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Biomedical subjects

H Otani

Publications and source records attributed to H Otani.

At least 73 records · Page 4Linked to original sources
PubMed2000

Cloning and characterization of a cyclic peptide synthetase gene from Alternaria alternata apple pathotype whose product is involved in AM-toxin synthesis and pathogenicity.

Afternaria afternata apple pathotype causes Alternaria blotch of susceptible apple cultivars through the production of a cyclic peptide host-specific toxin, AM-toxin. PCR (polymerase chain reaction), with primers designed to conserved domains of peptide synthetase genes, amplified several products from A. alternata apple pathotype that showed high similarity to other fungal peptide synthetases and were specific to the apple pathotype. Screening of a Lambda Zap genomic library with these PCR-generated probes identified overlapping clones containing a complete cyclic peptide synthetase gene of 13.1 kb in length with no introns. Disruption of this gene, designated AM-toxin synthetase (AMT), by transformation of wild-type A. afternata apple pathotype with disruption vectors resulted in toxin-minus mutants, which were also unable to cause disease symptoms on susceptible apple cultivars. AM-toxin synthetase is therefore a primary determinant of virulence and specificity in the A. alternata apple pathotype/apple interaction.

Alternaria↗
PubMed2000

Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a wortmannin-sensitive mechanism.

Insulin-like growth factor-I (IGF-I) has been shown to produce a short-term positive inotropic effect (PIE) in the myocardium under nonischemic conditions. IGF-I also conferred cytoprotection against ischemia and reperfusion injury in various organs. IGF-I may, therefore, facilitate the recovery of postischemic cardiac function. Isolated and crystalloid-perfused rat heart was subjected to 25 min of normothermic ischemia followed by 30 min of reperfusion. IGF-I produced PIE in a dose-dependent manner at concentrations ranging between 1 and 100 nM under nonischemic conditions. Although 1 nM isoproterenol produced much greater PIE and myocardial energy conversion efficiency (MECE) than did 65 nM IGF-I in this condition, the same concentration of IGF-I administered during reperfusion conferred better recovery of left ventricular function and MECE compared with isoproterenol. The improved cardiac performance by IGF-I was associated with lower release of creatine kinase (CK). Wortmannin (100 nM), a specific inhibitor of phosphatidylinositol kinase (PI-3 kinase), abrogated IGF-I-induced improvement of contractile function and inhibition of CK release in the postischemic heart. We conclude that IGF-I administered during reperfusion accelerates recovery of cardiac performance and mitigates myocardial injury through a wortmannin-sensitive mechanism.

Androstadienes↗
PubMed2000

Dietary coenzyme Q(10) supplement renders swine hearts resistant to ischemia-reperfusion injury.

To examine whether nutritional supplementation of coenzyme Q(10) (CoQ(10)) can reduce myocardial ischemia-reperfusion injury, a group of swine was fed a regular diet supplemented with CoQ(10) (5 mg x kg(-1) x day(-1)) for 30 days. Another group of pigs that were fed a regular diet supplemented with placebo served as a control. After 30 days, isolated in situ pig hearts were prepared and hearts were perfused with a cardiopulmonary pump system. Each heart was subjected to 15 min of regional ischemia by snaring of the left anterior descending coronary artery, followed by 60 min of hypothermic cardioplegic global ischemia and 120 min of reperfusion. After the experiments were completed, myocardial infarct size was measured by triphenyltrazolium chloride staining methods. Postischemic left ventricular contractile function was better recovered in the CoQ(10) group than in the control group of pigs. CoQ(10)-fed pigs revealed less myocardial infarction and less creatine kinase release from the coronary effluent compared with control pigs. The experimental group also demonstrated a smaller amount of malonaldehyde in the coronary effluent and a higher content of the endogenous antioxidants ascorbate and thiol. Significant induction of the expression of ubiquitin mRNA was also found in the hearts of the CoQ(10)-fed group. The results of this study demonstrate that nutritional supplementation of CoQ(10) renders the hearts resistant to ischemia-reperfusion injury, probably by reducing the oxidative stress.

Animals↗
PubMed2000

Hypermnesia: age-related differences between young and older adults.

