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Biomedical subjects

S Murata

Publications and source records attributed to S Murata.

At least 145 records · Page 8Linked to original sources

[Replacement of descending thoracic aorta using open proximal anastomosis under hypothermic circulatory arrest].

Open proximal anastomosis under hypothermic circulatory arrest was applied to eleven consecutive patients with descending aortic diseases. These patients included five aortic dissections and six thoracic aortic aneurysms. Fourth and 7th intercostal spaces were opened by left posterolateral thoracotomy. Cardiopulmonary bypass was established by right atrial drainage via femoral vein and main pulmonary artery. Arterial blood was perfused via femoral artery. The descending aorta was opened under hypothermic circulatory arrest with anal temperature of 20 degrees C, and the anastomosis of the proximal site of the graft was performed with bloodless field. After the proximal anastomosis was finished, the main graft was clamped and perfused via the branch of the graft. The distal anastomosis was performed during circulatory arrest of the lower body. Mean circulatory arrest time of the upper body was 31 min, and that of the lower body was 37 min. Nine of the patients arrive without any major complications, but two of them died due to postoperative low cardiac output syndrome and postoperative pneumonia. Open proximal anastomosis under hypothermic circulatory arrest may be useful for the replacement of the diseased descending aorta due to dissection or aortic aneurysm with mural thrombi because of the advantage of non-clamping anastomosis with bloodless surgical field.

Adult↗

[A case report of St. Jude medical aortic valve prosthesis thrombosis].

We report a case of successful semi-emergent redo aortic valve replacement for thrombosed prosthetic valve. Patient was a 59-year-old male who had undergone aortic valve replacement of St. Jude Medical prosthetic valve and open mitral commissurotomy 14 years ago. He suffered from pneumonia with hemosputum and admitted a neighbor hospital. But he was reffered to our medical center because of progressing dyspnea. We found the immobility of one of the leaflets of the prosthetic valve by cinefuluoroscopy. He was also diagnosed as prosthetic valve thrombosis and mitral valve restenosis using ultrasonic echocardiography. The thrombi were developed on the hinge of one of the leaflets, and they might be formed during the time he had got inappropriate anticoagulation therapy at the former hospital. We emphasise the importance of strict anticoagulation control for the patients valve replaced.

Aortic Valve↗

Lens development and crystallin distribution of the early onset hereditary cataract in the UPL rat.

The Upjohn Pharmaceuticals Limited (UPL) rat is a new dominant hereditary cataract model with two types of cataract formation, early onset (E-type) and late onset (L-type). In the UPL E-type rat cataracts have formed by the time the eyes open. The E-type rat also develops microphthalmos and buphthalmos. In this study, histological observations of cataract development in the E-type rats were performed during the period of fetal development, at birth and at 1, 3 and 62 weeks of age. In addition, the distribution of alpha- and gamma-crystallins in the developing lens was determined using anti-crystallin antisera. Abnormal elongation of the lens fibers was first observed on the 13th day of gestation. Stratification of lens epithelial cells was present on the 19th day of gestation and this change became more severe with age. There was no alteration in alpha- and gamma-crystallin expression during the fetal period. The continuity between the lens epithelial cells and lens fibers was lost at 3 weeks of age and it was assumed that differentiation of lens epithelial cells had ceased. These findings suggested that development of the UPL rat E-type cataract was related to an early abnormality in lens cell differentiation not involving crystallin expression.

Animals↗

Evolution of the active sequences of the HpaI short interspersed elements.

Ninety-nine members of the salmonid HpaI and AvaIII families of short interspersed repetitive elements (SINEs) were aligned and a general consensus sequence was deduced. The presence of 26 correlated changes in nucleotides (diagnostic nucleotides) from those in the consensus sequence allowed us to divide the members of the HpaI family into 12 subfamilies and those of the AvaIII family into two subfamilies. On the basis of the average sequence divergences and the phylogenetic distributions of the subfamilies, the relative antiquity of the subfamilies and the process of sequential changes in the respective source sequences were inferred. Despite the higher mutation rates of CG dinucleotides in individual dispersed members, no hypermutability of CG positions was observed in changes in the source sequences. This result suggests that sequences of SINEs located in a nonmethylated or hypomethylated genomic region could have been selected as source sequences for retroposition and/or that some CG sites are the parts of recognition sequences of retropositional machineries.

