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Biomedical subjects

S Murata

Publications and source records attributed to S Murata.

At least 199 records · Page 11Linked to original sources

A new lipopeptide biosurfactant produced by Arthrobacter sp. strain MIS38.

A biosurfactant termed arthrofactin produced by Arthrobacter species strain MIS38 was purified and chemically characterized as 3-hydroxydecanoyl-D-leucyl-D-asparagyl-D-threonyl-D- leucyl-D-leucyl-D-seryl-L-leucyl-D-seryl-L-isoleucyl-L-isoleucyl-L-as paragyl lactone. Surface activity of arthrofactin was examined, with surfactin as a control. Critical micelle concentration values of arthrofactin and surfactin were around 1.0 x 10(-5) M and 7.0 x 10(-5) M at 25 degrees C, respectively. Arthrofactin was found to be five to seven times more effective than surfactin. The minimum surface tension value of arthrofactin was 24 mN/m at a concentration higher than the critical micelle concentration. According to the oil displacement assay, arthrofactin was a better oil remover than synthetic surfactants, such as Triton X-100 and sodium dodecyl sulfate. Arthrofactin is one of the most effective lipopeptide biosurfactants.

Amino Acid Sequence↗

Selective beta 1-adrenoceptor agonist activity of denopamine and its derivatives in dogs.

Cardiovascular effects of intravenously administered denopamine and its derivatives were investigated in anesthetized dogs and their positive inotropic and hypotensive effects were compared. Structure-activity relationships were examined by modifying the methoxy group in ring B and the hydroxy group in ring A in structure II, a ring-fissioned product of trimetoquinol. Almost all test compounds demonstrated positive inotropic and chronotropic effects as well as hypotensive effects which were mediated by beta-adrenoceptors. With modification of the methoxy group in ring B, only 3,4-dimethoxy, 2,3,4-trimethoxy and 3,4,5-trimethoxy derivatives exhibited beta 1-adrenoceptor selectivity. The 3,4-dimethoxy derivative showed the most potent positive inotropic effect and the highest selectivity to beta 1-adrenoceptor. By structural modification of the hydroxyl group in ring A of the 3,4-dimethoxy derivatives, the potency of positive inotropic effect was affected, while beta 1-adrenoceptor selectivity of the derivatives with 3,5-dihydroxy, 3- and 4-monohydroxy groups were essentially maintained. Among beta 1-adrenoceptor selective compounds, the dose ratios between intravenous and intraduodenal administrations of catechol derivatives like isoproterenol were higher than those of non-catechol derivatives. The 4-monohydroxy derivative (racemic denopamine) exhibited the smallest dose ratio with a long-lasting action. Thus, we could identify selective beta 1-adrenoceptor agonists by the structural modification of a selective beta 2-adrenoceptor agonist, trimetoquinol. In this group of compounds, beta-hydroxy moiety was suggested to be requisite to potent beta-adrenoceptor stimulating action and 3,4-dimethoxyphenethyl structure was important for manifestation of beta 1-adrenoceptor selectivity.

Adrenergic beta-Agonists↗

Cephalosporins having a heterocyclic catechol in the C3 side chain. II. Improvement of pharmacokinetic profile.

7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido]-3- [propen-1-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6,7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood levels after intramuscular administration to mice and higher in vivo antibacterial activity than expected from their in vitro activity. The former cephalosporin (2a) gave well-balanced in vitro and in vivo antibacterial spectra including anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. The latter cephalosporin (2b) also showed good in vitro and in vivo activities against Gram-positive bacteria, especially against S. aureus A15036, a strain of MRSA, the in vivo activity being comparable to vancomycin but was lacking in anti-pseudomonal activity.

Animals↗

[Learning processing in an epileptic with amnesia after memory task repetition].

