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Biomedical subjects

Y Yoshimura

Publications and source records attributed to Y Yoshimura.

At least 343 records · Page 19Linked to original sources

Synthesis and biological activity of 1-(2-deoxy-2-C-fluoromethyl- and 2-C-hydroxymethylarabinofuranosyl)-cytosines.

We newly synthesized 1-(2-deoxy-2-C-fluoromethyl- and 2-C-hydroxymethyl-arabinofuranosyl)cytosines and evaluated their biological activities. The syntheses of these compounds were achieved by radical deoxygenation of tert-alcohol of 2'-position of the corresponding fluorohydrine and acetoxymethyl derivative. 1-(2-Deoxy-2-C-fluoromethylarabinofuranosyl)cytosine (5) showed potent antileukemic and anticytomegalovirus activities.

Antineoplastic Agents↗

[A case of coronary artery bypass grafting (CABG) with acquired tracheobronchomalacia].

Acquired tracheobronchomalacia is often overlooked because the symptoms are similar to those of chronic obstructive lung disease. A 55-year-old man underwent an emergency CABG because of unstable angina pectoris. CABG was performed uneventfully. On the third day after operation, severe cough and dyspnea were persisted, followed by the episode of ventricular fibilliration. Cardiopulmonary resuscitation was necessary. CT scan of the chest showed crescent narrow deformity from the lower trachea to the right main bronchus. Bronchoscopic examination revealed 90% stenosis of the trachea during coughing, and edematous tracheal mucosa. Acquired tracheobronchomalacia is an illness of the middle-aged and the elderly and tends to be progressive. Recently, because the patients for CABG have become older, tracheobronchomalacia should be taken into consideration.

Angina, Unstable↗

Spectral sensitivity of monochromatic ERG c-wave of chicken under color adaptation.

The spectral sensitivity of the ERG c-wave was studied in the chicken under yellow or red light adaptation of various intensities, ie, 1, 3, 4 and 5 W/m2 at the corneal surface in the former, and 3, 4 and 5 W/m2 in the latter. The peak wavelength of the spectral sensitivity curve of the c-wave amplitude under both yellow and red light adaptations was 520 or 540 nm, being shorter as compared with the peak wavelength (560 nm) under white light adaptation (Fukuda, 1989). Under the yellow or red light adaptation the sensitivity of the c-wave was suppressed at a range of longer wavelength, suggesting a possible isolation of the blue and green cone-driven c-wave responses. The peak (520 or 540 nm) and the shoulder (580 nm) in the spectral sensitivity curves were presumed to be derived from the three cone systems.

Adaptation, Ocular↗

[A case of Fontan operation for complex heart disease with good post-operative course by the management of hypothermia in coming off from cardiopulmonary bypass].

A 8-year-old boy with a complex heart disease was underwent Fontan operation with Glenn operation, and had a good post-operative course by the management of hypothermia in coming off from cardiopulmonary bypass around 31 degrees C. The hypothermic therapy was thought to be effective in acute stage after Fontan operation, because it improved tachycardia, decreased the systemic metabolism, redistributed the systemic arterial blood flow and increased the urinary output.

Child↗

[Mitral valve re-replacement for a patient with multiple myeloma].

Mitral valve re-replacement was successfully undertaken in a 70-year-old female patient with primary tissue failure of mitral bioprosthesis and multiple myeloma (MM) through right lateral thoracotomy with minimum dissection. Considering the post-operative anti-coagulant therapy, bioprosthesis was chosen in this complicated case. Patients with MM usually show a bleeding tendency associated with abnormally elevated IgG which covers the surface of coagulation factors. Safety range of serum IgG concentration in the patients with MM who require open heart surgery, have not defined yet. Excessive serum IgG leads the coagulation disorder and organ perfusion problem because of increase of blood viscosity. Those problems become serious when the serum IgG concentration exceed 2,500 mg/dl. (1) Only if serum IgG level below 2,5000 mg/dl, valve replacement will be able to perform safely with minimum dissection through the thoracotomy for patients with MM. (2) Bioprosthesis might be optionally chosen in such case (3). In case of serum IgG level over 2,500 mg/dl, preoperative plasma ex-change should be recommended.

Aged↗

[Changes in heart rate during and after enflurane-nitrous oxide anesthesia].

