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51.
52.
Azumi Ishizaki Kaori Matsushita Huyen Thi Thanh Hoang Dorothy M. Agdamag Cuong Hung Nguyen Vuong Thi Tran Toshiyuki Sasagawa Kunikazu Saikawa Raphael Lihana Hung Viet Pham Xiuqiong Bi Van Thanh Ta Thuc Van Pham Hiroshi Ichimura 《Journal of medical virology》2013,85(6):1069-1076
Human papillomavirus (HPV) has several intragenotypic variants with different geographical and ethnic distributions. This study aimed to elucidate the distribution patterns of E6 and E7 (E6/E7) intragenotypic variants of HPV type 16 (HPV‐16), which is most common worldwide, and HPV‐52, which is common in Asian countries such as Japan, the Philippines, and Vietnam. In previous studies, genomic DNA samples extracted from cervical swabs were collected from female sex workers in these three countries and found to be positive for HPV‐16 or HPV‐52. Samples were amplified further for their E6/E7 genes using type‐specific primers and analyzed genetically. Seventy‐nine HPV‐16 E6/E7 genes were analyzed successfully and grouped into three lineages: European (Prototype), European (Asian), and African‐2. The prevalences of HPV‐16 European (Prototype)/European (Asian) lineages were 19.4%/80.6% (n = 31) in Japan, 75.0%/20.8% (n = 24) in the Philippines, and 0%/95.8% (n = 24) in Vietnam. The 109 HPV‐52 E6/E7 genes analyzed successfully were grouped into four lineages, A–D; the prevalences of lineages A/B/C/D were, respectively, 5.1%/92.3%/0%/2.6% in Japan (n = 39), 34.4%/62.5%/0%/3.1% in the Philippines (n = 32), and 15.8%/73.7%/7.9%/2.6% in Vietnam (n = 38). The distribution patterns of HPV‐16 and HPV‐52 lineages in these countries differed significantly (P < 0.000001 and P = 0.0048, respectively). There was no significant relationship between abnormal cervical cytology and either HPV‐16 E6/E7 lineages or specific amino acid mutations, such as E6 D25E, E6 L83V, and E7 N29S. Analysis of HPV‐16 and HPV‐52 E6/E7 genes can be a useful molecular‐epidemiological tool to distinguish geographical diffusion routes of these HPV types in Asia. J. Med. Virol. 85: 1069–1076, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
53.
D.Z. Loesch R. Huggins E. Rogucka N.H. Hoang J.L. Hopper 《Annals of human biology》2013,40(6):479-490
Multivariate genetic models were fitted to data from 44 pairs of MZ and 42 pairs of DZ twin girls on weight, height, and skeletal maturation at the age of menarche, in order to obtain information on genetic relationships of those measures with the age of menarche. The relationships of all three physical measures with this age were largely genetically controlled, but a genetic system controlling skeletal maturity was identified as the only genetic determinant of menarcheal age, independent of those systems of the two remaining physical measures. Heritabilities of all individual traits considered in the study were uniformly high. Possible links of genetic information with hormonal functions determining menarche are discussed. 相似文献
54.
55.
Bassem R. Haddad Lei Gu Tuomas Mirtti Ayush Dagvadorj Paraskevi Vogiatzi David T. Hoang Renu Bajaj Benjamin Leiby Elyse Ellsworth Shauna Blackmon Christian Ruiz Mark Curtis Paolo Fortina Adam Ertel Chengbao Liu Hallgeir Rui Tapio Visakorpi Lukas Bubendorf Marja T. Nevalainen 《The American journal of pathology》2013,182(6):2264-2275
56.
