Association of left atrial phasic volumes with systemic arterial stiffness and ankle-brachial index in hypertensive patients.

Left atrial (LA) phasic volumes consist of reservoir, conduit and booster pump volumes. Arterial stiffness is linked to lower systemic arterial compliance (SAC) contributing to cardiac afterload. Arterial stiffness may be a modulator of LA phasic volumes. Echocardiography was performed in 161 hypertensive patients and in 50 normotensive subjects in order to assess biplane LA volumes (maximum, before atrial contraction, minimum), early and late diastolic mitral annular velocity (e' and a'), and LV stroke volume. LA emptying volumes (total, passive, active) were calculated from these LA volumes. Blood pressures were measured using an automated oscillometric device simultaneously at the four limbs for evaluating pulse pressure (PP) and ankle-brachial index (ABI). SAC was estimated by the ratio of LV stroke volume indexed by body surface area (BSA) divided by PP. All three LA volumes, LA total volume and LA active emptying volume were greater in hypertensive patients than in normotensive subjects. A multiple linear regression analysis indicated that LA passive emptying volume (reservoir=early diastole)/BSA correlated positively with ABI after being adjusted for age, gender, BSA, LV mass, max LA volume, e' and SAC in hypertensive patients. LA active emptying volume (booster=late diastole)/BSA correlated positively with SAC after being adjusted for age, gender, BSA, LV mass, LA volume before atrial contraction, a' and ABI. LA reservoir volume was associated with ABI, and LA booster volume was related to systemic arterial stiffness in hypertensive patients, suggesting the LA-arterial coupling in this clinical setting.

Intestinal epithelial culture under an air-liquid interface: a tool for studying human and mouse esophagi.

This study investigated whether an intestinal epithelial culture method can be applied to mouse and human esophageal cultures. The esophagi harvested from 1-day-old mice and adult humans were maintained in collagen gels. A commercially available culture medium for human embryonic stem cells was used for the human esophageal culture. We discovered that the intestinal epithelial culture method can be successfully applied to both mouse and human esophageal cultures. The long-term cultured esophageal organoids were rod-like luminal structures lined with myofibroblasts. We discovered that regeneration of the esophageal mucosal surface can be almost completely achieved in vitro, and the advantage of this method is that organoid cultures may be generated using host-derived fibroblasts as a niche. This method is a promising tool for mouse and human research in intestinal biology, carcinogenesis, and regenerative medicine.

Design and fabrication of a perpendicular magnetic tunnel junction based nonvolatile programmable switch achieving 40% less area using shared-control transistor structure.

A compact nonvolatile programmable switch (NVPS) using 90 nm CMOS technology together with perpendicular magnetic tunnel junction (p-MTJ) devices is fabricated for zero-standby-power field-programmable gate array. Because routing information does not change once it is programmed into an NVPS, high-speed read and write accesses are not required and a write-control transistor can be shared among all the NVPSs, which greatly simplifies structure of the NVPS. In fact, the effective area of the proposed NVPS is reduced by 40% compared to that of a conventional MTJ-based NVPS. The instant on/off behavior without external nonvolatile memory access is also demonstrated using the fabricated test chip.

Simultaneous optical mapping system of endocardial and epicardial excitation.

The cardiac excitation propagation during arrhythmia shows a three-dimensional complex excitation behavior. Numerous optical measurements of the propagation and action potentials of the cardiac muscles have been made to elucidate the detailed arrhythmia phenomenon. The conventional optical measurement system mainly observes the action potential signal of the epicardium, and the endocardial signal measurement without incising the heart is difficult. In addition, an incised heart no longer exhibits the natural excitation behavior. Therefore, we constructed a simultaneous measurement system that integrates the conventional epicardial measurement system and the endocardial measurement system by using an endoscope for an intact heart. Then, we proposed a line-laser registration method that can match correspondence between the epicardial and endocardial images for a short period. We demonstrated that this registration method has a sub-millimeter accuracy. Subsequently, we succeeded in simultaneous optical measurement of the excitation propagation of the epicardium and endocardium of the right heart wall by using an isolated rabbit heart.

