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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 217 records · Page 12Linked to original sources
PubMed1998

Increased cytosolic free Mg2+ and Ca2+ in platelets of patients with vasospastic angina.

This study was designed to test the hypothesis that the cellular metabolism of Ca2+ and Mg2+, which is important in platelet function, is abnormal in the platelets of patients with vasospastic angina. Cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ handling were determined in the platelets of 24 patients with vasospastic angina and 24 control subjects by use of mag-fura 2 and fura 2. Platelet aggregation was also examined. Basal [Mg2+]i and cytosolic free Ca2+ concentration ([Ca2+]i) in platelets were significantly higher in patients with vasospastic angina than in control subjects. The amplitude of the [Ca2+]i transient induced by thrombin (0.03-1.0 U/ml) was significantly increased in the presence, but not in the absence, of extracellular Ca2+ in patients with vasospastic angina, as compared with controls. Therefore, the influx of Ca2+ across the plasma membrane may be accelerated in vasospastic angina. Thrombin (0.1-1.0 U/ml)-induced maximum aggregation response was significantly greater in patients with vasospastic angina than in controls. Results suggest that increased [Mg2+]i and altered Ca2+ handling by platelets may be associated with coronary vasospasm.

Adenosine Diphosphate↗
PubMed1998

Benzamil blockade of brain Na+ channels averts Na(+)-induced hypertension in rats.

To determine the possible involvement of brain amiloride-sensitive Na+ channels in Na(+)-induced hypertension, we investigated the effects of benzamil hydrochloride, a specific blocker of these Na+ channels, on the acute pressor mechanisms of intracerebroventricular infusion of hypertonic NaCl and the continuous pressor mechanisms of Na(+)-induced chronic hypertension, such as deoxycorticosterone acetate-salt hypertensive or stroke-prone spontaneous hypertensive rats, and of non-Na(+)-induced hypertension, such as renovascular hypertensive rats. Intracerebroventricular preinjection with benzamil (1 or 10 nmol/kg) abolished the increase in mean arterial pressure, heart rate, abdominal sympathetic discharge, and plasma vasopressin concentration induced by an acute increase in cerebrospinal Na+ concentrations at intracerebroventricular infusion of 1.5 M hypertonic NaCl. Continuous intracerebroventricular infusion of benzamil (1 or 10 nmol.kg-1.day-1) for 7 days attenuated Na(+)-induced chronic hypertension in both deoxycorticosterone acetate-salt and stroke-prone spontaneous hypertensive rats, accompanied by reduction of urinary excretion of vasopressin and norepinephrine but not in renovascular hypertensive rats. Intravenous infusion of benzamil (10 nmol.kg-1.day-1) for 7 days affected neither arterial pressure nor urinary excretion of vasopressin and norepinephrine in either model of hypertension. Benzamil-blockable brain amiloride-sensitive Na+ channels are expected to function as one of the Na+ receptors in the brain and to be involved in the pressor mechanism of Na(+)-induced hypertension.

Amiloride↗
PubMed1998

Abnormal platelet Ca2+ handling accompanied by increased cytosolic free Mg2+ in essential hypertension.

To test the hypothesis that abnormal platelet Ca2+ handling in essential hypertension results from cellular Mg2+ deficiency, cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ metabolism were studied in mag-fura 2 and fura 2-loaded platelets from 30 essential hypertensive patients and 30 sex- and age-matched normotensive controls. Basal cytosolic free Ca2+ concentration ([Ca2+]i) and intracellular Ca2+ discharge capacity were higher in hypertensives than in normotensives (22 +/- 5 vs. 18 +/- 5 nM, P < 0.05; 743 +/- 250 vs. 624 +/- 144 nM, P < 0.05, respectively). The thrombin (0. 03-1.0 U/ml)-evoked [Ca2+]i response was also enhanced in platelets from hypertensives in both the absence and presence of extracellular Ca2+. However, basal [Mg2+]i was higher in hypertensives than in normotensives (437 +/- 110 vs. 353 +/- 85 microM, P < 0.05), whereas serum Mg2+ was similar in the two groups. These results oppose the Mg2+ deficiency hypothesis in platelets in essential hypertension.

Blood Platelets↗
PubMed1998

Extracorporeal shock wave lithotripsy for vesical lithiasis.

Between 1991 and 1997, 17 male patients with bladder stones underwent extracorporeal shock-wave lithotripsy (ESWL) therapy in our department. One patient required epidural anesthesia and 5 patients were treated under intravenous sedation. Complete fragmentation was achieved after a single session in 9 patients and 4 required 2 sessions. Four patients underwent initial ESWL followed by mechanical cystolithotripsy. No major complications were noted. Fourteen patients were stone-free within 1 week after the procedure. Four patients were treated by transurethral resection of the prostate (TUR-P) on the day after completion ESWL. In conclusion, ESWL therapy is a simple, effective and safe modality for the management of vesical lithiasis.

Aged↗
PubMed1998

Endothelial nitric oxide synthase gene is positively associated with essential hypertension.

Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n=458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyoto: odds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamoto: odds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto: 0.103 versus 0.050, P<0.0017; Kumamoto: 0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.

