecting horses and sheep, has been suggested to be associated with human psychiatric disorders. Thus far no extensive studies have been done, providing the evidence of BDV genome in normal human brain tissue. We therefore examined four brain regions of 30 normal autopsy brains for BDV p24 genome. By highly sensitive nested reverse transcriptase (RT)-mediated PCR analysis, we found positive PCR products in two brains: one in frontal and temporal cortices and hippocampus and another in frontal cortex and olfactory bulb. Our results suggest that BDV can infect human brain tissue latently, without causing an apparent neuropsychiatric disorder.

Adult↗
PubMed1997

Lack of effect of transmembrane gradient of magnesium and sodium on regulation of cytosolic free magnesium concentration in rat lymphocytes.

The regulation of the intracellular concentration of Mg2+ ([Mg2+]i) is not fully understood. The level of Mg in lymphocytes is a good predictor of total body Mg status. We measured [Mg2+]i and total Mg in rat lymphocytes by using, respectively, the fluorescent Mg2+ indicator mag-fura-2 and atomic absorption spectrophotometry. The basal [Mg2+]i in rat lymphocytes was 328 +/- 23 micromol/l. An elevation to 5 mmol/l or the removal of extracellular Mg2+ did not affect [Mg2+]i. A reduction in extracellular Na+ did not influence [Mg2+]i for 60 min. The total Mg concentration in lymphocytes also remained stable. Results suggest that the permeability of the plasma membrane to Mg2+ is very low, and that Na+/Mg2+ exchange is not involved in the regulation of [Mg2+]i in rat lymphocytes.

Animals↗
PubMed1997

Reduction in the ratio of beta-preprotachykinin to preproenkephalin messenger RNA expression in postmortem human putamen during aging and in patients with status lacunaris. Implications for the susceptibility to parkinsonism.

Gamma-aminobutyric acid (GABA)/substance P (SP) neurons and GABA/enkephalin (Enk) neurons in the striatum exert opposing influence on the regulation of movement. The loss of GABA/SP neurons results in hypokinetic disorders (parkinsonism), whereas the loss of GABA/Enk neurons results in hyperkinetic disorders (e.g. chorea). The present study determined age-related changes in the beta-preprotachykinin (the precursor of SP) and preproenkaphalin (the precursor of Enk) messenger RNA (mRNA) ratio in the postmortem human putamen using the reverse transcription-polymerase chain reaction (RT-PCR). The ratio of beta-preprotachykinin to preproenkephalin mRNA expression decreased with age. The reduction in the beta-preprotachykinin/preproenkephalin mRNA ratio was more marked in cases with multiple small infarcts (status lacunaris) in the putamen. These findings may in part explain the susceptibility of the elderly, particularly of those with ischemic changes in the striatum to hypokinetic disorders.

Adult↗
PubMed1997

Hyperventilation as a specific test for diagnosis of coronary artery spasm.

The hyperventilation test has been used as a clinical tool to induce coronary spasm. However, its diagnostic and prognostic values have not been fully elucidated. This study was designed to establish the sensitivity and specificity of the hyperventilation test and to clarify the characteristics of hyperventilation test-positive patients. We examined 206 patients in whom coronary spasm was documented by angiography (spasm group), and 183 patients without angina at rest in whom acetylcholine failed to induce spasm (nonspasm group). All patients performed vigorous hyperventilation for 6 minutes in the early morning. Of the spasm group patients, 127 showed positive responses to the test, including ST elevation (n = 111), ST depression (n = 15) and negative U wave (n = 1). None in the nonspasm group showed any ischemic electrocardiographic change. Thus, the sensitivity and specificity of this test for diagnosis of coronary spasm were 62% and 100%, respectively. In the spasm group, there were no significant differences between hyperventilation test-positive and test-negative patients in age, sex, the prevalence of hypertension, diabetes mellitus, obesity, smoking, and the number of diseased vessels. When clinical characteristics were compared, the proportions of the patients with high disease activity (> or =5 attacks a week), with severe arrhythmias (second- or third-degree atrioventricular block and/or ventricular tachycardia) during attacks, and with multivessel spasm were significantly higher in the hyperventilation test-positive patients than in the negative patients (69% vs 20%, p <0.0001; 31% vs 11%, p <0.005; and 58% vs 34%, p <0.01, respectively). These findings imply that hyperventilation is a highly specific test for the diagnosis of coronary artery spasm, and that hyperventilation test-positive patients are likely to have life-threatening arrhythmias during attacks and multivessel spasm.