We reported that some learning accomplished by an epileptic patient (YS) with organic amnesia after memory task repetition. YS's learning appeared inflexible; That was depending memory task procedural. The purpose of this paper is to investigate procedural learning processing in YS with memory disorder. We examined procedural learning in picture naming task repetition in YS and normal controls, using semantic priming paradigm. After start key press, a prime picture was displayed on the CRT display, thereafter, a target picture appeared. The subjects' task was to name the target picture aloud as rapidly and accurately as possible. In the examination, we manipulated a time interval between start key press and the prime on. Two interval conditions were used. One was the constant interval, 1010ms and another was varied interval, varied between 400ms and 1010ms. After conditioning session with constant interval, the test session with constant and varied interval was carried out. We analyzed reaction time (RT) in naming the picture targets in the test session in relation to the conditions. YS's RT in the test session with constant was shorter than in the test session with varied interval. No interval effects were found in the controls. The results indicated that previous experiment in conditioning session had larger effect on the YS's performance than the controls'. This suggests hypotheses that the learning in the patient with amnesia is tied to the specific conditions in the learning experience. The results can be explained in terms of procedural learning in YS, which is automatic processing.

Adult↗

[Case report of MRSA sepsis required two valve replacement twice a year--trying case with hyperthermal extracorporeal circulation].

We report a case in conjunction with MRSA sepsis, who needed re-mitral valve replacement (re-MVR) and re-tricuspid valve imposition (re-TVI), and who was successfully treated with a number of antibiotics in conjunction with hyperthermal extracorporeal circulation. Initially, we performed MVR and tricuspid valve superimposition on a 62-year-old woman lationing under the MRSA sepsis condition to control against heart failure. However, she developed a fever following the first operation, and MRSA was detected from her blood cultivation. She thus underwent treatment employing many kinds of antibiotics. A thickened C.E. valve at the tricuspid valve cardiac echogram suggested PVE, we performed a second operation of re-MVR and re-TVI about a year after the first operation. We used a tangl of antibiotics during the operation, adding Vancomycin into the extracorporeal circulation, and utilized hyperthermal extracorporeal circulation. This patient's postoperative course was uneventful, with no recurrence arising at 23 months after the second operation.

Anti-Bacterial Agents↗

[Image analysis on isolated colorectal tumor cells].

Image analysis of the nuclear morphology was performed on propidium iodide-stained isolated cells from 9 adenomas and 9 cancers of the colorectum. We analyzed DNA content, seven nuclear geometric features and four shape factors of tumor cells using an image cytometry system that has been developed in our laboratory. Nuclear breadth and the degree of contour irregularity of cancer cells were found to be significantly different from those of adenoma cells. The coefficients of variation (CV) of some nuclear features and the degree of contour irregularity were increased in cancer cells, while CV of the degree of circularity was increased in adenoma cells. Moreover, nuclear in G2 phase were found to be larger and more round than those in G1 phase. These results suggest that cell-cycle-related analysis of nuclear features would be a valid means to assess the nuclear morphology of colorectal tumors.

Adenocarcinoma↗

Hypothalamic-pituitary-adrenal axis function in chronic schizophrenia: association with clinical features.

The function of the hypothalamic-pituitary-adrenal axis (HPA-axis) and its association with clinical features in chronic schizophrenia were investigated. Twenty of 33 chronic schizophrenics exhibited an abnormal diurnal variation of the saliva cortisol level. The patients with abnormal diurnal variation gave higher scores for some negative symptoms than those with normal diurnal variation. On the dexamethasone suppression test (DST) of saliva samples, 13 of 34 chronic schizophrenics were abnormal. The patients with DST nonsuppression were more frequently classified into disorganized type and exhibited low scores of anxiety compared with the patients with normal suppression. The 9 patients who showed abnormal diurnal variation and DST nonsuppression were more frequently classified into disorganized type and showed higher scores of negative symptoms than the 9 patients who did not show any abnormal cortisol data. These results suggest that there might be some disturbance in the function of the HPA-axis in a group of chronic schizophrenics and that these patients might have severe negative symptoms.

Adult↗

Synthesis of the optically active trans-isomers of diltiazem and their cardiovascular effects and Ca-antagonistic activity.

