tbuckley/cabot-search huggingface dataset:
Consumption of PCB-contaminated sport fish and risk of spontaneous fetal death.
Authors: P Mendola, G M Buck, J E Vena, M Zielezny, L E Sever
Journal: Environmental Health Perspectives (1995)

Spontaneous fetal death has been observed among various mammalian species after exposure to polychlorinated biphenyls (PCBs). Our exposure-based cohort study assessed the relationship between consumption of PCB-contaminated Lake Ontario sport fish and spontaneous fetal death using 1820 multigravid fertile women from the 1990-1991 New York State Angler Cohort Study. Fish consumption data were obtained from food frequency questionnaires and history of spontaneous fetal death from live birth certificates. Analyses were stratified by number of prior pregnancies and controlled for smoking and maternal age. No significant increases in risk for fetal death were observed across four measures of exposure: a lifetime estimate of PCB exposure based on species-specific PCB levels; the number of years of fish consumption; kilograms of sport fish consumed in 1990-1991; and a lifetime estimate of kilograms eaten. A slight risk reduction was seen for women with two prior pregnancies at the highest level of PCB exposure (odds ratio = 0.36; 95% CI, 0.14-0.92) and for women with three or more prior pregnancies with increasing years of fish consumption (odds ratio = 0.97; 95% CI, 0.94-0.99). These findings suggest that consumption of PCB-contaminated sport fish does not increase the risk of spontaneous fetal death.
Serial quantification of lymphoid and myeloid mixed chimerism using multiplex PCR amplification of short tandem repeat-markers predicts graft rejection and relapse, respectively, after allogeneic transplantation of CD34+ selected cells from peripheral blood
Authors: F Fernández-Avilés, A Urbano-Ispizua, M Aymerich, D Colomer, M Rovira, C Martinez, E Nadal, C Talarn, E Carreras, E Montserrat
Journal: Leukemia (2003)
MicroRNA-29b Inhibits Diabetic Nephropathy in db/db Mice
Authors: Hai-Yong Chen, Xiang Zhong, Xiao R Huang, Xiao-Ming Meng, Yongke You, Arthur CK Chung, Hui Y Lan
Journal: Molecular Therapy (2013)

Inflammation and its consequent fibrosis are two main features of diabetic nephropathy (DN), but target therapy on these processes for DN remains yet ineffective. We report here that miR-29b is a novel therapeutic agent capable of inhibiting progressive renal inflammation and fibrosis in type 2 diabetes in db/db mice. Under diabetic conditions, miR-29b was largely downregulated in response to advanced glycation end (AGE) product, which was associated with upregulation of collagen matrix in mesangial cells via the transforming growth factor-β (TGF-β)/Smad3-dependent mechanism. These pathological changes were reversed by overexpressing miR-29b, but enhanced by knocking-down miR-29b. Similarly, loss of renal miR-29b was associated with progressive diabetic kidney injury, including microalbuminuria, renal fibrosis, and inflammation. Restored renal miR-29b by the ultrasound-based gene therapy was capable of attenuating diabetic kidney disease. Further studies revealed that inhibition of Sp1 expression, TGF-β/Smad3-dependent renal fibrosis, NF-κB-driven renal inflammation, and T-bet/Th1-mediated immune response may be mechanisms associated with miR-29b treatment in db/db mice. In conclusion, miR-29b may play a protective role in diabetic kidney disease and may have therapeutic potential for diabetic kidney complication.
TNF is a key mediator of the pronociceptive effects of mucosal supernatant from human ulcerative colitis on colonic DRG neurons
Authors: C. Ibeakanma, S. Vanner
Journal: Gut (2010)

