Showing papers by "Masakazu Yamagishi published in 2016"
Helmholtz Zentrum München1, University of Pavia2, Kanazawa University3, Gunma University4, Shiga University of Medical Science5, Kyoto University6, Xi'an Jiaotong University7, Institute of Chartered Accountants of Nigeria8, French Institute of Health and Medical Research9, University of Paris10, Nippon Medical School11
TL;DR: The probability of being a carrier of cLQTS disease-causing mutations can be predicted by simple clinical parameters, thus allowing possibly cost-effective genetic testing leading to cascade screening for identification of additional at-risk family members.
Abstract: Aims Acquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors.
Methods and results We screened for the five major LQTS genes among 188 aLQTS probands (55 ± 20 years, 140 females) from Japan, France, and Italy. Based on control QTc (without triggers), subjects were designated ‘true aLQTS’ (QTc within normal limits) or ‘unmasked cLQTS’ (all others) and compared for QTc and genetics with 2379 members of 1010 genotyped congenital long QT syndrome (cLQTS) families. Cardiac symptoms were present in 86% of aLQTS subjects. Control QTc of aLQTS was 453 ± 39 ms, shorter than in cLQTS (478 ± 46 ms, P < 0.001) and longer than in non-carriers (406 ± 26 ms, P < 0.001). In 53 (28%) aLQTS subjects, 47 disease-causing mutations were identified. Compared with cLQTS, in ‘true aLQTS’, KCNQ1 mutations were much less frequent than KCNH2 (20% [95% CI 7–41%] vs. 64% [95% CI 43–82%], P < 0.01). A clinical score based on control QTc, age, and symptoms allowed identification of patients more likely to carry LQTS mutations.
Conclusion A third of aLQTS patients carry cLQTS mutations, those on KCNH2 being more common. The probability of being a carrier of cLQTS disease-causing mutations can be predicted by simple clinical parameters, thus allowing possibly cost-effective genetic testing leading to cascade screening for identification of additional at-risk family members.
152 citations
TL;DR: It is demonstrated that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH cause by LDLR mutations.
Abstract: BACKGROUND It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mutation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene. METHODS AND RESULTS We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4-33.9], 21.1 mg/dl [IQR:11.7-34.9], and 5.0 mg/dl [IQR:2.7-8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL). CONCLUSIONS These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations.
63 citations
TL;DR: A quick cortisol assay (QCA) that uses immunochromatography and gold nanoparticles and can be performed either semiquantitatively or quantitatively was rapidly and easily performed at the point of care and improved the rate of successful AVS.
Abstract: Context: Adrenal vein sampling (AVS) is essential for identifying a surgically curable form of primary aldosteronism (PA), but accurate placement of the sampling catheter is technically challenging. Intraprocedural cortisol measurement can confirm the catheter's position, thereby increasing the AVS success rate. Objective and Methods: We developed a quick cortisol assay (QCA) that uses immunochromatography and gold nanoparticles and can be performed either semiquantitatively or quantitatively. The assay was evaluated in two studies. In a single-center study, PA patients were assigned to undergo AVS incorporating the semiquantitative QCA (n = 30), the quantitative QCA (n = 30), or without the QCA (n = 30), and the rates of successful AVS were determined. In a prospective multicenter randomized, controlled study, the success rates of AVS performed with (n = 148) or without (n = 145) the semiquantitative QCA were determined. Results: Cortisol concentrations were measured during AVS in 6 minutes or less in th...
51 citations
TL;DR: The results suggest that EPL and SPL are effective and safe for the treatment of PA and the long-term metabolic and renal effects of these MRAs should be further investigated.
