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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 307 records · Page 17Linked to original sources
PubMed1996

Nitric oxide activity is deficient in spasm arteries of patients with coronary spastic angina.

BACKGROUND: Coronary spasm can be induced by acetylcholine, serotonin, ergonovine, or histamine, all of which cause vasodilation when the endothelium is intact by releasing nitric oxide (NO). Coronary spasm is promptly relieved by nitroglycerin, which vasodilates through its conversion to NO. It is thus possible that NO release may be deficient in the spasm arteries in patients with coronary spastic angina (CSA). The aim of this study was to determine whether NO release is deficient in coronary arteries of patients with CSA. METHODS AND RESULTS: NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, was infused into coronary arteries in 21 patients with coronary spastic angina (CSA) and in 28 control patients. Coronary spasm was induced by intracoronary injection of acetylcholine and was documented angiographically in all patients with CSA. L-NMMA dose-dependently decreased basal luminal diameter of coronary arteries in control patients, whereas it had no effect on basal diameter of the spasm arteries in patients with CSA. L-NMMA abolished the dilator response to acetylcholine and enhanced the constrictor response to acetylcholine in control arteries, whereas it had no effect on the constrictor response to acetylcholine in spasm arteries. Intracoronary infusion of L-arginine did not affect the diameter of spasm or control arteries. The dilator response to nitroglycerin was increased markedly in spasm arteries compared with control arteries, whereas response to diltiazem did not differ between them. CONCLUSIONS: There is a deficiency in endothelial NO activity in spasm arteries, which leads to the supersensitivity of the artery to the vasodilator effect of nitroglycerin and to the vasoconstrictor effect of acetylcholine in patients with CSA. This deficient endothelial NO activity plays an important role in the pathogenesis of coronary spasm.

Acetylcholine↗
PubMed1996

Potentiation of the intracellular Ca2+ response to arginine vasopressin by increased cytosolic-free Mg2+ in rat vascular smooth muscle cells.

Although the inhibitory effects of extracellular Mg2+ on Ca2+ influx are well established, little is known about the effects of intracellular Mg2+ on Ca2+ handling. In the present study, the effects of cytosolic-free Mg2+ concentration in the physiological (submillimolar) range on Ca2+ handling were investigated after stimulation of rat vascular smooth muscle cells with arginine vasopressin. Cytosolic Mg2+ was manipulated by culturing cells in medium containing different Mg2+ concentrations. Peak cytosolic-free Ca2+ concentration responses to arginine vasopressin (1 mumol/1) were measured in the presence and absence of external Ca2+. The results suggest that an increase in cytosolic-free Mg2+ concentration increases both Ca2+ discharge from intracellular stores and Ca2+ influx, whereas a decrease in intracellular Mg2+ attenuates Ca2+ influx.

Animals↗
PubMed1996

Aberrant glycosylation of E-cadherin enhances cell-cell binding to suppress metastasis.

Introduction of the beta1-4 N-acetylglucosaminyltransferase (GnT-III) gene was reported to suppress metastasis in highly metastatic B16-hm murine melanoma cells (Yoshimura, M., Nishikawa, A. , Ihara, Y., Taniguchi, S., and Taniguchi, N.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 8754-8758). In this study, the effect of GnT-III gene transfer on E-cadherin was studied, since E-cadherin acts as a suppressor of metastasis. E-cadherin expression at cell-cell contacts of B16-hm cells expressing high GnT-III activity was greater than controls without affecting transcription. Lectin blotting showed that E-cadherin from GnT-III transfectants was glycosylated by ectopically expressed GnT-III. The glycosylated E-cadherin exhibited the delayed turnover and the decreased release from cell surface, as compared with the native E-cadherin, resulting in the elevated expression at the cell-cell border of GnT-III transfectants. Furthermore, cell-cell aggregation was enhanced in GnT-III transfectants, indicating that the glycosylated E-cadherin is biologically functional. These results suggest that the glycosylated E-cadherin contributes to the suppression of metastasis by the introduction of GnT-III gene into melanoma cells.

Animals↗
PubMed1996

Cerebral adenosine triphosphate-sensitive K+ channels may be impaired during acute cerebral ischemia in spontaneously hypertensive rats.

