Search PubMed⌕ Search

Biomedical subjects

M Kawase

Publications and source records attributed to M Kawase.

At least 145 records · Page 8Linked to original sources
PubMed1990

Synthesis and biological evaluation of 4-fluoro-, 7-fluoro-, and 4,7-difluoro-5,6-dihydroxytryptamines.

The 5,6-dihydroxytryptamine (5,6-DHT) derivatives 4-fluoro- and 7-fluoro-5,6-DHTs (26a,b) and 4,7-difluoro-5,6-DHT (26c) were synthesized from 3-fluoroanisole (1) and 1,4-difluoro-2,3-dimethoxybenzene (13), respectively. Efficient methods were developed for the conversion of 1 to 4-fluoro- and 7-fluoro-5,6-bis(benzyloxy)indoles (12a,b, respectively), and 13 to 4,7-difluoro-5,6-[( diphenylmethylene)dioxy]indole (19) via reductive cyclization of 2-nitro-beta-(dialkylamino)styrenes prepared in situ from 2-nitrotoluenes. Indoles 12a,b and 19 were then converted to 26a-c via the corresponding indole-3-acetonitriles. The fluorine-substituted 5,6-DHTs displayed increased phenol acidities, determined spectrophotometrically, and decreased inherent potential to undergo oxidation as determined by cyclic voltammetry. Fluorine substitution did not have a significant adverse effect on the cytotoxic potential as judged from the IC50 values of 117, 125, 135, and 92 microM for 26a,c and 5,6-DHT, respectively, for the inhibition of incorporation of [3H]thymidine into the DNA of neuroblastoma clone N-2a cells in culture. Surprisingly, 26a-c exhibited 32-, 23-, and 13-fold higher affinities, respectively, compared to 5,6-DHT for the serotonergic uptake system of N-2a cells as measured by the ability of 26a-c and 5,6-DHT to antagonize the uptake of [3H]5-HT into the N-2a cells. These desirable chemical and biological properties of 26a-c should make them useful tools for the study of the molecular mechanism of neurodegenerative action of 5,6-DHT.

5,6-Dihydroxytryptamine↗
PubMed1990

Mechanism of autoxidation of 5,7-dihydroxytryptamine: effect of fluorine substitution at positions 4 and/or 6.

Analogs of 5,7-dihydroxytryptamine (5,7-DHT), namely, 4-fluoro-, 6-fluoro-, and 4,6-difluoro-5,7-DHT's (30a-c) were synthesized starting from 4-fluorophenol (7a), 4-fluorobenzyl alcohol (12) and 2,4-difluorophenol (7b), respectively. Regiospecific hydroxylation and formylation ortho to fluoro groups, both via aryllithium intermediates, were made possible by the blocking effect of tert-butyldimethylsilyloxy functions and allowed the conversion of the starting materials to the key intermediates, namely, 3,5-bis(tert-butyldimethylsilyloxy)-2-fluoro-, 4-fluoro- and 2,4-difluorobenzaldehydes (11a, b and 19, respectively). The latter were converted in one step to the corresponding benzyloxybenzaldehydes, from which indole-2-carboxylates 22a-c were synthesized via azidostyrenes 21a-c, respectively. Decarbonylation of the indole-2-carboxaldehydes (24a-c) produced from 22a-c in two steps gave 2,3-unsubstituted indoles 25a-c, respectively. Introduction of the aminoethyl side chains on C-3 of 25a-c via the corresponding indole-3-acetonitriles, and subsequent debenzylation generated the hydroxytryptamines, which were isolated as their creatinine sulfate salts 30a-c, respectively. Cyclic voltammetric studies indicated that like 5,7-DHT, 30a-c undergo electrochemical oxidation in 1 M H2SO4 via the corresponding p-quinoneimine derivatives 31a-c by an electrochemical-chemical-electrochemical (ECE) process. The voltammetrically detectable products of the ECE process appear to be the corresponding 5-hydroxytryptamine-4,7-dione (6) derivatives 33a-c. The nature of the interaction of dissolved O2 with 30a-c at pH 7.4 appears to be strikingly different from that of 5,7-DHT, which undergoes autoxidation at pH 7.4 via the 4-hydroperoxy derivative 4 to the quinone 6.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1990

Endocrinological studies on TAP-144-SR, a sustained-release formulation of a potent GnRH agonist (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide), in male rats.

