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Biomedical subjects

Y Tamura

Publications and source records attributed to Y Tamura.

At least 541 records · Page 30Linked to original sources

Myocardial disorders caused by magnesium deficiency in diabetic KK mice.

Studies were made on the diabetic state and the pathogenesis of myocardial disorders in KK mice with the following results: (1) KK mice showed glucose intolerance, hyperinsulinemia and hyperlipidemia; (2) their electrocardiograms (ECGs) showed a marked left-axis deviation of the QRS vector; (3) they showed epicardial calcification and myocardial disorders; (4) the Ca content of their myocardiums was much higher, and the Mg contents in the erythrocytes and myocardiums were much lower than those of control mice; (5) the addition of Mg to the drinking water of KK mice normalized these changes, and suppressed their myocardial disorders, but did not normalize their ECG changes. These results suggested that Mg deficiency plays an important role in the development of myocardial disorders in KK mice.

Animals↗

[Phase II study of cisplatin in advanced esophageal cancer and gastric cancer].

Twenty-four patients with advanced gastric cancer and 4 patients with advanced esophageal cancer were treated with cisplatin at a dose of 80-100 mg/m2 for one day or 10-20 mg/m2 for 5 consecutive days every 3-4 weeks. As for gastric cancer, 21 of 24 were evaluable for this study according to the criteria of the Japan Society for Cancer Therapy. Four of 21 patients (19%) showed partial response (PR), 7 displayed no change (NC), and 10 evidenced progressive disease (PD). Among 4 PR cases, only one had effective primary lesion. As for esophageal cancer, all 4 patients were evaluable, while 2 showed no change (NC) and another 2 exhibited progressive disease (PD). Gastrointestinal toxicity occurred in 20 patients despite the use of anti-emetic drugs. Nephrotoxicity and hematological toxicity were observed in 14 patients and 22 patients, respectively. These did not impede the continuous treatment except one case of hematological toxicity. It was concluded that cisplatin is more effective for the metastatic lesion of gastric cancer than primary lesion.

Adenocarcinoma↗

[Limitation of myocardial infarct size by polyethylene glycol-conjugated superoxide dismutase in a canine model of 90 min coronary occlusion followed by 4 days of reperfusion].

The role of oxygen free radicals in the genesis of myocardial reperfusion injury is supported by the studies with superoxide dismutase (SOD) which provides protection against the extention of myocardial injury. However, the efficacy of SOD may be of limited value due to its short plasma half-life of 5-6 min. Conjugation of SOD to polyethylene glycol (PEG-SOD) increases the half-life to greater than 30 hours. Forty-two male, mongrel anesthetized dogs were subjected to occlusion of left circumflex coronary artery for 90 min followed by 4 days of reperfusion. Dogs were randomized to receive either PEG-SOD (1,000 U/kg) or PEG-Albumin via left atrium, starting 15 min before reperfusion and ending simultaneously with reperfusion, and were sacrificed 4 days later. The hearts were stained by ex vivo dual perfusion technique for the determination of myocardial infarct size. Infarct size expressed as a percent of area-at-risk in PEG-SOD (n = 13) and PEG-Albumin (n = 13) treated dogs differed significantly between groups: 29.2 +/- 1.6% vs 44.2 +/- 2.6%, respectively (p less than 0.01) with no observed difference in the size of area-at-risk: 46.0 +/- 1.6% vs 44.4 +/- 1.4% (n.s.). Hemodynamic parameters between groups did not differ during coronary artery occlusion and could not account for the effect of PEG-SOD on infarct size. Collateral blood flows to the inner 2/3 of the ischemic myocardium for both groups did not differ. Plasma SOD activity in PEG-SOD group initially exceeded 20 U/kg and sustained significantly for 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Enzymatic profiles of Erysipelothrix rhusiopathiae and Erysipelothrix tonsillae.

The enzymatic activities of 39 strains of Erysipelothrix rhusiopathiae and 34 of E tonsillae were determined with the API ZYM system. The profiles of these two species were very similar, differing solely in N-acetyl-beta-glucosaminidase activity. Whereas 90 per cent of strains of E rhusiopathiae exhibited strong activity with N-acetyl-beta-glucosaminidase, positive reactions were observed for this enzyme in only 24 per cent of strains of E tonsillae. These results support previous DNA-DNA hybridisation studies and suggest that E tonsillae is a new species of the genus Erysipelothrix.

Animals↗

[Idiopathic retroperitoneal fibrosis: report of 4 cases].

