Association of polycystic ovarian syndrome with human leukocyte antigen polymorphism in Korean women

Although several studies have demonstrated the genetic contribution to polycystic ovarian syndrome (PCOS), the cause of this syndrome remains unclear. The aim of this study was to elucidate the relationship between human leukocyte antigen (HLA) systems and PCOS in Koreans. We compared the HLA-A, B and DRB1 genotype distribution of 52 PCOS patients and 67 healthy Korean women. In addition, we investigated the association of HLA with free-testosterone level. HLA-A*11, A*31 and B*54 showed increased phenotype frequencies (PFs) in PCOS women compared to controls (p = 0.032, OR 2.79; p = 0.019, OR 6.05; p = 0.002, OR 6.40). HLA-DRB1*15 showed negative correlations with the free-testosterone concentration both in total subjects and PCOS patients (p = 0.024 and p = 0.008). The results of the study suggest mild associations of HLA alleles with pathophysiology of PCOS and/or testosterone production in PCOS. Further investigation in a large number of subjects, including subdivision and multi-population studies, will need to be conducted to prove the consistent or variable association in PCOS.     

Utilization of ancillary studies in the cytologic diagnosis of respiratory lesions: The papanicolaou society of cytopathology consensus recommendations for respiratory cytology

The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for sputum examination, bronchial washings and brushings, CT‐guided FNA and endobronchial ultrasound guided fine needle aspiration (EBUS‐FNA), as well as recommendations for classification and criteria, ancillary testing and post‐cytologic diagnosis management and follow‐up. All recommendation documents are based on the expertise of committee members, an extensive literature review, and feedback from presentations at national and international conferences. The guideline documents selectively present the results of these discussions. The present document summarizes recommendations for ancillary testing of cytologic samples. Ancillary testing including microbiologic, immunocytochemical, flow cytometric, and molecular testing, including next‐generation sequencing are discussed. Diagn. Cytopathol. 2016;44:1000–1009. © 2016 Wiley Periodicals, Inc.     

Association of human papillomavirus type 16 and its genetic variants with cervical lesion in Korea

Persistent human papillomavirus type 16 (HPV16) is the major risk factor for cervical cancer. HPV16 intratypic variants differ in their geographical distribution and oncogenic potential. This study aimed to analyze the distribution of HPV16 variants and their association with cervical lesion histopathology in Korean women. In total, 133 HPV16‐positive cervical samples from women admitted to Seoul National University Boramae Hospital were analyzed by sequencing E6, E7, and L1 genes and the long control region (LCR), and the variant distribution according to cervical lesion grade was determined. Isolates were grouped into a phylogenetic lineage, and A1‐3, A4, C, and D sublineages were detected in 54.1, 37.8, 0.7, and 7.4% of samples, respectively. The most commonly observed LCR variations were 7521G>A (91.5%), 7730A>C (59.6%), and 7842G>A (59.6%). Furthermore, A4 or D sublineage‐positive women had a higher risk for cervical cancer than women who were positive for A1–3. Among HPV phylogenetic clusters, A1–3 was the predominant sublineage, and within A1–3, the 350G polymorphism was highly frequent. These results differed from those of previous studies in Korea and other Asian countries. The findings suggest that cervical neoplasia incidence in HPV16‐infected patients could be affected by the distribution of HPV16 variants in the population.     

Delayed sternal closure does not reduce complications associated with coagulopathy and right ventricular failure after left ventricular assist device implantation

Delayed sternal closure (DSC) is occasionally adopted after implantation of left ventricular assist device (LVAD). Recent studies suggest that DSC be used for high risk group of patients with coagulopathy, hemodynamic instability or right ventricular failure. However, whether DSC is efficacious for bleeding complication or right ventricular failure is not known. This study is single center analysis of 52 patients, who underwent LVAD implantation. Of those 52 patients, 40 consecutive patients underwent DSC routinely. The sternum was left open with vacuum assist device after implantation of LVAD. Perioperative outcome of the patients who underwent routine DSC were compared with 12 patients who had immediate sternal closure (IC). Mean Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level of IC group and DSC group were 2.7 and 2.6, respectively. Postoperative bleeding (643 vs. 1469 ml, p?<?0.001), duration of inotropic support (109 vs. 172 h, p?=?0.034), and time to extubation (26 vs. 52 h, p?=?0.005) were significantly increased in DSC group. Length of ICU stay (14 vs. 15 days, p?=?0.234) and hospital stay (28 vs. 20 days, p?=?0.145) were similar. Incidence of right ventricular failure and tamponade were similar in the two groups. Routine DSC after implantation of an LVAD did not prove to be beneficial in reducing complications associated with coagulopathy and hemodynamic instability including cardiac tamponade or right ventricular failure. We suggest that DSC be selectively applied for patients undergoing LVAD implant.     

