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Biomedical subjects

S Miki

Publications and source records attributed to S Miki.

At least 55 records · Page 3Linked to original sources

A case of bowel necrosis due to acute mesenteric ischemia following pulsatile cardiopulmonary bypass.

We report a case of fatal bowel necrosis possibly caused by pulsatile cardiopulmonary bypass (CPB). An 80-year-old female underwent emergency coronary artery bypass grafting (CABG) for unstable angina. Pulsatile CPB was applied because of stenosis of bilateral carotid and renal arteries. On the third postoperative day, total bowel necrosis due to acute mesenteric ischemia was revealed at emergency laparotomy before her death. Pulsatile CPB may increase the risk of distal embolism of dislodged plaque in cases with severe aortic atheromatosis.

Acute Disease↗

Spontaneous retrograde dissection of the entire thoracic aorta originating in the abdominal aorta. Case report and review of the literature.

Spontaneous retrograde thoracic extension of the abdominal aortic dissection is extremely rare and difficult to manage. Only five cases have been previously reported in the English literature (dissection reaching the ascending aorta in four, dissection limited in the descending thoracic aorta in one), and all the cases of dissection which reached the ascending aorta were lethal. We herein report one case of a 37-year-old man who was operated on for spontaneous retrograde dissection of the entire thoracic aorta originating in the suprarenal abdominal aorta. Preoperative aortogram revealed the site of the intimal tear just above the celiac artery. He urgently underwent graft replacement of the descending thoracic aorta and the abdominal aorta with reimplantation of the thoracoabdominal visceral arteries. Although the patient had to undergo the second operation for the dissection of the remaining thoracic aorta four months postoperatively, he has been doing well 18 months after the second operation.

Adult↗

Hyperlipidemia enhancement of renal preneoplasia but not tumor formation is due to elevated apoptosis in the Eker rat.

The influence of a high-fat diet on the appearance of renal tumors was assessed in the Eker rat model of hereditary renal carcinoma. Examination of H&E-stained sections showed a significant increase in the number of microscopic solid adenomas in the high-fat group compared with the low-fat group, whereas there was no significant difference in the number of macroscopic tumors between the two groups. Where had the tumor buds gone? Staining for apoptotic bodies occasionally revealed apoptosis in and around the microscopic adenomas. In addition, an Eker rat renal tumor-derived cell line showed apoptosis when it was cultured with high concentrations of native and acetylated low-density lipoprotein. These findings suggested that tumor buds repeatedly appeared and disappeared in Eker rats on a high-fat diet.

Adenoma↗

Aripiprazole, a novel antipsychotic drug, inhibits quinpirole-evoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum.

Aripiprazole, a quinolinone derivative, is a new dopaminergic agent which has been recently developed and demonstrated to be clinically useful as an antipsychotic drug with reduced extrapyramidal motor side effects. Here, we found that aripiprazole competed [3H]spiperone binding with a 100-fold higher affinity than [3H]SCH23390 binding, and inhibited the quinpirole-induced facilitation of high-affinity GTPase activity in rat striatal membranes. The effects of chronic administration of aripiprazole and haloperidol on dopamine D2 receptor binding and mRNA level in rat striata were examined by a [3H]spiperone binding assay and a ribonuclease protection assay. Haloperidol induced a significant rise in Bmax of [3H]spiperone binding at 1 mg/kg and in the level of dopamine D2L receptor mRNA at 4 mg/kg. A high dose of aripiprazole (100 mg/kg) only tended to increase the Bmax of [3H]spiperone binding non-significantly, and had no effect on the level of dopamine D2L receptor mRNA. These results indicated that aripiprazole had an antagonistic activity to dopamine D2 receptors with a high affinity, but that the potency of aripiprazole to up-regulate dopamine D2 receptors in the striatum was much smaller than that of haloperidol. This small up-regulation may be related to the ability to aripiprazole to act without side effects including tardive dyskinesia.

Animals↗

5-aminocoumarans: dual inhibitors of lipid peroxidation and dopamine release with protective effects against central nervous system trauma and ischemia.

