Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are characterized by clonal proliferative hematopoiesis with increased blood cell count. Clonal expansion mechanisms in MPN and related disorders such as myelodysplastic syndromes (MDS) remain to be elucidated. Although mutations in the JAK2 gene lead to a proliferative hematopoiesis in majority of MPN and some MDS, the mutation alone does not cause a clonal expansion. In addition to JAK2 mutations, several genetic abnormalities, including TET2 and polycomb group genes involving epigenetic regulation have been reported in patients with MPN. Moreover, overexpression of HMGA2 due to removal of specific sites in its 3' untranslated region for regulatory let-7 micro RNAs may contribute to the proliferative hematopoiesis with conferring a growth advantage at the level of a hematopoietic stem cell in some cases with MPN.
Backgrounds. Elevated uric acid (UA) level is reported to be related to the development of left ventricular hypertrophy (LVH) which is associated with high incidence of ventricular tachycardia (VT) and sudden cardiac death. However, little is known about the association between serum UA levels and the occurrence of VT. Thus, we examined the relationship between serum UA levels and the appearance of VT in patients with LVH. Methods. The study subjects consisted of 167 patients (110 males, mean age 67.4 ± 12.7 years) with LVH detected by echocardiography. These patients were divided into two groups based on whether VT was presented (defined by more than 5 beats, n=27) or not (n=140) by 24-hour Holter ECG monitoring. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd), the E/A ratio and deceleration time of transmitral flow velocity were assessed by echocardiography in each group. In addition, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), sodium, potassium, hemoglobin, total bilirubin and UA were compared in each group. Results. Echocardiographic findings did not show the difference between the two groups. However, BUN and UA levels in the VT group were significantly higher than those in the Non-VT group (p< 0.01). eGFR was significantly lower in the VT group than that in the Non-VT group (p< 0.01). A multivariate logistic regression analysis identified the UA level as an independent predictive factor for the occurrence of VT (odds ratio 1.61, 95% confidence interval 1.1-2.2, p< 0.01). Conclusions. These results suggest that serum UA level is a useful marker for predicting ventricular arrhythmias in patients with LVH.
Objectives: We attempted to measure multiple autoantibodies simultaneously using line immunoassay (LIA) in patients with primary biliary cirrhosis (PBC) with or without anti-mitochondrial antibody (AMA) and patients with PBC-autoimmune hepatitis (AIH) overlap, and we examined the clinical significance of measuring these autoantibodies. Methods: The study population consisted of 80 patients with PBC (including 12 AMA-negative patients), 16 patients with PBC-AIH overlap and 40 patients with AIH as controls. Nine antibodies (AMA-M2, M2-3E, Sp100, PML, gp210, Ro-52, LKM-1, LC-1 and SLA/LP) were detected by LIA, and AMA-M2 and anti-centromere antibody (ACA) were detected by ELISA. We examined the relationship between these autoantibodies and clinical findings. Results: The positive prevalence of each autoantibody and ACA in the PBC group, as determined by LIA, was as follows: 13.8% for anti-Sp100, 8.7% for anti-PML, 40% for anti-gp210 and 27.5% for anti-Ro-52 antibodies and 32.5% for ACA. In the PBC-AIH overlap group, the prevalence of anti-gp210 antibody (68.7%) and that of anti-Ro-52 antibody (81.2%) were significantly higher than those in the PBC and AIH groups. Only a few patients were positive for 2 or more autoantibodies. Nine patients were determined to be negative for all autoantibodies by LIA, of whom 7 were positive for ACA. Patients positive for anti-gp210 antibody included more patients classified as stage 4 on histology than did the negative group. Those positive for ACA included more patents with varices than did the negative group. Conclusion: LIA can measure multiple autoantibodies simultaneously and thus is considered useful in diagnosing PBC and PBC-AIH overlap. In addition, ACA is a useful marker for identifying AMA-negative PBC.