Hypermnesia is a net improvement in memory performance that occurs across tests in a multitest paradigm with only one study session. Our goal was to identify possible age-related differences in hypermnesic recall. We observed hypermnesia for young adults using verbal (Experiment 1) as well as pictorial (Experiment 2) material, but no hypermnesia for older adults in either experiment. We found no age-related difference in reminiscence (Experiments 1 and 2), though there was a substantial difference in intertest forgetting (Experiments 1 and 2). Older, relative to young, adults produced more forgetting, most of which occurred between Tests 1 and 2 (Experiments 1 and 2). Furthermore, older, relative to young, adults produced more intrusions. We failed to identify a relationship between intrusions and intertest forgetting. We suggest that the age-related difference in intertest forgetting may be due to less efficient reinstatement of cues at test by older adults. The present findings reveal that intertest forgetting plays a critical role in hypermnesic recall, particularly for older adults.

Adolescent↗
PubMed1999

Surgical treatment for a supra sinotubular junctional saccular aneurysm associated with aortic regurgitation.

We reported a patient with a saccular ascending aortic aneurysm located just above the non-coronary sinotubular junction. The aneurysm produced severe aortic regurgitation and two episodes of cardiac tamponade. By intraoperative inspection, the border between the aneurysmal wall and non-dilated portion of the normal aortic wall was distinct, and the aortic valve leaflets and aortic annulus appeared normal. Aortic valve dysfunction appeared to be caused by dilation of the noncoronary sinotubular junction and mild distortion of the noncoronary sinus because of the aneurysmal formation. We performed patch closure of the aneurysmal ostium and repaired the dilated noncoronary sinotubular junction. Postoperative echocardiography and aortography demonstrated a good coaptation of the aortic valve leaflets with trivial aortic regurgitation. Although a rupture site, dissection or carcinomatous pericarditis which is attributable to the two episodes of cardiac tamponade could not be found, pathologic examination of the aneurysm wall revealed intramural blood leakage between the mucoid degenerated media and notably thickened adventitia. In addition, there was thinning and interruption of the elastic fibers of the media. These findings are consistent with a leaking aneurysm which cause the slow development of cardiac tamponade.

Aortic Aneurysm↗
PubMed1999

Molecular karyotypes for Alternaria plant pathogens known to produce host-specific toxins.

There are at least ten plant diseases caused by Alternaria species in which host-specific toxins (HSTs) are responsible for fungal pathogenicity. Of these HST-producers, seven are considered distinct pathotypes of the species Alternaria alternata, and the remaining three are among other species of pathogenic Alternaria. Inter- and intra-specific variation among Alternaria taxa, including HST-producers, was determined by electrophoretic karyotyping using pulsed-field gel electrophoresis. A. alternata including seven pathotypes of A. alternata and eight non-pathogenic strains had 9-11 chromosomal bands with estimated sizes ranging from 0.4 to 5.7 Mb. In contrast, Alternaria species that are morphologically distinct from A. alternata had 8-10 bands with sizes between 0.9 and 5.7 Mb. Estimated genome sizes of A. alternata and other Alternaria species ranged from 28.8 to 33.6 Mb and 25.1 to 30.7 Mb, respectively. Other species of pathogenic Alternaria were difficult to differentiate from A. alternata on the basis of chromosome-size polymorphisms alone, but Southern analysis using rDNA as a probe could, in some cases, differentiate between them. These results were cytologically confirmed by 4',6-diamidino-2-phenylindole (DAPI) staining and fluorescence in situ hybridization with a rDNA probe for mitotic metaphase chromosomes prepared by the germ-tube burst method.

Alternaria↗
PubMed1999

Apoptosis during inner ear development in human and mouse embryos: an analysis by computer-assisted three-dimensional reconstruction.

Apoptosis in the developing inner ear tissue of human (Carnegie stage 14 to 21, approximately 5 to 8 weeks of gestation) and mouse (10.5 to 14 days of gestation) embryos was systematically analyzed by a computer-assisted three-dimensional reconstruction of the serial histological sections and by the TUNEL method. Morphogenetic events such as folding between the utricular portion and endolymphatic duct, constriction of the junction of the saccule with the cochlea and folding of the vestibular portion to form the semicircular ducts were accompanied by a localized distribution of apoptosis. The apoptosis was also related to the innervation of the cochlear and vestibular epithelia from the sensory ganglion of the eighth cranial nerve and the differentiation of the otic epithelia into the sensory epithelia. These results suggest that apoptosis plays an important role in the development of the inner ear.

