The promoter -1031(T/C) polymorphism in tumor necrosis factor-alpha associated with polycystic ovary syndrome

<p>Abstract</p> <p>Background</p> <p>A <it>tumor necrosis factor-alpha </it>is a multifunctional pro-inflammation cytokine, which has been considered as one of pathogenic factors for various diseases. The promoter -1031(T/C) polymorphism in the <it>tumor necrosis factor-alpha </it>gene was reported that it plays a part in reproduction-related diseases. Among these, polycystic ovary syndrome (PCOS) is known to be a common gynecological disease of women in reproductive age women. Here, we performed a comparative study of -1031(T/C) polymorphism of <it>TNF-alpha </it>gene with PCOS in a Korean population.</p> <p>Methods</p> <p>The -1031(T/C) polymorphism of <it>TNF-alpha </it>gene was analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in a total of 217 PCOS patients and 144 matched female controls of healthy women. And statistical analysis was performed using HapAnalyzer. <it>X</it>²test and logistic regression were utilized analyze the association between two groups. A <it>p</it>-value under 0.05 was considered statistically significant.</p> <p>Results</p> <p>The genotype and allelic frequencies were in Hardy-Weinberg equilibrium (HWE). There was strong association between the -1031(T/C) polymorphism in the promoter region of <it>TNF-alpha </it>gene and PCOS (<it>p</it>-value = 0.0003, odd ratio (OR) = 2.53). In addition, the frequency of C allele was significantly higher in PCOS patients compared with controls. Sequence analyses also showed the -1031(T/C) polymorphism of <it>TNF-alpha </it>gene.</p> <p>Conclusion</p> <p>This is the first study on the -1031(T/C) polymorphism of <it>TNF-alpha </it>gene in PCOS. We concluded that the -1031(T/C) polymorphism of <it>TNF-alpha </it>gene is associated with PCOS in a Korean population. Therefore, it is possible that it may be considered as a clinical biomarker to diagnose for PCOS, and is helpful in understanding the etiology for the pathogenesis of PCOS.</p

Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

<p>Abstract</p> <p>Background</p> <p>Dimeric human erythropoietin (dHuEPO) peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg) mice expressing dHuEPO and to investigate the characteristics of these mice.</p> <p>Methods</p> <p>A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile), was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice.</p> <p>Results</p> <p>A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47) of tg mice expressing the <it>dHuEPO </it>gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11). We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females) were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764). Reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qRT-PCR) were used for validating the results of the microarray analysis of mRNA expression.</p> <p>Conclusions</p> <p>In conclusion, dHuEPO tg mice caused excessive erythrocytosis that led to abnormal blood composition, short lifespan, and abnormal splenomegaly. Further, we identified 2,672 genes associated with splenomegaly by microarray analysis. These results could be useful in the development of dHuEPO-producing tg animals.</p

Monoclinic and Correlated Metal Phase in VO_2 as Evidence of the Mott Transition: Coherent Phonon Analysis

In femtosecond pump-probe measurements, the appearance of coherent phonon oscillations at 4.5 THz and 6.0 THz indicating the rutile metal phase of VO_2 does not occur simultaneously with the first-order metal-insulator transition (MIT) near 68^oC. The monoclinic and correlated metal(MCM) phase between the MIT and the structural phase transition (SPT) is generated by a photo-assisted hole excitation which is evidence of the Mott transition. The SPT between the MCM phase and the rutile metal phase occurs due to subsequent Joule heating. The MCM phase can be regarded as an intermediate non-equilibrium state.Comment: 4 pages, 2 figure

Large enhancement of nonlinear terahertz absorption in intrinsic GaAs by plasmonic nano antennas

We demonstrate remarkably strong nonlinear terahertz (THz) effects in an intrinsic GaAs wafer patterned with a nanometer-width slot antenna array. The antenna near-field reaches 20 MV/cm due to the huge field enhancement in the plasmonic nano-structure (field enhancement factor, α ≅ 50). The THz fields are strong enough to generate high density free carriers (Nₑ > 10¹⁷ cm⁻³) via interband excitations associated with impact ionizations and thus to induce large absorption of the THz radiation (>35%). The nonlinear THz interactions take place in the confined region of nanometer-scale layer adjacent to the antenna.This is the publisher’s final pdf. The published article is copyrighted by the American Institute of Physics Publishing and can be found at: http://scitation.aip.org/content/aip/journal/apl

Expression of aldo-keto reductase family 1 member C1 (AKR1C1) gene in porcine ovary and uterine endometrium during the estrous cycle and pregnancy