Animals↗

Left ventricular end-systolic volume index in patients with ischemic cardiomyopathy predicts postoperative ventricular function.

BACKGROUND: We investigated the usefulness of the preoperative left ventricular end-systolic volume index (LVESVI) as a predictor of postoperative ventricular function. METHODS: We retrospectively reviewed the records of 310 patients who underwent coronary artery bypass grafting and identified 20 patients with ischemic cardiomyopathy with a preoperative ejection fraction less than 0.30. We determined the preoperative and postoperative ejection fraction, LVESVI, and left ventricular enddiastolic volume index using biplane left cineventriculography. Patients were divided into groups depending on whether their preoperative LVESVI was less than 100 mL/m2 (group A, n = 10) or greater than 100 mL/m2 (group B, n = 10). RESULTS: The mean ejection fraction increased significantly after coronary artery bypass grafting in group A from 0.25 +/- 0.05 to 0.40 +/- 0.09 (p < 0.01), but did not change significantly in group B (0.26 +/- 0.05 versus 0.23 +/- 0.06). The mean LVESVI decreased significantly in group A from 83.2 +/- 13.7 to 61.7 +/- 20.4 mL/m2 after operation (p < 0.05), but did not change significantly in group B (124.7 +/- 21.0 versus 121.5 +/- 37.6 mL/m2). In group B, 4 patients had signs of congestive heart failure during the follow-up period and had to be rehospitalized. CONCLUSIONS: The mean ejection fraction improved significantly after coronary artery bypass grafting in patients with a preoperative LVESVI less than 100 mL/m2, despite the presence of a global left ventricular ejection fraction less than 0.30. Our results suggest that the preoperative LVESVI predicts the postoperative status and left ventricular function in patients with ischemic cardiomyopathy.

Aged↗

A new retroviral vector for detecting mutations and chromosomal instability in mammalian cells.

A retroviral vector carrying both forward (neo) and backward (herpes simplex virus thymidine kinase or HSV-TK gene) selection markers was constructed as a substrate for mutational assay in mammalian cells. The cells infected with this virus are first selected with G418, mutagenized and then selected with the anti-herpes drug acyclovir (ACV). Since HSV-TK, but not the host TK, is capable of converting ACV to a toxic metabolite, cells retaining the intact HSV-TK gene fail to survive, while the cells carrying a mutated HSV-TK gene or which have lost the gene can form colonies in the presence of ACV, making it possible to detect the genetic defects in a positive manner. It is also possible to discriminate between small mutations and large deletions by checking the presence of the linked marker, neo. As a model experiment, we prepared an uncloned pool of rat fibroblast cells (CREF) infected with this virus and irradiated them with increasing doses of ultraviolet light. Dose-dependent increases in the number of ACV-resistant colonies were observed. Structural analysis of the HSV-TK gene in these clones revealed point mutations or small deletions in the majority of the cases. Since it requires no pre-existing genetic markers in the host cells, this system may be used for a wide variety of mammalian cells and provides a useful tool to assess both their susceptibility to various mutagens and their genomic instability.

Acyclovir↗

Interaction between nitric oxide and angiotensin II on antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs.