Animals↗
PubMed1999

Spatio-temporally regulated expression of receptor tyrosine kinases, mRor1, mRor2, during mouse development: implications in development and function of the nervous system.

BACKGROUND: Drosophila neurospecific receptor tyrosine kinases (RTKs), Dror and Dnrk, as well as Ror1 and Ror2 RTKs, isolated from human neuroblastoma, have been identified as a structurally related novel family of RTKs (Ror-family RTKs). Thus far, little is known about the expression and function of mammalian Ror-family RTKs. RESULTS: We have identified murine Ror-family RTKs, mRor1 and mRor2. Both mRor1 and mRor2 genes are induced upon neuronal differentiation of P19EC cells. During neuronal differentiation in vitro, the expression of mRor2 is transiently induced, although that of mRor1 increases continuously. During embryogenesis, the mRor1 gene is expressed in the developing nervous system within restricted regions and in the developing lens epithelium. The expression of mRor1 is sustained in the nervous system and is also detected in non-neuronal tissues after birth. In contrast, the expression of mRor2 is detected mainly in the developing nervous system within broader regions and declines after birth. Possible relationships of mRor1 and mRor2 genes with previously identified mutants have also been examined. CONCLUSIONS: The developmental expressions of mRor1 and mRor2, in particular in the nervous system, are differentially regulated, reflecting their expression patterns in vitro. mRor1 and mRor2 may thus play differential roles during the development of the nervous system.

Amino Acid Sequence↗
PubMed1999

Vitamin E treatment of experimental glomerular disease in rats.

BACKGROUND: Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary heart disease and it also inhibits the proliferation of VSMCs in vitro. Thus, we investigated the effect of vitamin E on glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two rat models of glomerular disease. METHODS: A remnant kidney rat model accelerated with hyperlipidemia was used to examine progressive glomerular sclerosis leading to chronic renal failure. A rat model of MC-proliferative GN was induced by the intravenous administration of absorbed rabbit anti-rat thymocyte serum (ATS). RESULTS: In the remnant kidney rat model, dietary supplementation with vitamin E (500 IU dl-alpha-tocopheryl acetate/kg) and cholesterol (2%) significantly inhibited glomerular sclerosis and macrophage infiltration in glomeruli relative to controls receiving basal and cholesterol-supplemented diets. In the ATS-induced GN model, glomerular cell proliferation (principally MCs) was lower in rats fed diets supplemented with vitamin E (1000 IU dl-alpha-tocopheryl acetate/kg) compared with controls fed the basal diet only. Although the degree of glomerular macrophage infiltration was similar in both groups, fewer proliferative cell nuclear antigen (PCNA)-positive cells were observed in the vitamin E group, suggesting that MC proliferation was suppressed via the inhibition of intracellular transduction. CONCLUSIONS: Supplemental dietary vitamin E suppresses MC proliferation and glomerular sclerosis in models of glomerular disease in rats. This action of vitamin E in experimental nephritis suggests the value of clinical trials testing the potential benefit of vitamin E in chronic GN patients.

Animals↗
PubMed1999

Ongoing clinical trials of lipid reduction therapy in patients with renal disease.