<h3>Objectives</h3> Abdominal pain is a serious cause of morbidity in patients with inflammatory bowel disease. To better understand the mechanisms and potentially identify new targets for treatment, the effects of inflammatory supernatant from colonic biopsies of patients with active ulcerative colitis (UC) on mouse colonic nociceptive dorsal root ganglia neurons were examined. <h3>Methods</h3> Acutely dissociated dorsal root ganglia neurons innervating the mouse colon were incubated in supernatants obtained from colonic biopsies from patients with UC. Whole-cell patch clamp recordings were obtained to examine the effects on neuronal excitability. The role of tumour necrosis factor α (TNFα) was studied using TNFα receptor (TNFR) knockout mice and comparing supernatant and TNFα actions. <h3>Results</h3> UC supernatants significantly decreased the rheobase and increased action potential discharge, indicating increased neuronal excitability. Human biopsies exhibited high levels of TNFα, and mouse colonic neurons only exhibited TNFR1 mRNA. Incubation with TNFα recapitulated the supernatant effects on neuronal excitability, and supernatant and TNFα actions were almost completely blocked in TNFR knockout mice. In voltage clamp studies, transient I<sub>A</sub> and I<sub>K</sub> currents were suppressed and Na<sub>v</sub> 1.8 currents were enhanced by TNFα and UC supernatant, suggesting that multiple underlying mechanisms contributed to the enhanced excitability. <h3>Conclusions</h3> UC supernatants enhance neuronal excitability of sensory dorsal root ganglia neurons innervating the colon. TNFα is a key mediator which acts at neuronal TNFR1 to modulate K<sub>v</sub> and Na<sub>v</sub> currents. Together these data provide a number of potential new targets for pain management in UC.
A NEW INCISION FOR CLAVICLE OPERATIONS
Authors: ROBERT SOUTTER
Journal: JAMA (1924)

Especially in women and young girls, it is often desirable to avoid a disfiguring scar in operations in the clavicular region. Keloid formation in the line of incision is not uncommon following torticollis and other operations in the region of the clavicle. In a case in which it was necessary to remove a large deformity of the clavicle due to an old ununited fracture, and in which, for cosmetic reasons, it was important not to have a large scar replace the deformity, I used the incision here described, which gave ample room for the operation, which was fairly extensive. As the supraclavicular region, lower neck, upper chest and outer sternal region could well be reached by the same approach, I venture to recommend this incision for operations not necessarily restricted to the clavicle, when the surgeon wishes to avoid a scar that will show. <h3>INCISION</h3> The incision extended from the
Prognostic value of serum laminin chronic alcholic liver disease (CALD)
Authors: E. González-Reimers, F. Sentolaria, A. Conde-Martel, F. Rodríguez-Moreno, A. Milena-Abril, E. Rodríguez-Rodríguez, J. Oramas-Rodríguez
Journal: Journal of Hepatology (1991)
Molecular Pathways: Translational and Therapeutic Implications of the Notch Signaling Pathway in Cancer
Authors: Rebecca A. Previs, Robert L. Coleman, Adrian L. Harris, Anil K. Sood
Journal: Clinical Cancer Research (2014)

Over 100 years have passed since the first observation of the notched wing phenotype in Drosophila melanogaster, and significant progress has been made to characterize the role of the Notch receptor, its ligands, downstream targets, and cross-talk with other signaling pathways. The canonical Notch pathway with four Notch receptors (Notch1-4) and five ligands (DLL1, 3-4, Jagged 1-2) is an evolutionarily conserved cell signaling pathway that plays critical roles in cell-fate determination, differentiation, development, tissue patterning, cell proliferation, and death. In cancer, these roles have a critical impact on tumor behavior and response to therapy. Because the role of Notch remains tissue and context dependent, alterations within this pathway may lead to tumor suppressive or oncogenic phenotypes. Although no FDA-approved therapies currently exist for the Notch pathway, multiple therapeutics (e.g., demcizumab, tarextumab, GSI MK-0752, R04929097, and PF63084014) have been developed to target different aspects of this pathway for both hematologic and solid malignancies. Understanding the context-specific effects of the Notch pathway will be important for individualized therapies targeting this pathway.
Abstract 4688: Novel prognostic subtype of hepatocellular carcinoma reflecting stem/maturational status of the tumor defined by Gd-EOB-DTPA-enhanced MRI and serum AFP
Authors: Taro Yamashita, Masao Honda, Shuichi Kaneko
Journal: Cancer Research (2014)