Changes in heart rate of 21 patients who received enflurane-nitrous oxide anesthesia were studied. They had no cardiac, pulmonary, nervous system and endocrine diseases. We measured coefficient of variation of R-R intervals (CV) and power spectrum of heart rate fluctuation in 6 periods, (1) control phase (the day before operation), (2) during operation under enflurane-nitrous oxide anesthesia, (3) ten minutes after endotracheal extubation, (4) sixty minutes after arrival in the recovery room, (5) the next morning and (6) the next evening. The patients who were 15-25 years old, showed larger value of CV and larger power of low frequency component (0.03-0.1 Hz, LFC) as well as high frequency component (0.2-0.45 Hz, HFC) compared with patients who were 40-50 years old during control phase. They showed a significant decrease of CV, LFC and HFC in period (2), (3) and (4) but not in (5) and (6). These evidences show that autonomic nervous system is impared after enflurane-nitrous oxide anesthesia until the next morning.

Adolescent↗

Possible multifunction of glucose transporter. Transport of nicotinamide by reconstituted liposomes.

A kinetic study of the uptake of nicotinamide by reconstituted liposomes containing the human erythrocyte glucose transporter, compared with that of D-glucose, demonstrated that the Km and Vmax. values were almost the same for each compound, and that the uptake of D-glucose was competitively inhibited by nicotinamide. At 20 mM concentration, 2-deoxy-D-glucose, 3-O-methyl-D-glucose and 4,6-O-ethylidene-D-glucose all caused 50% inhibition of nicotinamide uptake, but L-glucose and nicotinic acid were not inhibitory. Similar results were obtained for the uptake of D-glucose. Cytochalasin B binding to the liposomes was inhibited in a dose-dependent manner by either nicotinamide or D-glucose. Antibody for glucose transporter detected in band 4.5 by SDS/PAGE inhibited the uptake of D-glucose and nicotinamide. A possible uptake of nicotinamide by nucleoside transporter was excluded. In human erythrocytes, cytochalasin B binding was inhibited dose-dependently by either nicotinamide or D-glucose, and cytochalasin B depressed the uptake of both nicotinamide and 2-deoxy-D-glucose. These findings were well reproduced in the reconstituted liposomes. The very close similarities between uptake of nicotinamide and D-glucose suggest that the glucose transporter plays a direct role in transport of nicotinamide, which is structurally quite different from monosaccharides, and thus that the transporter is probably multifunctional.

Biological Transport↗

Angiotensin II directly induces follicle rupture and oocyte maturation in the rabbit.

To investigate the possible direct involvement of angiotensin II (Ang II) in ovulation and oocyte maturation, Ang II at 100 or 10 micrograms was administered at 2-h intervals in the in-vitro perfused rabbit ovaries. The addition of Ang II in the perfusate induced ovulation in vitro in the absence of gonadotropin, while ovulation did not occur in any contralateral control ovaries. However, the ovulatory efficiency in the Ang II-treated ovaries was significantly lower than in hCG-treated ovaries. Ang II significantly stimulated the meiotic maturation of ovulated ova and follicular oocytes. Concomitant addition of the specific receptor antagonist of Ang II, saralasin, 30 min before the onset of Ang II administration blocked Ang II-induced ovulation in a complete manner. Although saralasin did not inhibit completely hCG-induced ovulation and oocyte maturation, these results suggest that Ang II produced in the ovary may act locally in the process of ovulation.

Angiotensin II↗

Mutations in the Trp-Ser-X-Trp-Ser motif of the erythropoietin receptor abolish processing, ligand binding, and activation of the receptor.

The erythropoietin receptor (EPOR) is a member of the newly identified cytokine receptor superfamily. A common sequence motif, Trp-Ser-X-Trp-Ser (WSXWS), near the transmembrane domain is highly conserved in this family. To determine the function of this motif, we constructed deletion and insertion mutations in this part of the EPOR and introduced them into an interleukin-3 (IL-3)-dependent hematopoietic Ba/F3 cell line. Cells expressing the wild-type EPOR displayed 1,500 erythropoietin (EPO)-binding sites/cell with a single affinity of about 300 pM and proliferate in the presence of IL-3 or EPO. Ba/F3 cells expressing receptors mutated in the WSXWS motif displayed little EPO binding on the cell surface and did not grow in the presence of EPO. The mutant receptors were retained in the endoplasmic reticulum (ER) and, as such, were unable to bind EPO. A single Gly insertion between the two WS sequences caused defects in receptor structure and function similar to mutations lacking all or part of the WSXWS motif. The EPOR can be activated, resulting in proliferation independent of EPO either by an Arg129 to Cys point mutation or by association with the Friend spleen focus-forming virus (SFFV) envelope glycoprotein gp55. Introduction of the point mutation (Arg129 to Cys) did not activate any of the receptors mutated in the WSXWS motif. Moreover, gp55 did not activate the mutant receptors in Ba/F3 cells. Our study indicates that the WSXWS motif is critical for protein folding, ligand-binding, and signal transduction.