Optically active trans-isomers of diltiazem were synthesized and their cardiovascular effects were evaluated in anesthetized dogs and in isolated guinea pig hearts. Both (+)-2 (2R,3S) and (-)-2 (2S,3R) were much less active than diltiazem (1, 2S,3S) with short duration of action. No substantial enantiomeric difference in activity was seen between them. Their Ca-antagonistic activities on Ca(2+)-induced contractions in K(+)-depolarized canine basilar arteries were also examined. Absolute stereochemistry of (+)-2 was determined to be 2R,3S by X-ray crystallographic analysis.

Animals↗

Effect of Ca2+ antagonists on high-K+ evoked increase in [Ca2+]i in rat cerebral synaptosomes and hippocampal neurons.

By fura-2 fluorometry, we investigated the direct effects of Ca2+ antagonists including a new benzothiazepine, clentiazem, on the high-K(+)-evoked increase in the concentration of cytosolic free Ca2+ ([Ca2+]i) in rat cerebral synaptosomes and cultured hippocampal neurons. In both preparations, metal ions inhibited the high-K(+)-induced increase in [Ca2+]i, in the following order: La3+ greater than Cd2+ much greater than Ni2+. Although flunarizine and nicardipine inhibited the K(+)-induced increase in [Ca2+]i in synaptosomes, other Ca2+ antagonists, including clentiazem and nitrendipine, had little effect at 10 microM. In hippocampal neurons, clentiazem inhibited the K(+)-induced increase in [Ca2+]i at 10 microM, as did flunarizine and nicardipine. However, nifedipine and nitrendipine had little effect in either cultured neurons or in synaptosomes.

Animals↗

Acute hemodynamic effects of the active metabolite of imidapril, (4S)-3-((2S)-2-[N-((1S)-1-carboxy-3-phenyl-propyl)amino]propionyl)-1- methyl-2-oxoimidazolidine-4-carboxylic acid, and enalaprilat in anesthetized dogs.

The hemodynamic effects of imidapril, a novel nonsulfhydryl angiotensin-converting enzyme inhibitor, were examined in anesthetized dogs by the intravenous injection of its active metabolite 6366A ((4S)-3-((2S)-2-[N-((1S)-1-carboxy-3- phenylpropyl)amino]propionyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid, CAS 89371-44-8) and were compared to those of enalaprilat. 6366A (1-100 micrograms/kg) reduced the blood pressure and total peripheral resistance in a dose-dependent manner, while causing no marked changes in heart rate, LV dp/dtmax, and pulmonary arterial pressure. The cardiac output and stroke volume were slightly increased. Blood flow in the common carotid artery, the vertebral artery, and the femoral artery was reduced or tended to decrease, while the superior mesenteric arterial blood flow was increased. These effects were similar to those of enalaprilat. 6366A did not inhibit the pressor response of angiotensin II, but markedly inhibited that of angiotensin I, and the effects of 6366A on regional blood flow were opposite to those of angiotensin II. Thus, 6366A appears to produce its hemodynamic effects by angiotensin converting enzyme inhibition, as does enalaprilat. 6366A also tended to decrease myocardial oxygen consumption. These results suggested that the hemodynamic effects of imidapril on the heart and on regional blood flow are similar to those of enalapril.

Anesthesia↗

Changes in myocardial beta-adrenergic receptors during acute rejection of heterotopically transplanted rat hearts.

To evaluate changes of the myocardial beta-adrenergic receptors in acute cardiac graft rejection, the density and binding affinity value of the myocardial beta-adrenergic receptors in heterotopically transplanted rat isografts and allografts were analyzed. Hearts from Fisher rat donors were transplanted either to the Fisher rats (isografts) or to Lewis rats (allografts). Histologic examination of the allografts showed mild to moderate rejection on the seventh and fourteenth days and showed severe rejection on the twenty-first day after transplantation. The density values in the allografts and isografts similarly increased significantly (p < 0.05) above the normal level on the seventh and fourteenth days after transplantation. The density in allografts on the twenty-first day decreased significantly (p < 0.05) below the normal level, while that in isografts remained at the normal level. In contrast, the binding affinity value of myocardial beta-adrenergic receptors in both isografts and allografts did not change after transplantation. These results demonstrated that myocardial beta-adrenergic receptors presented upregulation in mild to moderate rejection, whereas these receptors presented downregulation in severe rejection. The data suggested that downregulation of myocardial beta-adrenergic receptors plays a major role in decreased cardiac contractility during severe rejection, but not during mild and moderate rejection.