We examined the effects of NG-nitro-L-arginine (NOARG) on antidiuresis and norepinephrine (NE) overflow in anesthetized dogs, induced by renal nerve stimulation (RNS), with or without blockade of an action of endogenous angiotensin II (AII) on the AT1 receptors by losartan. RNS (2.5-5.0 Hz) caused significant reductions in renal blood flow (RBF), glomerular filtration rate (GFR), filtration fraction (FF), urine flow (UF), and urinary excretion of sodium (UNaV) and increases in the differences in renal arteriovenous NE concentrations (NEC). Intrarenal arterial (i.r.a.) infusion of NOARG (40 micrograms/kg/min) significantly decreased RBF and UF, and increased FF, but did not alter GFR. When losartan 100 micrograms/kg/min was infused simultaneously, NOARG reduced RBF, UF, and GFR but had no effect on FF. With high-frequency RNS, NOARG enhanced the RNS-induced decreases in RBF, GFR, UF, and UNaV and the increases in NEC. During losartan infusion, NOARG-induced enhancements on renal actions in response to RNS were observed in a manner qualitatively similar to that without losartan. Most likely endogenous nitric oxide (NO) plays the role of inhibitory modulator of renal noradrenergic neurotransmission. Enhancement of renal noradrenergic neurotransmission induced by NO blockade is likely to be independent of an action of endogenous AII on the AT1 receptors.

Angiotensin II↗

Malignant schwannoma arising in patients with von Recklinghausen's disease: report of two cases and the comparison of mast cells between benign and malignant portions.

We described two cases of malignant schwannoma arising in patients with von Recklinghausen's disease and examined the mast cells infiltrated into histologic sections. One of the two cases histologically revealed apparent mast cell infiltration in some areas of malignant schwannoma as well as in the benign neurofibroma. The malignant lesion demonstrated significantly increased percentages of degranulated mast cells over the benign lesion using FITC-avidin staining. In an electron microscopic study, mast cells in the malignant lesion displayed empty granules, piecemeal degranulation, and canaliculi structures suggesting activation. These findings were not observed in the benign lesion. The other patient histologically showed no mast cells in the malignant lesion, although the benign neurofibroma in the patient disclosed numerous mast cells. The first patient had neither recurrence nor distant metastasis. On the other hand, the second patient without mast cells in the histology had multiple distant metastases.

Cell Count↗

Evaluation of the antithrombogenicity of a new microdomain structured copolymer.

A new antithrombogenic material was studied, fluorine-acryl-styrene-urethane-silicone (FASUS) copolymer, the theoretical basis of which attributed to its hydrophilic and hydrophobic microdomain structure. In this series of experiments, the blood compatibility of this copolymer was evaluated in vitro and ex vivo. For the in vitro evaluation, a whole blood clotting test and the microsphere column test were performed. For the ex vivo evaluation, two series of shunt tests in rabbits were performed, one was the arterioartery (A-A) shunt model, and the other was the arteriovenous (A-V) shunt model. The antithrombogenicity was assessed by measuring the shunt obstructive time in the A-A shunt experiment. The A-V shunt experiment was assessed by measuring the circulating platelet counts, platelet aggregability, activated partial thromboplastin time (APTT), and prothrombin time (PT). In the whole blood clotting test, FASUS revealed the significantly longer blood clotting time than that of the control glass tubings (19.7 +/- 1.0 versus 6.5 +/- 0.7 min, p < 0.001). In the microsphere column test, the coated group had a 30% reduction of the platelet number in the eluted blood in contrast with a marked decrease of 70% in the control group (p < 0.05). In the ex vivo A-A shunt experiment, the occlusion time for the FASUS-coated group was significantly longer than that of the control (109.7 +/- 17.3 versus 3.0 +/- 0.4 min, p < 0.05). The A-V shunt experiment showed that the FASUS copolymer suppressed the decrease in platelet counts and tended to improve prolonged APTT compared with that of the control. Clinically, in 25 patients, we placed coated FASUS copolymer into the cannulas for use in percutaneous cardiopulmonary support (PCPS) procedures. There was no evidence of thrombus on the blood contacting surface and no thromboembolism in major organs clinically or upon postmortem examination. In summary, this new copolymer may be effective in preventing thrombus formation in vitro, ex vivo, and in clinical situations.