Dose effects of oral estradiol on bone mineral density in Japanese women with osteoporosis.

OBJECTIVES: This 2-year study compared 0.5 and 1.0 mg oral estradiol (E(2)), with or without levonorgestrel (LNG), for the treatment of postmenopausal osteoporosis in Japanese women. METHODS: Japanese women with osteoporosis after natural menopause or bilateral oophorectomy were randomized to receive E(2) 0.5 or 1.0 mg/day with LNG 40 microg as required, or placebo, for 52 weeks. Women treated with E(2) in the first year continued therapy at the same doses in the second year. Efficacy, safety and pharmacokinetics were assessed. RESULTS: There were 73 women randomized to E(2) 0.5 mg, 157 to E(2) 1.0 mg and 79 to placebo. Lumbar bone mineral density at 52 weeks increased significantly more with E(2) 1.0 mg (p < 0.001) and 0.5 mg (p < 0.001) than with placebo (no change). After 2 years, a 10% increase in bone mineral density with E(2) 1.0 mg was significantly greater than with E(2) 0.5 mg (8%; p = 0.008). E(2) was associated with an acceptable safety and tolerability profile, with slightly more adverse events with E(2) 1.0 than 0.5 mg. Serum E(2) concentration increased in a dose-dependent manner. CONCLUSION: This study showed that E(2), at both 1.0 mg and 0.5 mg doses, was effective in increasing bone mineral density with an acceptable safety and tolerability profile in Japanese postmenopausal women with osteoporosis but that the bone mineral density response was higher with the 1.0 mg dose.

Incidence of Carboplatin-related hypersensitivity reactions in Japanese patients with gynecologic malignancies.

Carboplatin is one of the most commonly used and well-tolerated agents for gynecologic malignancies. The rate of hypersensitivity reactions (HSRs) in the overall population of patients receiving carboplatin has been reported to increase after multiple doses of the agent. We retrospectively analyzed the incidence, clinical features, management, or outcome of carboplatin-related HSRs in 113 Japanese patients with gynecologic malignancies and the possibility of rechallenge with the drug. We intravenously administered carboplatin after paclitaxel or docetaxel. Mild HSRs are resolved by temporary interruption of carboplatin infusion, an additional antihistamine, and/or a corticosteroid. If HSRs arose, carboplatin was diluted, not exceeding 1 mg/mL, and slowly infused over 2 hours in subsequent cycles. Ten patients experienced carboplatin HSRs, with an overall incidence of 8.85%. The first HSR episode was mild in all cases. When retreated with carboplatin, 4 exhibited severe HSRs. More than 9 cycles and/or more than 5000 mg of carboplatin administration significantly increased the incidence of HSRs. In particular, carboplatin treatment beyond 15 cycles and/or 8000 mg increased the risk of severe HSRs (P < 0.0001). The incidence of HSRs in the ovarian carcinoma group was significantly greater than that in the uterine carcinoma group (P = 0.0046). Careful attention should be paid to HSRs during carboplatin treatment beyond 9 cycles and/or 5000 mg. The rate of severe HSRs greatly increases beyond 15 cycles and/or 8000 mg. Further studies are needed to identify potential risk factors that may contribute to the development of carboplatin HSRs and to decrease the risk of reactions.

Low-dose estradiol for climacteric symptoms in Japanese women: a randomized, controlled trial.

