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Biomedical subjects

S Mochizuki

Publications and source records attributed to S Mochizuki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Inhibitory effect of egualen sodium: a new stable derivative of azulene on histamine release from mast cell-like cells in the stomach.

We studied the inhibitory effect of egualen sodium (ES) (sodium 3-ethyl-7-isopropyl-1-azulenesulfonate 1/3 hydrate, KT1-32), a new derivative and more stable compound than azulene, on histamine release from the mucosal histaminocytes and elucidated the mechanism for this action. ES prevented the histamine release from isolated mast cell-like cells of the guinea pig stomach induced by A23187 in a dose-dependent fashion. ES dose-dependently inhibited the histamine release from lung pieces of sensitized guinea pigs induced by an antigen-antibody reaction. ES also inhibited histamine release from rat peritoneal mast cells induced by compound 48/80 or antigen-antibody reaction. ES exhibited the membrane stabilizing activity on DPPC liposomes. These findings suggest that ES may prevent histamine release from histaminocytes induced by various stimuli and the stabilizing action of the cell membrane may be responsible for the inhibition of histamine release.

Androstanes↗
PubMed2001

Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-kappaB activation and alleviates myocardial ischemia/reperfusion injury.

Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin-mediated infiltration of neutrophils plays a key role in reperfusion injury. However, the mechanism of the P-selectin induction is not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration in coronary endothelial P-selectin expression. Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P-selectin induction in wild-type mice. In cultured endothelial cells, activation of GC-A augmented H2O2-induced P-selectin expression. Furthermore, ischemia/reperfusion-induced activation of NF-kappaB, a transcription factor that is known to promote P-selectin expression, is suppressed in GC-A-deficient mice. These results suggest that inhibition of GC-A alleviates ischemia/reperfusion injury through suppression of NF-kappaB-mediated P-selectin induction. This novel, GC-A-mediated mechanism of ischemia/reperfusion injury may provide the basis for applying GC-A blockade in the clinical treatment of reperfusion injury.

Animals↗
PubMed2001

The DD genotype of angiotensin converting enzyme polymorphism is a risk factor for coronary artery disease and coronary stent restenosis in Japanese patients.

Stent implantation has decreased the incidence of restenosis after coronary intervention, but has not eliminated it. The contribution of the angiotensin-converting enzyme (ACE) genotype to the development of coronary artery disease and restenosis after coronary stenting was investigated in 67 Japanese patients in whom 103 lesions in which stents had been successfully implanted were assessed by quantitative coronary angiography, before, immediately after coronary stenting, and during follow-up. The distribution of the patients with the DD, ID, and II genotypes was 13%, 54%, and 33%, respectively. The prevalence of multivessel disease in the DD genotype was significantly higher (DD genotype: 78%; ID genotype: 58%; II genotype: 27%, chi2=8.13, p=0.016) and the late loss in the DD genotype (1.43+/-0.96 mm) was significantly greater (ID genotype: 0.78+/-0.98 mm and II genotype: 0.79+/-0.88 mm, p<0.05 vs DD genotype). However, there was no significant difference in the restenosis rate among the 3 genotypes. The present study in Japanese patients indicates that the DD genotype is associated with more extensive coronary artery disease and progression of the inward remodeling within the stented lesion, which is primarily caused by neointimal hyperplasia.

Aged↗
PubMed2001

One month survival with the undulation pump total artificial heart in a goat.

The undulation pump is a small continuous flow displacement-type blood pump. The undulation pump total artificial heart (UPTAH) is a unique implantable total artificial heart using undulation pumps. An adult female goat weighing 45.8 kg was used for implantation. The natural heart was replaced with the UPTAH under extracorporal circulation. The cardiac output (CO) was maintained to 100 ml/kg/min by controlling the right pump manually. To prevent lung edema, the left pump was controlled automatically to maintain the left atrial pressure below 20 mm Hg. The CO was maintained for 2 weeks. Thereafter, the CO gradually decreased. The goat suddenly died because of a brain stroke on the 31st postoperative day. At autopsy, the cavity of the left atrial cuff was almost occupied by the big pannus-like thrombus, which was thought to be the cause of death. Improvement of the atrial cuff is necessary to obtain longer survival and is being modified. No thrombus was found inside the pumps. However, temperature rise in a left motor was a problem. Improvement of the efficiency in a motor is necessary. Although many problems still remained, 1 month survival could be obtained with this unique implantable TAH using continuous flow displacement-type blood pumps.

Animals↗
PubMed2000

Cloning, expression, and characterization of ferret 5-HT(3) receptor subunit.