Adult↗
PubMed1997

Extracellular Mg2+ inhibits capacitative Ca2+ entry in vascular smooth muscle cells.

BACKGROUND: Agonist-induced Ca2+ entry is thought to be mediated by capacitative Ca2+ entry other than L-type Ca2+ channels in vascular smooth muscle cells (VSMCs). The mechanism for capacitative Ca2+ entry has not been fully elucidated. Our objective was to examine the effect of external Mg2+ on capacitative Ca2+ entry in cultured rat aortic VSMCs. METHODS AND RESULTS: Three doses of external Mg2+ concentration (nominally 0, 1, and 5 mmol/L) were used. After exposure to 1 mumol/L, angiotensin II (Ang II) in Ca(2+)-free medium, addition of Ca2+ to the medium caused an increase in cytosolic free Ca2+ concentration ([Ca2+]i), indicating Ang II-induced Ca2+ influx. This Ca2+ influx was attenuated in cells preincubated with high external Mg2+ concentrations or with 1 mumol/L nifedipine. After VSMCs in Ca(2+)-free medium were exposed to 1 mumol/L thapsigargin, which inhibits the sarcoplasmic reticulum Ca(2+)-ATPase and depletes Ca2+ stores, addition of Ca2+ to the medium induced an increase in [Ca2+]i, indicating capacitative Ca2+ entry. This entry pathway was found to be independent of dihydropyridine-sensitive Ca2+ channels and inhibited by increased external Mg2+ concentration. External Mg2+ concentration did not influence Ca2+ efflux across the plasma membrane after stimulation with Ang II plus thapsigargin. CONCLUSIONS: Results suggest that in VSMCs, capacitative Ca2+ entry is reduced by external Mg2+. This mechanism may explain in part the inhibitory effect of external Mg2+ on Ca2+ handling.

Angiotensin II↗
PubMed1997

Expression of alpha and beta genes of human chorionic gonadotropin in lung cancer.

To confirm the ectopic production of human chorionic gonadotropin (hCG) in lung cancer, we attempted to detect the presence of mRNA transcripts of the alpha and beta genes for hCG in lung cancer tissues obtained from surgical operations. Although we were able to show the presence of hCG beta mRNA transcripts in lung cancer tissue by Northern blot, the sensitivity of the assay was too low for a precise analysis of hCG beta mRNA transcripts in most lung cancers. Using reverse transcription PCR (RT-PCR) and Southern blot analysis, however, various amounts of mRNA transcripts of hCG beta genes 3, 5, 7 and 8 were demonstrated in 9 of the 14 lung cancer tissues examined, while no mRNA transcripts were detectable in 12 normal lung tissues from the same patients. Our results are consistent with a clear difference in serum and urinary hCG beta levels observed between normal subjects and lung cancer patients. The expression of the hCG alpha gene, however, was detected in normal lung tissues more frequently than in lung cancer tissues using RT-PCR Southern blot. Our results strongly suggest the production of hCG beta as being part of the phenotype of malignantly transformed lung cells and further strengthen its superior specificity over intact hCG or hCG alpha as a tumor marker for lung cancers.

Aged↗
PubMed1997

Amyloid beta-protein deposition in the leptomeninges and cerebral cortex.