OBJECTIVES: To investigate two different doses of oral estradiol to reduce the number of hot flushes in Japanese women with climacteric symptoms. METHODS: Women (n = 211) aged 40-64 years who had experienced natural menopause or bilateral oophorectomy, with > or = three moderate/severe hot flushes per day in the week before study, were randomized to receive micronized estradiol (E2) 0.5 or 1.0 mg or placebo once daily for 8 weeks. The primary efficacy endpoint was percentage change in mean daily number of hot flushes over 7 days from baseline to final examination. RESULTS: Percentage change in mean daily number of hot flushes at final examination was similar for E2 0.5 mg and E2 1.0 mg (-79.58 +/- 28.29% vs. -82.49 +/- 25.31%, p = 0.555) but was significantly lower with placebo (-57.89 +/- 34.15%, p < 0.001 vs. E2, both doses). There was no significant difference in number of treatment-related adverse events occurring in the E2 0.5 and 1.0 mg groups (25% and 36.6%, respectively). The higher E2 dose showed more pronounced effects on symptom severity. CONCLUSIONS: The dose of 0.5 mg/day was effective as the oral E2 starting dose for treatment of hot flushes in Japanese women.

Role of Ca2+ mobilization and Ca2+ sensitization in 8-iso-PGF 2 alpha-induced contraction in airway smooth muscle.

BACKGROUND: Isoprostanes are prostaglandin (PG)-like compounds synthesized by oxidative stress, not by cyclooxygenase, and increase in bronchoalveolar lavage fluid of patients with asthma. The airway inflammation implicated in this disease may be amplified by oxidants. Although isoprostanes are useful biomarkers for oxidative stress, the action of these agents on airways has not been fully elucidated. OBJECTIVE: This study was designed to determine the intracellular mechanisms underlying the effects of oxidative stress on airway smooth muscle, focused on Ca(2+) signalling pathways involved in the effect of 8-iso-PGF(2 alpha). METHODS: Using simultaneous recording of isometric tension and F(340)/F(380) (an indicator of intracellular concentrations of Ca(2+), [Ca(2+)]i, we examined the correlation between tension and [Ca(2+)]i in response to 8-iso-PGF(2 alpha) in the fura-2 loaded tracheal smooth muscle. RESULTS: Augmented tension and F(340)/F(380) by 8-iso-PGF(2 alpha) were attenuated by ICI-192605, an antagonist of thromboxane A(2) receptors (TP receptors). Moreover, D609, an antagonist of phosphatidylcholine-specific phospholipase C, markedly reduced both the tension and F(340)/F(380) induced by 8-iso-PGF(2 alpha), whereas U73122, an antagonist of phosphatidylinositol-specific phospholipase C, modestly inhibited them by 8-iso-PGF(2 alpha). SKF96365, a non-selective antagonist of Ca(2+) channels, markedly reduced both tension and F(340)/F(380) by 8-iso-PGF(2 alpha). However, diltiazem and verapamil, voltage-dependent Ca(2+) channel inhibitors, modestly attenuated tension although their reduction of F(340)/F(380) was not different from that by SKF96365. Y-27632, an inhibitor of Rho-kinase, significantly attenuated contraction induced by 8-iso-PGF(2 alpha) without reducing F(340)/F(380), whereas GF109203X and Go6983, protein kinase C inhibitors, did not markedly antagonize them although reducing F(340)/F(380) with a potency similar to Y-27632. CONCLUSION: 8-iso-PGF(2 alpha) causes airway smooth muscle contraction via activation of TP receptors. Ca(2+) mobilization by SKF96365- and D609-sensitive Ca(2+) influx and Ca(2+) sensitization by Rho-kinase contribute to the intracellular mechanisms underlying the action of 8-iso-PGF(2 alpha). Rho-kinase may be a therapeutic target for the physiologic abnormalities induced by oxidative stress in airways.

Association of aortic valve sclerosis with thrombin generation in hypertensive patients.