Aged↗

Straight border sign of the liver: spectrum of CT appearances and causes.

Attenuation differences bordered by straight lines within the liver (the straight border sign) are sometimes seen at computed tomography (CT). This phenomenon, which was demonstrated with unenhanced CT over a dozen years ago, does not represent a hepatic mass and is often associated with vascular compromise. Major causes of the straight border sign include fatty liver, confluent fibrosis, radiation hepatitis, and vascular abnormalities such as tumor thrombus, thromboembolus, compression, and arterioportal shunt. The frequency of this finding increases when intense contrast enhancement is used, especially when contrast material is administered via the superior mesenteric artery (CT during arterial portography) or hepatic artery (CT arteriography). The use of spiral CT is apparently increasing the chances of encountering this sign in daily practice. To correctly interpret the straight border sign, one should consider the distribution (anatomic vs nonanatomic), the attenuation (low vs high), and the use and technique of contrast enhancement.

Contrast Media↗

Effect of temporary occlusion of the hepatic vein on dual blood in the liver: evaluation with spiral CT.

PURPOSE: To evaluate the contribution of hepatic veins to the dual blood supply in the liver under temporary hepatic venous occlusion. MATERIALS AND METHODS: Selected hepatic veins in 23 patients with liver tumors were temporarily occluded with a balloon catheter. Computed tomography (CT) arteriography, CT during arterial portography (CTAP), or both were performed with a spiral technique with and without temporary occlusion of a hepatic vein. RESULTS: After hepatic vein occlusion, a well-demarcated, wedge-shaped area of hypoattenuation was seen at CTAP and/or hyperattenuation was seen at CT arteriography in the following regions: left lobe (left hepatic vein), ventral part of the anterior segment and the medial segment except for the ventromedial part (middle hepatic vein), dorsal part of the anterior segment and the ventral part of the posterior segment (right hepatic vein), and dorsocaudal part of the right lobe (inferior right hepatic veins). CONCLUSION: After hepatic venous occlusion, the portal veins become draining veins and the occluded area is supplied with arterial blood alone.

Adult↗

Protein synthesis and rapid recovery of endothelium-dependent dilation after endothelial injury of pial arterioles.

A laser-dye technique is known to injure selectively microvascular endothelium in situ. With the use of the arterioles on the surface of the mouse brain (pial arterioles), the endothelial injury is manifest by loss of several endothelium-dependent responses, including the dilation produced by topical application of acetylcholine (ACh), bradykinin (BK), and calcium ionophore A-23187. The responses normally recover by 60 min following injury. The present study shows that inhibitors of protein synthesis prevent the recovery. Either actinomycin D (Act-D; 1 mg/kg) or cycloheximide (CX; 10 mg/kg) was injected intraperitoneally 35 min before the light-dye injury. The CX was used in separate studies with ACh, BK, and ionophore. In each study, recovery of the endothelium-dependent dilation failed to occur 60 min after injury, while recovery occurred in contemporary vehicle-treated controls. Act-D was used in separate studies of ACh and BK. Again, recovery of endothelium-dependent dilation was prevented. Neither CX nor Act-D inhibited the response to ACh in uninjured vessels. Thus response to ACh was intact in such arterioles 90 min after the injection of CX or Act-D. CX was also given to uninjured mice and was found to have no inhibitory action on the response to ionophore 90 min later. CX and Act-D inhibit protein synthesis by very different mechanisms, inhibition of translation and of transcription, respectively. Because both prevented recovery of the endothelium-dependent responses, we conclude that one or more rapidly synthesized proteins are required for the recovery.

Acetylcholine↗

Delayed platelet adhesion/aggregation at sites of endothelial injury in mouse cerebral arterioles after transient elevations of blood pressure and shear.