Abstract: The mineralocorticoid receptor (MR) is expressed in the kidneys and in adipose tissue, and primary aldosteronism (PA) is associated with metabolic syndrome. This study assessed the effects of MR blockade by eplerenone (EPL) and spironolactone (SPL) on blood pressure (BP) and metabolic factors in patients with PA. Fifty-four patients with PA were treated with one of two MRAs, EPL (25-100 mg daily, n=27) or SPL (12.5-100 mg daily, n=27) for 12 months. Visceral (VAT) and subcutaneous adipose tissue were quantified using CT and FatScan imaging analysis software. Body mass index, homeostasis model assessment-insulin resistance (HOMA-IR), serum creatinine, potassium and lipids, urinary albumin excretion (UAE) and plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were measured before and after treatment. EPL and SPL decreased BP and increased serum potassium levels to similar degrees. PAC and PRA did not differ between the two groups. Although treatment with the MRAs did not change HOMA-IR or serum lipids, they significantly decreased UAE and VAT (P<0.05). These results suggest that EPL and SPL are effective and safe for the treatment of PA. The long-term metabolic and renal effects of these MRAs should be further investigated.
46 citations
TL;DR: The annual 1-month CPC 1-2 rate after OHCA among elderly patients significantly improved, and the resuscitation of elderly patients in a selected population is not futile.
Abstract: BACKGROUND There is sparse data regarding the survival and neurological outcome of elderly patients with out-of-hospital cardiac arrest (OHCA). METHODS AND RESULTS OHCA patients (334,730) aged ≥75 years were analyzed using a nationwide, prospective, population-based Japanese OHCA database from 2008 to 2012. The overall 1-month survival with favorable neurological outcome (Cerebral Performance Category Scale, category 1 or 2; CPC 1-2) rate was 0.88%. During the study period, the annual 1-month CPC 1-2 rate in whole OHCA significantly improved (0.73% to 0.96%, P for trend <0.001). In particular, outcomes of OHCA patients aged 75 to 84 years and those aged 85 to 94 years significantly improved (0.98% to 1.28%, P for trend=0.01; 0.46% to 0.70%, P for trend <0.001, respectively). However, in OHCA patients aged ≥95 years, the outcomes did not improve. Multivariate logistic regression analysis indicated that younger age, shockable first documented rhythm, witnessed arrest, earlier emergency medical service (EMS) response time, and cardiac etiology were significantly associated with the 1-month CPC 1-2. Under these conditions, elderly OHCA patients who had cardiac etiology, shockable rhythm and had a witnessed arrest had acceptable 1-month CPC1-2 rate; 7.98% in cases where OHCA was witnessed by family, 15.2% by non-family, and 25.6% by EMS. CONCLUSIONS The annual 1-month CPC 1-2 rate after OHCA among elderly patients significantly improved, and the resuscitation of elderly patients in a selected population is not futile. (Circ J 2016; 80: 1153-1162).
38 citations
TL;DR: The incidence of type A AAD was common in patients who experienced out-of-hospital cardiopulmonary arrest, with a high rate of pre-hospital death, and aortic rupture to the intrapericardial space was considered the major cause of death.
Abstract: Postmortem computed tomography (PMCT) has been recently reported to be useful for detecting causes of death in the emergency department. In this study, the incidence and causes of death of type A acute aortic dissection (AAD) were investigated in patients who experienced out-of-hospital cardiopulmonary arrest (OHCPA) using PMCT. PMCT or enhanced computed tomography was performed in 311 of 528 consecutive patients experiencing OHCPA. A total of 23 (7%) of 311 patients were diagnosed with type A AAD based on clinical courses and CT findings. Eighteen consecutive patients who did not experience OHCPA were diagnosed with type A AAD during the same period. Pre-hospital death was observed in 21 (51%) of 41 patients with type A AAD. Bloody pericardial effusion was observed more frequently in patients who experienced OHCPA with type A AAD than in those who did not experience OHCPA with type A AAD (91% vs 28%, respectively; p <0.05). In conclusion, the incidence of type A AAD was common (7%) in patients who experienced OHCPA, with a high rate of pre-hospital death. Aortic rupture to the intrapericardial space was considered the major cause of death in patients who experienced OHCPA with type A AAD.
33 citations
TL;DR: To test the hypothesis that 1‐h plasma glucose in an oral glucose tolerance test is a better predictor of the development of diabetes than 2‐h Plasma glucose, independently of indices of insulin secretion or action in Japanese adults, a single study is conducted.