Aortic valve sclerosis (AVS) may predispose to a prothrombotic state, as AVS is predictor of cardiovascular events in hypertensive populations. Thrombin exerts non-thrombotic effects such as vessel tone regulation, progression of atherosclerosis and stimulation of atrial natriuretic peptide (ANP) secretion. We hypothesized that hypertensive patients with AVS may have a persistently activated thrombin generation. We studied 234 asymptomatic never-treated hypertensive patients (73 of them with AVS). Prothrombin F1+2 (F1+2), as a marker of thrombin generation and fibrin D-dimer, as a marker of thrombus formation, ANP and brain natriuretic peptide (BNP) were measured. Presence of AVS, aortic jet velocity and left ventricular diameter at diastole were determined by echocardiography. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula. F1+2 (median and interquartile range (IQR) = 1.05, 0.87-1.38 nM vs. 0.93, 0.72-1.16) and ANP (22, 14-37 pg ml(-1) vs. 17, 11-25) levels were greater, and glomerular filtration rate values (65+/-9 ml min(-1)/1.73 m2 vs. 68+/-11) were lower in hypertensive patients with AVS than in those without AVS. F1+2 (odds ratio, 95% CI = 2.94, 1.07-8.6) was independently associated with AVS after being adjusted for age, gender and the variables of cardiorenal functions measured. After 6 months of treatment using valsartan, F1+2 levels remained elevated in hypertensive patients with AVS (1.14, 0.83-1.42 nM vs. 1.07, 0.84-1.5, n=19), but decreased in those without AVS (1.01, 0.85-1.31 vs. 0.8, 0.84-1.78, n=27). Thrombin generation was associated with AVS in untreated hypertensive patients, and this association was persistent after blood-pressure-lowering treatment using valsartan.

Predictive value of von Willebrand factor for adverse clinical outcome in hypertensive patients with mild-to-moderate aortic regurgitation.

Plasma levels of von Willebrand factor (vWF), a marker of endothelial dysfunction/damage, are elevated in high-risk hypertensive patients and in patients with severe aortic regurgitation (AR). Patients with mild-to-moderate AR, frequently detected in hypertensive elderly, have additional left ventricular morphological and functional dysfunctions. We hypothesized that hypertensive patients with mild-to-moderate AR may have enhanced endothelial and/or left ventricular dysfunctions that may lead to a deteriorated prognosis. We measured vWF, prothrombin F1+2 (F 1+2) as a marker of thrombin generation, brain natriuretic peptide (BNP) in 104 hypertensive patients with mild-to-moderate AR and 66 hypertensive patients without AR. The left ventricular diameter at systole (LVDs) and left ventricular posterior wall thickness (LVWT) were determined by echocardiography and indexed by body surface area (LVDs/BSA and LVWT/BSA). VWF (median, interquartile range (IQR) 154, 120-196%) and BNP (34.7 pg ml(-1), 15-65%) levels were greater in patients with AR than in those without AR (135, 98-175% and 20, 10.3-49 pg ml(-1)). All patients were prospectively followed up for cardiac events during the period of median 43 months (IQR 31-81). Patients with AR had an increased risk of cardiac events (regression ratio (RR) 1.87, 95% confidence interval 1.28-2.87) when compared to those without AR. A multivariate Cox hazard analysis indicated that log vWF (RR 4.93) and log BNP (RR 1.9) were independent predictors in patients with AR. VWF was an independent predictor of clinical outcome in hypertensive patients with mild-to-moderate AR.

Neoadjuvant chemotherapy with weekly carboplatin and paclitaxel for locally advanced cervical carcinoma.

The efficacy and toxicity of neoadjuvant carboplatin and paclitaxel administered on a weekly schedule for locally advanced cervical carcinoma were evaluated. Thirty patients staged as IB2-IVA according to the FIGO were treated with carboplatin (AUC 2; an area under the time-concentration of 2 mg*min/ml based on creatinine clearance) and paclitaxel (60 mg/m(2)) intravenously, every week for six cycles. A type III radical hysterectomy was then undertaken. Thirty patients were enrolled in this study. An objective response was recorded in 26 patients (87%, 95% CI 70-95%). Progressive disease was not observed. Grade 3 neutropenia was observed in only two patients (7%), and grade 1 or 2 neuropathy was seen in six patients (20%). The combination of carboplatin and paclitaxel given in weekly schedule for advanced cervical carcinoma was highly active, permitting a high rate of subsequent surgical resectability. It was well tolerated. This regimen may provide improved outcomes with minimal toxicity.

