tbuckley/cabot-search huggingface dataset:
Voltage-Gated Sodium Channel Expression and Potentiation of Human Breast Cancer Metastasis
Authors: Scott P. Fraser, James K.J. Diss, Athina-Myrto Chioni, Maria E. Mycielska, Huiyan Pan, Rezan F. Yamaci, Filippo Pani, Zuzanna Siwy, Monika Krasowska, Zbigniew Grzywna, William J. Brackenbury, Dimis Theodorou, Meral Koyutürk, Handan Kaya, Esra Battaloglu, Manuela Tamburo De Bella, Martin J. Slade, Robert Tolhurst, Carlo Palmieri, Jie Jiang, David S. Latchman, R. Charles Coombes, Mustafa B.A. Djamgoz
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Ion channel activity is involved in several basic cellular behaviors that are integral to metastasis (e.g., proliferation, motility, secretion, and invasion), although their contribution to cancer progression has largely been ignored. The purpose of this study was to investigate voltage-gated Na+ channel (VGSC) expression and its possible role in human breast cancer. Experimental Design: Functional VGSC expression was investigated in human breast cancer cell lines by patch clamp recording. The contribution of VGSC activity to directional motility, endocytosis, and invasion was evaluated by in vitro assays. Subsequent identification of the VGSC α-subunit(s) expressed in vitro was achieved using reverse transcription-PCR, immunocytochemistry, and Western blot techniques and used to investigate VGSCα expression and its association with metastasis in vivo. Results: VGSC expression was significantly up-regulated in metastatic human breast cancer cells and tissues, and VGSC activity potentiated cellular directional motility, endocytosis, and invasion. Reverse transcription-PCR revealed that Nav1.5, in its newly identified “neonatal” splice form, was specifically associated with strong metastatic potential in vitro and breast cancer progression in vivo. An antibody specific for this form confirmed up-regulation of neonatal Nav1.5 protein in breast cancer cells and tissues. Furthermore, a strong correlation was found between neonatal Nav1.5 expression and clinically assessed lymph node metastasis. Conclusions: Up-regulation of neonatal Nav1.5 occurs as an integral part of the metastatic process in human breast cancer and could serve both as a novel marker of the metastatic phenotype and a therapeutic target.
Synergism of tapasin and human leukocyte antigens in resolving hepatitis C virus infection
Authors: Shirin Ashraf, Katja Nitschke, Usama M. Warshow, Collin R. Brooks, Arthur Y. Kim, Georg M. Lauer, Theresa J. Hydes, Matthew E. Cramp, Graeme Alexander, Ann-Margaret Little, Robert Thimme, Christoph Neumann-Haefelin, Salim I. Khakoo
Journal: Hepatology (2013)

CD8+ T-cell responses to hepatitis C virus (HCV) are important in generating a successful immune response and spontaneously clearing infection. Human leukocyte antigen (HLA) class I presents viral peptides to CD8+ T cells to permit detection of infected cells, and tapasin is an important component of the peptide loading complex for HLA class I. We sought to determine if tapasin polymorphisms affected the outcome of HCV infection. Patients with resolved or chronic HCV infection were genotyped for the known G/C coding polymorphism in exon 4 of the tapasin gene. In a European, but not a US, Caucasian population, the tapasin G allele was significantly associated with the outcome of HCV infection, being found in 82.5% of resolvers versus 71.3% of persistently infected individuals ( P = 0.02, odds ratio [OR] = 1.90 95% confidence interval [CI] = 1.11-3.23). This was more marked at the HLA-B locus at which heterozygosity of both tapasin and HLA-B was protective ( P &lt; 0.03). Individuals with an HLA-B allele with an aspartate at residue 114 and the tapasin G allele were more likely to spontaneously resolve HCV infection ( P &lt; 0.00003, OR = 3.2 95% CI = 1.6-6.6). Additionally, individuals with chronic HCV and the combination of an HLA-B allele with an aspartate at residue 114 and the tapasin G allele also had stronger CD8+ T-cell responses ( P = 0.02, OR = 2.58, 95% CI-1.05-6.5). Conclusion : Tapasin alleles contribute to the outcome of HCV infection by synergizing with polymorphisms at HLA-B in a population-specific manner. This polymorphism may be relevant for peptide vaccination strategies against HCV infection. (Hepatology 2013;53:881–889)
Gene Expression Profiling Identifies<i>BAX-δ</i>as a Novel Tumor Antigen in Acute Lymphoblastic Leukemia
Authors: Sara Maia, W. Nicholas Haining, Sascha Ansén, Zhinan Xia, Scott A. Armstrong, Nilufer P. Seth, Paolo Ghia, Monique L. den Boer, Rob Pieters, Stephen E. Sallan, Lee M. Nadler, Angelo A. Cardoso
Journal: Cancer Research (2005)