A series of 2,3-dihydro-5-benzofuranamines (5-aminocoumarans) were developed for the treatment of traumatic and ischemic central nervous system (CNS) injury. Compounds within this class were extremely effective inhibitors of lipid peroxidation in vitro and antagonized excitatory behavior coupled with peroxidative injury induced by spinal intrathecal injection of FeCl2 (mouse-FeCl2-it assay) in vivo. Selected compounds were tested for antagonistic activity on methamphetamine (MAP)-induced hypermotility resulting from dopamine release in the mouse brain. Among the compounds synthesized, compound 26n (2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl) methyl]-5-benzofuranamine) exhibited potent effects in these assays (inhibition of lipid peroxidation, IC50 = 0.07 microM; mouse-FeCl2-it assay, ID50 = 10.4 mg/ kg, po; MAP-induced hypermotility, 98% inhibition, 10 mg/kg, ip). The S-(+)-form of compound 26n dihydrochloride (TAK-218), which has 30 times more potent antagonistic activity on MAP-induced hypermotility than the R-(-)-form, improved more significantly the survival rate in the cerebral ischemia model (rat, 1-3 mg/kg, ip) during the period of 1-14 days after ischemia and decreased functional disorders in the traumatic brain injury model (rat, 0.1-1 mg/kg, ip) 3-14 days after injury. These results imply a role for dopamine in deterioration of CNS function after ischemic and traumatic injury. TAK-218 is a promising compound for the treatment of stroke and CNS trauma and is now under clinical investigation.

Animals↗

Reduction of insulin resistance attenuates the development of hypertension in sucrose-fed SHR.

We examined the effect of pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, on the development and maintenance of hypertension in sucrose-fed SHR. Nine-week-old male SHR received 12% sucrose dissolved in tap water as drinking water. For 5 weeks, half of the rats were given regular rat chow, and the rest were fed with rat chow containing 0.03% pioglitazone. In week 6, blood glucose and plasma insulin levels were examined before and after oral glucose administration by gavage. Sucrose treatment elicited a significant elevation of systolic blood pressure 3 weeks after the beginning of treatment; pioglitazone treatment attenuated this elevation. The insulin resistance and hyperinsulinemia observed in sucrose-fed SHR were prevented by pioglitazone treatment. Pioglitazone treatment also significantly reduced the urinary excretion of catecholamines and plasma renin activity, both of which were significantly greater in sucrose-fed SHR than in control SHR. Along with improving insulin sensitivity, pioglitazone treatment also attenuated the development of hypertension in SHR fed the regular rat chow, but not in WKY rats. These results indicate that insulin resistance and hyperinsulinemia play an important role in the development of hypertension in SHR probably through the activation of the renin-angiotensin system and sympathetic nervous outflow. This study also shows that chronic sucrose treatment exacerbated the development of hypertension through these mechanisms, precipitating insulin resistance.

Animals↗

Pulsatile compression of the rostral ventrolateral medulla in hypertension.

The rostral ventrolateral medulla (RVLM) has been known to be a major regulating center of sympathetic and cardiovascular activities. An association between essential hypertension and neurovascular compression of the RVLM has been reported in clinical observations, including magnetic resonance imaging (MRI) studies. To reconfirm this relationship, we performed MRI using a high-resolution 512 x 512 matrix in patients with essential and secondary hypertension and in normotensive subjects. The duration of hypertension and the degree of organ damage by hypertension were not significantly different between the two hypertension groups. Neurovascular compression of the RVLM was observed in 74% of the essential hypertension group, and the incidence of compression was significantly higher than in the secondary hypertension group (11%) or in the normotensive group (13%) (P < .01). These results from the clinical studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. Although blood pressure elevation by pulsatile compression of the RVLM in an experimental baboon model has already been reported, its underlying mechanism is not well known. Accordingly, we performed experiments to investigate whether pulsatile compression of the RVLM would increase arterial pressure and to elucidate the mechanism of the pressor response in rats. Sympathetic nerve activity, arterial pressure, heart rate, and plasma levels of epinephrine and norepinephrine were increased by pulsatile compression of the RVLM. The pressor response was abolished by intravenous treatment with hexamethonium or RVLM injection of kainic acid. In summary, the results from the MRI studies suggest that neurovascular compression of the RVLM is, at least in part, causally related to essential hypertension. This was supported by the results from experimental studies using rats indicating that pulsatile compression of the RVLM increases arterial pressure by enhancing sympathetic outflow.

Animals↗

Neurovascular compression of the rostral ventrolateral medulla related to essential hypertension.