Abstract Survival of patients with hepatocellular carcinoma (HCC) varies on an individually basis, even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI) has recently been introduced to evaluate hepatic lesions with regard to the activity of the organic anion transporter OATP1B3 as well as vascularity. Here we report that Gd-EOB-DTPA-Enhanced MRI and serum alpha-fetoprotein (AFP) status reflects the stem/maturation status of HCC with distinct biology and prognostic information. Atypical uptake of Gd-EOB-DTPA in the hepatobiliary phase was observed in ∼ 15% of HCCs. This uptake correlated with the low serum alpha-fetoprotein (AFP) levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A, and good prognosis. In contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP presented poor prognosis with the activation of an oncogene FOXM1. Knockdown of HNF4A in cancer cells, obtained from a surgically resected HCC showing atypical uptake of Gd-EOB-DTPA, resulted in the increase of AFP and FOXM1 and the loss of OATP1B3 expression accompanied with the mesenchymal morphological changes, enhanced cell proliferation and tumorigenesis in vivo. HCC classification based on EOB-MRI and serum AFP level (EOB-AFP classification) predicted overall survival in a retrospective cohort (n = 70), and its prognostic utility was validated in a multi-institution cohort of early-stage HCCs (n = 109). This non-invasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging to improve management algorithms, especially in early stage. Citation Format: Taro Yamashita, Masao Honda, Shuichi Kaneko. Novel prognostic subtype of hepatocellular carcinoma reflecting stem/maturational status of the tumor defined by Gd-EOB-DTPA-enhanced MRI and serum AFP. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4688. doi:10.1158/1538-7445.AM2014-4688
Liposomal Doxorubicin and the Accelerated Approval Process
Authors: George Tidmarsh
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: I would like to comment on Drs Joseph DiMasi and Henry Grabowski’s review, published in the January 10, 2007, issue of the Journal of Clinical Oncology. The authors failed to list Doxil (generically known as doxorubicin; Ortho Biotech Products, Bridgewater, NJ) in Table 1, which presented the new oncology drugs approved in the United States from 1990 to 2005. While this omission may seem trivial, it is not if one considers that Doxil was the first accelerated oncology drug approval and helped usher in an era of rapid drug approvals based on the surrogate marker, tumor response. Having defended Doxil before the Oncology Drug Advisory Committee leading to its approval, I have become keenly aware of the advantages and disadvantages of the accelerated approval process. As we now know, tumor shrinkage is not always a surrogate for improved survival or quality of life. Another major point overlooked in this review was that many industry sponsors of oncology drugs approved by this process have failed to submit confirmatory, postapproval trials as required under the accelerated approval process. Coupled with the high cost these drugs put on the health care system, many are left to think that commercial companies have abused the opportunity provided by the accelerated approval process. However, as oncologists, we all want promising therapies available for our patients as early as possible. Perhaps we should consider keeping the accelerated approval process available while restricting the reimbursement to the company until randomized, controlled trials showing an effect of survival or quality of life have been conducted. Alternatively, US oncologists must fully support phase III, randomized clinical trials comparing experimental therapies to best supportive care when there are no approved therapies for the indicated patient population.
Effect of Ethinyl Estradiol on Chronic Active Hepatitis
Authors: Joseph M. Guattery
Journal: Annals of Internal Medicine (1997)

