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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 739 records · Page 41Linked to original sources

Pharmacological studies on antidiarrheal effects of Hange-shashin-to.

We attempted to characterize the antidiarrheal action of Hange-shashin-to (TJ-14), a kampo medicine, by comparing its action with that of loperamide. The oral administration of TJ-14 caused the dose-dependent suppression of castor oil-induced diarrhea at 250 to 1000 mg/kg. No significant repression was noted by TJ-14 even at 1000 mg/kg, p.o. for diarrhea induced by pilocarpine, serotonin or barium chloride. Oral treatment with loperamide at 5 mg/kg markedly suppressed diarrhea induced by castor oil and barium chloride. Contractions of isolated guinea pig ileum in response to acetylcholine (1 x 10(-7) g/ml), histamine (1 x 10(-7) g/ml) or barium chloride (3 x 10(-4) g/ml) were little affected by TJ-14 at 10(-4) g/ml. The responses elicited by the three contractive drugs were dose-dependently suppressed by loperamide. TJ-14 did not affect the small intestinal transit even at an oral dose of 1000 mg/kg. On the other hand, the small intestinal transit was significantly suppressed by loperamide (5 mg/kg, p.o.). These results indicate that TJ-14 can effectively control castor oil-induced diarrhea, and that its antidiarrheal action was not based on the suppression of intestinal motility.

Animals↗

Studies on aromatase inhibitors. I. Synthesis and biological evaluation of 4-amino-4H-1,2,4-triazole derivatives.

Various 4-N-substituted amino-4H-1,2,4-triazole derivatives were synthesized and evaluated for aromatase-inhibitory activity (in vitro) and for pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis-inhibitory activity (in vivo). The 4-(4-cyanophenyl) amino derivative and 4-(4-nitrophenyl)amino derivative, each possessing a strong electron-withdrawing group on the phenyl moiety, showed potent aromatase-inhibitory activity. Structure-activity relationship studies indicated that 4-[(4-bromobenzyl)(4-cyanophenyl)amino]-4H-1,2,4-triazole (5k, YM511) is a highly potent aromatase inhibitor with IC50 values of 0.4 and 0.12 nM in in vitro experiments using rat ovary and human placenta, respectively, and an in vivo ED50 of 0.002 mg/kg in rats on oral administration. YM511 was also a weak inhibitor of other steroid hormone synthesis enzymes. These data suggest that YM511 is a highly selective aromatase inhibitor and may be a useful agent for the treatment of estrogen-dependent diseases such as breast cancer.

Aldosterone↗

Effect of S-ethylisothiourea, a putative inhibitor of inducible nitric oxide synthase, on mouse skin vascular permeability.

By dye leakage in mouse skin, we evaluated the inhibition of proinflammatory stimuli-induced plasma extravasation by a putative inhibitor of inducible nitric oxide synthase, S-ethylisothiourea. A low dose of S-ethylisothiourea (5 micrograms/kg) mimicked aminoguanidine in inhibiting the plasma extravasation elicited by lipopolysaccharide but not by 5-hydroxytryptamine or platelet-activating factor. A higher dose of S-ethylisothiourea (10 micrograms/kg) inhibited the plasma extravasation induced by 5-hydroxytryptamine slightly; however, it increased the basal dye leakage. Thus, S-ethylisothiourea may be used as a relatively specific inhibitor for inducible nitric oxide synthase in vivo.

Animals↗

Effects of Hoelen on the efferent activity of the gastric vagus nerve in the rat.

Hoelen is used to treat gastric disease in Eastern traditional medicine. The efferent activity on the gastric vagus nerve was studied in the rat, and the activity was found to increase after administration of Hoelen into the duodenum. In addition, we examined the effect of Hoelen fractions. Both the fraction containing polysaccharide and the triterpenoid-rich fraction increased activity significantly. Hoelen would thus appear useful for treating gastric disease by activating efferent activity of the gastric vagus nerve through the action of triterpenoid and polysaccharide.

Analysis of Variance↗

Timing of proceptive and receptive behavior of female goats in relation to the preovulatory LH surge.