Amino Acid Sequence↗

Homodimerization and constitutive activation of the erythropoietin receptor.

The erythropoietin receptor (EPO-R) is a member of the recently described cytokine receptor superfamily. A constitutively active (hormone independent) form of the EPO-R was isolated that has a single amino acid change in the exoplasmic domain, converting arginine-129 to cysteine (R129C). Since EPO-Rs containing R129S, R129E, and R129P mutations are functionally wild type, the presence of cysteine at residue 129, and not the loss of arginine, is required for constitutive activity. Several mutant forms of the EPO-R were analyzed; all constitutively active mutants form disulfide-linked homodimers, whereas EPO-responsive or inactive forms of the receptor do not. Monomers and disulfide-linked dimers of the constitutive receptor are present on the plasma membrane and bind EPO with a single affinity. Homodimerization of the EPO-R is likely to play a role in ligand-induced signal transduction, and disulfide-linked dimerization of the constitutive receptor may mimic this step.

Animals↗

Interaction of bovine serum albumin with the surface of a microcrystalline aluminum oxide hydroxide compound: a possible new type of phosphate adsorbent.

Aluminum hydroxide gel (ALG) has been effective for ameliorating acidosis associated with phosphatemia caused by hemodialysis. However, aluminum accumulation in the body causes severe side effects. As substitute for ALG, a new type of aluminum oxide hydroxide (tentatively named PT-A) was prepared with the hope of future clinical use. PT-A has a microcrystalline structure with a high resistance to pH change and has more phosphate-binding efficacy than ALG. It was tested for possible interaction with protein by adsorption test, zeta-potential analysis, X-ray diffraction, and scanning electron microscopy. Bovine serum albumin (BSA) was chosen as a model protein. The interaction of BSA with PT-A depended on the amount of adsorbent. Protein adsorption occurred rapidly and reached the maximal level at near neutral pHs. Phosphate adsorption was not affected by the presence of BSA, but the interaction of BSA with PT-A was significantly reduced by the presence of phosphate. Zeta-potential changes on the surface of PT-A indicated that the positively charged surface of PT-A was covered with negatively charged phosphate ions that repelled negatively charged BSA molecules. X-ray diffraction patterns indicated no observable structural alteration caused by adsorption of BSA or phosphate, and scanning electron microscopy revealed that BSA covered the outer surface of PT-A but did not cover small pores, where phosphate can freely penetrate.

Adsorption↗

Changes in protein kinase C activity in rat calvarial bone cells cultured in a low-calcium environment.

This enzyme activity was examined in bone cells cultured for 8-10 days; the calcium concentration was 1.87 +/- 0.05 (n = 10) mM in the control medium and 0.34 +/- 0.02 (n = 10) mM in the low-calcium medium. The activity was significantly lower in the low-calcium group than in the control (p less than 0.01). The cytosolic fraction decreased more than the membranous fraction. After restoration to a regular calcium environment, the protein kinase C activity recovered rapidly to near the control value. The extent of recovery was greater in the membranous than in the cytosolic fraction. These results suggest that the enzyme was inhibited in bone cells placed in a low-calcium environment, while the sensitivity in the membrane was enhanced.

Animals↗

Prototype of a reflux-preventing ureteral stent and its clinical use.

We have experimentally produced a ureteral stent which prevents vesicorenal reflux. This stent has a thin silicon sleeve at its distal end (intravesical portion). In a model experiment the sleeve demonstrated an excellent capability to prevent reflux. The sleeve allowed flow of fluid with minimal pressure rise. A patient with bilateral ureteral obstruction was managed with endoscopic insertion of a sleeved stent in the right ureter and a usual pigtail stent in left ureter. During cystography vesicorenal reflux was not observed on the right side while reflux occurred on the left side. Excretory urography forty days after stent placement demonstrated recovery of renal function and maintenance of drainage in both renal units. Thus, the drainage characteristic of this stent appears to be approximately the same as that of usual stent.