Letters1 January 1997Effect of Ethinyl Estradiol on Chronic Active HepatitisJoseph M. Guattery, MD, William W. Faloon, MD, and Daniel L. Biery, DOJoseph M. Guattery, MDUniversity of Rochester School of Medicine and Dentistry; Rochester, NY 14642Search for more papers by this author, William W. Faloon, MDUniversity of Rochester School of Medicine and Dentistry; Rochester, NY 14642Search for more papers by this author, and Daniel L. Biery, DOUniversity of Rochester School of Medicine and Dentistry; Rochester, NY 14642Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-1-199701010-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail [This letter was originally published in the 15 October 1996 issue of Annals. The accompanying figure (Figure 1) was inadvertently omitted from that issue.]TO THE EDITOR:A decrease in serum liver enzyme levels in patients with primary biliary cirrhosis during treatment with ethinyl estradiol [1] led to a study of this drug in six women with chronic inflammatory liver disease. Patient ages ranged from 28 to 72 years (mean, 60 years). All aspartate aminotransferase and other serum enzyme levels were greater than twice the normal level for more than 6 months. Examination of liver biopsy specimens showed inflammation, piecemeal ...References1. Guattery JM, Faloon WW. Effect of estradiol upon serum enzymes in primary biliary cirrhosis. Hepatology. 1987; 7:737-42. Google Scholar2. McFarlane IG. Autoimmunity and hepatotrophic viruses. Semin Liv Dis. 1991; II:223-33. Google Scholar3. Lumel F. Hepatitis C virus and autoimmunity: fortuitous association or reality? [Editorial] Gastroenterology. 1994; 107:1552-5. Google Scholar4. Terrault N, Wright T. Interferon and hepatitis C [Editorial]. N Engl J Med. 1995; 332:1519-21. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Rochester School of Medicine and Dentistry; Rochester, NY 14642 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByReview article: the management of cirrhosis in womenThe effects of hormonal contraceptive use among women with viral hepatitis or cirrhosis of the liver: a systematic reviewThe associated markers and their limitations for the primary screening of HCV carriers in public health examinationClinical course of pregnant women with chronic hepatitis C virus infection and risk of mother-to-child hepatitis C virus transmissionDecrease in serum ALT and increase in serum HCV RNA during pregnancy in women with chronic hepatitis C 1 January 1997Volume 126, Issue 1Page: 88KeywordsAutoimmune hepatitisDrugsEnzymesEstradiolHepatitis C virusHepatitis E virusInflammationLiverLiver fibrosisSerum glutamic oxaloacetic transaminase Issue Published: 1 January 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Clonal Origin of Epithelial Ovarian Carcinoma: Analysis by Loss of Heterozygosity, p53 Mutation, and X-Chromosome Inactivation
Authors: I. J. Jacobs, M. F. Kohler, R. W. Wiseman, J. R. Marks, R. Whitaker, B. A. J. Kerns, P. Humphrey, A. Berchuck, B. A. J. Ponder, R. C. Bast
Journal: JNCI Journal of the National Cancer Institute (1992)

It has been suggested that multiple sites of epithelial ovarian carcinoma on the peritoneal surface reflect polyclonal disease arising from multiple primary tumors in the peritoneal mesothelium, rather than monoclonal disease spread by metastases from one primary ovarian cancer.The purpose of this study was to investigate whether ovarian cancer has a monoclonal or polyclonal origin.DNA specimens were obtained from peripheral blood lymphocytes (normal DNA) and from multiple tumor deposits of 17 women with epithelial ovarian carcinoma: primary tumors, metastatic deposits, and ascites. The clonal origin of each tumor was determined by performing (a) analysis to detect loss of heterozygosity at five loci on chromosomes 5, 11, 13, and 17; (b) sequencing of exons 5-8 of the p53 gene; and (c) X-chromosome inactivation analysis of the phosphoglycerate kinase (PGK) gene.In 15 of the 17 cases analyzed, there was clear evidence of monoclonal origin. The probability that the genetic events documented in these 15 cases occurred as independent events in each tumor deposit ranged from 2.5 x 10(-1) to 3.7 x 10(-16). In two cases, the pattern of allelic deletion and p53 gene mutation was compatible with either a monoclonal origin or origin from two primary ovarian tumors.The results did not support the hypothesis that ovarian cancer is a multifocal, polyclonal disease. Instead, the data suggest that sporadic epithelial ovarian carcinoma has either a monoclonal or a dual primary origin.These findings have important implications for understanding of the natural history of ovarian cancer and for clinical strategies aimed at prevention and early detection. Further studies will be required to determine the clonal origin of familial hereditary ovarian cancer.
Differential effects of procainamide, lidocaine and acetylstrophanthidin on body surface potentials and epicardial conduction in dogs with chronic myocardial infarction
Authors: Cees D.J. de Langen, Robert F. Hanich, Eric L. Michelson, Alan H. Kadish, Joseph H. Levine, C.William Balke, Joseph F. Spear, E.Neil Moore
Journal: Journal of the American College of Cardiology (1988)
Women who accused GP of sexual molestation may have colluded against him
Authors: C. Dyer
Journal: BMJ (2012)

A family doctor accused of sexually molesting three women patients has had the General Medical Council case against him thrown out at half time because of inconsistencies in the women’s accounts and the possibility of collusion.

