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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 235 records · Page 13Linked to original sources
PubMed1998

[Vancomycin resistant enterococci].

Enterococci are normal intestinal flora in humans. Among enterococci, Enterococcus faecalis and Enterococcus faecium are frequently isolated and can become nosocomial pathogens in hospitals, especially in intensive care units and oncology wards. Recently, vancomycin-resistant enterococci (VRE) such as E. faecalis and E. faecium have caused a serious problem of hospital-acquired infections in Europe and the USA. VRE also has another aspect as a cause of community-acquired infections. Especially, avoparcin which had been used to enhance growth of food animals is documented as associated with the spread of VRE in European countries. In Japan, there have only been a few of reports about VRE so far. However, there evidence that VRE might become prevalent in many hospitals in Japan. In fact, we have already isolated another highly vancomycin-resistant E. faecium (VCM:MIC > 128 micrograms/ml) from a hospitalized diabetic patient. We should pay a careful attention to VRE and perform the following control measures: 1)re-education and re-training about hospital infection control procedures, 2) prudent use of vancomycin in clinical settings, 3)accurate report of VRE in clinical laboratories, and 4) good communications and collaborations among physicians, nurses and other health care personnel and laboratory technicians. We should learn more from countries in which VRE are already prevalent, and pursue further investigations, to prevent the spread of VRE in Japan.

Animals↗
PubMed1998

[Introductory review of diagnostic approach to arteriosclerosis].

Investigation of the pathogenesis of arteriosclerosis and/or atherosclerosis has been progressed using molecular biology. New concepts have been developed and, receptors and substances have been found clinically and experimentally, which have led us to create new methods of evaluating or diagnosing the grade of atherosclerosis lesion. Dealing with the new concepts or knowledge in this symposium, this introductory paper describes an overview of pathogenesis of atherosclerosis, from which the new methods of evaluating or diagnosing lesion has been exploited. The injury to the endothelium leads to endothelial cell dysfunction, which initiates the acceleration of LDL oxidation and increases adherence of monocytes, macrophages and T lymphocytes, migrating subendothelially and causing large foam cells to develop because of lipid accumulation. Macrophages and platelets release many growth factors, which accelerate the growth of vascular smooth muscle cells, forming fibrous plaque. In these pathogenic processes of atherosclerosis, angiotensin II participates in releasing growth factor for cell proliferation and hepatocyte growth factor (HGF) participates in revascularization of the sclerotic lesion, suggesting a candidate marker for atherosclerosis. Hyperlipidemia and hypercoagulation are the major factors in advanced atherosclerosis. Using new methods to evaluate or diagnose lesions, further therapy and prevention for atherosclerosis will progress in future.

Arteriosclerosis↗
PubMed1998

[Vascular endothelium-related factors and atherosclerosis/arteriosclerosis: serum hepatocyte growth factor as a possible indicator of vascular lesions].

To investigate the possible involvement of hepatocyte growth factor (HGF) with vascular lesions, we studied the relationship between serum HGF concentrations and the grades of retinal arteriosclerosis, coronary atherosclerosis proliferative changes in the retina of diabetic subjects, and activities of systemic vasculitis. Individuals with more advanced grades of retinal arteriosclerotic change showed higher serum HGF values (grade 0, 0.053 +/- 0.005 ng/ml ; grade 1, 0.144 +/- 0.022 ng/ml ; grade 2, 0.338 +/- 0.36 ng/ml ; grade 3, 0.526 +/- 0.051 ng/ml). The serum HGF concentration was increased in subjects with single- (0.200 +/- 0.012 ng/ml, double- (0.334 +/- 0.018 ng/ml) or triple- (0.379 +/- 0.022 ng/ml) vessel coronary heart diseases, compared with that in subjects with intact coronary arteries (0.112 +/- 0.008 ng/ml). Serum HGF in diabetes without retinopathy was lower than that in nondiabetic subjects (0.041 +/- 0.003 ng/ml vs 0.080 +/- 0.010 ng/ml, p < 0.05), but did not differ from that in other diabetic subjects with background retinopathy (0.058 +/- 0.007 ng/ml) or preproliferative retinopathy (0.048 +/- 0.010 ng/ml). Serum HGF was increased in patients with proliferative retinopathy without photocoagulation (0.213 +/- 0.025 ng/ml, p < 0.01), but not in those with photocoagulation (0.040 +/- 0.008 ng/ml). Serum HGF concentration was increased (p < 0.01) during the acute phase of Schönlein-Henoch purpura (0.31 +/- 0.15 ng/ml), a systemic vasculitis, but it returned to control levels during the remission phase (0.11 +/- 0.10 ng/ml). Increased serum HGF may be involved in the pathogenesis of arteriosclerosis/atherosclerosis, retinal neovascularization, or vasculitis, and measurement of serum HGF may be a useful test for predicting these vascular lesions.

Aged↗
PubMed1998

Roles of brain angiotensin II and C-type natriuretic peptide in deoxycorticosterone acetate-salt hypertension in rats.