<p>Abstract</p> <p>Background</p> <p>The aldo-keto reductase family 1 member C1 (AKR1C1) belongs to a superfamily of NADPH-dependent reductases that convert a wide range of substrates, including carbohydrates, steroid hormones, and endogenous prostaglandins. The 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) is a member of AKR family. The aims of this study were to determine its expression in the ovary and uterus endometrium during the estrous cycle and pregnancy.</p> <p>Methods</p> <p>Rapid amplification of cDNA ends (RACE) experiments were performed to obtain the 5' and 3' ends of the porcine <it>20alpha-HSD </it>cDNA. Reverse-transcriptase-PCR (RT-PCR), real-time PCR, northern blot analysis, and western blot analysis were performed to examine the expression of porcine 20alpha-HSD. Immunohistochemical analysis was also performed to determine the localization in the ovary.</p> <p>Results</p> <p>The porcine 20alpha-HSD cDNA is 957 bp in length and encodes a protein of 319 amino acids. The cloned cDNA was virtually the same as the porcine <it>AKR1C1 </it>gene (337 amino acids) reported recently, and only differed in the C-terminal region (the <it>AKR1C1 </it>gene has a longer C-terminal region than our sequence). The <it>20alpha-HSD </it>gene (from now on referred to as <it>AKR1C1</it>) cloned in this paper encodes a deletion of 4 amino acids, compared with the C-terminal region of <it>AKR1C1 </it>genes from other animals. Porcine AKR1C1 mRNA was expressed on day 5, 10, 12, 15 of the cycle and 0-60 of pregnancy in the ovary. The mRNA was also specifically detected in the uterine endometrium on day 30 of pregnancy. Western blot analysis indicated that the pattern of AKR1C1 protein in the ovary during the estrous cycle and uterus during early pregnancy was similar to that of <it>AKR1C1 </it>mRNA expression. The recombinant protein produced in CHO cells was detected at approximately 37 kDa. Immunohistochemical analysis also revealed that pig AKR1C1 protein was localized in the large luteal cells in the early stages of the estrous cycle and before parturition.</p> <p>Conclusions</p> <p>Our study demonstrated that AKR1C1 mRNA and protein are coordinately expressed in the luteal cell of ovary throughout the estrous cycle and in the uterus on day 30 of pregnancy. Thus, the porcine AKR1C1 gene might control important mechanisms during the estrous cycle.</p

Comparison of short-term clinical outcomes between Resolute Onyx zotarolimus-eluting stents and everolimus-eluting stent in patients with acute myocardial infarction: Results from the Korea Acute Myocardial infarction Registry (KAMIR)

Background: There are few studies which compare the efficacy and safety of the Resolute Onyx zotarolimus-eluting stent (O-ZES) and everolimus-eluting stent (EES) in patients with acute myocardial infarction (AMI). Therefore, the present study aimed to compare clinical outcomes of O-ZES and EES in patients with AMI undergoing successful percutaneous coronary intervention (PCI). Methods: From January 2016 to December 2016, the Korea Acute Myocardial Infarction Registry (KAMIR) enrolled 3,364 consecutive patients. Among them, O-ZES was used in 402 patients and EES was used in 1,084 patients. The primary endpoint was target lesion failure (TLF), as defined by composite of cardiac death, target vessel myocardial infarction (TV-MI), and ischemic driven-target lesion revascularization (ID-TLR) at 6 month clinical follow-up. Results: At 6 months, the incidence of TLF was not significantly different between O-ZES and EES group (4.0% vs. 3.9%, adjusted hazard ratio [HR] 1.17, 95% confidential interval [CI] 0.58–2.35, p = 0.665). O-ZES also showed similar results of cardiac death (3.7% vs. 3.4%, adjusted HR 1.25, 95% CI 0.59–2.63, p = 0.560), TV-MI (0.2% vs. 0.6%, adjusted HR 0.56, 95% CI 0.07–4.85, p = 0.600), ID-TLR (0.0% vs. 0.3%, p = 0.524), and definite or probable stent thrombosis (0.2% vs. 0.3%, adjusted HR 0.63, 95% CI 0.06–6.41, p = 0.696) when compared with EES. Conclusions: The present study shows that implantation of O-ZES or EES provided similar clinical outcomes with similar risk at 6-month of TLF and definite/probable ST in patients with AMI undergoing successful PCI

Refractory Duodenal Crohn's Disease Successfully Treated with Infliximab

Crohn's disease (CD) may involve any part of the gastrointestinal tract, from the mouth to the anus. Approximately >90% of cases occur in the small bowel and colon. Upper gastrointestinal involvement, especially duodenal manifestation, is relatively rare. Therefore, adequate medical treatment for duodenal CD has not yet been established. We report a case of CD with duodenal involvement. A 46-year-old man with Crohn's ileocolitis presented to our hospital with right upper quadrant pain. An endoscopy showed a deep excavated ulcer with deformity at the duodenal bulb, and he was initially treated with azathioprine (1 mg/kg), Pentasa (3.0 g/day), and a proton pump inhibitor for 1 year. However, the deep ulcer did not heal. Therefore, infliximab infusion therapy was initiated, and the duodenal lesion completely resolved on follow-up esophagogastroduodenoscopy. We report a case of duodenal CD that completely resolved following infliximab infusion, with a review of the literature

Molecular characterization of bovine placental and ovarian 20α-hydroxysteroid dehydrogenase

The enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD) catalyzes the conversion of progesterone to its inactive form, 20α-hydroxyprogesterone. This enzyme plays a critical role in the regulation of luteal function in female mammals. In this study, we conducted the characterization and functional analyses of bovine 20α-HSD from placental and ovarian tissues. The nucleotide sequence of bovine 20α-HSD showed significant homology to that of goats (96%), humans (84%), rabbits (83%), and mice (81%). The mRNA levels increased gradually throughout the estrous cycle, the highest being in the corpus luteum (CL) 1 stage. Northern blot analysis revealed a 1.2 kb mRNA in the bovine placental and ovarian tissues. An antibody specific to bovine 20α-HSD was generated in a rabbit immunized with the purified, recombinant protein. Recombinant 20α-HSD protein produced in mammalian cells had a molecular weight of ∼37 kDa. Bacterially expressed bovine 20α-HSD protein showed enzymatic activity. The expression pattern of the 20α-HSD protein in the pre-parturition placenta and the CL1 stage of the estrous cycle was similar to the level of 20α-HSD mRNA expression. Immunohistochemical analysis also revealed that bovine 20α-HSD protein was intensively localized in the large luteal cells during the late estrous cycle

Immunogenicity and Safety of Diphtheria-tetanus Vaccine in Adults

This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (<0.1 U/mL). After the first dose of Td vaccine, 92.6% and 77.6% of subjects gained protective antibody concentrations (≥0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus