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Biomedical subjects

Y Yoshimura

Publications and source records attributed to Y Yoshimura.

At least 199 records · Page 11Linked to original sources

[Warm heart surgery facilitates atrioventricular valve repair].

The valve structure varies with cases in children's atrioventricular valvular regurgitation. Filling the left ventricle simply with cold saline solution and testing the valve competency in the cold cardioplegic arrest do not clarify true valve function, although it was the widely used method. Three dimensional evaluation of the lesion in the dynamic and more nearly normal state and the very fine operative procedure in the static state are required for the successful repair. For this purpose we employed the warm heart surgery on 12 children for valve repair (age 1.3-10.1 years, body weight 6.6-28.2 kg). Because no topical cooling was used, preparation of the heart from the adhesion caused by previous operation was not necessary. The aorta was cross clamped at the temperature of 34 degrees of centigrade with continuous coronary perfusion and the lesion in the valve structure and the regurgitation stream were inspected in the beating state, then the repair was performed in the arrest state obtained by infusing the potassium into the coronary perfusion line. Beating and arrest was repeated 2-5 times by on-off potassium infusion until the repair seems satisfactory. In two cases, the repair was not feasible and mitral valve replacement was performed, but in other 10 cases, the postoperative regurgitation decreased down to the grade 2. Despite prolonged aortic cross clamping (65-216 min), post-operative course was quite satisfactory without low-output syndrome in any cases. Postoperatively administered maximum dose of Dopamine was 4.0 +/- 2.2 micrograms/kg/min. CK-MB at 1 POD was also within normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Temperature

[Application of the warm heart surgery to the open heart surgery in children].

Application of the warm heart surgery to the children's open heart surgery has been reluctant, because keeping the operative field dry thought to be difficult. In this report, the clinical result of 22 cases of children's open heart surgery using warm heart surgery (Warm Group) was compared with that of other 25 cases using conventional cold cardioplegia (Cold Group). In warm group, rectal temperature was kept at 34 degrees C, continuous coronary perfusion rate was 3 ml/kg/min, and potassium ion concentration for inducing the initial cardiac arrest was 20 mEq/l, and the maintaining dose was 12-17 mEq/l. There were two deaths in Cold group. In warm group, keeping the operative field dry was not difficult by using the specially devised small sucker (2 mm diameter) and, if necessary, temporarily stopping the coronary perfusion (maximum for 7 min). Aorta cross cramping time/total extracorporeal circulation time, CK-MB at 1-POD and maximum dose of dopamine and dobutamine proved the better myocardial protection in warm group (p < 0.01). From this study, it was concluded that warm heart surgery can be applied for children with no difficulty, and showed superior myocardial protection.

Body Temperature

Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of potential prodrugs of benzimidazole-7-carboxylic acids.

In order to improve the oral bioavailability (BA) of 2-butyl-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimid azole - 7-carboxylic acid (3: CV-11194) and 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl]-1H-benzimidazole-7-carboxylic acid (4: CV-11974), novel angiotensin II (AII) receptor antagonists, chemical modification to yield prodrugs has been examined. After selective tritylation of the tetrazole rings in 3 and 4, treatment of N-tritylated benzimidazole-7-carboxylic acids (6, 7) with a variety of alkyl halides, followed by deprotection with hydrochloric acid, afforded esters of 3 and 4. Mainly 1-(acyloxy)alkyl esters and 1-[(alkoxycarbonyl)oxy]alkyl esters, double ester derivatives, were synthesized. Their inhibitory effect on AII-induced pressor response in rats and oral BA were investigated. (Pivaloyloxy)methyl and (+/-)-1-[[(cyclohexyloxy)-carbonyl]oxy]ethyl esters of 3 and 4 showed marked increases in oral bioavailability which significantly potentiated the inhibitory effect of the parent compounds on AII-induced pressor response. Among them, (+/-)-1-[[(cyclohexyloxy)carbonyl]oxy]ethyl 2- ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimida zole- 7-carboxylate (10s, TCV-116) was selected as a candidate for clinical evaluation.

Administration, Oral

A mouse homolog of the Escherichia coli recA and Saccharomyces cerevisiae RAD51 genes.

Analysis of mitotic and meiotic recombination in mammalian cells has been hampered by the complexity of the reactions involved as well as lack of mutants. Furthermore, none of the genes involved in the process has yet been identified. In budding yeast, Saccharomyces cerevisiae, the RAD51 gene is essential along with other genes of the RAD52 epistasis group for mitotic and meiotic recombination and DNA repair. The Rad51 protein is structurally similar to Escherichia coli RecA protein, which is required in homologous recombination and SOS responses in bacteria. Here we report the isolation of a mouse homolog of the yeast RAD51 gene. The amino acid sequence predicted from the gene shows 83% and 55% homology with those of the yeast RAD51 and the E. coli recA product, respectively. The mouse gene complemented a rad51 mutation of S. cerevisiae with sensitivity to methyl-methanesulfonate, which produces double-strand breaks of DNA. This gene is expressed in the thymus, testis, ovary, spleen, and intestine, suggesting that its product is involved in mitotic and meiotic recombination in addition to DNA repair.

Amino Acid Sequence

ADP modifies the function of the glucose transporter: studies with reconstituted liposomes.

Modification of function of the glucose transporter by nucleotides was studied by using liposomes reconstituted with the human erythrocyte glucose transporter. ADP enclosed in the liposomes inhibited the uptake of D-glucose and nicotinamide in a dose-dependent manner, but other enclosed nucleotides (ATP, AMP, CDP, GDP, UDP) showed no effect on the uptake of both. Only intraliposomal ADP was effective, and extra-liposomal ADP was not, under our experimental conditions. Intraliposomal ADP did not change Km, but decreased Vmax to approximately one-third of control for uptake of both D-glucose and nicotinamide. However, the binding and the affinity of cytochalasin B to the reconstituted liposomes were not affected by intraliposomal ADP. The uptake of uridine was not changed in the presence of ADP, indicating that the nucleoside transporter co-existing in the liposomal membranes is not regulated by ADP. Human erythrocytes whose intracellular ATP was decreased by Ca2+ ionophore A23187 also showed decreased uptake of 2-deoxy-D-glucose and nicotinamide. This phenomenon was very similar to that found in the liposomes. These findings suggest the possibility that the function of the glucose transporter is directly and negatively modified by an increased concentration of intracellular ADP.

Adenosine Diphosphate

c-fos m-RNA expression after treatment with fetal bovine serum and epidermal growth factor for osteoblastic MC3T3-E1 cells cultured in a low calcium environment.

This paper examines the existence of c-fos mRNA expression in osteoblastic MC3T3-E1 cells cultured in a low calcium environment. The MC3T3-E1 cells were placed in a serum free medium for 24 hours after subconfluence and then the cells were treated with fetal bovine serum and epidermal growth factor for 0, 5, 10, 15, 30, or 60 minutes. The c-fos m-RNA expression was found in the MC3T3-E1 cells cultured in both normal medium (control group) and low Ca medium (low Ca groups). The degree of expression was significantly higher in the low Ca group than in the control group in each treatment period (p < 0.01) and in both groups, after the treatment with FBS or EGF, the expression levels increased with time at 5 and 10 minutes but decreased at 15 minutes. Thereafter, levels increased again to reach to a maximum at 30 minutes after which it decreased rapidly. On the other hand, in both groups, after the treatment with EGF, the expression increased at 30 minute. This suggests that the MC3T3-E1 cells placed in a low calcium environment react to restore cell functioning to normal at the gene level.

Animals

Automated high-performance liquid chromatographic determination of hydroxylysylpyridinoline and lysylpyridinoline in urine using a column-switching method.

An on-line urine clean-up system was developed for the simultaneous determination of free and total pyridinoline, hydroxylysyl-pyridinoline (HP) and lysylpyridinoline (LP) by high-performance liquid chromatography (HPLC) using a column-switching technique. The method is based on a combination of gel permeation chromatography (GPC) and ion-pair reversed-phase HPLC. In the GPC column, pyridinoline is preseparated from endogenous urinary substances with 0.03 M heptafluorobutyric acid (HFBA) as the mobile phase. After column switching, the eluate fraction containing pyridinoline is further separated by ion-pair chromatography using an octadecylsilica (ODS) column with 0.03 M HFBA-acetonitrile (81:19) as the mobile phase. The detection limits were 36 and 44 pmol/ml for free and total HP, respectively, and 44 pmol/ml for both free and total LP at a signal-to-noise ratio of 3. The coefficients of variation for free and total pyridinoline were 1.5 and 3.5%, respectively. The determination of one sample including the clean-up is completed within 25 min. This system is precise and is useful for the determination of pyridinoline in large amounts of urine. The usefulness of pyridinoline as a biomedical marker for bone resorption was also examined.

Amino Acids

Effect of intravenous immunoglobulin on inhibition of fibrinogen binding to platelets by sera from patients with immune thrombocytopenia.

We previously described an ELISA to measure the inhibition of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) binding to fibrinogen due to immune complexes and/or anti-platelet antibodies from patients with immune thrombocytopenia (ITP) or HIV-related ITP. Circulating immune complexes (CIC) were the main factor in the inhibition of GPIIb/IIIa binding to fibrinogen in HIV-related ITP, whereas in non-HIV ITP, inhibition was only partially due to CIC; anti-platelet antibodies specific to GPIIIa were also shown to play a role. In this study, we correlated the rise in the platelet count after intravenous immunoglobulin (IVIG) infusion with the decrease in inhibition of fibrinogen binding to GPIIb/IIIa by the sera of patients with ITP and HIV-related ITP. In the majority of the patients' sera tested, as the platelet count increased following the administration of IVIG, the degree of inhibition of GPIIb/IIIa binding to fibrinogen decreased. We also observed a decrease and/or disappearance of the antibodies specific to GPIIb and/or GPIIIa after IVIG administration. In HIV-seronegative ITP patients, the decrease or disappearance of anti-platelet antibodies directly correlated with the decreased inhibition of GPIIb/IIIa binding to fibrinogen by the 2% PEG supernatants of sera which contained anti-platelet antibodies. These findings suggest that IVIG directly affects the binding of CIC and anti-platelet antibodies to platelets and thereby improves platelet survival. Our results also suggest that the anti-idiotypic effect may contribute to IVIG's therapeutic action. In contrast, in the HIV-seropositive group, the decreased inhibition by PEG precipitates after IVIG administration was more strongly associated with an increase in the platelet count.

Antibodies

Mechanism of phosphate adsorption to a three-dimensional structure of boehmite in the presence of bovine serum albumin.

A new microcrystalline boehmite (tentatively named PT-A) was synthesized as an efficient phosphate adsorbent to replace aluminum hydroxide gel. The characteristic structure of PT-A was examined by nitrogen adsorption/desorption, X-ray diffraction, deviation microscopy, and scanning electron microscopy to establish a pore structural model of PT-A. With this model structure, the details of the mechanism of interaction between PT-A and phosphate in the presence of bovine serum albumin (BSA) are discussed. PT-A is a spherical particle with a diameter of approximately 100 microns and a porous surface structure, and its inside is packed with boehmite microcrystals (crystallite size, 2 nm). PT-A has three types of pores in its structure: a micropore with a narrow size-distribution, a mesopore with a broad size-distribution, and a macropore (radii of pores are 0.7, 1-20, and approximately 300 nm, respectively). When phosphate was incubated with PT-A in human gastric and intestinal juices or in an aqueous solution containing BSA, the amounts of phosphate adsorbed by PT-A were not affected by the presence of proteins. The nitrogen adsorption/desorption isotherms and energy dispersive X-ray analyses demonstrated that phosphate could diffuse to the smaller tunnels freely even if the external surface of PT-A was covered with BSA. It was also demonstrated that the main site of adsorption for phosphate was in micropores of PT-A, whereas BSA was adsorbed only to the external surface and none entered inside smaller tunnels consisting of micro- and mesopores.

Adsorption

Immunolocalization of androgen receptor in the small, preovulatory, and postovulatory follicles of laying hens.

Previous studies have indicated that androgens may act directly on the ovarian follicles to regulate their functions. The aim of this study was to localize androgen receptor (AR) in the small, preovulatory and postovulatory follicles of laying hens by an immunocytochemical method and Western blot analysis. Small follicles embedded in the stroma (SF), small white follicles protruding from the surface of ovary (SWF), the third largest (F3) and largest follicles (F1), and the most recent postovulatory follicle (POF) were obtained from hens approximately 4 or 10 hr before the expected time of ovulation. Frozen sections of these follicles were immunostained by using anti-human AR antibody. Furthermore, the granulosa cells and theca tissue of preovulatory follicles (F1 and F2) approximately 4 hr before the expected time of ovulation were processed for western blot analysis for AR. The majority of granulosa cell of SF showed negligible AR immunoreaction, whereas all of the granulosa cells of SWF, F3, F1, and POF exhibited a strong AR immunoreaction. Thecal interstitial cells in SWF, F3, and F1 stained positive for AR, and those in POF showed only a weak immunoreaction. The thecal fibroblasts of SWF, F3, and F1 also showed a positive AR immunoreaction, whereas those of POF stained weakly. No significant difference in the AR localization in the ovary was observed between 4 and 10 hr before the expected time of ovulation. Western blot analysis indicated that the granulosa cells and thecal tissue contained AR protein of molecular weight of approximately 120,000.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Calcium control of actin-myosin-based contraction in Triton-treated murine bladder tumor cells.

Using mouse bladder tumor cells (MBT-2 cells) and epithelial cells, the present study evaluated the functional characteristics of the actomyosin system in bladder cancer cells. An immunofluorescence study demonstrated the presence of contractile proteins (actin and myosin) in MBT-2 cells as well as bladder epithelial cells. Triton-treated MBT-2 cells and epithelial cells showed a Ca(2+)-dependent contraction. This was inhibited by N-ethylmaleimide-modified myosin subfragment 1 (NEM-S1), demonstrating that the interaction between actin and myosin is responsible for the contraction of Triton-treated cells. The extent of Ca(2+)-dependent contraction was much greater in MBT-2 cells than in epithelial cells. These results suggest that MBT-2 cells possess a locomotive apparatus consisting of actin and myosin, and that Ca2+ can activate this actomyosin system, leading to the contraction or active locomotory movement of tumor cells.