Abstract: Aims
To test the hypothesis that 1-h plasma glucose in an oral glucose tolerance test is a better predictor of the development of diabetes than 2-h plasma glucose, independently of indices of insulin secretion or action in Japanese adults.
Methods
A historical cohort study was conducted in 1445 Japanese workers who did not have diabetes. The association between 1-h plasma glucose and the development of Type 2 diabetes was analysed.
Results
Overall, 95 of the study participants developed Type 2 diabetes during a mean follow-up of 4.5 years. The area under the receiver-operating characteristic curve for 1-h plasma glucose for future diabetes [0.88 (95% CI 0.84–0.91)] was greater than that for 2-h plasma glucose [0.79 (95% CI 0.74–0.84)], and for insulinogenic [0.73 (95% CI 0.68–0.78)] and disposition indices [0.79 (95% CI 0.74–0.84); P < 0.05]. Compared with the first quartile, the hazard ratio for future diabetes in the fourth quartile of 1-h plasma glucose was 42.5 [95% CI 5.7–315.2 (P < 0.05)] and the hazard ratio in the fourth quartile of 2-h plasma glucose was 4.4 [95% CI 1.8–10.8 (P < 0.05)], after adjustments for covariates including fasting plasma glucose. The significance of the elevated hazard ratio in the fourth quartile of 1-h plasma glucose was maintained after adjustments for 2-h plasma glucose, insulinogenic index or disposition index, whereas the elevation of the hazard ratio in the fourth quartile of 2-h plasma glucose was diminished and was no longer significant after adjustments for 1-h plasma glucose.
Conclusions
One-hour plasma glucose had a greater association with the future development of Type 2 diabetes than did 2-h plasma glucose, independently of oral glucose tolerance test-derived indices of insulin action in a Japanese population.
32 citations
TL;DR: The BleeMACS registry collaborative will allow development and validation of a risk score for prediction of major bleeding during follow-up for patients receiving contemporary therapies for acute coronary syndrome.
Abstract: BackgroundBleeding events after an acute coronary syndrome have a negative impact on prognosis. Available risk scores are limited by suboptimal accuracy, prediction of only in-hospital events and absence of patients treated with new antiplatelet agents in the current era of widespread use of percuta
29 citations
TL;DR: The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG 4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG3+PCs infiltrate systemic organs.
Abstract: Multicentric Castleman disease is a benign lymphoproliferative disorder with heterogenous clinical symptoms and involves systemic organs in addition to lymph nodes. Elevated serum IgG4 levels and IgG4-positive plasma cell (IgG4+PC) infiltrates have been reported in lymph nodes, lung and skin in some multicentric Castleman disease cases, resembling IgG4-related disease (IgG4-RD) histologically. However, no report has been available regarding IgG4+PC infiltration in the kidneys of multicentric Castleman disease. Here, we report 2 cases of multicentric Castleman disease complicated by IgG4-related disease (IgG4-RD) histologically. However, there has been no report published on PC-rich tubulointerstitial nephritis, lymphadenopathy, with numerous IgG4+PC infiltration, and elevated serum IgG4 levels, mimicking IgG4-RD. The blood examinations revealed systemic inflammation and elevated C-reactive protein and interleukin-6 levels. Corticosteroid therapy was partially effective in both cases, and combination therapy of corticosteroid and tocilizumab was needed in both cases. Moreover, after triple therapy with corticosteroid, rituximab and cyclophosphamide were used in 1 case to tame the severe inflammation. The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG4+PCs infiltrate systemic organs.
28 citations
TL;DR: It is suggested that pre-treatment renal insufficiency and serum IgE elevation predict renal atrophy development after glucocorticoid therapy in IgG4-RKD.