Ferrets (Mustela putorius furo) are useful animals for determining anti-emetic activity via 5-HT(3) receptors in vivo. We isolated a cDNA encoding the 5-hydroxytryptamine (5-HT) type 3A receptor subunit (5-HT(3A)) from ferret colon, expressed it in a human embryonic kidney cell line and determined its pharmacological properties. The open reading frame of the isolated cDNA encoded a 483-amino acid protein, corresponding to the shorter splice variant of 5-HT(3A) receptors. Splice variants were no longer detected by reverse transcriptase-polymerase chain reaction. The ferret 5-HT(3A) receptor exhibits a high degree of amino acid sequence identity (>/=80%) to that of other species. Binding studies demonstrated the following rank order of potency for agonists: meta-chlorophenylbiguanide (mCPBG)>2-methyl-5-hydroxytryptamine (2-Me-5-HT)=5-HT, and for antagonists: ondansetron=tropisetron>(+)-tubocurarine>metoclopramide. Electrophysiological studies revealed that mCPBG was a partial agonist and 2-Me-5-HT was an almost fully effective agonist compared to 5-HT.

Alternative Splicing↗
PubMed2000

Simultaneous measurements of temperature and pH in vivo using NMR in conjunction with TmDOTP5-.

NMR techniques for temperature and pH measurements have attracted increasing interest in recent years, motivated in part by the growing importance of medical hyperthermia for the treatment of cancer. The chemical shifts of thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetrakis(methylene phosphonate) (TmDOTP5-) have been studied as a function of temperature and pH. The results demonstrate that TmDOTP5- resonance shifts are highly sensitive to temperature (approximately 1.0 ppm/degrees C) and pH (approximately 3.2 ppm/pH unit) at clinically relevant field strengths. A new method is presented which utilizes two magnetically non-equivalent protons in TmDOTP5- for simultaneous NMR measurements of both temperature and pH. The difference in the chemical shift values of pairs of 1H resonances provides a temperature sensitivity of about 1.6 ppm/ degrees C. The technique is demonstrated in live rats undergoing ultrasound-induced hyperthermia therapy.

Animals↗
PubMed2000

Surgical cryoablation for frequent premature ventricular contraction originating in the left sinus of Valsalva.

Cryoablation in the left ventricular outflow tract and aortic valve replacement were conducted in a 70-year-old man with frequent premature ventricular contraction and nonsustained ventricular tachycardia complicated by Sellers grade 4 aortic regurgitation. The earliest endocardial activation site during premature ventricular contraction was confirmed by a preoperative electrophysiological study of the left sinus of Valsalva. Cryoablation preceded valvulectomy followed by aortic valve replacement. Clinical symptoms of premature ventricular contraction disappeared immediately after surgery.

Aortic Valve↗
PubMed2000

Cloning and analysis of the replication origin and the telomeres of the large linear plasmid pSLA2-L in Streptomyces rochei.

The replication origin and both terminal segments were cloned from the large linear plasmid pSLA2-L in Streptomyces rochei 7434AN4. The basic replicon consists of a 1.9-kb DNA fragment, which contains the genetic information required for autonomous replication in circular form. Sequence analysis revealed two ORFs, RepL1 and RepL2, with no similarity to any of the replication initiator proteins in the database. Deletion and mutational analysis showed that RepL1 is essential for replication and RepL2 has a subsidiary function. The origin of replication may be located 800 bp upstream of repL1. Sequencing of the left and right terminal segments revealed the presence of 12 palindromes. The sequence of the first 90 bp, including palindromes I-IV, shows great similarity to that of other Streptomyces linear chromosomes and plasmids. These results suggest that the internal replication origins of the linear replicons vary widely, in contrast to the high degree of conservation of their telomeres.

Amino Acid Sequence↗
PubMed2000

Effect of dietary control on plasma nitrate level and estimation of basal systemic nitric oxide production rate in humans.

It is of great interest and value to evaluate the systemic nitric oxide (NO) production rate in humans under various conditions. However, the currently available estimation methods are troublesome and time-consuming. We thus aimed at developing a simple method to estimate the basal systemic NO production rate in humans based on a steady-state analysis, i.e., a balance between the systemic NO production rate and the total nitrate elimination rate. Plasma nitrate concentrations of young healthy volunteers (n = 7 in group 1: n = 9 in group 2) were measured for 2 days. In group 1, all subjects had the same meals for 7 days prior to the plasma nitrate measurement. In group 2, all subjects were allowed free diets. The plasma nitrate concentrations were highly influenced by dietary nitrite/nitrate intake in both groups and reached the steady-state levels after 14-h fasting. Accordingly, the basal systemic NO production rates were estimated from the plasma nitrate concentrations after 14-h fasting (group 1, 630 +/- 37 nmol min(-1) = 0.78 +/- 0.03 micromol kg(-1) h(-1); group 2, 597 +/- 45 nmol min(-1) = 0.66 +/- 0.05 micromol kg(-1) h(-1), P = not significant vs group 1). These estimated values were comparable to the values obtained by other methods. In conclusion, the present estimation method with 14-h fasting using a single-compartment analysis was found to be a simple approach to quantitative evaluation and intra- and interindividual comparisons of the basal systemic NO production rates in humans.