BACKGROUND: Lipid abnormalities in renal disease are associated with both a progressive decline in renal function and cardiovascular complications. Whether or not lipid anomalies are causal is not yet clear. Experimental studies have demonstrated that potentially atherogenic lipoproteins, such as low density lipoproteins (LDL), are associated with renal pathophysiological changes that result in progressive glomerular and interstitial damage and an ultimate reduction in renal function. These findings indicate that hyperlipidemia accelerates glomerular and interstitial damage in renal disease. Clinical studies also show that renal function declines more rapidly among patients with primary renal disease or diabetic nephropathy who have hyperlipidemia. However, few reports have demonstrated the effect of hypolipidemic agents on the progression of renal function among patients with renal disease, and those renal patients who were treated with lipid-lowering agents have not been clinically studied under large-scale controlled conditions. In addition, although cardiovascular complications are the most important factors associated with mortality in dialysis patients, randomized, large-scale trials studying the relationship between therapeutic intervention by lipid-lowering agents and prevention of cardiovascular complications have not been implemented. METHODS: We reviewed controlled and uncontrolled reported studies that examined the effects of lipid-lowering therapy in patients with renal disease. RESULTS: Most studies showed that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce cholesterol-rich apolipoprotein (apo)B-containing lipoproteins with no effects on renal function or proteinuria among patients with progressive renal disease. Small uncontrolled studies show that simvastatin and probucol moderately reduce proteinuria among patients with membranous nephropathy. One small retrospective study showed that long-term vitamin E therapy reduces aortic calcification in dialysis patients. CONCLUSIONS: Prospective, randomized large-scale trials including ongoing clinical trials of lipid reduction therapy and therapeutic interventions such as the use of the combination therapy with hypolipidemic agents and angiotensin converting enzyme (ACE) inhibitors, vitamins, or LDL apheresis are urgently required. Such trials will clarify the effect of treating dyslipidemia on the progression of renal insufficiency and dialysis-related cardiovascular complications.

Blood Component Removal↗
PubMed1999

Evaluation of serum lipid abnormalities in chronic nephritis.

BACKGROUND: In glomerular disease, disorders of lipid metabolism are suspected as factors exacerbating glomerular dysfunction. Although many reports have been published regarding metabolic disorders of lipids in renal disease, including nephrotic syndrome and chronic renal failure, there have been few published reports describing metabolic disorders of lipids in chronic nephritis. Therefore, in patients with IgA nephritis, we evaluated correlations between serum lipid levels and renal function and proteinuria. METHODS: In 191 patients with IgA nephritis, we evaluated the correlations between serum lipid levels and renal function [creatinine clearance (CCr)] and proteinuria (UP). Serum lipids examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoproteins, phospholipids (PL), lipoprotein(a) [Lp(a)], and malondialdehyde (MDA). RESULTS: Significant correlations were observed between serum lipid levels and CCr, UP, and age. There were no abnormalities in the mean values of respective serum lipids examined. Although TC levels increased with age, HDL-C levels were not correlated with age. Hyperlipidemia was observed in 39.8% of subjects. Significant correlations were observed between levels of TC, TG, PL, LDL-C, apoB, apoC-II, and apoC-III and Ccr, UP, and age. Significant correlations were also observed between levels of MDA, apoB/apoA-I, apoE/apoC-III, and Ccr and age, as well as between apoE levels and UP and age. The levels of apoA-I and apoA-I/apoA-II ratio were significantly correlated with UP alone, whereas the apoC-II/apoC-III ratio was significantly correlated with Ccr alone. There were no significant correlations between levels of HDL-C, apoA-II, and Lp(a) and Ccr, UP, and age. CONCLUSIONS: Age, proteinuria, and renal function were related with changes in serum lipid levels in IgA nephritis. There were correlations between proteinuria and levels of apoA, as well as between renal function and apoC levels.

Adult↗
PubMed1999

Lysophosphatidylcholine up-regulates IL-1 beta-induced iNOS expression in rat mesangial cells.

BACKGROUND: Nitric oxide (NO), a simple molecule synthesized from L-arginine by NO synthases (NOS), has been identified to play an important role in cell communication, cell defense and cell injury. Several studies have shown that glomeruli from rats with immune-mediated glomerular inflammation have increased production of NO. Recently, it was also reported that inducible NOS (iNOS) is localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased human glomeruli. On the other hand, while oxidized low density lipoprotein (ox-LDL) has been suggested to be related to progression of glomerular disease, the mechanism remains unknown. We investigated the effect of lysophosphatidylcholine (LPC), a modified phospholipid produced during LDL oxidation, on iNOS expression in rat mesangial cells. METHODS AND RESULTS: Treatment of mesangial cells with interleukin-1 beta (IL-1 beta) induced iNOS activity measured as nitrite levels in cell culture supernatants. Treatment with LPC had no effect. In contrast, coincubation with LPC and IL-1 beta resulted in a markedly higher nitrite content compared to that after incubation with IL-1 beta alone. Western blot analysis revealed that LPC caused a significant increase in the formation of iNOS protein in the presence of IL-1 beta. CONCLUSION: These findings suggest that LPC may contribute to progression of glomerular inflammation by augmenting IL-1 beta-induced iNOS expression.