We report 4 cases of idiopathic retroperitoneal fibrosis (IRF). Two cases were demonstrated by surgical biopsy, and in one of them ureterolysis was performed at the same time. After pathological diagnosis, these two patients were treated by steroid therapy. The other two patients were suspected to have acute renal failure due to IRF, and they were treated by nephrostomy or by double-J ureteral stent. In one of them retroperitoneal fibrous tissue had almost disappeared on CT examination. None of these 4 patients have had recurrence of IRF.

Acute Kidney Injury↗

Mechanism of protection induced in mice against Erysipelothrix rhusiopathiae infection by treatment with porcine antiserum to the culture filtrate of an attenuated strain.

The mechanism of protection induced in mice against challenge with a virulent strain of Erysipelothrix rhusiopathiae by porcine antiserum to the culture filtrate (CF) of an attenuated strain was investigated. Death and bacterial growth in the spleens of mice challenged with the virulent strain were completely prevented by treatment with the antiserum. The protective effect of the serum was markedly decreased in mice in which polymorphonuclear leucocytes (PMN) were depleted by cyclophosphamide (CY) treatment but not in mice in which macrophages were blocked selectively by carrageenan (CG). The phagocytic rate of PMN and the number of bacteria ingested by PMN were significantly higher in mice treated with the antiserum than in mice treated with normal serum. These results indicate that anti-CF serum exerts its protective effect by opsonic activity and that opsonized E. rhusiopathiae are eliminated mainly by PMN.

Agglutination Tests↗

Comparative effect of leukotriene B4 and leukotriene B5 on calcium mobilization in human neutrophils.

Leukotriene B4 (LTB4) is reported to exert its biological activity in neutrophils through the increase in cytosolic free calcium that follows binding to its specific receptor. Leukotriene B5 has been shown to be far less active than LTB4. Therefore we compared the capacity of LTB4 and LTB5 to stimulate the rise in cytosolic free calcium using fura-2-loaded human neutrophils, to assess the relationship between the calcium mobilizing activity and biological potency of LTB4 and LTB5. At any concentration tested, LTB5 was less active than LTB4 in increasing cytosolic free calcium. ED50 for LTB4 and LTB5 were 5 X 10(-10) M and 5 X 10(-9) M, respectively. The difference in the binding affinities of LTB4 and LTB5 to the LTB4 receptor has been reported to explain the difference in their biological activities. In the present study we further demonstrated that the calcium mobilizing activity of LTB4 and LTB5 also correlates the different biological activity of the two compounds.

Calcium↗

In vitro effect of trichosanic acid, a major component of Trichosanthes japonica on platelet aggregation and arachidonic acid metabolism in human platelets.

The in vitro effect of trichosanic acid (TCA; C18:3, omega-5), a major component of Trichosanthes japonica, on platelet aggregation and arachidonic acid (AA) metabolism in human platelets was studied. TCA dose-dependently suppressed platelet aggregation of platelet rich plasma and washed platelets. TCA decreased collagen (50 micrograms/ml)-stimulated production of thromboxane B2 (TXB2) and 12-hydroxyhepta-decatrienoic acid (HHT) in a dose-dependent manner, while that of 12-hydroxyeicosatetraenoic acid (12-HETE) was rather enhanced. The conversion of exogenously added [14C]AA to [14C]TXB2 and [14C]HHT in washed platelets was dose-dependently reduced by the addition of TCA, while that to [14C]12-HETE was increased. Similar observations were obtained when linolenic acid (LNA; C18:3, omega-3) was used. These results suggest that TCA may decrease TXA2 formation in platelets, probably due to the inhibition of cyclooxygenase pathway, and thereby reduce platelet aggregation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Cytochemical demonstration of guanase in human liver using yellow tetrazolium.

Histochemical studies of human guanase (guanine deaminase) have seldom been undertaken, in part because of technical difficulties which result in heavy background staining. We reported a modified procedure for histochemical demonstration of guanase in human tissues involving hydrolytic deamination of the substrate guanine to xanthine via guanase, and then oxidation of xanthine to uric acid, with concomitant reduction of nitrotetrazolium blue (NBT). In this report, we describe a modification of this method for cytochemical demonstration of guanase at the fine structural level using yellow tetrazolium in place of NBT for determination of the intracellular distribution of guanase in human hepatocytes. In the hepatocytes, the reaction products were seen to be concentrated in the nucleus, in mitochondria, cisternae of the smooth and/or rough-surfaced endoplasmic reticulum, and lysosomes. The precise locations of the reaction product in the cisternae of the nuclear envelope, chromosomes, and nucleus could not be determined. However, the reaction products in the mitochondria were clearly seen to be located in the spaces of cristae. This information of the intracellular distribution of guanase in normal hepatocytes will be useful in determining the physiological role of this enzyme and in further studies on diseased hepatocytes including those in non-A non-B hepatitis.