Adult↗
PubMed2000

Effects of magnesium and its mechanism on the incidence of reperfusion arrhythmias following severe ischemia in isolated rat hearts.

Magnesium sulfate (Mg) has been widely used for the treatment of ventricular arrhythmias (VF) in patients with coronary artery disease. However, the mechanisms of prevention on the incidence of VF have not been defined. The aim of study was to investigate the role of Mg in the prevention of VF and the mechanism of those effects. Series 1 studied antiarrhythmic effects on VF. Isolated rat hearts were perfused in the working heart mode with Krebs'-Henseleit bicarbonate buffer (KHB). Whole heart ischemia was induced by a one-way ball valve with 300 beats/min electrical pacing for 10 minutes followed by 20 minutes of aerobic reperfusion. After control perfusion, Mg was added from 5 minutes before ischemia and was continued to the end of ischemia (1.2 mM for the control group and 2.4, 3.6, 4.8, and 9.6 mM for the study animals) or during reperfusion (3.6 mM). Left ventricular pressure, aortic flow, and ECG were monitored. Series 2 studied the effect of Mg on [Ca2+]i. Hearts were perfused by the Langendorff mode and were loaded with 4 microM of Fura 2/AM as a [Ca2+]i indicator. Ca2+ was monitored using the ratio of Fura-2 fluorescence intensity at excitation wavelengths of 340 and 380 nm. The hearts were subjected to a 20 minutes of low-flow ischemia followed by 20 minutes of aerobic reperfusion. Then 3.6 mM Mg was added to the KHB medium during ischemia. The duration of VF was significantly suppressed in the 2.4, 3.6, and 4.8 mM/L Mg-added groups (472 +/- 173, 779 +/- 159, and 525 +/- 202 second, respectively) when compared with the control group (1200 seconds). Magnesium sulfate suppressed the fluorescence ratio of the diastolic Ca2+ level at the end of 20 minutes of ischemia from 40.5 +/- 3.6% to 9.0 +/- 1.0% (P < 0.05 vs. control hearts). These results suggested that Mg had a beneficial effect on VF and that the optimal Mg concentration was between 2.4 and 4.8 mM. The mechanism of the prevention of VF by Mg could be through the inhibition of [Ca2+]i retention during ischemia.

Animals↗
PubMed2000

Analysis of hemodynamic response with 1/R control on biventricular bypass goat.

A conductance and arterial pressure based method (1/R control) to determine the cardiac output (CO) of a total artificial heart (TAH) was developed to provide a central nervous system with control over the output of TAH. In order to clarify the deference in hemodynamic response between natural heart and 1/R control, biventricular bypass was introduced in the goat. After 2 pneumatically driven sac-type blood pumps were connected to the natural heart, the pulmonary artery was totally clamped to acquire 100% right heart bypass, and the ascending aorta was stenosed to acquire about 60 to 90% left heart bypass; 1/R control was performed substituting the output of the right artificial heart for the CO. The results demonstrated that stable control could be achieved. A discrepancy was often seen between the pulse rate (PR) of the artificial heart and the heart rate (HR) in absolute value. However, the relative changes of PR were quite similar to that of HR for the most part, indicating that the responses of 1/R control were the duplication of natural cardiac responses in normal daily activity.

Animals↗
PubMed2000

Development of a miniature undulation pump for the distributed artificial heart.

Research of the distributed artificial heart is important not only to acquire the means of individual organ perfusion but also to clarify the characteristics of the organ and the mechanism of blood distribution. To investigate the distributed artificial heart, the miniature undulation pump was developed. The outer diameter and the thickness of the developed pump were 38 mm and 11 mm, respectively. The priming volume of the pump was 3.2 ml. The total size including the motor unit was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1 chip motor controller. More than 5 L/min of continuous output could be obtained. The results showed that the developed miniature undulation pump system had enough performance for individual organ perfusion.

Biomechanical Phenomena↗
PubMed2000

Using one rotary blood pump to produce separate pulsatile circulations in the upper and lower halves of the body.

Separate systemic circulations with pulsatile flow were obtained using 1 rotary blood pump as a left ventricular assist device. The outlet of the pump was divided into 2 conduits, 1 connected to the upper half of the body and the other connected to the lower half. An electric actuator that clamped the 2 outlet conduits alternately provided pulsatile flows. An in vitro experiment showed that the pulsatility phases of the upper and lower halves of the body were complementary with pulsatile flow, and an in vivo experiment showed that controlled flow distributions of continuous flows could be obtained.