The temporal relation between the luteinizing hormone (LH) surge and the occurrence of two components of sexual behavior was investigated in female goats. Behavior observation and blood sampling were carried out every 2-6 hr from 26 hr before through 116 hr after prostaglandin (PG) administration which was given to induce luteolysis during the mid-luteal phase. The preovulatory LH surge appeared 30-100 hr after PG injection, and it continued for 6.5 +/- 0.4 hr. Although the interval from PG injection to the onset of the LH surge differed considerably among individuals, the proceptivity (defined as an approach to a male with vigorous tail-swishing) and the receptivity (defined as an acceptance of male's mounting or copulation) occurred well synchronized with the LH surge in each female. The proceptivity and receptivity were observed from -7.4 +/- 1.7 hr to 16.8 +/- 1.5 hr and from -2.6 +/- 1.6 hr to 13.0 +/- 2.0 hr, respectively, with regard to the LH surge onset (0 hr). Thus the proceptivity appeared first and lasted longest, and the receptivity was always seen around the time of the LH surge suggesting an existence of causal relationship between these two preovulatory events. The present results support the view that the female goat has evolved an efficient behavioral strategy such that it actively attracts males before it becomes fully receptive of male's approach to mate, when the LH surge occurs simultaneously to ensure a high conception rate at the subsequent ovulation.

Animals↗

Ehlers-Danlos syndrome and congenital heart anomalies.

Two sisters with Ehlers-Danlos syndrome, inherited as an autosomal recessive trait, and congenital heart disease are herein reported. One was a 20-year-old woman with Ehlers-Danlos syndrome and multiple aphthous stomatitis, bronchial asthma, an emphysematous lung, a ventricular septal defect and a bilateral inguinal hernia due to hyperextensibility and joint hypermobility. The other was a 17-year-old girl with the same syndrome and an atrial septal defect, a ventricular septal defect and patent ductus arteriosus. The combination of Ehlers-Danlos syndrome and congenital heart anomalies in these siblings suggest a common genetic defect to be the cause of these diseases.

Adult↗

Spinal arachnoid cyst developing after surgical treatment of a ruptured vertebral artery aneurysm: a possible complication of topical use of fibrin glue. Case report.

A case is reported of a 59-year-old man with a spinal arachnoid cyst accompanied by spinal arachnoiditis. The patient developed symptoms after treatment for a ruptured vertebral artery aneurysm, in which fibrin glue was used for reconstruction of the suboccipital bone defect. It is believed that the fibrin glue may have played a role in forming the arachnoid cyst. The authors urge the readers to keep in mind the possibility of subclinical spinal arachnoiditis in the patients with aneurysmal subarachnoid hemorrhage and suggest that care should be taken to avoid any possible adverse effect of fibrin glue.

Administration, Topical↗

YM90K: pharmacological characterization as a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonist.

We investigated the pharmacological properties and neuroprotective actions of a novel alpha-amino-3-hydroxy-5-methylisoxazole-y-propionate (AMPA)/kainate receptor antagonist, [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride (YM90K); formerly YM900], in comparison with those of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX). YM90K selectively displaced [3H]-AMPA binding (Ki = 0.084 microM) and was less potent in inhibiting [3H]-kainate (Ki = 2.2 microM), [3H]-L-glutamate (N-methyl-D-aspartate-sensitive site; Ki > 100 microM) and [3H]-glycine (strychnine-insensitive site; Ki = 37 microM) binding to rat brain membranes. YM90K co-injected with AMPA or kainate into the rat striatum protected cholinergic neurons against AMPA- or kainate-induced neurotoxicity. YM90K showed potent suppressive activity against audiogenic seizure in DBA/2 mice; ED50 values of YM90K and NBQX against tonic seizure were 2.54 and 7.17 mg/kg (i.p.), respectively. The duration of the anticonvulsant effects of YM90K and NBQX was 30 min, indicating that both compounds possess short action. In a global ischemia model, YM90K (15 mg/kg i.p. x 3), NBQX (30 mg/kg i.p. x 3) and CNQX (60 mg/kg i.p. x 3) significantly prevented the delayed neuronal death in the hippocampal CA1 region in Mongolian gerbils when administered 1 h after 5-min ischemia. In addition, the therapeutic time window for the neuroprotective effect of YM90K (30 mg/kg i.p. x 3) was 6 h. In a focal ischemia model, YM90K (30 mg/kg i.v. bolus+10 mg/kg/h for 4 h) reduced the volume of ischemic damage in the cerebral cortex in F344 rats. Thus, YM90K was shown to be a potent and selective antagonist for AMPA/kainate receptors in vitro and in vivo. This compound may provide a therapeutic effect in various neurodegenerative disorders such as ischemic stroke in which glutamate neurotoxicity is thought to play a critical role in neuronal damage.

Animals↗

[Operative corrections of funnel chest depend on age group].