Abstract The identification of new tumor-associated antigens (TAA) is critical for the development of effective immunotherapeutic strategies, particularly in diseases like B-cell acute lymphoblastic leukemia (B-ALL), where few target epitopes are known. To accelerate the identification of novel TAA in B-ALL, we used a combination of expression profiling and reverse immunology. We compared gene expression profiles of primary B-ALL cells with their normal counterparts, B-cell precursors. Genes differentially expressed by B-ALL cells included many previously identified as TAA in other malignancies. Within this set of overexpressed genes, we focused on those that may be functionally important to the cancer cell. The apoptosis-related molecule, BAX, was highly correlated with the ALL class distinction. Therefore, we evaluated BAX and its isoforms as potential TAA. Peptides from the isoform BAX-δ bound with high affinity to HLA-A*0201 and HLA-DR1. CD8+ CTLs specific for BAX-δ epitopes or their heteroclitic peptides could be expanded from normal donors. BAX-δ–specific T cells lysed peptide-pulsed targets and BAX-δ–expressing leukemia cells in a MHC-restricted fashion. Moreover, primary B-ALL cells were recognized by BAX-δ–specific CTL, indicating that this antigen is naturally processed and presented by tumor cells. This study suggests that (a) BAX-δ may serve as a widely expressed TAA in B-ALL and (b) gene expression profiling can be a generalizable tool to identify immunologic targets for cancer immunotherapy.
Recognition of Adult T-Cell Leukemia/Lymphoma Cells by CD4+ Helper T Lymphocytes Specific for Human T-Cell Leukemia Virus Type I Envelope Protein
Authors: Hiroya Kobayashi, Toshihiro Nagato, Mitsuru Yanai, Kensuke Oikawa, Keisuke Sato, Shoji Kimura, Masatoshi Tateno, Ryusuke Omiya, Esteban Celis
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Human T-cell leukemia virus type I (HTLV-I) can cause an adult T-cell leukemia/lymphoma (ATLL). Because ATLL is a life-threatening lymphoproliferative disorder and is resistant to chemotherapy, the establishment and enhancement of T-cell immunity to HTLV-I through the development of therapeutic vaccines could be of value. Thus, the identification of HTLV-I epitopes for both CD8+ and CD4+ T cells should facilitate the development of effective vaccines. Although numerous HTLV-I epitopes for CTLs have been identified, few epitopes recognized by CD4+ helper T cells against this virus have been described. Experimental Design: Synthetic peptides prepared from several regions of the HTLV-I envelope (Env) sequence that were predicted to serve as helper T-cell epitopes were prepared with use of computer-based algorithms and tested for their capacity to trigger in vitro helper T-cell responses using lymphocytes from normal volunteers. Results: The results show that the HTLV-I–Env317–331, and HTLV-I–Env384–398-reactive helper T lymphocytes restricted by HLA-DQw6 and HLA-DR15, respectively, could recognize intact HTLV-I+ T-cell lymphoma cells and, as a consequence, secrete lymphokines. In addition, HTLV-I Env196–210-reactive helper T lymphocytes restricted by HLA-DR9 were able to directly kill HTLV-I+ lymphoma cells and recognize naturally processed antigen derived from killed HTLV-I+ lymphoma cells, which was presented to the helper T cells by autologous antigen-presenting cells. Conclusions: The present findings hold relevance for the design and optimization of T-cell epitope-based immunotherapy against HTLV-I–induced diseases such as ATLL.
Transfemoral endoluminal repair of abdominal aortic aneurysm with bifurcated graft
Authors: S.W. Yusuf, D.M. Baker, S.C. Whitaker, P.W. Wenham, B.R. Hopkinson, T.A.M. Chuter
Journal: The Lancet (1994)

Traditional open repair of abdominal aortic aneurysm has disadvantages. We present our experience of transfemoral endoluminal repair with a bifurcated graft system. 29 patients with aortic aneurysm over 5.5 cm in diameter and 1 with a 3.2 cm aneurysm and bilateral iliac stenosis were assessed; 5 were suitable for the procedure. The operation was successful in all the patients, without haemodynamic compromise or major complications. This technique has the potential to reduce morbidity and mortality from abdominal aortic aneurysm. Further modifications are required to make it applicable to most aneurysms.
EU drive to free movement of doctors across Europe could damage patient safety, warns GMC
Authors: A. O'Dowd
Journal: BMJ (2011)

Plans by the European Commission to simplify legislation that allows doctors and nurses to work anywhere in the European Union could have a detrimental effect on the safety of patients, claims the United Kingdom’s medical regulator.