Aminohydrolases↗

Isolation of genomic DNA controlling mouse melanoma antigen defined by monoclonal antibody.

We have isolated the genomic DNA controlling the expression of murine specific melanoma antigen by employing cosmid shuttle vector and monoclonal antibody. Transfection of the cosmid library derived from mouse melanoma cells into human melanomas and repeated cell sortings of the fluorescence-bright population enabled us to enrich the antigen-positive transfectants. We rescued a 34.8 kb DNA fragment from the transfectants by in vitro packaging and showed it to be responsible for the antigen expression. However, we noticed instability of the antigen expression when the selection pressure imposed by the cell sorting was removed. This seemed to be due to the fact that the insert DNA was preferentially deleted from this cosmid vector without loss of the vector sequence itself.

Animals↗

Stiffness changes in frog skeletal muscle during contraction recorded using ultrasonic waves.

1. A technique has been developed with which the stiffness changes in frog skeletal muscle can be continuously recorded by measuring the propagation velocity of ultrasonic waves (3-7 MHz) with negligibly small perturbations to the contractile system. 2. The resting muscle stiffness was 2.256 +/- 0.002 x 10(9) N/m2 (S.D.) at 1-2 degrees C (n = 10) and 2.480 +/- 0.007 x 10(9) N/m2 at 19-20 degrees C (n = 12) in the longitudinal direction, and 2.223 +/- 0.008 x 10(9) N/m2 at 1-2 degrees C (n = 8) and 2.437 +/- 0.007 x 10(9) N/m2 at 19-20 degrees C (n = 9) in the transverse direction. 3. The resting muscle stiffness measured with ultrasonic waves was virtually insensitive to the resting force development, i.e. the extension of the parallel elastic component. 4. The longitudinal muscle stiffness increased during isometric contraction at a rate faster than the force development. The amount of increase of the longitudinal stiffness in an isometric tetanus at 2.2 microns sarcomere length was 2.4 +/- 0.1 x 10(7) N/m2 at 1-2 degrees C (n = 10) and 6.5 +/- 1.3 x 10(7) N/m2 at 19-20 degrees C (n = 12). 5. On the other hand, the transverse muscle stiffness decreased during isometric contraction at a rate faster than the force development. The amount of decrease of the transverse stiffness in an isometric tetanus at 2.2 microns sarcomere length was 5.6 +/- 0.1 x 10(7) N/m2 at 1-2 degrees C (n = 8) and 6.4 +/- 0.3 x 10(7) N/m2 at 19-20 degrees C (n = 9). 6. The amount of both the longitudinal and the transverse stiffness changes during an isometric tetanus decreased linearly with increasing sarcomere length, indicating that the stiffness changes during contraction reflect the formation of cross-links between the myofilaments. 7. Both the longitudinal and the transverse stiffness increased when resting muscle was put into rigor state. The rigor muscle stiffness was insensitive to small stretches, i.e. the strain of the rigor cross-links. 8. These results are discussed in connection with the behaviour of cross-bridges during isometric contraction and in rigor.

Animals↗

Antiseptic and antibiotic resistance plasmid in Staphylococcus aureus that possesses ability to confer chlorhexidine and acrinol resistance.

Plasmid pSAJ1 from a methicillin- and gentamicin-resistant strain of Staphylococcus aureus had am molecular size of 50 kilobases and conferred resistance not only to kanamycin, gentamicin, tobramycin, amikacin, benzalkonium chloride, acriflavin, and ethidium bromide but also to chlorhexidine. In addition, the cloned antiseptic resistance gene(s) manifested acrinol resistance in Escherichia coli.

Acridines↗

Superoxide dismutase conjugated to polyethylene glycol provides sustained protection against myocardial ischemia/reperfusion injury in canine heart.