Abstract: In immunoglobulin G4-related kidney disease (IgG4-RKD), focal or diffuse renal cortical atrophy is often observed in the clinical course after glucocorticoid therapy. This study aimed to clarify the factors related to renal atrophy after glucocorticoid therapy in IgG4-RKD. We retrospectively evaluated clinical features including laboratory data and computed tomography (CT) findings before and after glucocorticoid therapy in 23 patients diagnosed with IgG4-RKD, all of whom were followed up for more than 24 months. Seventeen patients were men, and six were women (average age 62.0 years). Average follow-up period was 54.9 months. The average estimated glomerular filtration rate (eGFR) at diagnosis was 81.7 mL/min/1.73 m2. All patients had had multiple low-density lesions on contrast-enhanced CT before glucocorticoid therapy, and showed disappearance or reduction of these lesions after it. Pre-treatment eGFR and serum IgE level in 11 patients in whom renal cortical atrophy developed 24 months after the start of glucocorticoid therapy were significantly different from those in 12 patients in whom no obvious atrophy was found at that time (68.9 ± 30.1 vs 93.5 ± 14.1 mL/min/1.73 m2, P = 0.036, and 587 ± 254 vs 284 ± 263 IU/mL, P = 0.008, respectively). Pre-treatment eGFR and serum IgE level were also significant risk factors for renal atrophy development 24 months after the start of therapy with an odds ratio of 0.520 (per 10 mL/min/1.73 m2, 95% confidence interval (CI) 0.273–0.993, P = 0.048) and 1.090 (per 10 IU/mL, 95% CI: 1.013–1.174, P = 0.022), respectively, in age-adjusted, sex-adjusted, serum IgG4 level-adjusted logistic regression analysis. Receiver operating characteristic curve analysis showed that eGFR of less than 71.0 mL/min/1.73 m2 and serum IgE of more than 436.5 IU/mL were the most appropriate cutoffs and yielded sensitivity of 63.6% and specificity of 100%, and sensitivity of 90.9% and specificity of 75.0%, respectively, in predicting renal atrophy development. This study suggests that pre-treatment renal insufficiency and serum IgE elevation predict renal atrophy development after glucocorticoid therapy in IgG4-RKD.
26 citations
TL;DR: A 13-year-old Japanese female initially diagnosed with familial hypercholesterolemia is genetically diagnosed with sitosterolemia and familial Mediterranean fever using WES for the first time, using a comprehensive approach useful for identifying causative mutations for multiple unrelated inheritable diseases.
Abstract: Whole exome sequencing (WES) technologies have accelerated genetic studies of Mendelian disorders, yielding approximately 30% diagnostic success. We encountered a 13-year-old Japanese female initially diagnosed with familial hypercholesterolemia on the basis of clinical manifestations of severe hypercholesterolemia (initial LDL cholesterol=609 mg/dl at the age of one) and systemic intertriginous xanthomas with histories of recurrent self-limiting episodes of fever and arthritis. Both her phenotypes seemed to co-segregate in a recessive manner. We performed WES on this patient, who was considered a proband. Among 206,430 variants found in this individual, we found 18,220 nonsense, missense, or splice site variants, of which 3,087 were rare (minor allele frequency ≤ 0.01 or not reported) in 1000 Genome (Asian population). Filtering by assuming a recessive pattern of inheritance with the use of an in silico annotation prediction tool, we successfully narrowed down the candidates to the compound heterozygous mutations in the ABCG5 gene (c.1256G＞A or p.Arg419His/c.1763-1G＞A [splice acceptor site]) and to the double-compound heterozygous mutations in the MEFV gene (c.329T＞C/C or p.Leu110Pro/c.442G＞C/C or p.Glu148Val). The patient was genetically diagnosed with sitosterolemia and familial Mediterranean fever using WES for the first time. Such a comprehensive approach is useful for identifying causative mutations for multiple unrelated inheritable diseases.
TL;DR: A 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD) is described, which suggests that a condition closely mimicking IgG 4-RD may develop without IgG3-positive plasma cells.
Abstract: We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD). Radiology and histology showed characteristics of IgG4-related tubulointerstitial nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell infiltration in each organ. This case suggests that a condition closely mimicking IgG4-RD may develop without IgG4-positive plasma cells and those exceptional cases should also be taken into account in the differential diagnosis of IgG4-RD.
TL;DR: Low ECG voltage indexes may reflect increased myocardial fibrosis in patients with HC, and the total QRS voltage and Sokolow-Lyon indexes were positively correlated with LVEF and negatively correlated with the extent of LGE-determined myocardian fibrosis.