To further investigate the process of amyloid beta-protein (Abeta) deposition, we determined, using sensitive enzyme immunoassays, the levels of Abeta40 and Abeta42 (Abetas) in the soluble and insoluble fractions of the leptomeninges (containing arachnoid mater and leptomeningeal vessels) and cerebral cortices from elderly control subjects showing various stages of Abeta deposition and from patients affected by Alzheimer's disease (AD). In both locations, insoluble Abeta levels were higher by orders of magnitude than soluble Abeta levels. Soluble Abeta levels in cortices were much lower than those in leptomeninges. In insoluble Abeta in the cortex, Abeta42 was by far the predominant species, and Abeta42 in AD cortices was characterized by the highest degree of modifications in the amino terminus. In contrast, this Abeta42 predominance was not observed in insoluble Abeta in the leptomeninges, which were found to be able to accumulate Abetas to an extent similar to that in the cortex, on a weight basis. The levels of insoluble Abeta in the leptomeninges or cortex generally correlated with the degree of cerebral amyloid angiopathy or the abundance of senile plaque, respectively. However, the presence of plaque-free cortical samples showing significant levels of insoluble Abeta42 suggests that biochemically detectable Abeta accumulation precedes immunocytochemically detectable Abeta deposition in the cortex.

Aged↗
PubMed1997

Flow-mediated, endothelium-dependent dilatation of the brachial arteries is impaired in patients with coronary spastic angina.

Coronary spasm is induced by acetylcholine, serotonin, ergonovine, or histamine, all of which cause vasodilation when the endothelium is intact, and is promptly relieved by nitroglycerin, which vasodilates through the direct action on smooth muscle. Endothelial dysfunction is therefore possibly involved in the pathogenesis of coronary artery spasm. The aim of this study was to determine whether endothelium-dependent vasodilation is impaired in the peripheral arteries of patients with coronary spastic angina. Flow-dependent vasodilation of the brachial arteries during reactive hyperemia after the transient arterial occlusion was examined by using the high-resolution ultrasound technique in 35 patients with coronary spastic angina and 35 controls. Flow-dependent vasodilation of the brachial arteries was impaired in patients with coronary spastic angina compared with controls (5.9% +/- 4.2% vs 9.6% +/- 3.4%, p < 0.001) although the percent increase in blood flow during reactive hyperemia was not different between the two groups. The dilator response to nitroglycerin was preserved in patients with coronary spastic angina compared with controls (18.6% +/- 5.1% vs 16.2% +/- 3.9%, p < 0.04). The results indicate that endothelium-dependent vasodilation of the brachial arteries is impaired in patients with coronary spastic angina. Thus endothelial vasomotor dysregulation may also be present in the systemic arteries as well as coronary arteries in patients with coronary spastic angina.

Adult↗
PubMed1997

A shape memory airway stent for tracheobronchomalacia in children: an experimental and clinical study.

The authors have designed a coil airway stent using a thermal shape-memory titanium-nickel alloy (SMA) to relieve airway collapse in children. A characteristic of alloy allowed the stent to be enclosed in the thin introducer tube and to position it bronchoscopically in the collapsed airway. When the stent is warmed to 37 to 40 degrees C, it expands to the memorized diameter and stents the airway. In eight rabbits, an experimental model of potentially fatal tracheomalacia was created by fracturing the tracheal cartilages. The stents of 6 mm in diameter and 15 mm in length were placed, and then the stents were recovered to their original shape within 1 minute. All rabbits except one showed no respiratory symptoms during the follow-up period. Results of bronchoscopy performed 6 and 10 months after implantation showed satisfactory patency of the trachea. The rabbits were killed for histological evaluation 6 to 28 months after implantation. The specimens showed little proliferation of granulation and no dislodgement of the stents. This procedure was attempted in two children who had severe bronchomalacia. One 5-year-old patient underwent implantation with a stent of 5 mm in diameter and 25 mm in length into the left main bronchus. The patient was relieved from apneic attacks. The stent was removed 2 years after implantation after a remarkable improvement of ventilation. The other patient with left bronchomalacia, age 1 year 2 months, underwent implantation with a 5-mm x 20-mm stent. The animal experiment and clinical experience indicated that (1) this stent can be easily inserted and removed bronchoscopically, (2) the stent has good tissue compatibility and little interference of mucociliary function, and (3) the SMA stent is a promising therapeutic adjunct in the management of children with severe tracheobronchomalacia.