Roles of P2X receptors and Ca2+ sensitization in extracellular adenosine triphosphate-induced hyperresponsiveness in airway smooth muscle.

BACKGROUND: The release of adenosine triphosphate (ATP) from the airway epithelial cells during the inflammatory process is considered to play an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease. OBJECTIVE: This study was designed to determine whether extracellular ATP is involved in the bronchial hyperresponsiveness as an interaction between epithelium and smooth muscle in the airways. METHODS: We examined the contractile response to methacholine (MCh) before and after exposure to low concentrations (< or = 10 microm) of ATP in isolated, epithelium-denuded guinea-pig tracheal smooth muscle by measuring isometric tension. Intracellular Ca2+ concentrations ([Ca2+]i) were assessed by fluorescent intensities of fura-2. RESULTS: MCh-induced contractile force was increased with no change in [Ca2+]i after exposure to 10 microm ATP for 15 min. The ability of ATP to enhance the MCh-induced contraction was markedly attenuated by suramin, a non-selective P2 receptor inhibitor. Pre-incubation with ATPgammaS, a non-hydrolysable analogue of ATP and alpha,beta-meATP, a P2X agonist, also enhanced the MCh-induced contraction. In contrast, uracil triphosphate, a P2Y agonist, did not affect the MCh-induced contraction. Y-27632, a Rho-kinase inhibitor, suppressed the ability of ATP to enhance the MCh-induced contraction. Moreover, PP1 and PP2, Src tyrosin kinase inhibitors, suppressed the enhancement of MCh-induced contraction by ATP. CONCLUSION: Pre-treatment with ATP induces hyperresponsiveness to MCh mediated by Ca2+ sensitization via the P2X receptor in airway smooth muscle. The present findings suggest the possible involvement of both the Rho-kinase and Src pathways in the intracellular mechanism of this phenomenon.

Predictive value of heart-type fatty acid-binding protein for left ventricular remodelling and clinical outcome of hypertensive patients with mild-to-moderate aortic valve diseases.

Heart-type fatty acid-binding protein (H-FABP), a marker of acute myocardial infarction and a soluble cytosolic protein, may be released following left ventricular remodelling in cardiac overloaded hearts caused by hypertension, aortic regurgitation (AR) or aortic stenosis (AS). Our aim was to investigate if H-FABP levels are associated with left ventricular remodelling and clinical outcome in hypertensive patients with AR or AS. H-FABP and brain natriuretic peptide (BNP) were measured, glomerular filtration rate (GFR) was estimated using the modification of diet in renal disease (MDRD) equation, and left ventricular dimension at systole corrected for body surface area (LVDs/BSA) and relative wall thickness (RWT) were determined by echocardiography in hypertensive patients with mild-to-moderate AR (n=78), those with mild-to-moderate AS (n=73) and those without valvular heart diseases (HT) (n=50). H-FABP levels were significantly higher in AR (4.9+/-3 ng/ml) and in AS (4.5+/-3) than in HT (3.4+/-1) and BNP (65+/-73 pg/ml, 76+/-75, 35+/-22). H-FABP correlated with LVDs/BSA in AR (beta=0.23, P<0.05), and RWT in AS (beta=0.18, P<0.05) after adjustment for age, gender and all the other variables. AS and AR patients were prospectively followed up for cardiac events during 34+/-19 months. A multivariate Cox hazard analysis indicated H-FABP was an independent predictor of outcome both in AR (relative risk (RR)=7.61, 95% CI=2.39-25.3) and AS (RR=13.6, 95% CI=3.27-66.9). H-FABP, associated with left ventricular remodelling, is useful in predicting clinical outcome in hypertensive patients with mild-to-moderate aortic valve diseases.