Abdomen↗

Cerebral vasodilating and spasmolytic actions of a new Ca-antagonist, clentiazem (TA-3090), in anesthetized animals.

The effect of a new 1,5-benzothiazepine calcium antagonist, clentiazem (TA-3090), on the cerebral circulation was studied in anesthetized animals. Intravenous infusion of clentiazem at doses of 2.5, 5, and 10 micrograms/kg/min increased vertebral blood flow without causing hypotension in anesthetized dogs. After i.v. injection to anesthetized dogs, clentiazem, diltiazem, and papaverine all dose-dependently increased the regional cerebral blood flow and raised the intracranial pressure (ICP). However, the effect of clentiazem on the ICP was weaker than that of diltiazem and papaverine. In anesthetized monkeys, clentiazem (3-100 micrograms/kg, i.v.) increased the internal carotid blood flow to the intracranial tissues. In anesthetized cats, topical or i.v. clentiazem inhibited basilar artery vasospasm induced by the topical application of serotonin, prostaglandin F2 alpha, and incubated blood. These findings suggest that clentiazem has favorable properties as a cerebral vasodilator.

Animals↗

Prophylactic effects of a new 1,5-benzothiazepine calcium antagonist on stroke in salt-loaded stroke-prone spontaneously hypertensive rats.

The influence of chronic treatment with clentiazem ((+)(2S,3S)-3-acetoxy-8-chloro-5-[2-(dimethylamino)ethyl]-2,3-dihydro- 2-(4-methoxyphenyl)-1,5-benzothiazepin-4 (5H)-one maleate, TA-3090), on blood pressure, incidence of stroke, stroke-related mortality and histological changes of the brain and other organs were examined in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP that were fed an 8% NaCl-containing diet began to die of a stroke 3 weeks after salt-loading, accompanied by decreases in body weight and food intake. Most of the rats (16 out of 18) died by the 8th week of salt-loading. Chronic treatment with clentiazem (300 or 1000 ppm) delayed the occurrence of stroke and death in a dose-related manner without any hypotensive action when measured by the tail-cuff method. However, examination of circadian changes in arterial blood pressure with implanted cannula under a freely-moving condition 3 weeks after salt-loading revealed that 1000 ppm clentiazem produced significant hypotension in the dark phase but not in the light phase. Histological studies (3 weeks after salt-loading) showed that 1000 ppm Clentiazem significantly suppressed the cerebral and renal damages, and vascular hypertrophy in all organs studied. Thus, clentiazem prevents stroke and also protects renal damage and vascular hypertrophy in salt-loaded SHRSP. The hypotensive effect and organ-protective action by clentiazem may be involved in its prophylactic action against stroke.

Animals↗

[Progress in microscopic image analysis and the trend of image cytometry].

Image cytometry has recently developed prominently based on the digital imaging of cell morphology brought about by great advances in microcomputer hardware and software, electronics etc. This method is characterized by the quantitation of both the amount of intracellular bioactive materials and cell morphology, and is expected to further advance many cell analysis techniques involving automated cytology, chromosome image analysis, automated histopathology, viable cell analysis, 3D image construction, etc. The present use is still minimal, and advances in both hardware and software for cyto-histologic recognition are essentially necessary. Perhaps by the end of this century, more sophisticated and faster machines for automated cyto-histologic analysis will appear, replacing many microscopic techniques of presently subjective observation in the biomedical field.

Cell Cycle↗