Disagreement regarding the cardioprotective role of superoxide dismutase may relate to the use of different durations for induction of ischemic injury and reperfusion. The present study employed superoxide dismutase conjugated to polyethylene glycol (PEG-SOD), which has a half-life greater than 30 hours. Two protocols differing in the mode of administration and the duration of the reperfusion interval were used. Dogs were subjected to occlusion of the circumflex coronary artery for 90 minutes, then reperfused for 6 hours (Protocol A) or 4 days (Protocol B). The dogs received either polyethylene glycol conjugated to albumin (PEG-ALB) or PEG-SOD (1,000 U/kg). In Protocol A, treatment was administered starting 15 minutes before coronary occlusion and continued for 2 hours, terminating 15 minutes after reperfusion. Infarct size was determined 6 hours later. In Protocol B, the conjugated proteins were given 15 minutes before reperfusion and ended simultaneously with reperfusion. Infarct size was measured after 4 days. Infarct size (percentage of area at risk) in control (n = 9) and treated (n = 9) dogs in Protocol A differed between groups: 46.7 +/- 3.5% versus 28.3 +/- 2.9%, respectively (p less than or equal to 0.005); risk regions did not differ: 42.8 +/- 1.5% versus 43.8 +/- 2.1%, respectively. Myocardial salvage also was observed in Protocol B. Infarct size in control (n = 13) and treated (n = 13) groups was 44.2 +/- 2.6% versus 29.2 +/- 1.6%, respectively (p less than or equal to 0.005), with risk regions being 44.4 +/- 1.4% versus 46.0 +/- 1.6% (p = NS). Hemodynamic variables did not differ during the period of coronary artery occlusion. The respective collateral blood flows to the inner two thirds of the ischemic myocardium determined 60 minutes after occlusion were 0.05 +/- 0.01 ml/min/g and 0.06 +/- 0.04 ml/min/g (p = 0.806) for the PEG-ALB and PEG-SOD treated groups, respectively. Infarct size was related inversely to collateral blood flow in the PEG-ALB treated group. This relation shifted downward (analysis of covariance, p = 0.017). Plasma SOD activity in Protocols A sustained for 6 hours. Significant enzymatic activity was present after 4 days in Protocol B. Previous negative studies with native SOD may be related to the short half-life of its free-radical scavenging capacity, which compromises the chances of observing a protective effect after 4 days of reperfusion. The present results support our previous observations, as well as those of other investigators, demonstrating that superoxide dismutase can reduce that component of myocardial injury associated with reperfusion.

Animals↗

Functional differences in cholesterol ester hydrolase and acyl-coenzyme-A/cholesterol acyltransferase between the outer and inner zones of the guinea pig adrenal cortex.

Previous studies clearly demonstrated that cells isolated from the chromatically distinct inner (primarily zona reticularis) and outer (zona fasciculata and zona glomerulosa) zones of the guinea pig adrenal cortex have vastly different steroidogenic capabilities; the outer zone produces far more cortisol than the inner zone, and mitochondrial cholesterol side-chain cleavage activity in the inner zone is not modulated by ACTH. Thus, in this study we have investigated the characteristics and properties of cholesterol ester hydrolase (CEHase) and acyl-coenzyme-A/cholesterol acyltransferase (ACAT) in the outer and inner zones of the guinea pig adrenal to clarify the zonal difference in cholesterol metabolism. CEHase showed two pH optima at around pH 4.5 and pH 7.5 in the outer zone, while optimum activity in the inner zone was found only around pH 4.5, suggesting a lack of neutral CEHase in the inner zone. The acid CEHase was found mainly in the lysosomal fraction, and the neutral CEHase was located mainly in the microsomal fraction. The neutral CEHase activity in the outer zone was significantly enhanced by ether stress, while the acid CEHase activity was not changed in either of the two zones by stress. The basal activity of ACAT was significantly higher in the outer zone than in the inner zone. The present experiments also demonstrated that the inner zone always showed lower ACAT activity than the outer zone even when added cholesterol exogenously. It is suggested that the relatively low activity of ACAT may not always be explained by the reduced content of cholesterol in the microsomal fraction of zona reticularis. ACAT activity in the outer zone was significantly decreased by ether-induced stress, but that in the inner zone was not changed. The content of esterified cholesterol in whole homogenate and the microsomal fraction was significantly decreased in the outer zone, but not in the inner zone, by ether stress. Thus, the decrease in esterified cholesterol after ether stress seems to relate to increased neutral CEHase activity and decreased ACAT activity in the outer zone. The present observation clearly indicates that the lack of neutral CEHase and the lesser activity of ACAT in the inner zone than in the outer zone may contribute to the impaired cholesterol metabolism in the inner zone.

Acyl Coenzyme A↗