Abstract: Classic electrocardiographic (ECG) voltage indexes have been applied to screen for left ventricular (LV) hypertrophy in hypertrophic cardiomyopathy (HC). However, it is unclear whether low ECG voltage reflects deteriorated electrical forces because of replacement of the myocardium by fibrotic tissues in HC. We investigated correlations between classic ECG voltage indexes (Cornell, total QRS voltage, and Sokolow-Lyon) and cardiac magnetic resonance (CMR) parameters focusing on the impact of low ECG voltage on the LV ejection fraction (LVEF) and myocardial fibrosis in HC. We studied 108 consecutive patients with HC who underwent CMR imaging with late gadolinium enhancement (LGE). Nineteen patients with complete right or left bundle branch block were excluded, leaving 89 patients for analysis (age 61.0 ± 13.9 years; 58 men). Of the 3 voltage indexes, the total QRS voltage and Sokolow-Lyon indexes were positively correlated with LVEF. For discriminating patients with end-stage HC (LVEF <50%) from patients with HC and preserved LVEF (≥ 50%), receiver-operating characteristic analysis revealed an excellent area under the curve of 0.87 for the total QRS voltage index and 0.90 for the Sokolow-Lyon index, whereas the area under the curve for the Cornell index was only 0.54 (p <0.01). Moreover, these 2 voltage indexes were negatively correlated with the extent of LGE-determined myocardial fibrosis when adjusted by the LV maximal wall thickness. In conclusion, low ECG voltage indexes may reflect increased myocardial fibrosis in patients with HC.
TL;DR: Early rhythm conversion from an initial non-shockable to a shockable rhythm and subsequent shock delivery is associated with increased odds of 1-month CPC 1-2 in OHCA patients aged 18-74 years but not in those aged ≥75 years.
TL;DR: WES combined with CADD score and HHE gene data may be useful even in HCM, and the MYL3 Arg94His variant was associated with high disease penetrance and substantial interventricular septal hypertrophy.
TL;DR: A current understanding of the genetic architecture mostly derived from CVAS is provided, and several updates on the progress and limitations of RVAS for lipids and CAD are provided.
Abstract: Blood lipid levels are highly heritable and modifiable risk factors for coronary artery disease (CAD), and are the leading cause of death worldwide These facts have motivated human genetic association studies that have the substantial potential to define the risk factors that are causal and to identify pathways and therapeutic targets for lipids and CADThe success of the HapMap project that provided an extensive catalog of human genetic variations and the development of microarray based genotyping chips (typically containing variations with allele frequencies ＞ 5%) facilitated common variant association study (CVAS; formerly termed genome-wide association study, GWAS) identifying disease-associated variants in a genome-wide manner To date, 157 loci associated with blood lipids and 46 loci with CAD have been successfully identified, accounting for approximately 12%-14% of heritability for lipids and 10% of heritability for CAD However, there is yet a major challenge termed "missing heritability problem," namely the observation that loci detected by CVAS explain only a small fraction of the inferred genetic variations To explain such missing portions, focuses in genetic association studies have shifted from common to rare variants However, it is challenging to apply rare variant association study (RVAS) in an unbiased manner because such variants typically lack the sufficient number to be identified statisticallyIn this review, we provide a current understanding of the genetic architecture mostly derived from CVAS, and several updates on the progress and limitations of RVAS for lipids and CAD
TL;DR: The rate of in-stent restenosis in large-size coronary lesions was transiently higher in the first 8 months for patients implanted with BMS compared with DES in which no in-Stent thrombosis and TLR beyond 2 years were observed.