Actins

Effects of growth hormone on follicle growth, oocyte maturation, and ovarian steroidogenesis.

OBJECTIVES: To assess the effects of GH on follicle growth, oocyte maturation, ovulation, and ovarian steroidogenesis. DESIGN: In vitro perfused rabbit ovary. INTERVENTIONS: The rabbit ovaries were perfused with medium alone, with GH at 1, 10, 100, or 200 ng/mL, or with 50 IU hCG for 12 hours. MAIN OUTCOME MEASURES: The follicle diameter, the percent change in follicle diameter, the percentage of oocytes achieving germinal vesicle breakdown, and the production of P and E2 by the perfused rabbit ovaries. RESULTS: The addition of GH to the perfusate increased the follicle diameter at 12 hours after perfusion in a dose-dependent manner. The percent change in follicle diameter in GH-treated ovaries did not differ significantly from that in hCG-treated ovaries at each time point of perfusion. However, ovulation did not occur in either the control ovaries or the experimental ovaries treated with GH. Exposure to GH at a concentration of > 10 ng/mL significantly stimulated the resumption of meiosis, as compared with the contralateral control ovaries. Although the concentration of P in the perfusate did not differ significantly between GH-treated and control ovaries, GH stimulated E2 production by the perfused rabbit ovaries in a dose-dependent manner. CONCLUSIONS: Growth hormone acts on the rabbit ovary to stimulate follicle growth, oocyte maturation, and ovarian E2 production.

Animals

Comparative study of hormonal dynamics in pregnant and nonpregnant cycles during pulsatile subcutaneous administration of human menopausal gonadotropin in anovulatory infertile women.

OBJECTIVE: To assess the clinical relevance of daily hormonal changes for achieving a successful pregnancy in anovulatory infertile women. DESIGN: A comparative study of hormonal dynamics in pregnant and nonpregnant cycles during the pulsatile subcutaneous administration of hMG. Subjects received subcutaneous injection of either 9.375 IU or 14.0625 IU of hMG diluted in 50-microL physiological saline (total daily dose, 150 or 225 IU) at 90-minute intervals by means of a portable peristaltic pump. SETTING: Kyorin University Hospital and Ichikawa General Hospital. PATIENTS: We analyzed 18 pregnant and 42 nonpregnant cycles in 17 patients with secondary hypothalamic/pituitary amenorrhea who conceived after receiving pulsatile hMG treatment. Another 14 women with normal spontaneous ovulation, including 14 pregnant and 15 nonpregnant cycles, served as controls. MEASUREMENTS: Serum concentrations of LH, FSH, E2, and P were measured, and the P:E2 ratio was determined. RESULTS: Serum concentrations of LH and FSH did not differ significantly between the pregnant and nonpregnant cycles. Serum levels of P and E2 were significantly higher during the hMG treatments than those of the spontaneous ovulatory cycles throughout the follicular and luteal phases. Up to the midluteal phase, the P and E2 values in the nonpregnant cycles during the hMG treatments did not differ significantly from those in the pregnant cycles. The P:E2 ratios were comparable between the pulsatile stimulatory cycles and the normal spontaneous ovulatory cycles. However, the P:E2 ratio in the early and midluteal phases was significantly greater in the pregnant cycles than in the nonpregnant cycles. CONCLUSION: The P:E2 ratio in the early and midluteal phases is a more important indicator of hormonal function for implantation than the absolute levels of either P or E2.

Adult

Superoxide anion generation from peripheral blood neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine in oromaxillary cancer patients.

Superoxide anion (O2-) generation levels in peripheral blood neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine were evaluated in patients with oromaxillary cancer. The levels in patients with benign tumors were nearly equal to those of normal controls. Patients with squamous cell carcinoma in stage I and II had levels that were widely distributed. On the other hand, O2- generation levels in the advanced stages (III and IV) of squamous cell carcinoma showed lower levels than those of controls (P < .01). All cases of oromaxillary carcinoma showed low levels of O2- generation within 1 month before death compared with controls (P < .01). The generation levels of O2- in the posttreatment period were lower than those before combination cancer treatments. Among cancer treatments such as chemotherapy, surgery, and irradiation, the latter had the strongest effects on O2- generation. These results suggest that low levels of O2- generation by peripheral blood neutrophils may reflect a worsening status of oromaxillary cancer patients.

Adenocarcinoma