Satyan S. Kalkunte Stefan Neubeck Wendy E. Norris Shi-Bin Cheng Stefan Kostadinov Dang Vu Hoang Aftab Ahmed Ferdinand von Eggeling Zahir Shaikh James Padbury Goran Berg Anders Olofsson Udo R. Markert Surendra Sharma 《The American journal of pathology》2013,183(5):1425-1436
Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother and fetus. Understanding its pathogenesis and causative biomarkers is likely to yield insights for prediction and treatment. Herein, we provide evidence that transthyretin, a transporter of thyroxine and retinol, is aggregated in preeclampsia and is present at reduced levels in sera of preeclamptic women, as detected by proteomic screen. We demonstrate that transthyretin aggregates form deposits in preeclampsia placental tissue and cause apoptosis. By using in vitro approaches and a humanized mouse model, we provide evidence for a causal link between dysregulated transthyretin and preeclampsia. Native transthyretin inhibits all preeclampsia-like features in the humanized mouse model, including new-onset proteinuria, increased blood pressure, glomerular endotheliosis, and production of anti-angiogenic factors. Our findings suggest that a focus on transthyretin structure and function is a novel strategy to understand and combat preeclampsia.Preeclampsia occurs in 5% to 8% of pregnancies worldwide and is a major cause of fetal and maternal morbidity and mortality.1–3 It is a heterogeneous disease with varied presentations from mild self-limited hypertension and proteinuria to severe forms with significant end-organ dysfunction and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets).3 Although the cause of preeclampsia and its appropriate treatment remain elusive, this syndrome has been proposed to reflect at least two stages of complications during pregnancy. These begin with preclinical manifestations at the maternal-fetal interface, followed by systemic clinical symptoms.1,2 Hypertension, proteinuria, and edema, with a variable degree of fetal growth restriction, are the cardinal features of preeclampsia.3 Because the placenta is the nutritional and immunological gateway to normal fetal development and pregnancy outcome, placenta-related events are believed to be central to the pathogenesis of this disease. Evidence exists for the release of disease-initiating molecules into maternal circulation that triggers the clinical symptoms.1,4 Placental and systemic anomalies reflected by circulating placental debris, inflammation, impaired remodeling of spiral arteries, placental hypoxia/ischemia, excess production of anti-angiogenic factors [soluble fms-like tyrosine kinase-1 (sFlt-1)], and soluble endoglin (sEng), and angiotensin receptor autoantibodies have all emerged as contributors to the pathophysiological characteristics of preeclampsia.2,4–14Preeclampsia has remained enigmatic because of lack of well-defined etiology and animal models. Although normal mice do not develop preeclampsia spontaneously, mouse models have been judged to be particularly useful to uterine diseases and pregnancy complications because many similarities in female reproduction and placentation have been identified between the two species.15 Moreover, their tractable genetics provide an effective way to probe mechanisms more deeply than many other species.15–17 We recently showed that sera from preeclamptic women could function as a source of novel causative factors that induced hypertension, proteinuria, and kidney pathological characteristics, as well as intrauterine growth restriction (IUGR), in IL-10−/− mice in a pregnancy-specific manner.18 IL-10 functions as a potent vascular and anti-inflammatory cytokine and has been shown to be present at significantly reduced levels in preeclampsia placental tissue.19,20 Preeclampsia serum (PES) was found to disrupt endovascular cross talk between trophoblasts and endothelial cells and to induce placental hypoxia and excess production of sFlt-1 and sEng,18 soluble factors known to precipitate maternal symptoms.21,22 These results from our serum-based humanized mouse model suggest that the pathophysiological characteristics of preeclampsia are more complex than previously thought and are likely to involve interactions and dysregulation of multiple factors. By using serum proteomic screening by surface-enhanced laser-desorption ionization-time-of-flight (SELDI-TOF), our results suggest that PES contains a reduced abundance of transthyretin, a plasma transport protein for the thyroid hormone, thyroxine, and retinol-binding protein.23 More important, transthyretin has been widely studied for its role in amyloid diseases associated with protein misfolding and aggregation, resulting in deposits of toxic, fibrillar aggregates in specific organs.24–26 Dysregulated or reduced transthyretin has also been implicated in Alzheimer disease, and overexpression of a wild-type human transthyretin transgene has been shown to ameliorate the disease in the transgenic murine model of human Alzheimer disease.27,28 Transthyretin in its native form assumes a homotetrameric quaternary configuration (approximately 14 kDa per monomer). Post-translational modifications of the monomer result in detection of several isoforms.29 Circulating transthyretin is also a validated marker of malnutrition and has a putative role in oocyte maturation and inflammation.30–32 Although the presence of transthyretin during implantation in mice and in the placenta and trophoblasts in humans has been reported,33,34 its functional role in normal pregnancy or adverse pregnancy outcomes has not been recognized. We hypothesize that transthyretin in preeclampsia is structurally and functionally dysregulated and contributes to the onset of this serious pregnancy complication. Herein, we present complementary in vitro and in vivo approaches, which show that endogenously altered transthyretin is a preeclampsia-causing agent and that native transthyretin has the ability to block the onset of preeclampsia-like features. 相似文献
57.