Airway Obstruction↗
PubMed1997

Hydroxyapatite ceramics with selected sintering additives.

Several sintering additives for hydroxyapatite (HA) have been tested in order to enhance its sinterability without decomposing the HA and/or decreasing bioactivity and biocompatibility, additionally providing a weak interface for HA ceramics. The ion species of sintering additives were selected from those in the mineral constituents of hard tissues and bioactive glasses. After investigation of phase diagrams in the CaO-P2O5-additive systems, and analysis of physiochemical properties of the additives, several sintering aids for HA have been chosen. Subsequently, densification, phase composition, grain growth and fracture behaviour of HA containing 5 wt% of each additive, sintered at 1000-1100 degrees C, have been studied. H3BO3, CaCl2, KCl, KH2PO4, (KPO3)n and Na2Si2O5 did not enhance densification of HA. K2CO2, Na2CO3, KF and sodium phosphates improved the densification significantly. Expect for KCl and some sodium phosphates, all the additives caused formation of large quantities of undesired beta-tricalcium phosphate or CaO; therefore, they are not appropriate for HA. In the case of sodium phosphate additives, it was possible to avoid formation of CaO or beta-tricalcium phosphate by control of the additive quantity and chemical composition. beta-NaCaPO4 has been found to be an effective sintering agent which causes neither decomposition of HA nor formation of other undesired phases.

Biocompatible Materials↗
PubMed1997

A novel slow excitatory postsynaptic current in substantia gelatinosa neurons of the rat spinal cord in vitro.

Whole-cell patch-clamp recordings were made from neurons in the substantia gelatinosa of adult rat spinal cord slices with attached dorsal root to study a slow synaptic current evoked by focal or dorsal root stimulation. Repetitive focal stimulation with a monopolar electrode positioned within substantia gelatinosa elicited a slow excitatory postsynaptic current preceded by a fast excitatory postsynaptic current in 73 of 83 neurons. A similar slow excitatory postsynaptic current was also elicited by stimulation of A delta afferent fibres. The amplitude of slow excitatory postsynaptic currents was unchanged when the recording electrode contained guanosine-5'-O-(2-thiodiphosphate). The slow excitatory postsynaptic current and current evoked by aspartate revealed similar reversal potentials and showed a marked outward rectification at holding potentials more negative than -30 mV, while the glutamate-induced current exhibited a relatively linear voltage relationship. In addition, the slow excitatory postsynaptic currents were reversibly occluded during the aspartate-induced current but were not occluded during the glutamate-induced current. The slow excitatory postsynaptic currents evoked by focal stimulation were depressed but not abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) or by 6-cyano-7-nitroquinoxaline-2,3-dione together with DL-2-amino-5-phosphonopentanoic acid (100 microM). Similarly, the aspartate- and glutamate-induced currents were also resistant to these antagonists. These observations suggest that a transmitter released from interneurons or descending fibres which are activated in part by A delta afferents, mediates a slow excitatory postsynaptic currents in substantia gelatinosa neurons and that an excitatory amino acid is implicated in the generation of the slow excitatory postsynaptic current, although the receptor appears to differ from the known ligand-gated channels. C afferents are unlikely to contribute to the slow excitatory postsynaptic current. This slow synaptic response may participate in the pain pathway and play an important role in the processing of nociceptive information in the spinal dorsal horn.

Animals↗
PubMed1997

Nitric oxide-mediated flow-dependent dilation is impaired in coronary arteries in patients with coronary spastic angina.