To elucidate the role of cerebral adenosine triphosphate (ATP)-sensitive K+ channels (KATP) on arterial pressure regulation during acute cerebral ischemia in spontaneously hypertensive rats (SHR), intracerebroventricular (i.c.v.) injections of either glibenclamide, a specific blocker of KATP, or pinacidil, a KATP opener, were performed in SHR and Wistar-Kyoto rats (WKY). Intracerebroventricular injections of glibenclamide elicited a vasopressor response in WKY with bilateral ligation of the carotid arteries, whereas the response was smaller in SHR. It increased plasma AVP, but decreased pituitary AVP in WKY with ligation, but not in SHR. Systemic administration of an AVP V1 receptor antagonist, OPC-21268, abolished the vasopressor responses to i.c.v. injections of glibenclamide in WKY. Bilateral ligation of the carotid arteries augmented the vasodepressor responses to i.c.v. injections of pinacidil in WKY, but not in SHR. Cerebral KATP may play a role in buffering a rise in arterial pressure by inhibiting the release of AVP from the pituitary glands during acute cerebral ischemia in WKY, but this mechanism might be deranged in SHR, probably due to impaired responsiveness of cerebral KATP to ischemia.

Adenosine Triphosphate↗
PubMed1996

Bisecting N-acetylglucosamine on K562 cells suppresses natural killer cytotoxicity and promotes spleen colonization.

beta 1-4 N-acetylglucosaminyltransferase (GnT-III) catalyzes the formation of bisecting N-acetylglucosamine (GlcNAc) in the biosynthesis of N-linked oligosaccharides. To examine the effect of bisecting GlcNAc on the natural killer (NK) cytotoxicity, the GnT-111 gene was introduced into NK-sensitive K562 cells that have no detectable GnT-III activity. We obtained three clones stably expressing high GnT-III (positive transfectants). Introduction of the GnT-III gene resulted in an increase of bisecting GlcNAc and a decrease of external sialic acid as well as tri- and tetraantennary sugars, as judged by flow cytometry. Compared to controls, the NK cytotoxicity was completely blocked against positive transfectants. The binding of effector cells to positive transfectants was also decreased. After s.c. injection into nude mice, positive transfectants produced spleen colonization, although no spleen lesions were formed by control cells. In nude mice depleted of NK cells by anti-asialo GM1 antibody, both positive transfectants and controls produced spleen colonization equally. These results indicate that K562 cells expressing GnT-III are resistant to NK cytotoxicity, resulting in spleen colonization in nude mice.

Acetylglucosamine↗
PubMed1996

Modulation of L-type Ca current by denopamine, a nonparenteral partial beta 1 stimulant, in rabbit ventricular cells.

The effects of denopamine, a nonparenteral partial beta agonist which is used clinically in Japan, on the L-type Ca2+ current (ICa) were examined in rabbit ventricular cells. Denopamine stimulated basal ICa with a maximum response of +33.2% and a concentration for half-maximal response (EC50) of 0.039 microM. The maximum response of ICa was only a quarter of that induced by isoprenaline (ISO), while 10 microM denopamine elicited 70-75% of the maximum inotropic response in the papillary muscle preparations. The denopamine stimulation of ICa was abolished by selective beta 1 antagonists (atenolol or bisoprolol). Pretreatment with forskolin or dialysis with cAMP also abolished the stimulation. Denopamine, in turn, inhibited ISO-stimulated ICa. This inhibition was not affected by pretreatment with pertussis toxin or prazosin. The presence of denopamine at various concentrations caused a rightward shift in the concentration/response curve for ISO stimulation of ICa. The Schild plot for this effect had a slope of 0.99 and Kp of 0.20 microM. In the presence of guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) (0.5 mM) in the pipette, denopamine (10 microM) stimulated the ICa to 86 +/- 5% of the maximum response induced by ISO. These findings indicate that denopamine modulates ICa exclusively through the beta 1 adrenoceptor-adenylate cyclase pathway, that the stimulatory GTP-binding protein regulates the agonistic potency of denopamine, and that the signal from the beta 1 adrenoceptors is amplified between ICa and the tension development, which would contribute to the spare capacity of beta adrenoceptors.

Adenylyl Cyclases↗
PubMed1996

Skip metastasis and hidden N2 disease in lung cancer: how successful is mediastinal dissection?