The General Medical Council gave a stark warning about the commission’s plans when giving evidence on 30 June to the House of Lords EU social policies and consumer protection subcommittee, as part of its inquiry into the mobility of healthcare professionals.

Peers on the committee are holding the inquiry in response to the ongoing European Commission review of its directive on the mutual recognition of professional qualifications—which aims to have all member states recognise each other’s healthcare qualifications and simplify the movement of …
Primary aldosteronism and its variants
Authors: C Gomez-Sanchez
Journal: Cardiovascular Research (1998)

Time for primary reviews 33 days.

Primary aldosteronism is an adrenal abnormality in which there is an excessive production of aldosterone above that required for electrolyte homeostasis which is not driven by known stimulators of aldosterone secretion, although these may retain some degree of modulatory activity on aldosterone secretion. In the early years following the description of primary aldosteronism, the etiology was ascribed to the autonomous production of aldosterone by an adrenal adenoma for which surgical treatment resulted in the resolution of the hypokalemia and cure or improvement of the hypertension in many cases [1]. At this time the possibility of aldosteronism due to adrenal hyperplasia was not recognized. The traditional clinical picture was characterized by salt-sensitive hypertension associated with hypokalemia and suppression of renin secretion [1]. A major emphasis in the selection of patients for consideration for diagnostic procedures for primary aldosteronism was the presence of spontaneous or easily-induced hypokalemia, resulting in an underestimation of the incidence of primary aldosteronism [2, 3]. Once identified, normokalemic primary aldosteronism was found to be common; many patients with primary aldosteronism are normokalemic most of the time [2, 4, 5]. The widespread commercial availability of methods to easily measure aldosterone and plasma renin activity (PRA) allowed the screening of patients with essential hypertension, irrespective of the serum potassium, and has led to the recognition that primary aldosteronism has higher prevalence than previously recognized [2, 6, 7]. Various stimulatory and localization maneuvers have led to the recognition that there are several types of primary aldosteronism with variable response to surgery [8–10]. The purpose of this mini review is to succinctly address the issues of prevalence, sub types and pathogenesis of primary aldosteronism so that appropriate therapy may be chosen.

Curable forms of hypertension have a special appeal for …
Evaluation of the Modification of Diet in Renal Disease Study Equation in a Large Diverse Population
Authors: Lesley A. Stevens, Josef Coresh, Harold I. Feldman, Tom Greene, James P. Lash, Robert G. Nelson, Mahboob Rahman, Amy E. Deysher, Yaping (Lucy) Zhang, Christopher H. Schmid, Andrew S. Levey
Journal: Journal of the American Society of Nephrology (2007)

Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease. Performance of the Modification of Diet in Renal Disease (MDRD) Study equation varies substantially among populations. To describe the performance of the equation in a large, diverse population, estimated GFR (eGFR) was compared to measured GFR (mGFR) in a cross-sectional analysis of 5504 participants in 10 studies that included measurements of standardized serum creatinine and urinary clearance of iothalamate. At eGFR &lt;60 ml/min per 1.73 m<sup>2</sup>, the MDRD Study equation had lower bias and higher precision than at eGFR ≥60 ml/min per 1.73 m<sup>2</sup>. The accuracy of the equation, measured by the percent of estimates that fell within 30% of mGFR, was similar for eGFR values above or below 60 ml/min per 1.73 m<sup>2</sup> (82% and 84%, respectively). Differences in performance among subgroups defined by age, sex, race, diabetes, transplant status, and body mass index were small when eGFR was &lt;60 ml/min per 1.73 m<sup>2</sup>. The MDRD Study equation therefore provides unbiased and reasonably accurate estimates across a wide range of subgroups when eGFR is &lt;60 ml/min per 1.73 m<sup>2</sup>. In individual patients, interpretation of GFR estimates near 60 ml/min per 1.73 m<sup>2</sup> should be interpreted with caution to avoid misclassification of chronic kidney disease in the context of the clinical setting.
CLINICAL OUTCOME OF PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING PERCUTANEOUS CORONARY INTERVENTION WITH BARE-METAL VERSUS DRUG-ELUTING STENTS: INSIGHTS FROM THE AFCAS REGISTRY
Authors: Marja Kaarina Puurunen, Tuomas Kiviniemi, Axel Schlitt, Andrea Rubboli, Pasi Karjalainen, Fausto Biancari, Wail Nammas, Paulus Kirchhof, Gregory Lip, Juhani Airaksinen
Journal: Journal of the American College of Cardiology (2014)
Improving biliary-enteric drainage in primary sclerosing cholangitis: experience with endoscopic methods.
Authors: M Lombard, M Farrant, J Karani, D Westaby, R Williams
Journal: Gut (1991)