The paradoxical effects of TAP-144-SR, a biodegradable sustained-release formulation of a potent GnRH agonist (TAP-144, leuprolide acetate) were evaluated in male rats by comparing its potency with that of TAP-144 solution. A single sc injection of TAP-144-SR (equivalent to 0.1 mg/kg/day as TAP-144), prepared by encapsulating the agonist in microcapsules of copoly (DL-lactic/glycolic acid), suppressed serum levels of androgens, and the levels remained suppressed for 4 weeks. The potency of the paradoxical effects of TAP-144-SR was evaluated 4 weeks after treatment by comparing it with that of TAP-144 solution administered daily for 4 weeks. Both daily injections of TAP-144 solution and a single injection of TAP-144-SR (equivalent to 0.02, 0.2 or 2 mg/kg/day as TAP-144) decreased the weight of the testes, prostates and seminal vesicles in a dose-dependent manner in a 4-week assay in male rats. TAP-144-SR was more effective than TAP-144 solution in reducing these organ weights. Serum and pituitary concentrations of LH and FSH and serum testosterone levels were also lower in TAP-144-SR-treated than in TAP-144 solution-treated rats. These results indicate that the paradoxical effects were more extensive upon TAP-144-SR treatment, suggesting that maintaining constant serum TAP-144 levels results in more extensive desensitization of the pituitary and testes. These results also suggest advantages of TAP-144-SR over TAP-144 solution in both efficacy and convenience as an anti-prostatic tumor agent.

Androgens↗
PubMed1990

Study of the internal structure of the infantile zygomatic bone.

External measurements of the zygomatic bone have been reported, but there are no reports on the internal structure. We studied the internal structure of the zygomatic bone and determined the changes in cortical bone width, cortical bone ratio to total cross-sectional area, and trabecular bone width through six periods of tooth growth and development. Zygomatic bone were fixed in resin and sliced, then the cross-sectional specimens were photographed with soft X-rays. The images were analyzed with an image processor. The specimens included the surrounding cortical bone and its internal spongy substance. The cortical bone width, cortical bone ratio, and trabecular bone width increased significantly from the period of deciduous dentition to the first early period of mixed dentition, but leveled off after that. This indicates that in addition to the growth and development of the zygomatic bone itself, its structure is also affected by the forces generated in the maxilla by mastication.

Bone Density↗
PubMed1990

[A case report of the pectoralis major muscle flap in the successful management of severe mediastinal infection].

A severe, post-mediansternotomy, mediastinitis was treated with pectoral muscle flap method. About 10 days after CABG this patient had purulent discharge, high fever, and unstable sternum. Under a diagnosis of mediastinitis, wound irrigation and systemic administration with antibiotics began, but these managements were ineffective. Therefore, we closed the chest primarily by the pectoral muscle flap method. Successful primary closure of the chest was accomplished.

Aged↗
PubMed1989

Accelerated bone resorption in senescence-accelerated mouse (SAM-P/6).

Age-associated changes in the femoral bone and in urine and serum composition were studied to understand the low bone mass in a substrain of senescence-accelerated mouse (SAM), SAM-P/6. Age-matched normal SAM-R/1 mice were used as controls. After 13 weeks of age, the concentration of hydroxyproline in the femur of SAM-P/6 was slightly but significantly lower. The urinary excretion rates of cAMP and calcium were higher in SAM-P/6 throughout the whole experimental period, and those of hydroxyproline and phosphorus were higher after 8 weeks. The serum concentrations of calcium and inorganic phosphorus of SAM-P/6 were higher at 13 and 20 weeks. At 5 weeks, the serum alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP) activities of SAM-P/6 were significantly higher. Furthermore, the serum of SAM-P/6 significantly stimulated calcium release from cultured fetal rat ulna. Since urinary cAMP and TRAP in the serum reflect the circulating level of parathyroid hormone and osteoclastic function, respectively, the present results suggest that, in SAM-P/6, accelerated bone resorption produced by a putative hyperparathyroid state causes the decrease in bone mass.

Aging↗
PubMed1989

Quantitative and morphological studies on the trabecular bones in the condyloid processes of the Japanese mandibles. Comparisons between dentulous and edentulous specimens.

Using dentulous and edentulous specimens, mathematical morphology was applied to quantities bone morphology measurements, of the trabecular bones in the condyloid processes, which form the temporomandibular joint and are the center of mandibular motion. There is a tendency for trabecular bone density and width in edentulous specimens to be comparatively lower than for dentulous specimens and a similar decrease in continuity of the trabecular bones. Values for specific length are highest in dentulous specimens, indicating a greater degree of interlocking. A degree of regularity is observed in trabecular bone orientation; in edentulous specimens trabecular bones other than major ones are fewer and thinner.

Adolescent↗
PubMed1989

[Asynchronous quadruplicate malignancies: cancer of the stomach, breast and uterus and acute leukemia].

A 71-year-old female was admitted to the Fukui Red Cross Hospital because of abnormal genital bleeding in Feb., 1987. She underwent gastrectomy for early gastric cancer (IIc) 5 years earlier, mastectomy for early breast cancer (stage I) 3 years earlier and radiation therapy (60Co 350rad x 25 days) and chemotherapy (5FU, 200 mg/day, orally) for uterine cancer (stage IIb) 2.5 years earlier. These 3 cancers had quite different histological features one from the other. Laboratory investigation revealed leukocytosis (216, 100/microliters) with 90% blasts. The bone marrow was hyperplastic with 87% blasts. Although 90% of blasts had myeloperoxidase activity, surface marker analysis of the blasts revealed T-cell (CD2, CD3) phenotypes suggesting that the disease was so-called hybrid acute leukemia. She died of intracranial hemorrhage on the 2nd hospital day. An autopsy showed generalized leukemic infiltration and residual uterine cancer without metastasis to other sites. In our country, quadruplicate malignancies including hematological malignancy have been rarely described. The possible pathogenesis of multiple cancers has been discussed.