Drainage↗

Tongue cancer treated with irradiation: assessment with MR imaging.

We examined the usefulness of MRI in differentiating post-radiation scar tissue from the residual tumour. Ten consecutive patients who underwent MR imaging before and after radiation therapy were assessed prospectively. T1- and T2-weighted images using a 1.5 unit were obtained in 10 patients (3 T1, 6 T2, 1 T3) at 1 week before irradiation, and 2 weeks, 2 months, 4 months, 6 months and every 6 months thereafter following completion of radiation. Although all T2 and T3 tumours demonstrated high signal intensity compared to muscle on T2-weighted images, the T1 tumour could be demonstrated in only one of three patients. Six patients in whom the primary tumour clinically disappeared demonstrated low signal intensity on T2-weighted images until 4 months after completion of radiation therapy (range 1 week to 4 months). This study suggests that MRI can detect primary tumours larger than T2 (2 cm), and may be useful in assessing the effectiveness of therapy for tongue cancer.

Adult↗

Direct effect of gonadotropin-releasing hormone agonists on the rabbit ovarian follicle.

OBJECTIVE: To determine if gonadotropin-releasing hormone agonist (GnRH-a)-induced oocyte maturation and degeneration can be attributed to the direct actions on the follicle. DESIGN: Mature rabbit follicle culture. INTERVENTIONS: The mature follicles were cultured with human chorionic gonadotropin (hCG) (100 ng/mL), buserelin acetate (10(-9) to 10(-6) M), leuprolide acetate (10(-9) to 10(-6) M), or buserelin acetate (10(-7) M) with a GnRH antagonist (10(-8) to 10(-6) M) for 14 hours. MAIN OUTCOME MEASURES: The percentage of oocytes achieving germinal vesicle breakdown, the oocyte degeneration rate, prostaglandins (PG) production by mature follicles, and the frequency of fertilization and embryonic development. RESULTS: Gonadotropin-releasing hormone agonist induced the meiotic maturation of follicle-enclosed oocytes in a dose-dependent manner while concomitantly increasing oocyte degeneration. The simultaneous addition of GnRH antagonist inhibited significantly GnRH-a-induced oocyte maturation and PG production by the mature follicles. Furthermore, a GnRH antagonist reversed the oocyte degeneration rate that had been increased by GnRH-a. The rates of normal fertilization and early embryonic development were significantly reduced in the oocytes matured by GnRH-a as compared with those matured by hCG. CONCLUSIONS: Gonadotropin-releasing hormone agonist acts directly on mature rabbit follicles to trigger the oocytes to undergo meiotic maturation, but oocytes matured in vitro by GnRH-a are not necessarily cytoplasmically mature.

Animals↗

Effects of prolactin on ovarian plasmin generation in the process of ovulation.

The present study was undertaken to assess the effects of prolactin (PRL) on gonadotropin-induced plasmin generation in the in vitro-perfused rabbit ovary. The ovarian plasmin activity was determined by measuring plasmin bound to its major inhibitor, alpha 2-plasmin inhibitor (alpha 2 PI-Plm). In the first experiment, exposure to hCG enhanced ovarian alpha 2 PI-Plm generation from 1.2 +/- 0.3 ng/min/ovary in unstimulated ovaries to 2.9 +/- 0.3 ng within 2 h. The concentration of alpha 2 PI-Plm reached a maximum at 4 h and then declined. A second peak occurred 8 h after hCG administration; however, the ovarian alpha 2 PI-Plm generation without hCG was very low throughout the entire perfusion period. In the subsequent experiment, the addition of PRL(10-10(3) ng/ml) to the perfusate inhibited hCG-induced ovulation in a dose-dependent manner. Exposure to PRL at 10(3) ng/ml significantly (p less than 0.05) inhibited hCG-induced alpha 2 PI-Plm generation in ovaries throughout the entire perfusion period. Furthermore, PRL inhibited hCG-stimulated alpha 2 PI-Plm generation at 4 h after hCG administration in the perfused rabbit ovaries in a dose-dependent manner. In conclusion, PRL directly inhibits hCG-induced ovulation in rabbit ovary, at least in part, by a mechanism depending upon inhibition of the plasmin-generating system in the preovulatory follicles.

Animals↗