Acute cholecystitis due to strangulation of a floating gallbladder by the lesser omentum.

We report a unique case of acute cholecystitis due to strangulation of a floating gallbladder by the lesser omentum, which could be detected by abdominal ultrasonography. We believe this case to be the first case of reported literatures in English.

Connexins in the sinoatrial and atrioventricular nodes.

The sinoatrial node (SAN) and the atrioventricular node (AVN) are specialized tissues in the heart: the SAN is specialized for pacemaking (it is the pacemaker of the heart), whereas the AVN is specialized for slow conduction of the action potential (to introduce a delay between atrial and ventricular activation during the cardiac cycle). These functions have special requirements regarding electrical coupling and, therefore, expression of connexin isoforms. Electrical coupling in the center of the SAN should be weak to protect it from the inhibitory electrotonic influence of the more hyperpolarized non-pacemaking atrial muscle surrounding the SAN. However, for the SAN to be able to drive the atrial muscle, electrical coupling should be strong in the periphery of the SAN. Consistent with this, in the center of the SAN there is no expression of Cx43 (the principal connexin of the working myocardium) and little expression of Cx40, but there is expression of Cx45 and Cx30.2, whereas in the periphery of the SAN Cx43 as well Cx45 is expressed. In the AVN, there is a similar pattern of expression of connexins as in the center of the SAN and this is likely to be in large part responsible for the slow conduction of the action potential.

Involvement of reduced sensitivity to Ca in beta-adrenergic action on airway smooth muscle.

BACKGROUND: It is well known that beta-adrenoceptor agonists (beta-agonists) cause relaxation in airway smooth muscle mediated by a reduction in the concentration of intracellular Ca2+ ([Ca2+](i)). However, little is currently known regarding whether reduced sensitization to Ca2+ is involved in the beta-adrenergic relaxation. OBJECTIVE: This study was designed to determine the intracellular mechanisms underlying suppression of Ca2+ sensitization in beta-adrenergic relaxation (Ca(2+)-independent relaxation by beta-agonists). Methods Isometric tension and [Ca2+](i) were simultaneously measured in fura-2-loaded strips isolated from guinea-pig tracheal smooth muscles. The relationships between tension and [Ca2+](i) were examined in the inhibitory action of isoprenaline (ISO) and other cAMP-related agents against methacholine-induced contraction. RESULTS: The concentration-inhibition curve for ISO against methacholine in tension was significantly dissociated from the curve for ISO in [Ca2+](i). In ISO-induced relaxation, a reduction in tension was significantly greater than that in [Ca2+](i.) This phenomenon was mimicked by other cAMP-related agents: forskolin and dibutyryl-cAMP. In contrast, the inhibitory action of SKF-96365, a non-selective inhibitor of Ca(2+) channels, was associated with that in [Ca2+](i). In the presence of Rp-cAMPS, an inhibitor of protein kinase A (PKA), ISO caused an equivalent relaxation with less reduction in [Ca2+](i). The effects of ISO were not affected by Y-27632, an inhibitor of Rho-kinase, or by bisindolylmaleimide, an inhibitor of protein kinase C. ISO failed to inhibit contraction elicited by calyculin A, an inhibitor of myosin phosphatase. Conclusion beta-Adrenergic action antagonizes not only Ca2+ mobilization but also Ca2+ sensitization in methacholine-induced contraction. The cAMP/PKA-independent, G(s)-direct action is more potent in Ca(2+)-independent relaxation by beta-agonists than the cAMP/PKA-dependent pathway. Moreover, myosin phosphatase is a fundamentally affected protein in the reduced response to Ca2+ mediated by beta-agonist. Our results may provide evidence that this Ca2+ desensitization is a novel target for a reliever medication using rapid-acting beta-agonists in acute asthma management.

Computer three-dimensional reconstruction of the sinoatrial node.