Acute Disease↗
PubMed1989

[Tricuspid valve replacement in the true annulus of Ebstein's anomaly without involvement of atrioventricular conduction disturbance].

Two female patients with Ebstein's anomaly, aged 12 and 45 years, underwent new procedures of tricuspid valve replacement in the true annulus without involvement of atrioventricular conduction disturbance. The first patient had a relatively small atrialized right ventricle. A Dacron patch was sutured on the atrialized portion from the right ventricular side. Buttress stitches were placed on the whole of the atrialized ventricle except at the part of the His' bundle. A porcine valve was sutured in the true annulus of the tricuspid valve and on the top of the patch. The second patient had a fairly large atrialized ventricle, and plication was made only in the inferior part of the atrialized ventricle form the coronary sinus. A porcine valve was sutured in the true tricuspid annulus except at the part of Koch's triangle, where the porcine valve was placed on the false annulus.

Bioprosthesis↗
PubMed1989

[Application of epicardial approach technique to the anterior-paraseptal type Wolff-Parkinson-White syndrome].

The patient with the anterior-paraseptal type WPW syndrome was operated upon with closed heart technique (so-called epicardial approach) of cryosurgery. Following intraoperative electrophysiologic studies, with ultrasonic aspirator, the epiannular fat-pad of the anterior right atrium was completely dissected to the epicardial side of the tricuspid annulus. Then the anterior paraseptal accessory pathway on the tricuspid annulus was ablated by cryosurgery (-65 degrees C, 3 min, total 9 trials). With this method, cardiotomy and establishment of cardiopulmonary bypass were not necessary to divide the accessory pathway, and significant hemodynamic instability was not caused. But in the case of accessory pathway near interatrial septum (for example, anterior paraseptal or posteroseptal) WPW syndrome, although cryoprobe was applied just adjacent to the AV node, careful ECG monitoring throughout cryosurgery obviated the injury to the AV node.

Adult↗
PubMed1988

High-performance liquid chromatographic determination of formate as benzimidazole in biological samples.

Formate was determined as benzimidazole by high-performance liquid chromatography after reaction with o-phenylenediamine at 130 degrees C for 2 h in 1 M perchloric acid. The useful concentration range was 1.6-40 mumol/l and the determination limit was 20 pmol. The recoveries from rat liver homogenate and human urine were 90.3 +/- 2.9 and 89.4 +/- 2.5%, respectively. Using this method, the activity of formaldehyde dehydrogenase in biological samples could be measured, and also the formate concentration in the liver and urine of rats to which methanol had been administered.

Aldehyde Oxidoreductases↗
PubMed1988

2-Mercaptoethylamine, a competitive inhibitor of spermidine synthase in mammalian cells.

Spermidine synthase from rat ventral prostate was inhibited by 2-mercaptoethylamine (MEA). Inhibition of spermidine synthase by MEA was competitive with respect to one of the substrates putrescine, but not competitive with respect to the other substrate decarboxylated S-adenosylmethionine. MEA markedly depressed spermidine and spermine contents in human erythroid leukemia K562 cells, suggesting that these changes resulted from the inhibitory effect of MEA on spermidine synthase in situ.

Animals↗
PubMed1988

Study of the effect of an anti-androgen (oxendolone) on experimentally induced canine prostatic hyperplasia. I. Morphological analysis.

To investigate the effect of anti-androgens on BPH, Oxendolone (OXD), a pure anti-androgen, was tested in experimentally induced BPH in 17 beagle dogs, alone or in combination with medroxyprogesterone acetate (MPA) which displays both anti-androgenic and anti-estrogenic activity. The relatively early stage of canine BPH was induced by administration of 3 alpha-androstanediol (3 alpha-A) plus estradiol (E2) for 6 months and followed by testosterone propionate (TP) plus E2 for another 6 months during the anti-androgenic treatment. By the manipulation with T, a decrease in volume of glandular component associated with a relative increase in stromal tissue was achieved, which mimics human BPH histology. The prostate substituted with T and E2, however, gradually decreased in size. Therefore the effect of OXD or OXD + MPA was not significant against the untreated controls (T-E control). The weight of the prostate in these OXD +/- MPA groups was however significantly reduced as compared to that of BPH controls which received 3 alpha-A and E2 throughout the experimental period. On histological examination, atrophic changes were observed in the hormone-treated groups compared to the T-E control. The finding was the most striking in the OXD + MPA group with small non-involuted acini scattered in the abundant stomal tissue. This was almost identical to the appearances of castrated control groups. Atrophy may be due not only to the anti-androgenic but also to the anti-estrogenic property of MPA. A report on the hormonal background of this experiment will appear in the second article.

Androstane-3,17-diol↗