The rostral ventrolateral medulla (RVLM) is thought to serve as a final common pathway for the integration of central cardiovascular information and to be important for the mediation of central pressor responses. An association between essential hypertension and neurovascular compression of the RVLM has been reported. To confirm this relationship and to quantitatively measure the distances between the RVLM and the neighboring arteries, we performed magnetic resonance imaging using a high-resolution 512x512 matrix and magnetic resonance angiography in 49 subjects (21 patients with essential hypertension, 10 patients with secondary hypertension, and 18 normotensive subjects). One patient with essential hypertension was excluded from the evaluations because of inadequate assessment due to poor images. Neurovascular compression of the RVLM was observed in 15 of 20 (75%) patients with essential hypertension. In contrast, neurovascular compression was observed in only 1 of 10 (10%) patients with secondary hypertension and only 2 of 18 (11%) normotensive subjects. The rate of observed neurovascular compression in the essential hypertension group was significantly higher than that in the secondary hypertension group and the normotensive group (P<.01 for both). The distances between the RVLM and the nearest arteries in the essential hypertension group were significantly shorter than those in the other groups (P<.05 for all). On the other hand, the distances between the surface of the medulla oblongata and the nearest arteries did not differ among these three groups. These results suggest that neurovascular compression of the RVLM, but not of the other regions of the medulla oblongata, is particularly related to essential hypertension.

Adult↗

Chronic angiotensin blockade with candesartan cilexetil in DOCA/salt hypertensive rats reduces cardiac hypertrophy and coronary resistance without affecting blood pressure.

To determine whether angiotensin II participates in the pathogenesis of cardiac hypertrophy and impairs coronary circulation in DOCA/salt hypertension, DOCA hypertensive rats were treated with candesartan cilexetil for 8 wk. DOCA/salt hypertension was induced in Wistar rats by removing the right kidney and subcutaneously injecting deoxycorticosterone acetate once a week. Control rats were given subcutaneous injections of saline and maintained on a normal diet. After 4 wk of observation, the angiotensin II receptor antagonist candesartan cilexetil was administered by oral gavage for 8 wk to 14 rats. Systolic blood pressure was measured weekly with the tail-cuff method. After 12 wk, the rats were killed and prepared. The isolated hearts were perfused by a Langendorff apparatus at constant flow. Perfusion pressure was measured by a small-volume transducer, and perfusion flow was recorded by a drop counter. Development of hypertension was not prevented by candesartan cilexetil treatment, but development of cardiac hypertrophy was inhibited. Minimum coronary vascular resistance (MCVR) obtained upon infusing adenosine into the isolated hearts was significantly higher in DOCA/salt hypertensive rats than in sham-operated controls. The elevated MCVR in DOCA/salt hypertensive rats was decreased by the administration of candesartan cilexetil for 8 wk. Thus, candesartan cilexetil regressed cardiac hypertrophy and improved coronary vascular resistance without affecting high blood pressure. These findings suggest that angiotensin II plays an important role in the pathogenesis of cardiac hypertrophy in DOCA/salt hypertension and that cardiac hypertrophy increases coronary vascular resistance.

Angiotensin Receptor Antagonists↗

Mid-term results of mitral valve replacement combined with chordae tendineae replacement in patients with mitral stenosis.

BACKGROUND AND AIMS OF THE STUDY: Although many studies have found that preservation of the continuity between the mitral annulus and the papillary muscles during mitral valve replacement improves postoperative left ventricular performance in patients with mitral regurgitation, much less research has been done in this respect in patients with mitral stenosis. We reviewed our experience with mitral valve replacement combined with chordae tendineae replacement in 29 patients with mitral disease, 26 of whom had mitral stenosis. METHODS: During mitral valve replacement, continuity between the papillary muscle and annulus was restored with expanded polytetrafluoroethylene (ePTFE) mattress sutures, which were threaded into the compact portion of each papillary muscle and placed at the 2, 4, 8 and 10 o'clock positions in the mitral annulus. Postoperatively, the patients were followed by echocardiographic assessment and exercise (stress) radionuclide angiography testing. The stress test results were compared with those in patients who had undergone traditional mitral valve replacement, and also those in normal people. RESULTS: There were no hospital deaths, complications, or cardiac deaths or events during a median follow up of two-and-a-half years. Echocardiography showed no postoperative cardiac dilatation. The stress tests found no significant differences between the ejection fraction in mitral stenosis patients who underwent conventional mitral valve replacement and in those who had valve replacement combined with ePTFE chordae tendineae replacement. CONCLUSIONS: A direct advantage of chordae-preserving mitral valve replacement over conventional replacement with respect to postoperative global left ventricular performance in patients with mitral valve stenosis has not been demonstrated. However, postoperative regional left ventricular contraction in patients with mitral stenosis has been observed to be better among those who have undergone the chordae-preserving procedure. Additional investigations are needed to elucidate the effects of this procedure in mitral stenosis, but we believe that the technique improves left ventricular performance and may decrease the risk of left ventricular rupture.

Adult↗

Surgical management of aortic regurgitation associated with ventricular septal defect.

