http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Defective erythropoiesis caused by mutations of the thyroid hormone receptor α gene
Park, Sunmi,Han, Cho Rong,Park, Jeong Won,Zhao, Li,Zhu, Xuguang,Willingham, Mark,Bodine, David M.,Cheng, Sheue-yann,Grimes, H. Leighton Public Library of Science 2017 PLoS genetics Vol.13 No.9
<▼1><P>Patients with mutations of the <I>THRA</I> gene exhibit classical features of hypothyroidism, including erythroid disorders. We previously created a mutant mouse expressing a mutated TRα1 (denoted as PV; <I>Thra1</I><SUP>PV/+</SUP> mouse) that faithfully reproduces the classical hypothyroidism seen in patients. Using <I>Thra1</I><SUP>PV/+</SUP> mice, we explored how the TRα1PV mutant acted to cause abnormalities in erythropoiesis. <I>Thra1</I><SUP>PV/+</SUP> mice exhibited abnormal red blood cell indices similarly as reported for patients. The total bone marrow cells and erythrocytic progenitors were markedly reduced in the bone marrow of <I>Thra1</I><SUP>PV/+</SUP> mice. <I>In vitro</I> terminal differentiation assays showed a significant reduction of mature erythrocytes in <I>Thra1</I><SUP>PV/+</SUP> mice. In wild-type mice, the clonogenic potential of progenitors in the erythrocytic lineage was stimulated by thyroid hormone (T3), suggesting that T3 could directly accelerate the differentiation of progenitors to mature erythrocytes. Analysis of gene expression profiles showed that the key regulator of erythropoiesis, the <I>Gata-1</I> gene, and its regulated genes, such as the <I>Klf1</I>, <I>β-globin</I>, <I>dematin</I> genes, <I>CAII</I>, <I>band3 and eALAS</I> genes, involved in the maturation of erythrocytes, was decreased in the bone marrow cells of <I>Thra1</I><SUP>PV/+</SUP> mice. We further elucidated that the <I>Gata-1</I> gene was a T3-directly regulated gene and that TRα1PV could impair erythropoiesis via repression of the <I>Gata-1</I> gene and its regulated genes. These results provide new insights into how TRα1 mutants acted to cause erythroid abnormalities in patients with mutations of the <I>THRA</I> gene. Importantly, the <I>Thra1</I><SUP>PV/+</SUP> mouse could serve as a preclinical mouse model to identify novel molecular targets for treatment of erythroid disorders.</P></▼1><▼2><P><B>Author summary</B></P><P>Patients with mutations of the <I>THRA</I> gene exhibit erythroid disorders. The molecular pathogenesis underlying erythroid abnormalities is poorly understood. In <I>Thra1</I><SUP>PV/+</SUP> mice expressing a dominant negative mutant TRα1PV, we found abnormal red blood cell indices similar to patients. Total bone marrow cells, the clonogenic potential of erythrocytic progenitors, and terminal differentiation of erythrocytes were markedly decreased in <I>Thra1</I><SUP>PV/+</SUP> mice. We elucidated that <I>Gata-1</I>, a key erythroid gene, was directly positively regulated by TRα1. The erythroid defects in <I>Thra1</I><SUP>PV/+</SUP> mice were due, at least partly, to the TRα1PV-mediated suppression of the <I>Gata-1</I> gene and its down-stream target genes. Over-expression of <I>Gata-1</I> rescued impaired terminal differentiation. Our studies elucidated molecular mechanisms by which TRα1 mutants caused erythroid disorders in patients. The present study suggests that therapies aimed at GATA1 could be tested as a potential target in treating erythroid abnormalities in patients.</P></▼2>
Reducing the unexpectedly high rate of injuries caused by NOTES gastrotomy creation.