Animals↗
PubMed1999

Phospholipase A2 activity in ox-LDL-stimulated mesangial cells and modulation by alpha-tocopherol.

BACKGROUND: Oxidized LDL increases the production of both prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in rat mesangial cells. These increases were suppressed by antioxidants such as alpha-tocopherol (alpha-Toc) or probucol. METHODS: We investigated the mechanism by which oxidized LDL leads to an increase in PGE2 production using rat mesangial cells in culture. We also examined how alpha-Toc supresses this augmentation, by measuring intracellular Ca2- and phospholipase A2 (PLA2) activity. RESULTS: In rat mesangial cells, oxidized LDL increased PLA2 activity by increasing the intracellular calcium ion content, which resulted in the induction of PGE2 production. On the other hand, pretreatment of cells with alpha-Toc, which resulted in a large uptake of alpha-Toc in cell membranes, markedly suppressed the augmentation of PGE2 production and PLA2 activity by oxidized LDL in a dose dependent manner. However, cytosolic PLA2 partially purified from mesangial cells was not inhibited by alpha-Toc despite an increase of alpha-Toc. CONCLUSION: These results suggest that the augmentation of PLA2 activity in mesangial cells by oxidized LDL in a result of oxidative stresses, and that the antioxidant action of alpha-Toc is responsible for the suppression of augmentation of PLA2 activity observed in mesangial cells exposed to oxidized LDL.

Animals↗
PubMed1999

Effect of simvastatin on the lipid profile of hemodialysis patients.

BACKGROUND: Simvastatin, a 3-hydroxy 3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitor, is used widely for treatment of hypercholesterolemia. Simvastatin may be a suitable treatment for dyslipidemia in hemodialysis (HD) patients. However, investigation of the side-effects and safety of long-term administration of simvastatin to HD patients has been limited. In this study, we investigated the effects and safety of simvastatin and its effects on lipoprotein metabolism in hypercholesterolemic patients on HD. METHODS: Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol (TC) levels (200 mg/dl) or low high-density lipoprotein cholesterol (HDL-C) levels (35 mg/dl). Every four weeks, serum lipids, apolipoprotein, lipoprotein (a) [Lp(a)] and malondialdehyde (MDA) levels were measured. In addition, lipid levels were determined in each lipoprotein fraction separated by ultracentrifugation. RESULTS: After 24 weeks of simvastatin administration, TC significantly decreased by 25.7%, and low-density lipoprotein cholesterol (LDL-C) was significantly decreased by 33.6%. Triglyceride (TG) and HDL-C showed no significant changes. Apolipoprotein (apo) B significantly decreased by 24.5% and apo E by 30.0%. No significant changes were observed in the other apolipoproteins. MDA was also significantly decreased, whereas Lp(a) was not significantly altered. In the lipoprotein fractions, very LDL cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), LDL1 cholesterol (LDL1-C), and LDL2 cholesterol (LDL2-C) showed significant decreases. No particular side-effects were observed during the 12 months of simvastatin administration. CONCLUSIONS: These results suggest that simvastatin appears to be safe and effective in HD patients with hypercholesterolemia.

Aged↗
PubMed1999

Factors associated with calcification of the abdominal aorta in hemodialysis patients.