The methods of correcting funnel chest are various and many. It's necessary to select the proper method depending on the age group. For children, sternal elevation by Ravitch's procedure produces to better results without prosthesis. For adolescent patients, the elevated sternum can be maintained by Kirschner's wires. Furthermore, adult patients have severe chest wall deformities with calcificated costal cartilage. The methods sternal elevation methods cause an unsatisfactory by postoperative appearance for adult patients with funnel chest. Two adult patients, 20 and 48-year-old men, underwent the sternal turnover methods with complete sternal blood supplies. The procedures of the new method turn over the sternal body crossing bilateral internal thoracic vessels and abdominal rectal muscles. No chest wall deformities were seen and the patency of internal thoracic arteries and superior epigastric arteries was revealed by postoperative arteriography.

Adolescent↗

[Current status and 21 century in the laser transmyocardial revascularization (LTMR)].

Recently, much attention has been paid to promote endovascular intervention for the patients with ischemic heart disease and occlusive peripheral arterial disease. There are a few patients for whom coronary artery bypass grafting and repeated PTCA can not be carried out, because small branches or diffuse stenoses of the coronary arteries. To resolve these problems author tried to supply arterial blood from the left ventricle into the ischemic myocardium through new channels created into the myocardium by CO2 laser. Consequently, it could be clarified that this procedure could be hemodynamically, or histologically used as an alternative transmyocardial revascularization (TMR) by laser. Finally, this TMR was clinically employed in 1985. Mechanism, technique and its results of TMR are discussed in detail.

Angioplasty, Balloon, Coronary↗

[Urgent allogeneic bone marrow transplantation using a preparative regimen of cyclophosphamide anti-human thymocytes rabbit globulin in a patient with severe aplastic anemia with pneumonia].

A 16-year-old girl was diagnosed as having severe aplastic anemia (SAA) had received emergency complicated by sever pneumonia. She had an HLA-identical younger brother and been urgently transplantation with her brother's marrow following a preparative regimen of CY+rabbit antithymocyte globulin (ATG). Granulocyte transfusions carried out before and after the transplant prevented exacerbation of the pneumonia. The pneumonia was cured in association with the hematopoietic recovery after BMT. No signs or symptoms of acute or chronic graft-versus-host disease were recognized and her hematological data are normal. The rabbit ATG was thought to be effective in preventing rejection and could be used in the preparative regimen instead of total body irradiation.

Adolescent↗

[Usefulness of PCR-SSCP using non-RI coloration method as a routine genetic analysis].

The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis is considered as one of useful routine genetic analyses. However, that PCR-SSCP has been analyzed using radioisotope (RI) such as [32P] labeled compounds. So that, it was difficult to use this method routinely at clinical laboratories. In this paper, we compared with an RI mediated and a non-RI coloration mediated PCR-SSCP analysis regarding to those of sensitivity, time and money cost, respectively. The coloration method had enough sensitivity to detect one of cholesteryl ester transfer protein gene mutations. The time and money cost of non-RI coloration mediated method were more advantageous than the RI mediated one. Therefore, it is shown that the non-RI coloration mediated PCR-SSCP analysis is very useful for the routine genetic analysis at clinical laboratories.

Carrier Proteins↗

Successful surgical treatment of cardiac cirrhosis. Tricuspid surgery and plasma exchange.

A patient with cardiac cirrhosis due to severe tricuspid regurgitation associated with a mitral valve lesion successfully underwent mitral and tricuspid valve replacement. Preoperative rest cure with liver supporting therapy for 5 months was used to maximize hepatic and cardiac function. Postoperatively, jaundice developed despite improvements in cardiac function. Plasma exchange was performed nine times over a period of 10 days with the liver function improved. He was discharged with New York Heart Association class I symptoms and normal liver function 2 months following surgery.

Heart Valve Prosthesis↗

Expression of tenascin in normal and diseased human kidneys.

Expression of tenascin was studied in normal human adult and fetal kidney specimens, and in renal tissues biopsied from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that tenascin was present weakly in the mesangial area and interstitium, but was absent from the glomerular capillaries. In the fetal kidney, tenascin was detected in the interstitium, but not in the immature glomeruli. In kidney tissues biopsied from patients with various renal diseases, expression of tenascin was associated with increased mesangial expansion and tubulointerstitial changes. In situ hybridization showed that tenascin mRNA was expressed in the renal tissues, but tenascin mRNA and tenascin protein were occasionally dissociated. These findings indicate that expression of tenascin is associated with mesangial expansion and also with tubulointerstitial changes in human glomerulonephritis. Tenascin expression may contribute to repair of injured glomeruli and interstitium.