Nobuhiro Takemae Tung Nguyen Long Thanh Ngo Yasuaki Hiromoto Yuko Uchida Vu Phong Pham Tsutomu Kageyama Shizuko Kasuo Shinichi Shimada Yasutaka Yamashita Kaoru Goto Hideyuki Kubo Vu Tri Le Hung Van Vo Hoa Thi Do Dang Hoang Nguyen Tsuyoshi Hayashi Aya Matsuu Takehiko Saito 《Archives of virology》2013,158(4):859-876
The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production. 相似文献
58.
Masatoshi Okamatsu Tatsuya Nishi Naoki Nomura Naoki Yamamoto Yoshihiro Sakoda Kenji Sakurai Huy Duc Chu Long Pham Thanh Long Van Nguyen Nam Van Hoang Tien Ngoc Tien Reiko Yoshida Ayato Takada Hiroshi Kida 《Virus genes》2013,47(2):317-329
To estimate the prevalence of avian influenza virus infection in Vietnam, surveillance was conducted in domestic and wild birds from households, live-bird markets, slaughtering sites, and bird sanctuaries in Vietnam between October 2010 and October 2012. Of the 4,550 samples collected, 226 influenza A virus isolates were obtained from domestic ducks, muscovy ducks, and chickens. Of these, 25 and 22 H5N1 highly pathogenic avian influenza viruses (HPAIVs) were isolated from apparently healthy domestic ducks in live-bird markets and slaughtering sites in northern and southern Vietnam, respectively. The HA genes of H5 viruses isolated from birds in northern Vietnam phylogenetically belonged to the genetic clade 2.3.2.1 and those in southern Vietnam belonged to the genetic clade 1.1. In addition, 39 H3, 12 H4, 1 H5, 93 H6, 2 H7, 18 H9, 3 H10, and 11 H11 viruses were isolated. Phylogenetic and antigenic analyses of the H6 and H9 viruses revealed that they were closely related to the isolates obtained from domestic poultry in China. Phylogenetic analyses of internal gene segments of these isolates revealed that these viruses were circulating in both domestic and wild birds in Asia and reassortment events had occurred frequently. Therefore, it will be important to continue the surveillance and strict controls over the movement and trade of poultry and poultry products in order to eradicate H5N1 HPAIV from Asia. 相似文献
59.
60.
Allison J. Armstrong Maria Sol Collado Brad R. Henke Matthew W. Olson Stephen A. Hoang Christin A. Hamilton Taylor D. Pourtaheri Kimberly A. Chapman Marshall M. Summar Brian A. Johns Brian R. Wamhoff John E. Reardon Robert A. Figler 《Molecular genetics and metabolism》2021,132(1):71-82
Propionic Acidemia (PA) and Methylmalonic Acidemia (MMA) are inborn errors of metabolism affecting the catabolism of valine, isoleucine, methionine, threonine and odd-chain fatty acids. These are multi-organ disorders caused by the enzymatic deficiency of propionyl-CoA carboxylase (PCC) or methylmalonyl-CoA mutase (MUT), resulting in the accumulation of propionyl-coenzyme A (P-CoA) and methylmalonyl-CoA (M-CoA in MMA only). Primary metabolites of these CoA esters include 2-methylcitric acid (MCA), propionyl-carnitine (C3), and 3-hydroxypropionic acid, which are detectable in both PA and MMA, and methylmalonic acid, which is detectable in MMA patients only (Chapman et al., 2012). We deployed liver cell-based models that utilized PA and MMA patient-derived primary hepatocytes to validate a small molecule therapy for PA and MMA patients. The small molecule, HST5040, resulted in a dose-dependent reduction in the levels of P-CoA, M-CoA (in MMA) and the disease-relevant biomarkers C3, MCA, and methylmalonic acid (in MMA). A putative working model of how HST5040 reduces the P-CoA and its derived metabolites involves the conversion of HST5040 to HST5040-CoA driving the redistribution of free and conjugated CoA pools, resulting in the differential reduction of the aberrantly high P-CoA and M-CoA. The reduction of P-CoA and M-CoA, either by slowing production (due to increased demands on the free CoA (CoASH) pool) or enhancing clearance (to replenish the CoASH pool), results in a net decrease in the CoA-derived metabolites (C3, MCA and MMA (MMA only)). A Phase 2 study in PA and MMA patients will be initiated in the United States. 相似文献