Six jaundiced patients with primary sclerosing cholangitis and a dominant biliary stricture were managed by endoscopic placement of endoprostheses. Five showed considerable improvement within weeks of stenting: their serum bilirubin concentration fell from mean (range) 266 mumol/l (63-681) to 65 mumol/l (10-280) after one month. One patient required a liver transplant at five months because of continued deterioration in hepatic function. Follow up of 12-49 months in the remaining five patients shows sustained biochemical improvement, with repeat cholangiograms indicating doubling of the minimum calibre of the extrahepatic bile duct in four patients and considerable shortening of stricture length in three. Three patients developed sepsis at the time of the initial endoprosthesis insertion: surgical drainage was necessary in one. Endoscopic methods of improving biliary-enteric drainage in jaundiced patients with primary sclerosing cholangitis may be preferable to surgical and percutaneous methods, which may complicate subsequent liver transplantation.
Intraoperative Evaluation of Breast Tumor Margins with Optical Coherence Tomography
Authors: Freddy T. Nguyen, Adam M. Zysk, Eric J. Chaney, Jan G. Kotynek, Uretz J. Oliphant, Frank J. Bellafiore, Kendrith M. Rowland, Patricia A. Johnson, Stephen A. Boppart
Journal: Cancer Research (2009)

Abstract As breast cancer screening rates increase, smaller and more numerous lesions are being identified earlier, leading to more breast-conserving surgical procedures. Achieving a clean surgical margin represents a technical challenge with important clinical implications. Optical coherence tomography (OCT) is introduced as an intraoperative high-resolution imaging technique that assesses surgical breast tumor margins by providing real-time microscopic images up to 2 mm beneath the tissue surface. In a study of 37 patients split between training and study groups, OCT images covering 1 cm2 regions were acquired from surgical margins of lumpectomy specimens, registered with ink, and correlated with corresponding histologic sections. A 17-patient training set used to establish standard imaging protocols and OCT evaluation criteria showed that areas of higher scattering tissue with a heterogeneous pattern were indicative of tumor cells and tumor tissue in contrast to lower scattering adipocytes found in normal breast tissue. The remaining 20 patients were enrolled into the feasibility study. Of these lumpectomy specimens, 11 were identified with a positive or close surgical margin and 9 were identified with a negative margin under OCT. Based on histologic findings, 9 true positives, 9 true negatives, 2 false positives, and 0 false negatives were found, yielding a sensitivity of 100% and specificity of 82%. These results show the potential of OCT as a real-time method for intraoperative margin assessment in breast-conserving surgeries. [Cancer Res 2009;69(22):8790–6]
The balance between adipogenesis and osteogenesis in bone regeneration by platelet-rich plasma for age-related osteoporosis
Authors: Hen-Yu Liu, Alexander T.H. Wu, Ching-Yu Tsai, Kuei-Ru Chou, Rong Zeng, Ming-Fu Wang, Wen-Chang Chang, Shiaw-Min Hwang, Ching-Hua Su, Win-Ping Deng
Journal: Biomaterials (2011)
'Back to Moon, on to Mars' Becomes Space Medicine's 1990s Rallying Cry
Authors: Jeanette Smith
Journal: JAMA (1990)

THE FINAL DECADE of the 20th century and the first quarter of the 21st century are likely to be critical for the United States' space program and its medical aspects. To maintain US preeminence in space research, the 1988 national space policy of (then) President Reagan reaffirmed the need for initiatives such as a permanently staffed space station. Now, at the request of President Bush, the National Space Council (which is headed by Vice President Quayle) is pondering a National Aeronautics and Space Administration (NASA) study that calls for such a space station in the 1990s as the first step in a multiphase effort that has important implications for space medicine. This late 20th century space station would be followed by a return—this time for much longer stays—to the moon by humans early in the 21st century. After that would come the long-discussed manned mission to Mars. In accordance with
Sequential appearance of intestinal mucosal cell types in the right and caudate liver lobes of furan-treated rats
Authors: Lynne W. Elmore, Alphonse E. Sirica
Journal: Hepatology (1992)