BACKGROUND: Cardiovascular and cerebrovascular injury caused by arteriosclerosis has been the major cause of the death in hemodialysis (HD) patients. We quantitatively analyzed and evaluated the severity of abdominal aortic calcification in HD patients in comparison to risk factors for arteriosclerosis. METHODS: One hundred thirty-seven HD patients were examined. Using image analysis software, areas of the calcified abdominal aorta were quantitatively analyzed on plain computerized tomography images. Other factors such as blood pressure (BP), lipid levels, and calcium (Ca) x phosphorus (Pi) value were also analyzed. RESULTS: Patients with a higher one-year average of systolic BP showed a higher severity of abdominal aortic calcification. That is, the severity of abdominal aortic calcification in patients with a one-year systolic BP average above 160 mm Hg was 31.5 +/- 13.6%, and this severity was significantly higher than that in patients with a one-year systolic BP average of less than 120 mm Hg (8.0 +/- 7.7%, P < 0.01). The severity of abdominal aortic calcification in patients demonstrating risk values of ectopic calcification, that is serum Ca x Pi > or = 60 (mg/dl), on more than 4 of 24 measurements within one year (25.8 +/- 13.6%) was significantly higher than the severity of aortic calcification in patients demonstrating this value less than four times in one year (P < 0.05). There was no correlation between levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, lipoprotein(a), and severity of abdominal aortic calcification. CONCLUSIONS: Systolic BP levels and the product of serum Ca and Pi were related to the severity of abdominal aortic calcification in HD patients. These observations suggested that BP control, as well as control of serum Ca and Pi levels, was important in preventing the progression of abdominal aortic arteriosclerosis.

Age Factors↗
PubMed1999

Acute in vivo effects of ACTH by exo utero microinjection on differentiation, steroidogenesis and proliferation of fetal mouse adrenocytes.

Mouse embryos on embryonic day (E)13 or 14 were treated with ACTH1-24 by exo utero microinjection and the adrenal was examined after 16 and 32 h. Light microscopic morphometry showed that the ACTH treatment increased cell size and decreased cell density of the adrenocortical cells. Bromodeoxyuridine-labeling index did not alter significantly after the ACTH treatment. By immunohistochemistry, both number of cells expressing 11beta-hydroxylase and the staining intensity increased in the ACTH-treated glands compared to controls whereas expression of aldosterone synthase was detectable in neither the treated nor control groups. Ultrastructurally, the adrenocytes of the inner cortical zone of the ACTH-treated glands were characterized by strikingly increased content of the smooth endoplasmic reticulum, increased mitochondria with more vesicular cristae, lipid droplets with a much higher electron density along with the distribution altered from that in controls. All of the significant differences between the ACTH-treated and control glands occurred at 16 h but not at the 32 h interval. The present results indicated that the mouse fetal adrenocytes are already sensitive to ACTH during early period (E13 and 14) of their functional differentiation. In vivo acute treatment of ACTH stimulates cell-size, increase of fetal adrenocytes but not proliferation, and may directly or indirectly regulate multiple steps of the steroidogenic process of the fetal mouse adrenal.

Adrenal Cortex↗
PubMed1999

Characterization of a novel missense mutation in the pore of HERG in a patient with long QT syndrome.

INTRODUCTION: A new strategy to elucidate the molecular mechanisms underlying the long QT syndrome (LQTS) is now available with genetic mutational analyses and characterization of ion channel mutations. METHODS AND RESULTS: In a 26-year-old woman with LQTS, we identified a novel missense mutation in the pore of HERG by using polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) and sequencing of her genomic DNA. The mutation resulted in an amino acid substitution of a positively charged lysine for a highly conserved uncharged asparagine at codon 629 (N629K). Whole cell, patch clamp studies were conducted in COS7 cells by transfecting with wild-type (WT) and/or the mutant N629K HERG. The WT HERG produced an I(Kr)-like, E-4031-sensitive conductance with an inward rectification. In contrast, the cells transfected with the N629K HERG did not display any time-dependent current. Cotransfection of WT and N629K HERG (at a ratio of 1:1) produced a significantly smaller conductance when compared with WT HERG (WT 59.9 +/- 7.3 pA/pF [n = 22] vs WT+N629K 5.5 +/- 2.3 pA/pF [n = 11]; P < 0.01), but did not alter K+ ion selectivity and tail current-voltage dependence. Because aprindine hydrochloride was effective in preventing ventricular tachycardias, we also tested the effect of the drug on WT HERG (I(Kr)) and KvLQT1/KCNE1 (I(Ks)) currents expressed in COS7. CONCLUSION: Functional analyses of a novel missense mutation in the pore of HERG suggest that the mutation causes marked reduction of I(Kr) via a dominant negative effect.

Adult↗