Abstract: Although drug-eluting stents (DES) for percutaneous coronary intervention (PCI) have dramatically reduced the incidence of in-stent restenosis, their deployment for large-size coronary lesions is still controversial because of problems such as late in-stent thrombosis and late catch-up in DES. We aimed to evaluate the long-term outcome beyond 2 years of bare metal stents (BMS) as compared with DES in large vessels. Consecutive 228 patients who underwent PCI with large-size stents (>3.5 mm in diameter) in our hospital were enrolled in this study. The end points of this study are target lesion revascularization (TLR) and occurrence of major adverse cardiac events (MACE) for subject patients. We analyzed 183 patients (152 men, mean age 65.8 ± 10.5 years) whose outcome could be followed up for at least 2 years. At the first 8-month follow-up, clinically driven TLR rate was significantly higher in patients who received BMS than those who received DES (17.2 vs. 2.2 %, p < 0.05), although the rate of TLR was not different between the 2 groups beyond 8 months. Thus, overall rate of TLR was higher in BMS than in DES (22.7 vs. 5.4 %, p < 0.05). Under these conditions, the higher rate of TLR for BMS was observed in simple as well as complex lesions with or without diabetes, although there were no significant differences in MACE between BMS and DES. Multivariate analysis showed that BMS was an only independent factor of TLR at the 8 month follow-up period [p = 0.004, odds ratio 9.58, 95 % confidence interval (2.10–43.8)]. These results demonstrate that the rate of in-stent restenosis in large-size coronary lesions was transiently higher in the first 8 months for patients implanted with BMS compared with DES in which no in-stent thrombosis and TLR beyond 2 years were observed. We suggest using the DES even in large-size coronary lesions in terms of short- and long-term outcomes.
TL;DR: In patients undergoing PCI for ACS, BTs increase the risk of reAMI only in those admitted for STEMI, and not in those with NSTE-ACS, and these results may help physicians to choose appropriate BT administration according to the admission diagnosis.
TL;DR: Extremely low HDL cholesterol levels could be a useful marker for poor prognosis, not necessarily related to cardiovascular diseases, in Japanese patients with extremely low cholesterol levels.
TL;DR: The use of the 2011 criteria will facilitate the diagnosis of LQTS and will decrease the number of false negative results.
TL;DR: The results supported a role for the polymorphism rs1023159 of the SLC19A1 gene, alone or in combination, as a risk factor for ASD, but the findings were not consistent after multiple testing corrections.
Abstract: Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with complex genetic etiology. Recent studies have indicated that children with ASD may have altered folate or methionine metabolism, suggesting that the folate-methionine cycle may play a key role in the etiology of ASD. SLC19A1, also referred to as reduced folate carrier 1 (RFC1), is a member of the solute carrier group of transporters and is one of the key enzymes in the folate metabolism pathway. Findings from multiple genomic screens suggest the presence of an autism susceptibility locus on chromosome 21q22.3, which includes SLC19A1. Therefore, we performed a case-control study in a Japanese population. In this study, DNA samples obtained from 147 ASD patients at the Kanazawa University Hospital in Japan and 150 unrelated healthy Japanese volunteers were examined by the sequence-specific primer-polymerase chain reaction method pooled with fluorescence correlation spectroscopy. p < 0.05 was considered to represent a statistically significant outcome. Of 13 single nucleotide polymorphisms (SNPs) examined, a significant p-value was obtained for AA genotype of one SNP (rs1023159, OR = 0.39, 95% CI = 0.16-0.91, p = 0.0394; Fisher's exact test). Despite some conflicting results, our findings supported a role for the polymorphism rs1023159 of the SLC19A1 gene, alone or in combination, as a risk factor for ASD. However, the findings were not consistent after multiple testing corrections. In conclusion, although our results supported a role of the SLC19A1 gene in the etiology of ASD, it was not a significant risk factor for the ASD samples analyzed in this study.
TL;DR: Total risk management that focused on LDL-C, BP, and HbA1c had a beneficial impact on the coronary plaque regression in diabetic patients with ACS.