Adult↗
PubMed1998

Increased serum concentrations of human hepatocyte growth factor in proliferative diabetic retinopathy.

Human hepatocyte growth factor (hHGF) is a powerful inducer of angiogenesis. We investigated the relationship between serum hHGF concentrations and proliferative diabetic retinopathy, the major characteristic of which is retinal neovascularization. Serum hHGF concentrations were measured in diabetic (n = 135) and nondiabetic subjects (n = 80). The mean serum hHGF concentration in diabetic subjects without retinopathy was lower than that in nondiabetic subjects [0.041 +/- 0.003 ng/mL (n = 62) vs. 0.080 +/- 0.010 ng/mL (n = 80); P < 0.05], but was not different from that in diabetic subjects with background retinopathy (0.058 +/- 0.007 ng/mL; n = 26) or preproliferative retinopathy (0.048 +/- 0.010 ng/mL; n = 10). The mean serum hHGF concentration was increased in subjects with proliferative retinopathy who had not undergone photocoagulation (0.213 +/- 0.025 ng/mL; n = 24), but not in those who had undergone photocoagulation (0.040 +/- 0.008 ng/mL; n = 13). Circulating hHGF may be involved in the mechanism of neovascularization in the proliferative diabetic retinopathy, and measurement of serum hHGF may be helpful in predicting the presence of proliferative retinopathy in diabetic subjects.

Adult↗
PubMed1998

Simultaneous elevation of the levels of circulating monocyte chemoattractant protein-1 and tissue factor in acute coronary syndromes.

The levels of circulating monocyte chemoattractant protein-1 (MCP-1) and tissue factor (TF) were examined on admission in 46 consecutive patients with acute coronary syndromes (ACS) and 30 patients with stable exertional angina (SEA). The plasma levels of both MCP-1 and TF were higher in the ACS patients than in the SEA patients (MCP-1: p<0.001; TF: p<0.001). Only the circulating TF level related to the number of diseased vessels. A positive correlation between plasma MCP-1 and TF levels was found (r=0.476, p<0.001). These results suggest that circulating MCP-1 plays an important role in the pathogenesis and/or development of ACS.

Acute Disease↗
PubMed1998

Occult papillary thyroid carcinoma in Hashimoto's thyroiditis presenting as a metastatic bone tumor.

Some occult thyroid carcinomas are hypothesized to regress and be eventually obliterated. We report here a patient whose condition supports this hypothesis. A 51-year-old male with primary hypothyroidism due to Hashimoto's thyroiditis suffered from a rib bone tumor. He had a diffuse goiter with no nodular lesion. Serum FT4 and TSH concentrations were 0.8 ng/dl and 36.4 microU/ml on taking 100 microg/day of T4. Anti-Tg- and -TPO-Ab were strongly positive (99 and 1380 U/ml). The iodine 123 scintigraphy demonstrated clear accumulation in the rib tumor, whereas the thyroid was scarcely visible. Biopsy of the rib tumor showed papillary proliferation of large atypical cells, which were immunohistochemically positive for thyroglobulin. Metastatic bone tumor of papillary thyroid carcinoma was therefore strongly suspected. He underwent a total thyroidectomy and the thyroid was stepwise sectioned completely at 3 mm intervals. The thyroid condition was diagnosed as Hashimoto's thyroiditis demonstrating diffuse and dense fibrosis, lymphocyte infiltration with lymphoid follicles and flattened atrophied follicles, but no carcinomatous foci were found. He was treated with I-131 and scintigraphy after the ingestion showed distinct accumulation in the rib tumors similar to that before thyroidectomy. No other abnormal uptake was observed. It is suggested that the primary occult thyroid papillary carcinoma regressed and was obliterated possibly by some immunologic or other host-resistance factors after it metastasized to the distant bone.

Bone Neoplasms↗
PubMed1998

Rapid diagnosis of oral tuberculosis by amplification of Mycobacterium DNA from paraffin embedded specimens.

The polymerase chain reaction (PCR) assay is a powerful tool for quick diagnosis of various infectious diseases. We applied this technique as well as conventional histopathological examination to diagnose oral tuberculosis. Ziehl-Neelsen staining of oral mucosal specimens often fails to detect Mycobacterium (M.) tuberculosis due to the low number of bacteria in the tissue. Specific primers and probes were synthesized based upon the nucleotide sequence of the 65 kDa membrane protein of M. tuberculosis. DNA extracted from the paraffin-embedded tissue was amplified using taq polymerase. PCR assay detected M. tuberculosis in 5 of 6 samples. Although the gene segments from these species were quite similar, the gamma 32P labeled noligonucleotide probes distinguished between M. tuberculosis and M. fotuitum by southern blot hybridization. In all specimens that were Ziehl-Neelsen negative, M. tuberculosis DNA was detected by PCR. These results suggest that PCR is a useful means of diagnosing mycobacterium infection.

Adult↗
PubMed1998

Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosarcoma in vivo.