Surgical treatment for congenital aortic regurgitation (AR) with ventricular septal defect (VSD) in pediatric patients carried out between 1979 and 1994 was reviewed. Aortic commissural valvuloplasty (AVP) was performed on prolapsed cusps in 34 patients (mean age 6.3 +/- 3.3 years (range: 2 to 24 years) with AR and VSD. The preoperative grade of AR was 2.6 +/- 0.8 measured angiographically by Sellers' classification. Patients had greater than moderate AR in conjunction with subpulmonary (n = 16), perimembranous (n = 15) or mixed type VSD (n = 3). In total, 25 right coronary cusps (RCC), five non-coronary cusps (NCC) and one left coronary cusp were repaired. In two cases, both RCC and NCC were plicated. One case had bicuspid valve and both cusps were repaired. There were no operative or late deaths. Moreover, the AR grade of the 25 cases has been below mild during a mean of 11.3 years follow up, though seven cases (22%) have developed above moderate AR. The two cases with persistent AR required redo AVP, with one having aortic valve replacement eventually after redo surgery. The operative findings showed cusp perforation on the repair site, or cusp elongation. However, the overall event-free rate analyzed by the Kaplan-Meier method was sufficiently favorable, with 96.6 +/- 3.4% for 5 years and 92.8 +/- 4.9% for 10 years. We conclude that aortic valvuloplasty for aortic regurgitation and VSD in pediatric patients is beneficial, with low mortality and reoperation rates.

Adolescent↗

Functional and possible physical association of scavenger receptor with cytoplasmic tyrosine kinase Lyn in monocytic THP-1-derived macrophages.

Acetyl LDL (modified low-density lipoprotein), which is thought to be taken up through scavenger receptor A (SR-A), rapidly induced the appearance of phosphotyrosine proteins in monocytic THP-1-derived macrophages in vitro. The two alternative forms of Lyn (p53 and p56) were found to be tyrosine-phosphorylated within 30 s after the stimulation with acetyl LDL. The catalytic activity of Lyn measured by an in vitro kinase assay had also increased in acetyl LDL-stimulated THP-1-derived macrophages. Furthermore, Lyn could be co-immunoprecipitated with SR-A from the cell lysate. These observations suggest a functional and possible physical association of SR-A with Lyn in THP-1-derived macrophages, and also imply a possible involvement of Lyn in SR-A signal transduction.

Amino Acid Sequence↗

Clinical evaluation of the efficacy of an antithrombin agent "Argatroban" combined with exercise therapy on increase of the skeletal muscle blood flow.

Argatroban has selective antithrombin activity and widely used for treatment of ASO. In this study we investigated vasodilating activity of Argatroban besides antithrombin activity in ASO patients. Three patients who have undergone F-P bypasses previously which were all occluded received 10 mg or 20 mg of Argatroban per day intravenously for 4 weeks. Skin temperature were measured before and after administration of Argatroban at the point of 1, 2, 4 weeks which increased 2.3-6.0 degrees C after administration of Argatroban. Subjective symptoms were also improved and these patients became to be able to walk 1.5-3.3 km. These patients were also given PGE, intravenously, however, temperature increase was less than 1.1 degrees C. These results showed that Argatroban has not only antithrombin activity but also significant vasodilating activity resulting in increase of skeletal muscle blood flow.

Aged↗

Evidence for direct association of Vpr and matrix protein p17 within the HIV-1 virion.

Vpr is one of the auxiliary proteins of HIV-1 and is selectively incorporated into the virion by a process involving the C-terminal p6 portion of the Gag precursor Pr55. Vpr and the matrix protein p17 are the components of the viral preintegration complex and appear to play important roles in the nuclear transport of proviral DNA in nondividing cells. In the present study, we have demonstrated by coimmunoprecipitation experiments that Vpr associates with matrix protein p17 but not with capsid protein p24 within the HIV-1 virion. Experiments employing the yeast two-hybrid GAL4 assay for protein-protein interactions also demonstrated a direct association between Vpr and the C-terminal region of matrix protein p17. Association of Vpr and the matrix protein p17 within the mature virion is consistent with their collaborative role in the nuclear transportation of the viral preintegration complex in nondividing cells such as macrophages.

Animals↗

Warm heart operation in a patient with myotonic dystrophy.

Myotonic dystrophy is the most severe form of myotonic disorder. Hypothermia or hyperkalemia may cause generalized muscle contraction during heart operations. We successfully repaired an atrial septal defect and pulmonary stenosis in a patient with myotonic dystrophy using systemic normothermia with continuous normokalemic coronary perfusion. This is the second reported case of a patient with myotonic dystrophy who underwent a cardiac operation.

Adult↗