Out of 703 consecutive patients who underwent lung cancer surgery from 1986 to 1994, 562 were studied with an emphasis on lymph node metastasis. Skip metastasis was defined as metastasis to the upper mediastinum without involvement of the carinal, hilar, or intrapulmonary nodes. Twenty-nine patients had skip metastasis, accounting for 17% of the 175 with N2 disease. Except for one patient with a huge tumor, there was no lower-lobe disease. Patients with N2 disease nodes were categorized into the following groups: (1) 32 with false negative N2 that could not be detected macroscopically on the specimen; (2) 64 with true positive N2, detected macroscopically on the specimen; and (3) 79 patients with obvious N2. Positive carinal nodes were found in 12 of 70 N2 patients who underwent upper lobectomy, and in 60 of the (105) remaining N2 patients who had other types of surgery. We conclude that upper mediastinal dissection should be carried out in patients with adenocarcinoma in the upper lobe, because skip and undetectable metastasis are not rare. However, dissection of the carinal nodes with upper-lobe tumors, and of the upper mediastinum with lower-lobe tumors, can be omitted when the gross and frozen section findings are negative in the upper mediastinum and both the carinal and hilar nodes.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Thyroid hormone-free albumin: charcoal treatment or resin treatment.

Free thyroid hormone measurement by means of immunoassay kits is greatly influenced by the altered serum albumin and free fatty acid (FFA) levels. In the evaluation of these kits, it is therefore essential to study the interferences due to these factors by adding FFA or thyroid hormone-free human serum albumin (HSA) to the assay mixture, but little attention has been paid to the selection of albumin. In the present study, FFA content in various preparations of thyroid hormone-free HSA was compared. Charcoal-treated HSA was free from both thyroid hormone and FFA, whereas anion exchange resin-treated HSA was only free from thyroid hormone. Commercially available "FFA-free HSA" was also free from thyroid hormone. Our results suggest that attention must be paid to the nature of albumin when studying the interference by albumin in free thyroid hormone measurement and that commercially available "FFA-free HSA" is a ready-to-use thyroid hormone-free HSA when HSA free from both FFA and thyroid hormone is desired.

Artifacts↗
PubMed1996

Property of receptor for vasoactive intestinal contractor (VIC) expressed in Xenopus oocytes injected with mRNA from rat intestine.

Property of receptor for vasoactive intestinal contractor (VIC), a peptide related to the endothelin family, expressed in Xenopus oocytes by injecting mRNA obtained from the intestine of rat, were studied using the voltage-clamp method. Inward-current responses to VIC (1 nM-100 nM) were evoked in a concentration-dependent manner in mRNA-injected oocytes. Non-injected and water-injected oocytes failed to respond to VIC. The reversal potential for the VIC response was around -20 mV and the depolarizing shift was approximately 18 mV, when the external concentration of Cl-was halved, in agreement with the Nernst equation. The response to VIC was suppressed either by the external application to BAPTA/AM (10 microM) or by pertussis toxin 0.5 microgram/ml). These results indicate that the receptor for VIC, functionally expressed in Xenopus oocytes injected with rat intestinal mRNA, is coupled to pertussis toxin-sensitive G-protein and its activation leads to mobilization of intracellular Ca2+.

Animals↗
PubMed1996

Processing and mechanical properties of hydroxyapatite reinforced with hydroxyapatite whiskers.

Hydrothermally synthesized HAp fine crystals/HAp whiskers mixtures have been used for the preparation of HAp/0-30% (whiskers) composites. The composites have been fabricated by pressureless sintering and hot-pressing. The best mechanical properties and the highest densities have been achieved for composites hot pressed at 1000 degrees C (2 h, 30 MPa in flowing Ar). Their density was in the range of 90-97% of the theoretical density. Fracture toughness (Klc) of the composites reflected their microstructure and had the value of 1.4 MPa m1/2 (as compared with Klc = 1.0 MPa m1/2 for the non-reinforced HAp matrix). Compressive prestressing of the HAp matrix and crack deflection (both derived from the residual stress field) contributed to the increase of fracture toughness. Other toughening mechanisms have not been observed. HAp/HAp (whiskers) composites exhibited improved toughness without degradation of biocompatibility, because the HAp whiskers acted both as a reinforcement and as a biocompatible phase. Problems related to biocompatibility and mechanical properties of available HAp-based composites were also discussed.

Biocompatible Materials↗
PubMed1996

Increased plasma levels of B-type natriuretic peptide in patients with unstable angina.

This study was designed to examine the plasma levels of B-type or brain natriuretic peptide (BNP), as well as A-type or atrial natriuretic peptide (ANP) in patients with unstable angina as compared with those in patients with stable exertional angina and control subjects. We measured the plasma levels of BNP and ANP in 33 patients with unstable angina, 20 patients with stable exertional angina, and 20 control subjects. The plasma levels of BNP were significantly increased in patients with unstable angina compared with those in patients with stable exertional angina and control subjects, respectively (39.5 +/- 29.4 pg/ml vs 15.1 +/- 8.0 pg/ml; p < 0.01 and 39.5 +/- 29.4 pg/ml vs 10.3 +/- 6.4 pg/ml; p < 0.01, respectively). On the other hand, there was no significant difference in the plasma levels of ANP among the three groups. Furthermore, in patients with unstable angina, the plasma levels of BNP decreased significantly after the medical treatment (from 39.5 +/- 29.4 pg/ml to 15.8 +/- 11.0 pg/ ml; p < 0.01), whereas the plasma levels of ANP did not change. We conclude that the plasma levels of BNP are increased in the majority of patients with unstable angina and that the increased levels decrease toward normal after treatment.