Animals↗
PubMed2000

Angiotensin II-induced cardiomyocyte hypertrophy and cardiac fibrosis in stroke-prone spontaneously hypertensive rats.

Angiotensin-converting enzyme inhibitors (ACEIs) cause regression of hypertensive left ventricular hypertrophy (LVH) by reducing angiotensin II, increasing bradykinin, or both. The mechanisms of these cardioprotective effects remain controversial. The aims of this study were to determine whether the cardioprotective effects of ACEIs are mediated by reducing angiotensin II and whether ACEIs ameliorate the morphologic, physiologic, and biochemical changes in the hearts of stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs were treated with hydralazine, captopril, or candesartan, an angiotensin II type 1 receptor (AT1R) antagonist, from age 12 to 24 weeks. We measured systolic blood pressure (SBP), left ventricular weight (LVW), left ventricular (LV) myocyte cross-sectional area (myocyte size), LV Interstitial collagen volume fraction (ICVF), perivascular collagen area/luminal area ratio (PVCA/LA), the medial area to luminal area ratio (MA/LA), the relative amount of V3 myosin heavy chain (MHCV3), and coronary reserve maximum (coronary flow max/ventricular weight (CFmax/VW)). These parameters were compared with those of untreated SHRSPs and Wistar-Kyoto rats (WKYs). SHRSPs exhibited decreased coronary reserve and LVH with an increase in myocyte size, PVCA/LA, MA/LA, and MHCV3 at 12 weeks of age. In addition to these changes, 24-week-old SHRSPs showed an increase in ICVF. The LVW, coronary reserve, myocyte size, PVCA/LA, ICVF, and MHCV3 of SHRSPs treated with captopril or candesartan all approached control values. In contrast, hydralazine decreased only ICVF. These results suggest that ACEIs regress LVH and normalize coronary reserve by modulating the effects of angiotensin II via AT1R on the induction of cardiomyocyte hypertrophy, perivascular fibrosis, and medial thickening of intramyocardial coronary arteries in SHRSPs. We concluded that these effects, in addition to the reduction of SBP, are important in causing the regression of LVH.

Angiotensin Receptor Antagonists↗
PubMed2000

Alteration of CDKN2/p16 in human astrocytic tumors is related with increased susceptibility to antimetabolite anticancer agents.

A slowly proliferating cell fraction in tumors shows reduced sensitivity to cell cycle-dependent anticancer agents. To understand the molecular basis of drug resistance observed in brain tumors, we examined the relationship between alteration of p16, a cyclin dependent kinase inhibitor whose functions are frequently lost in many human gliomas, and chemosensitivity of tumor cells to various kinds of anticancer agents. Alterations of the p16 gene that include mutation(s) and homozygous deletion as well as p16 protein expression level, were examined in 56 specimens of astrocytic tumors. Their in vitro chemosensitivities to 30 kinds of anticancer agents were analyzed with flow cytometry which detects drug-induced cell death. We found that the alterations were correlated with increased sensitivity to antimetabolite anticancer agents but not with other kinds of agents, including alkylating agents, antibiotics, topoisomerase inhibitors and antimicrotubule agents. The present results suggest that p16 plays a role in determining chemosensitivity of brain tumors, depending on pharmacological mechanisms of anticancer agents. Proper understanding of the molecular machinery which regulates the chemosensitivity may contribute to the choice of anticancer agents for individual patients.

Antimetabolites, Antineoplastic↗
PubMed1999

New ether-à-go-go K(+) channel family members localized in human telencephalon.

A cDNA encoding a novel voltage-gated K(+) channel protein was isolated from human brain. This protein, termed BEC1, is 46% identical to rat elk in the ether-à-go-go K(+) channel family. The BEC1 gene maps to the 12q13 region of the human genome. Northern blot analysis indicates that BEC1 is exclusively expressed in human brain, where the expression is concentrated in the telencephalic areas such as the cerebral cortex, amygdala, hippocampus, and striatum. By in situ hybridization, BEC1 is detected in the CA1-CA3 pyramidal cell layers and the dentate gyrus granule cell layers of the hippocampus. Specific signals are also found in neocortical neurons. Transfection of mammalian L929 and Chinese hamster ovary cells with BEC1 cDNA induces a voltage-gated outward current with a fast inactivation component. This current is insensitive to tetraethylammonium and quinidine. Additionally, a second related gene BEC2 was isolated from human brain. BEC2 is also brain-specific, located in the neocortex and the striatum, and functional as a channel gene. Phylogenetic analysis indicates that BEC1 and BEC2 constitute a subfamily, together with elk, in the ether-à-go-go family. The two genes may be involved in cellular excitability of restricted neurons in the human central nervous system.

Amino Acid Sequence↗