Large interrelated clusters of repetitive elements (REs) and RE arrays predominantly represent reference mouse chromosome Y

The vast majority of the mouse and human genomes consist of repetitive elements (REs), while protein-coding sequences occupy only ～3 %. It has been reported that the Y chromosomes of both species are highly populated with REs although at present, their complete sequences are not available in any public database. The recent update of the mouse genome database (Build 38.1) from the National Center for Biotechnology Information (NCBI) indicates that mouse chromosome Y is ～92 Mb in size, which is substantially larger than the ～16 Mb reported previously (Build 37.2). In this study, we examined how REs are arranged in mouse chromosome Y (Build 38.1) using REMiner-II, a RE mining program. A combination of diverse REs and RE arrays formed large clusters (up to ～28 Mb in size) and most of them were directly or inversely related. Interestingly, the RE population of human chromosome Y (NCBI Build 37.2-current) was less dense, and the RE/RE array clusters were not evident in comparison to mouse chromosome Y. The annotated gene loci were distributed in five different regions and most of them were surrounded by unique RE arrays. In particular, tandem RE arrays were embedded into the introns of two adjacent gene loci. The findings from this study indicate that the large and interrelated clusters of REs and RE arrays predominantly represent the unique organizational pattern of mouse chromosome Y. The potential interactions among the clusters, which are populated with various interrelated REs and RE arrays, may play a role in the structural configuration and function of mouse chromosome Y.     

Effects of black cohosh on the plasminogen activator system in vascular smooth muscle cells

Objective

The rhizome of the Cimicifuga racemosa plant (commonly known as black cohosh) has been used for menopausal complaints. Studies regarding the cardiovascular effects of black cohosh are lacking. We investigated the effect of black cohosh on the plasminogen activator system in cultured vascular smooth muscle cells (VSMCs).

Methods

VSMCs were isolated from rat aortae. Expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) proteins were evaluated by Western blot analysis and enzyme-linked immunosorbent assay, respectively. The activities of PAI-1 and t-PA in the conditioned media were assessed by fibrin overlay zymography. A 40% 2-propanol extract of black cohosh was used.

Results

Black cohosh extract (BcEx) stimulated the protein expression of PAI-1, but it did not affect that of t-PA. Vitamin E, a potent antioxidant, inhibited the BcEx-induced increase in PAI-1 expression, while ICI 182,780, an estrogen receptor antagonist, had no effect. Fibrin overlay zymography revealed that BcEx increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA by inducing a binding to PAI-1.

Conclusions

BcEx induces PAI-1 protein expression in the VSMCs likely via an oxidant mechanism. It also stimulates the enzyme activity of PAI-1 and reduces that of free t-PA. These findings suggest that black cohosh might exert a negative influence on fibrinolysis.     

The Effects of Single Nucleotide Polymorphisms in Korean Patients with Early-onset Atrial Fibrillation after Catheter Ablation

BackgroundThis study evaluated the status of single nucleotide polymorphisms (SNPs) in Korean patients with early-onset (< 40 years old) atrial fibrillation (AF) and their effects on the outcome after catheter ablation.MethodsA total of 89 patients (35.7 ± 3.7 years, 81 males) with drug-refractory AF (paroxysmal 64.0%) who underwent catheter ablation were included in this study. Sixteen SNPs, including rs13376333, rs10465885, rs10033464, rs2200733, rs17042171, rs6843082, rs7193343, rs2106261, rs17570669, rs853445, rs11708996, rs6800541, rs251253, rs3807989, rs11047543, and rs3825214, were genotyped. Serial 48-hour Holter monitoring was conducted to detect AF recurrences during long-term follow up.ResultsWild-type genotypes of rs11047543 (GG; 26/69 [37.7%] vs. GA; 13/18 [72.2%] vs. AA; 0/0 [0%], P = 0.009) and rs7193343 (CC; 0/7 [0%] vs. CT; 22/40 [55.0%] vs. TT; 18/41 [43.9%], P = 0.025) and the homozygous variant of rs3825214 (AA; 16/31 [51.6%] vs. AG; 22/43 [51.2%] vs. GG; 2/13 [15.4%], P = 0.056) were significantly associated with a lower rate of late recurrence. When the patients were assigned to four groups according to the number of risk alleles (n = 0–3), there were significant differences in recurrence rate (n = 0; 0/3 vs. n = 1; 2/13 [15.4%] vs. n = 2; 24/52 [46.2%] vs. n = 3; 13/17 [76.5%], P = 0.003). When correcting for multiple variables, rs11047543 (hazard ratio [HR], 2.723; 95% confidence interval [CI], 1.358–5.461; P = 0.005) and the number of risk alleles (HR, 2.901; 95% CI, 1.612–5.219; P < 0.001) were significantly associated with recurrence of AF after catheter ablation.ConclusionPolymorphisms on rs7193343 closest to ZFHX3 (16q22), rs3825214 near to TBX5 (12q24), and rs11047543 near to SOX5 (12p12) modulate the risk for AF recurrence after catheter ablation. The number of risk alleles of these 3 SNPs was an independent predictor of recurrence during long-term follow up in Korean patients with early-onset AF.