Adult↗
PubMed1996

Natriuretic peptides in the treatment of heart failure.

BACKGROUND: This study was designed to examine the hemodynamic, renal, and hormonal effects of infusion of A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with congestive heart failure (CHF). METHODS AND RESULTS: We infused synthetic human ANP or BNP at a rate of 0.1 microgram/kg/ min in patients with CHF and control subjects. ANP and BNP infusion decreased pulmonary capillary wedge pressure (ANP: from 24 +/- 1 to 12 +/- 2 mmHg; BNP: from 21 +/- 3 to 14 +/- 4 mmHg, P < .01, respectively) and systemic vascular resistance (ANP: from 2,129 +/- 293 to 1,737 +/- 293 dyne.sec.cm-5; BNP: from 2,485 +/- 379 to 1,771 +/- 195 dyne.sec.cm-5, P < .01, respectively), and increased stroke volume index (ANP: from 26 +/- 4 to 32 +/- 4 mL/m2; BNP: from 26 +/- 4 to 32 +/- 4 mL/m2, P < .01, respectively) in patients with CHF. ANP and BNP infusion increased urine volume (ANP: from 0.7 +/- 0.3 to 4.5 +/- 3.3 mL/min, BNP; 0.8 +/- 0.2 to 5.3 +/- 1.0 mL/min, P < .01, respectively). excretion of sodium (ANP: from 53 +/- 26 to 478 +/- 389 microEq/min, P = NS; BNP: from 77 +/- 21 to 754 +/- 108 microEq/min, P < .01) and chloride (ANP: from 61 +/- 31 to 470 +/- 369 microEq/min, P = NS, BNP; from 74 +/- 20 to 709 +/- 103 microEq/min, P < .01) in patients with CHF. In the hormonal analysis, ANP and BNP infusion had inhibitory effects on reninangiotensin aldosterone system and the sympathetic nervous system. CONCLUSION: We conclude that ANP and BNP infusion improves left ventricular function in patients with CHF by vasodilation and prominent natriuretic action.

Aged↗
PubMed1996

In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product.

The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo anti-tumour effects of a humanised antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its murine counterpart, mu4D5, for the direct antiproliferative activity against the c-erbB-2-overexpressing SK-BR-3 cell line. In vivo treatment of severe combined immunodeficient (SCID) mice carrying the c-erbB-2-overexpressing 4-1ST human gastric carcinoma xenograft with 4hu4D5 revealed that the recombinant protein had potent anti-tumour activity. Furthermore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was significantly augmented with rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might perform better in patients than predicted from preclinical studies.

Animals↗
PubMed1996

P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo.

We examined whether the increased expression of P-glycoprotein (P-gp) encoded by the human multidrug resistance gene MDR1 is related to the acquired multidrug resistance of lung cancer in vivo. We estimated the chemosensitivity of lung cancer xenografts (LC-6, adenocarcinoma; Lu-24, small-cell cancer) by calculation of relative tumour growth (T/C%, treated/control) in vivo, based on statistical significance determined by the Mann-Whitney U test (P < 0.01, one-sided). MDR1 gene expression levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) assay. P-gp production and P-gp localisation were examined by Western blotting and by immunohistochemical analysis respectively. LC-6 and Lu-24 were initially sensitive to both vincristine (VCR, 1.6 mg kg-1: LC-6, 45%; Lu-24, 39%) and doxorubicin (DOX, 12 mg kg-1: LC-6, 26%; Lu-24, 27%) in vivo. VCR-resistant variants (LC-6R, 66% and Lu-24R, 68%) selected with VCR (0.4 mg kg-1, x 9) significantly acquired cross-resistance to DOX (LC-6R, 55% and Lu-24R, 55% respectively). RT-PCR assay showed increased levels of MDR1 expression in LC-6R and Lu-24R with stable MDR1 expression levels. P-gp expression levels were elevated, and the percentage of P-gp-positive tumour cells increased in both LC-6R and Lu-24R. These results suggest that P-gp/MDR1 overexpression is related to acquired multidrug resistance in lung cancer in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