Sohn, Dae Kyung,Turner, Brian G,Gee, Denise W,Willingham, Field F,Sylla, Patricia,Cizginer, Sevdenur,Konuk, Yusuf,Brugge, William R,Rattner, David W Springer International 2010 Surgical endoscopy Vol.24 No.2
<P>Despite the wide range of natural orifice transluminal endoscopic surgery (NOTES) procedures reported to date using a transgastric endoscopic approach, complications associated with gastrotomy creation have not been described. This study was conducted to identify the incidence and types of complications related to gastrotomy creation with the needle knife puncture and balloon dilatation technique for NOTES access to the peritoneal cavity.</P>
Zachary Spiritos,Parit Mekaroonkamol,Bassel F. El-Rayes,Seth D. Force,Steven A. Keilin,Qiang Cai,Field F. Willingham 대한소화기내시경학회 2017 Clinical Endoscopy Vol.50 No.5
Esophageal cancer has a poor overall prognosis and is frequently diagnosed at a late stage. Conventional treatment for metastatic esophageal cancer involves chemotherapy and radiation. Local disease control plays a significant role in improving survival. Endoscopic spray cryotherapy is a novel modality that involves freezing and thawing to produce local ablation of malignant tissue via ischemic mechanisms. Spray cryotherapy has been shown to be effective, particularly for early T-stage, superficial esophageal adenocarcinomas. We present the case of a 72-year-old-male with locally recurrent stage IV esophageal adenocarcinoma and long-term survival of 7 years to date, with concurrent chemoradiation and serial cryoablation. He remains asymptomatic and continues to undergo chemotherapy and sequential cryoablation. The findings highlight the long-term safety and efficacy of cryotherapy in combination with chemoradiation, and suggest that cryoablation may have an additive role in the treatment of advanced stage esophageal adenocarcinoma.
Jonathan B. Reichstein,Vaishali Patel,Parit Mekaroonkamol,Sunil Dacha,Steven A. Keilin,Qiang Cai,Field F. Willingham 대한소화기내시경학회 2020 Clinical Endoscopy Vol.53 No.1
Background/Aims: There are conflicting opinions regarding the management of recurrent acute pancreatitis (RAP). While somephysicians recommend endoscopic retrograde cholangiopancreatography (ERCP) in this setting, others consider it to be contraindicatedin patients with RAP. The aim of this study was to assess the practice patterns and clinical features influencing the management of RAPin the US. Methods: An anonymous 35-question survey instrument was developed and refined through multiple iterations, and its use wasapproved by our Institutional Review Board. The survey was distributed via email to 408 gastroenterologists to assess the practicepatterns in the management of RAP in multiple clinical scenarios. Results: The survey was completed by 65 participants representing 36 of the top academic/tertiary care centers across the country. Approximately 90.8% of the participants indicated that they might offer or recommend ERCP in the management of RAP. Multinomiallogistic regression analysis revealed that ductal dilatation and presence of symptoms were the most predictive variables (p<0.001) foroffering ERCP. Conclusions: A preponderance of the respondents would consider ERCP among patients with RAP presenting to tertiary care centersin the US. Ductal dilatation, presence of symptoms, and pancreas divisum significantly increased the likelihood of a recommendationfor ERCP
Sylla, Patricia,Sohn, Dae Kyung,Cizginer, Sevdenur,Konuk, Yusuf,Turner, Brian G,Gee, Denise W,Willingham, Field F,Hsu, Maylee,Mino-Kenudson, Mari,Brugge, William R,Rattner, David W Springer International 2010 Surgical endoscopy Vol.24 No.8
<P>The feasibility of transanal rectosigmoid resection with transanal endoscopic microsurgery (TEM) was previously demonstrated in a swine nonsurvival model in which transgastric endoscopic assistance also was shown to extend the length of colon mobilized transanally.</P>
Epidemiology of early esophageal adenocarcinoma
Thuy-Van P. Hang,Zachary Spiritos,Anthony M. Gamboa,Zhengjia Chen,Seth Force,Vaishali Patel,Saurabh Chawla,Steven Keilin,Nabil F. Saba,Bassel El-Rayes,Qiang Cai,Field F. Willingham 대한소화기내시경학회 2022 Clinical Endoscopy Vol.55 No.3
Background/Aims: Endoscopic resection has become the preferred treatment approach for select early esophageal adenocarcinoma(EAC); however, the epidemiology of early stage disease has not been well defined. Methods: Surveillance Epidemiology and End Results (SEER) data were analyzed to determine age-adjusted incidence rates amongmajor epithelial carcinomas, including EAC, from 1973 to 2017. The percent change in incidence over time was compared according totumor subtype. Early T-stage, node-negative EAC without metastasis was examined from 2004 to 2017 when precise T-stage data wereavailable. Results: The percent change in annual incidence from 1973 to 2017 was 767% for EAC. Joinpoint analysis showed that the average annualpercent change in EAC from 1973 to 2017 was 5.11% (95% confidence interval, 4.66%−5.56%). The annual percent change appearedto plateau between 2004 and 2017; however, early EAC decreased from 2010 to 2017, with an annual percent change of −5.78%. Conclusions: There has been a 7-fold increase in the incidence of EAC, which was significantly greater than that of the other major epithelialmalignancies examined. More recently, the incidence of early EAC has been decreasing. Approximately one in five patients hasnode negative, potentially resectable early stage disease.