Retired GP Kenneth Thompson, 68, from Belfast, was accused of having sexual intercourse with “EC,” who claimed to have been abused by various relatives as a child. He was also accused of persuading her to masturbate him and perform oral sex, saying it was “therapy” and would save her marriage, and performing an …
Ultrasonographic Detection of Lymph-Node Metastases in Superficial Carcinoma of the Esophagus
Authors: S. Natsugoe, H. Yoshinaka, T. Morinaga, M. Shimada, M. Baba, T. Fukumoto, H. J. Stein, T. Aikou
Journal: Endoscopy (1996)

The presence or absence of lymph-node metastasis is the single most important factor in determining the strategy for treating superficial carcinoma of the esophagus. In this study, ultrasound (US) and endoscopic ultrasonography (EUS) were used in the diagnosis of lymph-node metastases, and the accuracy and limitations of these methods were assessed.Prospectively, 37 patients with superficial esophageal cancer were studied by US and EUS before surgery, and the results were compared with the histological findings. Twelve of the patients had histologically confirmed lymph-node metastases. Ultrasonographic images of the lymph nodes were classified into three types, based on their boundaries and internal echoes.The sensitivity, specificity, and accuracy of predicting mediastinal lymph-node metastasis by EUS diagnosis were 80.0%, 87.5%, and 86.5%, respectively. The sensitivity, specificity, and accuracy of US in the assessment of cervical and abdominal lymph-node metastasis were 71.4%, 86.7%, and 83.3%, respectively. In cases in which there was a solitary metastatic lymph node, the detection rate was higher than in cases with two or more positive nodes. Most metastatic lymph nodes correctly diagnosed by US and EUS were larger than 6 mm and had tumor involving more than one-third of their cross-sectional area.In patients with superficial esophageal carcinomas, US is accurate in staging cervical and abdominal lymph nodes. EUS is accurate in staging mediastinal lymph nodes.
Systemic to Pulmonary Venous Shunting in Superior Vena Cava Obstruction
Authors: BRIAN GALE, CLARA CHEN, K JENNIE CHUN, JANET LAN, JACOB CYNAMON, LEONARD M. FREEMAN
Journal: Clinical Nuclear Medicine (1990)

Obstruction of the superior vena cava is commonly associated with the development of several collateral venous pathways. Right-to-left systemic to pulmonary venous shunting, however, rarely has been reported. This paper describes a case in which a previously unsuspected shunt, manifested by the striking visualization of myocardial and thyroid tissue in addition to other findings, was discovered on a routine lung perfusion scan. Imaging, as well as radiologic studies are presented in the investigation of this phenomenon.
Segmentally arranged seborrhoeic keratoses with impending atypia and squamous cell carcinoma in an elderly woman
Authors: E. Livingstone, U. Hillen, C. Hafner, S. Piel, L. Groesser, D. Schadendorf, R. Happle
Journal: British Journal of Dermatology (2014)

Epidermal naevi (EN) are considered mosaic disorders. Postzygotic mutations are thought to occur during early embryogenesis. They are usually arranged along Blaschko's lines and tend to be noted either at birth or shortly thereafter. Skin tumours arising on EN are occasionally reported, with ongoing discussion as to whether these are collision tumours or a malignant transformation of the EN. We describe a 76‐year‐old woman with segmentally arranged seborrhoeic keratoses that showed impending atypia and, in one lesion, even overt malignant transformation. In biopsies from various lesions we found FGFR3 and PIK3CA hotspot mutations but there was no consistent pattern of mutations explaining the premalignant or malignant growth. So far it is unclear whether the precancerous changes as noted in this elderly patient can be taken as an unusual manifestation of one of the established types of EN, or whether this may represent a separate disorder that could be called 'SASKIA naevus'. The acronym would stand for segmentally arranged seborrhoeic keratoses with impending atypia.
Impact of thoracic aortic spontaneous echocardiographic contrast on long-term cardiovascular prognosis: relation to cardiac rhythm
Authors: Constadina Aggeli, Alexadra Frogoudaki, Spyros Lambrou, Stela Brill, John Barbetseas, John Skoumas, Christos Pitsavos, Christodoulos Stefanadis, Pavlos Toutouzas
Journal: Journal of the American College of Cardiology (2002)
BENEFIT OF MANUAL THROMBECTOMY IN LIMITING INFARCT EXPANSION DURING PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Doo Sun Sim, Youngkeun Ahn, Yun Hyeon Kim, Song Choi, Hyun Ju Seon, Jum Suk Ko, Min Goo Lee, Keun Ho Park, Hyun Ju Yoon, Nam Sik Yoon, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang
Journal: Journal of the American College of Cardiology (2011)