Adult↗

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1993)].

Bacteria isolated from respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981, and the Ikemotor et al. have been investigating susceptibilities of the isolates of various antibacterial agents and antibiotics, and the relationships between the isolates and backgrounds of the patients and so forth each year. We discuss the results in detail. In 20 institutions around the entire Japan from October 1993 to September 1994, 584 strains of bacteria were isolated mainly from sputa of 473 patients with respiratory tract infections and presumed to be the etiological agents. MICs of various antibacterial agents and antibiotics were determined against 91 strains of Staphylococcus aureus, 98 strains of Streptococcus pneumoniae, 122 strains of Haemophilus influenzae, 91 strains of Pseudomonas aeruginosa (non-mucoid), 34 strains of Pseudomonas aeruginosa (mucoid), 42 strains of Moraxella subgenus Branhamella catarrhalis, 25 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were measured except the strains which died during transportation. 1. S. aureus S. aureus strain sfor which MICs of methicillin was higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 56.0%, but this frequency of the drug resistant bacteria was lower than the previous year's 61.4%. Arbekacin and vancomycin showed the highest activities against MRSA and MIC80s were 1 microgram/ml. 2. S. pneumoniae Benzylpenicillin among the penicillins showed potent activities against S. pneumoniae. Cefuzonam, cefotaxime and cefmenoxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; carbapenems, showed the most potent activity, and MIC90 was 0.063 microgram/ml. 3. H. influenzae All the drugs tested were quite active against H. influenzae. Cefotaxime, cefmenoxime, cefuzonam and cefixime among the cephems showed the most potent activities, and MIC90 were 0.063 microgram/ml against H. influenzae. Ofloxacin also showed MIC90 of 0.063 microgram/ml. 4. P. aeruginosa (mucoid) Tobramycin showed the most potent activity against P. aeruginosa (mucoid), and MIC80 was 1 microgram/ml. Ceftazidime, cefsulodin, imipenem, aztreonam, gentamicin and ciprofloxacin showed potent activities with MIC80s of 2 micrograms/ml. 5. P. aeruginosa (non-mucoid) Tobramycin showed the highest activity against P. aeruginosa (non-mucoid), and MIC80 was 1 microgram/ml, followed by ciprofloxacin with MIC80 of 2 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested had relatively low activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae. The activities of all drugs except ampicillin and minocycline were high against K. pneumoniae. Cefozopran, imipenem and carumonam showed the highest activities and MIC80s were 0.125 microgram/ml. Flomoxef showed the next highest activities with an MIC80 of 0.25 microgram/ml. 7. M.(B.) catarrhalis Imipenem showed the most potent activity against M.(B.) catarrhalis, with an MIC80 of 0.063 microgram/ml, followed minocycline and ofloxacin with their MIC80s of 0.125 microgram/ml. We also investigated year to year changes in the background of patients, as well as types of respiratory infectious diseases, and the etiological agents. As for patients background, there were many infectious diseases found among patients a high age bracket, and the patients over age 60 accounted for 61.3% of the diseases. The distribution by respiratory tract infections was as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest numbers of cases with 31.1% and 26.0%, respectively, followed by bronchiectasis with 10.4%. In this year chronic bronchitis under age 29 were 41.7%, thus was much higher than 12.5% in previous year. This marked change was first noted in your research during the recent 5 years. As for frequencies of etiologic bacteria by respiratory tract infections, S. pneumoniae (ABSTRACT TRUNCATED)

Aged↗

[Surgical-treatment for active infective endocarditis].

The results of surgical treatment of active native infective endocarditis in 24 patients were analyzed. Fifteen of 24 (63%) patients were successfully cured by operation. Three of the 8 patients with severe cardiac failure who underwent emergency operation died of low cardiac output syndrome and bleeding early postoperatively. One of the 6 patients with late death had preoperative cerebral embolism and died of multiple organ failure. Five of them had annular infection. Among 6 patients with annular infection, 3 patients who had Staphylococcus epidermidis and Gram negative bacterium as a causative microorganism had a short duration within 4 weeks from the onset to operation. Two died suddenly in the long-term period after surgery because of prosthetic valve detachment. The second operation were required for other 4 patients because of prosthetic valve endocarditis or perivalvular leakage. Three of them were lost from low cardiac output syndrome. These findings suggested that delayed surgical intervention may be a major causative factor resulting in high surgical mortality. For patients with active native infective endocarditis, an early aggressive operation should be considered prior to congestive heart failure and the destruction of the annulus.

Adult↗