OBJECTIVES: This study sought to examine whether flow-dependent dilation is impaired at the site of coronary artery spasm in patients with coronary spastic angina. BACKGROUND: Physiologic stimuli such as exercise and exposure to cold have been shown to cause an increase in coronary blood flow, leading to flow-dependent dilation of coronary arteries in normal subjects, but cause coronary constriction in patients with coronary spastic angina. METHODS: A maximal increase in blood flow was induced selectively in the left anterior descending coronary artery (LAD) by infusion of adenosine through a Doppler flow catheter tip in the midportion of the LAD in 10 patients with coronary spastic angina, all with angiographically demonstrated spasm of the LAD, and in 11 control patients. Coronary artery diameter at the proximal site of the LAD (exposed to increased flow but not to adenosine) was measured by quantitative angiography. RESULTS: Flow-dependent dilation of the proximal LAD was found to be less in spasm arteries than in control arteries. Infusion of NG-monomethyl-L-arginine (L-NMMA) in the proximal LAD suppressed flow-dependent dilation in control arteries but had no significant effect on spasm arteries. The dilator response to nitroglycerin was not impaired in spasm coronary arteries. CONCLUSIONS: Our results indicate that flow-dependent coronary dilation is impaired in spasm arteries, partly due to a deficiency in endothelial nitric oxide bioactivity, which in turn may contribute to the increase in coronary tone during physiologic stimuli in patients with coronary spastic angina.

Adenosine↗
PubMed1997

Flow cytometric analysis of Thy-1 expression in CD34-positive acute leukemia.

We analyzed the expression of the Thy-1 antigen (CD90) in CD34+ acute leukemia using two-color flow cytometry. Leukemic cells were obtained from the bone marrow (BM) and/or the peripheral blood (PB) of 57 patients: 37 with acute myelogenous leukemia (AML) including nine with secondary AML following myelodysplastic syndrome (MDS/AML), and 20 with acute lymphoblastic leukemia (ALL) including three with chronic myelogenous leukemia in blast crisis (CML-BC) of the lymphoid type. Among these patients, one (3.6%) with de novo AML, two (22.2%) with MDS/AML, three (17.6%) with de novo ALL, and two (66.7%) with CML-BC coexpressed CD34 and Thy-1 (CD34+ Thy-1+) on more than 20% of the mononuclear cells within 'lymph' plus 'blast' window. Thy-1 was rarely expressed in de novo acute leukemia especially in AML. Interestingly, in 1 patient with CML-BC, the leukemic cells in BM were divided into two subpopulations (CD34+ Thy-1low and CD34+ Thy-1high), whereas most of the CD34+ leukemic cells in PB were Thy-1high. However, the mechanism for the mobilization of CD34+ Thy-1high leukemic cells into the PB is unknown.

Acute Disease↗
PubMed1997

Effects of angiotensin-converting enzyme inhibitor on plasma B-type natriuretic peptide levels in patients with acute myocardial infarction.

BACKGROUND: Plasma levels of B-type natriuretic peptide (BNP) are markedly increased in patients with heart failure and acute myocardial infarction. The changes in plasma BNP levels in the treatment of acute myocardial infarction with angiotensin-converting enzyme inhibitors have not been examined well. This study was designed to examine the effects of early angiotensin-converting enzyme inhibitor therapy on plasma BNP levels in patients with acute myocardial infarction. METHODS AND RESULTS: We measured the plasma levels of B-type natriuretic peptide over the time course for 2 weeks in 30 patients with acute myocardial infarction in whom either imidapril (n = 15) or placebo (n = 15) was given at random immediately after admission. Plasma BNP levels increased and reached a peak of 192 +/- 28 pg/ML 16 hours after administration; thereafter, the levels decreased and then again increased, forming the second peak of 217 +/- 38 pg/ML on the fifth day (biphasic pattern). On the other hand, plasma BNP levels increased and reached a peak level of 190 +/- 22 pg/ML 16 hours after admission and then decreased from 2 days after admission until the second week in the imidapril group (monophasic pattern). Left ventricular ejection fraction measured in the second week was significantly higher in the imidapril group than in the control group (62.2 +/- 1.1% vs 51.2 +/- 3.6%, P < .01). CONCLUSION: It is concluded that plasma BNP levels followed a monophasic pattern after imidapril treatment, whereas a biphasic pattern was followed after placebo, and that plasma BNP levels constitute a marker of ventricular dysfunction in the treatment of acute myocardial infarction with angiotensin-converting enzyme inhibitors.

Adult↗