OBJECTIVE: To investigate the roles of brain angiotensin II and C-type natriuretic peptide (CNP) in the hypertensive mechanism of deoxycorticosterone acetate (DOCA)-salt hypertension. METHODS: We injected 50 microg/kg CV-11 974, an angiotensin II type-1 receptors antagonist, 30 nmol/kg CNP-22, or the vehicle (artificial cerebrospinal fluid) into the cerebral ventricle or intravenously 5 min before the intracerebroventricular infusion of 1.5 mol/I NaCl solution for 30 min into either male normotensive Wistar rats or DOCA-salt hypertensive rats anesthetized with urethane, and their arterial pressures and heart rates were continuously recorded. Blood (2 ml) was collected at the end of the infusion for the measurement of plasma concentration of arginine vasopressin. We infused 10 or 50 microg/kg per day CV-11 974, 10 or 50 nmol/kg per day CNP-22, or the vehicle (1 microl/h) into the cerebral ventricles of DOCA-salt hypertensive rats for 7 days by using osmotic minipumps, and measured their systolic arterial pressures, pulse rates, and urinary excretions of vasopressin. RESULTS: Intracerebroventricular pre-administrations of CV-11 974 and of CNP-22 inhibited increases in mean arterial pressure, heart rate, and plasma vasopressin concentration induced by intracerebroventricular infusion of 1.5 mol/l NaCl into normotensive rats; increases in hemodynamics and plasma level of vasopressin induced by intracerebroventricular infusion of 1.5 mol/l NaCl were suppressed by intracerebroventricular pre-injections of CV-11 974, but not of CNP-22, into DOCA-salt hypertensive rats. Continuous intracerebroventricular infusions of 50 microg/kg per day CV-11 974 attenuated hypertension in DOCA-salt treated rats, accompanied by a reduction in urinary excretion of vasopressin. Continuous intracerebroventricular infusions of 50 nmol/kg per day CNP-22, however, affected neither hypertension nor urinary excretion of vasopressin in DOCA-salt hypertensive rats. CONCLUSION: Brain angiotensin II could play a role in the pressor mechanism of DOCA-salt hypertension by increasing release of vasopressin via type 1 receptors. That brain CNP has an inhibitory effect on release of vasopressin in acute experiments indicates that the impairment of this inhibitory effect of brain CNP on secretion of vasopressin could be involved in the pathogenesis of DOCA-salt hypertension in rats.

Angiotensin II↗
PubMed1998

[Usefulness of heart rate variability for evaluating cardiac autonomic nervous function].

To investigate the effect of gastric ulceration on cardiac autonomic nervous function, 24-hour ambulatory electrocardiograms were recorded in patients with artificial gastric ulcers caused by endoscopic treatment of gastric tumors. Their cardiac autonomic nervous activity was assessed by both time- and frequency-domain analyses of heart rate variability obtained from electrocardiogram recordings. The results were compared with those from patients who had undergone endoscopic treatment of esophageal varices or colorectal tumors, or gastrointestinal endoscopy alone. Parameters of time-domain analysis decreased significantly with the formation of gastric ulcers. Because parameters of frequency-domain analysis did not change in the group with gastric ulcers, this decrease in parameter of time-domain analysis suggests increased activity of cardiac sympathetic nervous system. There were no changes in the parameters of either time- or frequency-domain analysis in other groups. These results suggest that artificial gastric ulceration modifies cardiac sympathovagal balance, favoring cardiac sympathetic activity, while artificial esophageal and colon ulcers have no effect on cardiac autonomic nervous activity. Heart rate variability analysis is a useful method of evaluating possible implications between gastric ulceration and cardiac autonomic nervous function.

Aged↗
PubMed1998

Molecular heterogeneity of hCGbeta--related glycoproteins and the clinical relevance in trophoblastic and non-trophoblastic tumors.

We analyzed immunoreactive hCG/hCGbeta (IR-beta) in the sera and urine of patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme immunoassays (EIAs) specific for intact hCG, free hCG beta, and beta-core fragment of hCG (beta-CF). In trophoblastic diseases, while intact hCG and free hCGbeta were contained in both serum and urine, the beta-CF could be detected only in the urine of the patients. The relative contribution of the beta-CF to the total urinary IR-beta accounted for about 30-50% in normal early pregnancy and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that intact hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic diseases, and suggested that the ratios of intact hCG, free hCGbeta, and beta-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-beta was also investigated in the sera and urine of the patients with cervical, endometrial, ovarian, lung, and bladder carcinomas. We found that even when IR-beta could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-beta. The chromatographic study indicated that these urinary IR-beta were essentially attributed to beta-CF, leading to the evaluation of urinary beta-CF as a tumor marker. The positive rated of urinary beta-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG beta by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when beta -CF is measured in urine of the patients.

Antibodies, Monoclonal↗
PubMed1998

[Neovascularization and HGF: neovascularization in proliferative diabetic retinopathy and intraocular HGF].

Human hepatocyte growth factor (hHGF) has a strong angioneogenetic action. The present study was designed to investigate the possible involvement of hHGF in neovascularization in proliferative diabetic retinopathy by measuring vitreous hHGF concentration, and to examine the gene expression of hHGF in retinal Müller cells, which are presumed to play a role in proliferative diabetic retinopathy. Patients who had undergone pars plana vitrectomy were studied (33 diabetic patients with proliferative retinopathy and 20 nondiabetic subjects). The mean vitreous hHGF concentration was higher (p < 0.0001) in diabetic subjects with proliferative retinopathy (5.7 +/- 0.7 ng/ml) than in nondiabetic subjects (1.6 +/- 0.2 ng/ml). Furthermore, diabetic subjects with iris neovascularization, which is suggestive of advanced retinal ischemia, showed higher values of mean vitreous hHGF concentration than those without iris neovascularization (7.3 +/- 1.2 ng/ml [n = 14] vs. 4.5 +/- 0.7 ng/ml [n = 19], p < 0.01). Expression of hHGF gene was detected in cultured human Müller cells. Our results indicate that hHGF may be produced in the eye by retinal cells such as Müller cells and may play a role in neovascularization of proliferative diabetic retinopathy.

Diabetic Retinopathy↗
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↗