BACKGROUND AND PURPOSE: Prior research showed that injection of angiotensin II (Ang II) produces a transient elevation of blood pressure (BP) and shear in pial arterioles. This inhibited platelet adhesion/aggregation at a site of subsequently injured endothelium. The present study attempted to confirm the Ang II finding with a different method of endothelial injury, to test the hypothesis that the effect on adhesion/aggregation was a consequence of prolonged release of "classic" endothelium-derived relaxing factor (released by acetylcholine [Ach]; EDRFACh) produced by the preceding transient elevation in shear, and to show with the use of norepinephrine rather than Ang II that the effect of a preceding elevation of BP was independent of the pressor agent used. METHODS: Focal platelet adhesion/aggregation was elicited in cerebral surface (pial) arterioles by producing minimal endothelial damage with a helium-neon laser/Evans blue dye technique. Vessels were observed by intravital microscopy. We recorded the time required for the laser to elicit adhesion/aggregation in control mice and in mice given Ang II in a dose of 16 micrograms/25 g IP. This dose produces an abrupt and significant elevation of BP and shear, which return to baseline levels in less than 30 minutes. Laser/dye damage of endothelium and resultant adhesion/aggregation of platelets were not induced until after BP and shear returned to basal levels. The effect of topical Ang II on damage-induced adhesion/aggregation was also tested. In addition, mice injected with Ang II were treated with either topical indomethacin 40 micrograms/mL or topical Ng-monomethyl L-arginine (L-NMMA; 10(-6) mol/L) in an effort to prevent the preceding increase in shear from inhibiting subsequent adhesion/aggregation. Finally, norepinephrine instead of Ang II was used to transiently raise BP (and shear) in an effort to delay subsequently induced adhesion/aggregation. RESULTS: Platelet adhesion/aggregation at the injured site was significantly delayed by a prior transient rise in shear produced by either Ang II or norepinephrine. Locally applied Ang II failed to influence adhesion/aggregation, although a previous study showed that such Ang II reaches the endothelium. Locally applied indomethacin had no effect on inhibition of platelet adhesion/aggregation, but locally applied L-NMMA prevented the prior transient elevation of shear from inhibiting adhesion/aggregation at a subsequently injured site. CONCLUSIONS: Elevation of BP with consequent elevation of shear inhibits local platelet adhesion/aggregation even when the latter is initiated by endothelial damage produced after return of shear to basal levels. The direct action of Ang II on endothelium is not responsible for the effect on adhesion/aggregation, and indeed the effect is independent of the pressor agent. The pharmacological data, together with the literature, support the hypothesis that increased shear causes an increased release of EDRFACh, which may continue for at least some minutes after return of shear to normal levels.

Angiotensin II↗

Effects of phosphoramidon on endothelin-1 and big endothelin-1 production in human aortic endothelial cells.

Using cultured human aortic endothelial cells, we examined the effects of phosphoramidon, an endothelin converting enzyme (ECE) inhibitor, on the release of endogenous endothelin-1 (ET-1) and big endothelin-1 (big ET-1), and on the generation of ET-1 from exogenously applied big ET-1. Phosphoramidon, at concentrations of 10(-6) to 2 x 10(-4) M, caused a biphasic alteration of the ET-1 release, i.e., at lower concentrations of the drug, there were slight but unexpected increases of the release, whereas higher concentrations led to a decrease which is due to the drug-induced inhibition of ECE. The former effect appears to be based on the inhibition of ET-1 degradation by neutral endopeptidase 24.11 (NEP), since kelatorphan, a specific NEP inhibitor, produced a similar increasing effect on ET-1 release. Phosphoramidon enhanced the big ET-1 release from the cells in a concentration-dependent manner. When high concentrations of phosphoramidon were added, there was a dramatic increase in the release of big ET-1, which cannot be explained only by the drug-induced inhibition of ECE. This increase in big ET-1 release appeared to be partly due to a transient stimulation of the expression of prepro ET-1 mRNA. The amount of ET-1 generated from exogenously applied big ET-1 was markedly decreased by phosphoramidon in a concentration-dependent manner. In a similar fashion, phosphoramidon markedly inhibited ECE activity of the membrane fraction of cultured cells. Thus, ET-1 generation from exogenously applied big ET-1 reflects the functional phosphoramidon-sensitive ECE activities in human aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Enhancement of norepinephrine and angiotensin II-induced renal effects by NG-nitro-L-arginine, a nitric oxide synthase inhibitor.