We examined the expression levels of P-glycoprotein (P-Gp)/the human multidrug resistance gene (MDR1) and in vivo chemosensitivity in the 7 osteosarcoma xenografts. Three of seven (43%) osteosarcoma xenografts expressed MDR1 by reverse transcriptase-polymerase chain reaction (RT-PCR). The OSS-516R xenograft selected with vincristine (VCR) from the MDR1-negative xenograft OSS-516, which was sensitive to VCR and doxorubicin (DOX), acquired cross-resistance to DOX. In the OSS-516R, RT-PCR assay showed definite MDR1 expression and immunohistochemical analysis demonstrated P-Gp-positive tumor cells. These results suggest that P-Gp/MDR1 overexpression is related to multidrug resistance in human osteosarcoma in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Change in intraocular pressure after intraocular lens implant during a follow-up period of over 10 years].

Changes in intraocular pressure were studied in 141 eyes following intraocular lens implant. The average observational time was twelve years. We tried to fix both loops of the implant in the ciliary sulcus. The intraocular pressure increased over the ten year interval at 0.19 mmHg per year. Twenty-seven of the 141 eyes developed glaucoma. We studied the intraocular pressure of the cases with or without complications. Thirty-eight eyes had complications, fifteen eyes (39%) developed secondary glaucoma, and three eyes (8%) developed glaucomatous visual field defect. In twenty-three cases without secondary glaucoma, the intraocular pressure increased over a three-year interval after surgery and remained constant thereafter. 103 eyes had no complications to influence the intraocular pressure, twelve eyes (12%) developed secondary glaucoma, and four eyes (4%) developed glaucomatous visual field defect. In 91 cases without secondary glaucoma, the intraocular pressure increased over a five-year interval after surgery at 0.28 mmHg per year and remained constant thereafter. We recommend regular examination, especially during the initial five-year period when the intraocular pressure is apt to increase even if complications are not evident.

Adult↗
PubMed1998

Astrocytes containing amyloid beta-protein (Abeta)-positive granules are associated with Abeta40-positive diffuse plaques in the aged human brain.

Amyloid beta-protein (Abeta) is the major component of senile plaques that emerge in the cortex during aging and appear most abundantly in Alzheimer's disease. In the course of our immunocytochemical study on a large number of autopsy cases, we noticed, in many aged nondemented cases, the presence of unique diffuse plaques in the cortex distinct from ordinary diffuse plaques by immunocytochemistry. The former were amorphous, very faintly Abeta-immunoreactive plaques resembling diffuse plaques, but they stained for Abeta40 and were associated with small cells containing Abeta-positive granules. A panel of amino- and carboxyl-terminal-specific Abeta antibodies showed that such Abeta40-positive diffuse plaques and cell-associated granules were composed exclusively of amino-terminally deleted Abeta terminating at Abeta40, -42, and -43. Double immunostaining also showed that those Abeta-immunoreactive granules are located in astrocytes and not in microglia or neurons. Immunoelectron microscopy revealed that nonfibrillar Abeta immunoreactivity was located within lipofuscin-like granules in somewhat swollen astrocytes. These findings raise the possibility that astrocytes take up Abeta and attempt to degrade it in lysosomes in the aged brain.

Adult↗
PubMed1998

Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma.

Recently, the N-terminal fragment of proatrial natriuretic peptide (N-terminal proANP) has been proposed as a marker of chronic congestive heart failure. In this study, we established a two-step immunoradiometric assay using monoclonal antibodies and synthetic N-terminal proANP (1-67) as a standard. It allows us to measure plasma N-terminal proANP in only 4 h without prior extraction. The detection limit of this assay was 15 pmol/L for a 100 microL sample of plasma. Within-run CVs ranged from 1.7% to 2.9% and between-run CVs ranged from 4.2% to 5.1%. The dilution curves of plasma samples showed good linearity and analytical recovery was 89-104%. The mean (+/-SD) N-terminal proANP in plasma of 33 healthy subjects was 188 (+/-71) pmol/L and 1030 (+/-411) pmol/L in 25 patients with heart failure. Our immunoradiometric assay is rapid and precise enough for routine determination of N-terminal proANP in human plasma.

Antibodies, Monoclonal↗
PubMed1998

Quantitation of amyloid beta-protein (A beta) in the cortex during aging and in Alzheimer's disease.

In this study we sought to learn about when and how amyloid beta-protein (A beta) accumulates in the cortex of normal individuals and about the difference in the A beta accumulation between normal aged and Alzheimer's disease (AD) brains. From consecutive autopsy cases and AD cases, hippocampus CA1 and occipitotemporal cortex T4 were sampled for A beta quantitation by the well characterized two-site enzyme immunoassays (EIAs). There was a strong tendency toward A beta 42 accumulation between the ages of 50 and 70 years in T4 and a little later in CA1. The A beta 42 levels were consistently higher in T4 than those in CA1 in any given case. The levels of A beta 42 in AD brains were significantly higher than those in control brains, and the extent of A beta 42 amino-terminal modification was also much greater in AD brains than that in control brains. Even in cases in which no senile plaques were immunocytochemically detected, EIAs clearly showed that significant amounts of A beta 42 already had accumulated. In contrast to A beta 42, A beta 40 showed no apparent age-dependent accumulation, and its high levels were found to be associated with AD.

Adult↗