Abstract: Aim Diabetic patients with coronary artery disease have a high incidence of cardiovascular events, which was associated with increased coronary plaque volume. Low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) play pivotal roles in the progression of coronary plaque. Several trials have shown that intervention for a single risk factor reduced the development of coronary plaque progression. However, it remained uncertain whether total risk management for LDL-C, BP, and glycosylated Hb (HbA1c) has a beneficial effect on coronary plaque volume in diabetic patients. Methods This study was a sub-study of the JAPAN-ACS that was a prospective, randomized, open-label trial that evaluated the impact of intensive lipid-lowering therapy on coronary plaque volume in patients with acute coronary syndrome (ACS). Among a total of 252 patients, 73 diabetic patients were analyzed. We examined the impact of total risk management (LDL-C ＜80 mg/dL, systolic BP ＜130 mmHg, and HbA1c ＜6.5%) on changes in coronary plaque volume. The patients were divided into four groups according to the number of risk factors that achieved the target value. Results Baseline characteristics were similar among the groups. The degree of coronary plaque regression was greater in patients who achieved total risk management. The number of risk factors that achieved the target level was associated with the extent of the coronary plaque volume reduction in a dose-dependent manner. Conclusion Total risk management that focused on LDL-C, BP, and HbA1c had a beneficial impact on the coronary plaque regression in diabetic patients with ACS.
TL;DR: In the setting of the ACS, the new anti-platelets drugs appear to be safe and efficacious at mid-term follow-up independently from the geographic area.
TL;DR: BP improved similarly in both groups over the 12-month study period, but BMI, waist circumference, and LDL-cholesterol were decreased in the eplerenone group, while glycohemoglobin was elevated in the HCTZ group.
Abstract: Experimental models recently suggested an interaction between aldosterone and adipose tissue, but clinical investigation has been limited. We studied the effects of eplerenone compared to hydrochlorothiazide (HCTZ) on blood pressure (BP), glucose, and lipid levels in 50 patients with essential hypertension (EHT) and type 2 diabetes mellitus whose BP failed to reach target levels with 8 mg of candesartan alone. BP improved similarly in both groups over the 12-month study period, but BMI, waist circumference, and LDL-cholesterol were decreased in the eplerenone group, while glycohemoglobin was elevated in the HCTZ group.
TL;DR: UKD was detected in <1 in 1000 subjects who underwent renal biopsies, however, in subjects meeting all of the above criteria, abnormal THP accumulation was detected, suggesting that renal biopsy with immunostaining for THP is a good tool for diagnosing UKD.
Abstract: Background: Uromodulin kidney disease (UKD) is an inherited kidney disease caused by a uromodulin (UMOD) gene mutation. The UMOD gene encodes the Tamm–Horsfall protein (THP), which is the most abundant protein in healthy human urine. Because of its rarity, the incidence of UKD has not been fully elucidated. The purpose of the present study is to clarify the frequency of UKD among patients who underwent renal biopsy. Methods: Immunostaining for THP was performed for patients <50 years of age with renal insufficiency and hyperuricemia without overt urinalysis abnormality from renal biopsy databases. Serum and urinary THP concentrations were evaluated in available individuals. Results: Fifteen patients were selected for immunostaining from a total of 3787 patients. In three independent patients, abnormal THP accumulation in renal tubular cells was observed. A novel missense A247P UMOD mutation was detected in two of the three patients, including one having a typical family history of familial juvenile hyperuricemic nephropathy. Serum and urinary THP concentrations of all available patients with UMOD A247P mutation were significantly lower than those of controls. Conclusions: In thepresent study, UKD was detected in <1 in 1000 subjects who underwent renal biopsies. However, in subjects meeting all of the above criteria, abnormal THP accumulation was detected in 20% (3/15), suggesting that renal biopsy with immunostaining for THP is a good tool for diagnosing UKD. Also, low serum THP concentration detected in the present subjects might be a good diagnostic marker or important in understanding the pathogenesis of UKD.
TL;DR: Results demonstrate that favorable clinical outcomes could be achieved by the filter-type DP device in AMI, particularly in patients with CHF, and could predict CHF by multivariate analysis.