BACKGROUND: There is an effort to build an anatomically and biophysically detailed virtual heart, and, although there are models for the atria and ventricles, there is no model for the sinoatrial node (SAN). For the SAN to show pacemaking and drive atrial muscle, theoretically, there should be a gradient in electrical coupling from the center to the periphery of the SAN and an interdigitation of SAN and atrial cells at the periphery. Any model should include such features. METHODS AND RESULTS: Staining of rabbit SAN preparations for histology, middle neurofilament, atrial natriuretic peptide, and connexin (Cx) 43 revealed multiple cell types within and around the SAN (SAN and atrial cells, fibroblasts, and adipocytes). In contrast to atrial cells, all SAN cells expressed middle neurofilament (but not atrial natriuretic peptide) mRNA and protein. However, 2 distinct SAN cell types were observed: cells in the center (leading pacemaker site) were small, were organized in a mesh, and did not express Cx43. In contrast, cells in the periphery (exit pathway from the SAN) were large, were arranged predominantly in parallel, often expressed Cx43, and were mixed with atrial cells. An approximately 2.5-million-element array model of the SAN and surrounding atrium, incorporating all cell types, was constructed. CONCLUSIONS: For the first time, a 3D anatomically detailed mathematical model of the SAN has been constructed, and this shows the presence of a specialized interface between the SAN and atrial muscle.

Analysis of QT Interval Prolongation With Heart Failure by Simulation of Repolarization Process.

It has been postulated that action potential duration (APD) is prolonged and IKs, a slow component of delayed rectifier potassium current, decreases in heart failure. We have reported that QT interval is prolonged and expression weight of KCNE1, coding IKschannel, increases in patients with heart failure. Since it is known that increase in KCNE1 increases the maximum conductance of IKschannel, the mechanism of APD prolongation is not explained by over expression of KCNE1. In this study, we construct a cardiac membrane action potential simulation model based on the experimental data from Xenopus oocytes expressed KCNQ1 and KCNE1 to investigate the relationship between increase in KCNE1 and APD. In addition, we investigated effect of reduction in Ca2+-independent transient outward potassium current (Ito) on APD in heart failure. In simulation, APD at 5ng KCNE1 was 180.96ms, which was 4.63% longer than that at 1ng KCNE1 (APD=172.96ms) and 55.9% longer than that at 0.2ng KCNE1 (APD=110.96ms. In the cases of KCNQ1 alone and 0.2ng KCNE1 coinjected, APD shortened as density of Itodecreased, and APD prolonged as density of Itodecreased in other cases. This study shows that increase in KCNE1 expression level makes maximum conductance of IKschannel increase and IKschannel open slowly and conductance of IKschannel decrease according to the APD time scale. Therefore increasing the KCNE1 expression level may prolong APD with this mechanism. This method of constructing a simulation model based on experiments helps to explain the relationship between potassium currents and QT interval prolongation.

Expression of nuclear factor of activated T cells mRNA in maternal peripheral blood cells.

PROBLEM: In T lymphocytes, nuclear factor of activated T cells (NF-AT) regulates the induction of cytokine genes upon antigenic stimulation. This study was designed to analyse the relationship between NF-AT and pregnancy. METHOD OF STUDY: With informed consent, peripheral blood cells (PBCs) were obtained from non-pregnant (n = 114), pregnant (n = 604), and puerperal women (n = 52). The expression of NF-AT2 and NF-AT3 mRNAs in PBCs was measured by a quantitative reverse transcriptase-polymerase chain reaction method. RESULTS: In the early pregnancy period, in successful pregnancy, both NF-AT2 and NF-AT3 mRNAs increased significantly, whereas in cases of spontaneous abortion they did not change significantly. After peaking, they decreased gradually and were re-elevated in the ninth and tenth gestational month. In the puerperal period, NF-AT3 mRNAs decreased, but NF-AT2 mRNA showed a comparatively high expression level. CONCLUSION: These findings suggested that in humans NF-AT signal transduction might be involved in alloantigenic recognition and tolerance and play important roles, especially in the early and late period of pregnancy.