We investigated whether endogenous nitric oxide (NO) has a role as an inhibitory modulator of norepinephrine (NE)- and angiotensin II (Ang II)-induced renal effects in anesthetized dogs. Intrarenal arterial infusion of NE (100 ng/kg/min) or Ang II (10 ng/kg/min) decreased renal blood flow (RBF), glomerular filtration rate (GFR) and urine formation. The NE- or Ang II-induced renal effects were augmented by the intrarenal administration of a NO synthase inhibitor, NG-nitro-L-arginine (NOARG), at doses (10 and 40 micrograms/kg/min) which did not affect the mean arterial blood pressure and heart rate. The stimulating activity of NOARG on NE- or Ang II-induced renal effects were abolished by the simultaneous administration of L-arginine, a NO precursor. These findings suggest that endogenous NO, which is probably generated within the kidney, functions as an inhibitory modulator in NE- or Ang II-induced renal vasoconstriction and antidiuresis.

Amino Acid Oxidoreductases↗

Antithrombotic effect of TA-993, a novel 1,5-benzothiazepine derivative, in conscious rats.

Since reported experimental models of thrombosis are not suitable for comparison of several drugs by oral administration, we developed a convenient model for this purpose by applying direct current through an intravascular electrode. In conscious rats, which were implanted with anodal electrodes in the abdominal aorta on the day before the experiment, application of 200 microA of direct current induced the formation of a platelet-rich thrombus around the intravascular electrode. Using this model, we studied the antithrombotic effect of the novel antiplatelet agent TA-993, (-)-cis-3-acetoxy-5-(2-(dimethylamino)ethyl)-2,3-dihydro-8-methyl-2-(4- methylphenyl)-1,5-benzothiazepin-4(5H)-one maleate, and compared its effect with other antiplatelet agents. TA-993 at doses of 30 mg/kg, p.o. or more by single administration or at doses of 10 mg/kg or more by repeated administration dose-dependently suppressed the thrombus formation. Aspirin (10 mg/kg, p.o. or more), cilostazol (100 mg/kg, p.o.) and ticlopidine (30 mg/kg, p.o. or more) also suppressed the thrombus formation by single administration. These results suggest that TA-993 has a comparable antithrombotic effect with other antiplatelet agents, and thus it is a possible remedy for thrombotic and embolic diseases.

Administration, Oral↗

Sulfamethizole absorption test for the assessment of gastric emptying. Comparison with scintigraphic method.

BACKGROUND: To investigate whether the sulfamethizole absorption test can be applied for the assessment of gastric emptying, we measured comparatively plasma sulfamethizole concentration and gastric emptying as determined by scintigraphy in 15 subjects. METHODS: After the ingestion of a solid-liquid meal that contained sulfamethizole and radioisotope (technetium-99m-labeled diethylenetriaminepentaacetic acid), the plasma sulfamethizole concentrations were measured every 15 to 60 min up to 180 min. The initial emptying time (duration after ingestion until 10% reduction in radioactivity of the stomach) and the exponential curve in the cumulative reduction of radioactivity were used as indicators of gastric emptying. RESULTS: The initial emptying time was significantly correlated with the sulfamethizole concentration at 15 min after ingestion (r = -0.64, p < 0.05). A close correlation was observed between the rate of decrease in radioactivity and sulfamethizole concentration at 60 min after ingestion (r = 0.80, p < 0.001). CONCLUSIONS: The sulfamethizole absorption test can be used for the evaluation of gastric motility. Two points of measurement, 15 and 60 min after ingestion, are sufficient to demonstrate the initial and subsequent gastric emptying.

Female↗