Abstract: Aim Although distal embolization during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) deteriorates cardiac function, whether distal protection (DP) can improve prognosis is still controversial. We investigated whether a filter-type DP device, Filtrap®, could improve long-term outcomes after PCI for AMI. Method We studied 164 patients (130 men, mean age: 65.7 years) who underwent PCI. Patients were divided into two groups based on the use of Filtrap®. The occurrence of congestive heart failure (CHF) and major adverse cardiac events (MACE) defined as cardiac death, recurrent AMI, and target vessel revascularization were compared. Result Between DP (n=53, 41 men, mean age: 65.5 years) and non-DP (n=111, 89 men, mean age: 65.8 years) groups, although there was significantly greater plaque area in the DP group than in the non-DP group, there were no significant differences in coronary reperfusion flow after PCI. Interestingly, patients with CHF in the non-DP group exhibited a higher CK level than those in the DP group. During a 2-year follow-up period, cumulative CHF was significantly lower in the DP group than in the non-DP group (log-rank p=0.018), and there was no significant difference in the MACE rate (log-rank p=0.238). The use of DP device could not predict MACE, but could predict CHF by multivariate analysis (odds ratio=0.099, 95% CI: 0.02-0.42, p=0.005). Conclusion These results demonstrate that favorable clinical outcomes could be achieved by the filter-type DP device in AMI, particularly in patients with CHF.
TL;DR: The balance between good solubility and high crystallinity is an advantageous characteristic of 2,6-bis(4-pentylphenylphenylethynyl)anthracene (1) as discussed by the authors.
Abstract: The balance between good solubility and high crystallinity is an advantageous characteristic of 2,6-bis(4-pentylphenylethynyl)anthracene (1). Organic field-effect transistors featuring either a vacuum-deposited film or a simple drop-cast film of 1 both showed high hole mobilities of 0.94 and 0.63 cm2 V−1 s−1, respectively.
TL;DR: The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy, which may impact the prevention of atherosclerosis differently.
Abstract: Background
This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetimibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH is usually treated by coadministration of these three drugs.
TL;DR: The results demonstrate the existence of common antigen(s) shared by patients with IgG4-RD, and identify four identical sequences of IgVH-CDR3 existed between patients, one of the four sequences was detected in all patients.
Abstract: Objective: We investigated class switch reaction (CSR) in affected organs and evaluated whether the same or genetically related clones exist in IgG4-RD.Methods: We studied three patients with IgG4-RD. Total cellular RNA was extracted from salivary glands and peripheral blood and lung tissue. Activation-induced cytidine deaminase (AID) and immunoglobulin heavy chain third complementarity determining region (IgVH-CDR3) of IgM and IgG4 were detected by reverse transcription polymerase chain reaction (RT-PCR). We analyzed the clonal relationship of infiltrating IgG4-positive cells, as compared with IgM. We determined the existence of common clones among organs and patients.Result: AID was expressed in salivary glands of all patients and lung tissue in one. Closely related IgVH-CDR3 sequences in infiltrating IgG4-positive cells were detected in salivary glands and lung tissue. Identical IgVH-CDR3 sequence between IgM and IgG4 in salivary glands was detected in one patient, indicating CSR in salivary gl...
TL;DR: A 78-year-old-woman, with a history of non-valvular atrial fibrillation, had been taking dabigatran for twelve months and was referred to the authors' hospital due to epigastralgia which was resistant to omeprazole administration, thus confirming the diagnosis of dabig atran-induced exfoliative esophagitis.
Abstract: A 78-year-old-woman, with a history of non-valvular atrial fibrillation, had been taking dabigatran for twelve months and was referred to our hospital due to epigastralgia which was resistant to omeprazole administration. Esophagogastroduodenoscopy revealed longitudinal sloughing mucosal casts in the mid-esophagus (Picture 1, 2) without any remarkable findings in the esophagogastric junction, thus confirming the diagnosis of dabigatran-induced exfoliative esophagitis. The patient’s symptoms rapidly improved without the need to discontinue dabigatran after being instructed to drink a sufficient amount of water and maintain an upright position immediately after ingesting the medication. To date, a few cases of dabigatran-induced esophagitis (DIE) have been reported, although a recent study showed that DIE was found in approximately 20% of patients taking dabigatran, including those without any symptoms (1, 2). Tartaric acid cores, which are coated with dabigatran, are thought to adhere to the esophageal wall and thereby cause DIE. Regarding treatment, the discontinuation of dabigatran, the administration of a proton pump inhibitor, and/or patient education on proper ingestion techniques have all been advocated.