Furan rapidly induces in rat liver a unique, lobe-specific pattern of development of intestinal metaplasia and associated cholangiofibrosis. To establish early cell-precursor relationships in the genesis of this cholangiofibrosis, a time-course study was conducted in which young adult male Fisher 344 rats received furan by gavage at a daily dose of 45 mg/kg body wt over a 32-day treatment period. An analysis of individual liver lobes obtained at different time points from these animals during furan treatment revealed the following sequence of histopathological changes, which were located mainly in the right and, to a lesser extent, the caudate liver lobes: day 1, severe hepatonecrosis in zone 3 extending into zone 2 of the liver acini; days 3 to 5, presence of a diffuse inflammatory cell infiltrate in hepatonecrotic areas, which gradually resolved; day 7, prominent bile ductule hyperplasia in tissue sections exhibiting marked loss of normal liver parenchyma; day 9, continued replacement of injured liver by hyperplastic bile ductule tissue, which now contained occasional metaplastic glandular structures composed of columnar basophilic epithelial cells; days 12 to 16, increasing cell diversity in the developing metaplastic glands, with the sequential appearance of goblet cells, Paneth cells and serotonin-positive neuroendocrine cells; and day 32, typical cholangiofibrosis defined by hyperplastic bile ductule-type structures in association with an increased number of metaplastic intestinal glands and progressively more dense fibrotic stroma. Interestingly, at 16 and 32 days the cellular composition of the newly formed metaplastic intestinal glands in liver closely resembled that of the crypts of Lieberkühn in the normal adult rat small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)
Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity
Authors: Austin M Dulak, Petar Stojanov, Shouyong Peng, Michael S Lawrence, Cameron Fox, Chip Stewart, Santhoshi Bandla, Yu Imamura, Steven E Schumacher, Erica Shefler, Aaron McKenna, Scott L Carter, Kristian Cibulskis, Andrey Sivachenko, Gordon Saksena, Douglas Voet, Alex H Ramos, Daniel Auclair, Kristin Thompson, Carrie Sougnez, Robert C Onofrio, Candace Guiducci, Rameen Beroukhim, Zhongren Zhou, Lin Lin, Jules Lin, Rishindra Reddy, Andrew Chang, Rodney Landrenau, Arjun Pennathur, Shuji Ogino, James D Luketich, Todd R Golub, Stacey B Gabriel, Eric S Lander, David G Beer, Tony E Godfrey, Gad Getz, Adam J Bass
Journal: Nature Genetics (2013)
Safety profile of adenosine stress perfusion imaging: Results from the adenoscan multicenter trial registry
Authors: Manuel D. Cerqueira, Mario S. Verani, Markus Schwaiger, Jaekyeong Heo, Abdulmassih S. Iskandrian
Journal: Journal of the American College of Cardiology (1994)

Objectives. The purpose of this study was to determine the safety of adenosine infusion at 140 μg/kg per min in conjunction with radionuclide imaging in 9,256 consecutive patients. Background. Adenosine produces maximal myocardial hyperemia directly with a rapid onset of action. In addition, when used in conjunction with radtonuclide perfusion imaging, it has proven efficacy for the diagnosis of coronary artery disease in patients unable to exercise. Because the ultrashort half-life (<10 s) allows dose titration and rapid reversal of side effects, it may be safer than other available pharmacologic agents. Methods. Patients were prospectively entered at 21 clinical sites. Information on safety and adverse events during and immediately after adenosine infusion was maintained in the Adenoscan Multicenter Trial Registry. Results. The infusion protocol was completed in 80% of patients, required dose reduction in 13% and was terminated early in 7%. Interpretable imaging studies were obtained in 98.7% of patients, and 0.8% of patients received aminophylline. Minor and well tolerated side effects were reported in 81.1% of patients. There were no deaths, one myocardial infarction, seven episodes of severe bronchospasm and one episode of pulmonary edema. Transient atrioventricular (AV) node block occurred in 706 patients (first-degree in 256, second-degree in 378 and third-degree in 72) and resolved spontaneously in most patients (n = 508) without alteration in the adenosine infusion. There were no sustained episodes of AV block. Patients >70 years of age had an increased risk of developing AV block (age <70,7.05% vs. ≥ 70, 9.44%, p = 0.001, relative risk 1.37). Conclusions. Adenosine infusion is safe. Vasodilator and negative dromotropic side effects are generally well tolerated. Serious side effects are relatively rare, and they reverse with termination of adenosine infusion. Interpretable radionuclide studies were obtained in 98.7% of patients and aminophylline reversal was seldom required.