Aim: The aim of this small-scale study is to explore support-seeking behavior among mothers at high-risk of mental health problems on community basis in Japan. Methods: A survey using one month home visit data was conducted among mothers who registered their pregnancy at Shirakawa City Health Center, Fukushima, from April to September 2010. Probable postpartum depression at one month postpartum was assessed using the Japanese version of the Edinburgh Postnatal Depression Scale and the mother's bonding to her child at one month postpartum was measured by the Bonding Questionnaire. Results: A total of 118 out of 217 registered mothers were available for analysis. The proportion of probable depression among first time and experienced mothers was 12% and 3%, and that of low bonding was 43% and 13%, respectively. Factors that showed significant associations with probable depression and/or low-bonding among first-time mothers were financial difficulty, obstetrical problems, unhappy feeling towards pregnancy, younger maternal age, later gestational week at registration; associated factors among experienced mothers were financial difficulty and obstetrical problems. At the time of pregnancy, 35 (90%) of first-time mothers and 22 (31%) of experienced mothers expressed the intention to attend antenatal classes. None of the risk factors for probable depression or low-bonding were associated with the mother's intention to attend antenatal classes in this study. Conclusion: Pregnancy history, obstetrical problems, sociodemographic information and maternal feeling toward pregnancy should be carefully screened in antenatal phase, and those at risk of postpartum mental health problems should be screened and actively invited to antenatal classes.
Bacterial infection (i.e., Streptococcus sanguinis) has been suggested to be related to pathogenesis and/or symptom of Behcet's disease (BD). Toll-like receptor 9 (TLR9) plays an important role in both the innate and adaptive immune systems by recognizing a component of bacterial DNA (i.e., CpG-DNA). Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) in TLR9 were associated with infectious and autoimmune/autoinflammatory diseases. In this study, we detected five SNPs with BD patients in a Japanese population. Allele frequency analysis of the three common SNPs (-1486: T/C (promoter region), 1174: A/G (intron 1), 2848: G/A (exon 2; Pro545Pro)) showed no statistically significant difference between the BD patients and the healthy controls. However, genotyping analysis revealed that the homozygous genotypes -1486CC and 1174GG were significantly more frequent in the BD patients compared to the healthy controls (P=0.048 and P=0.027, respectively). The homozygous diplotype distribution C-G-A/C-G-A was significantly more frequent in the BD patients compared to the healthy controls (P=0.041). For reporter gene assay, the plasmid construct carrying diplotype distribution C-G/C-G of the -1486T/C and 1174A/G SNPs showed significantly higher luciferase activity compared to the plasmid construct carrying diplotype distribution T-A/T-A (P=0.019). These results suggested an association of the homozygous genotypes and homozygous diplotype configuration of the TLR9 SNPs with susceptibility to BD in the Japanese population.
Background: Coronary flow reserve (CFR) provides essential information about the coronary microvasculature. Chronic kidney disease (CKD) is a risk factor for cardio-cerebrovascular diseases. We hypothesized that low CFR is associated with CKD and long-term cardio-cerebrovascular events in the patients without obstructive coronary artery diseases and vasospasm. Method and Results: In this study, 73 patients suspected with coronary artery disease but had no epicardial coronary stenosis and vasospasm were enrolled. There were 13 CKD patients and CFR was measured using the Doppler flow wire methods in the left anterior descending artery. CFR was significantly lower in CKD group than non-CKD group (3.13±0.6 vs. 4.00±1.1, P=0.007). From multivariate logistic regression analysis, the independent factor associated with the presence of CKD was only CFR (odds ratio 3.85, 95% confidence interval 1.27-11.70, P=0.017). In the patients with low CFR (≤ 2.8), cardio-cerebrovascular events were more common than those with normal CFR (CFR > 2.8). Besides, in the patients who had both low CFR and CKD, long-term cardio-cerebrovascular events were more likely to occur than those with normal CFR or non-CKD. Conclusions: Our data suggest that low CFR is associated with CKD and cardio-cerebrovascular events in the patients without coronary stenosis and vasospasm.
Severe ketoacidosis induces heart failure and cardiac arrest, but its mechanism is unknown. Recently, hydroxy-carboxylic acid receptor 2 (HCA2) was found to be a receptor for a ketone body, β-hydroxybutyric acid (BHB), and is coupled with Gi-GTP binding protein. HCA2 expression was reported in the guinea pig heart. Therefore, using guinea pig cardiac myocytes, we investigated effects of BHB on L-type Ca2+ current pre-augmented with β-adrenoceptor agonist, isoproterenol under the whole-cell voltage clamp. BHB significantly reduced the Ca2+ current pre-augmented with isoproterenol. The effect of BHB was concentration dependent with IC50 of 1.1 mM. Nicotinic acid (NA), another ligand for HCA2, also exerted an effect on the Ca2+ current similar to that of BHB. The effects of BHB and NA were reduced by a specific Gi inhibitor, pertussis toxin in the pipette solution. Our results suggest that BHB activates Gi-coupled signal transduction pathway via HCA2 in guinea pig cardiac myocytes. The HCA2-mediated signal transduction may be associated with ketoacidosis-induced cardiac suppression.