tbuckley/cabot-search huggingface dataset:
Abstract 1354: New chemical tools for disrupting the Mcl-1/BH3 protein-protein interaction
Authors: Daniele Pernazza, Kenichiro Doi, Harshani Lawrence, Saïd Sebti, Hong-Gang Wang, Nicholas Lawrence
Journal: Cancer Research (2011)

Abstract Anti-apoptotic members of the Bcl-2 protein family, such as Bcl-2, Bcl-xL and Mcl-1, are among the most effective inhibitors of apoptosis and are frequently upregulated in various types of human cancer. A number of pro-apoptotic proteins share only the BH3 domain with other members of the Bcl-2 family, so called BH3-only proteins, and appear to function essentially as transdominant inhibitors by binding to anti-apoptotic Bcl-2 family proteins and neutralizing their cell-survival activity. The development of small molecules to mimic the BH3 proteins has been an intense area of research. However, to date available Bcl-2 family proteins inhibitors are either pan-inhibitors such as (−)-gossypol (which simultaneously inhibits Bcl-xl/BH3, Bcl-2/BH3 and Mcl-1/BH3 interactions) or are selective for the Bcl-xl/BH3 and Bcl-2/BH3 interactions. Hence a selective Mcl-1/BH3 inhibitor would greatly aid investigating the role of Mcl-1 in cancer and in drug resistance. Our current study is centered on the identification and the synthesis of small molecule selective inhibitors of the Mcl-1/BH3 interaction. To this aim we interrogated the hit-list from inhibitors of the MLSCN screen of the Mcl-1-NOXA interaction [(Emory, AID 1417) TR-FRET screen for Mcl-1-NOXA inhibitors]. Selected compounds were purchased and assessed for activity in a fluorescence polarization and ELISA assay, to reveal the hit HLM050001 (FP IC50 0.8 ± 0.1 µM; ELISA IC50 19.3 ± 2.5 µM). HLM050001binding to Mcl-1 is currently being assessed via co-crystallization and other biophysical techniques. We will report the synthesis and biological evaluation of focused libraries based on the initial hit and designed by modeling and docking to Mcl-1. Structure activity relationship studies around the hit will be disclosed as well as the outcomes of further rounds of chemical design and biological assessment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1354. doi:10.1158/1538-7445.AM2011-1354
Tissue organ distribution and behavioral effects of platinum following acute and repeated exposure of the mouse to platinum sulfate.
Authors: B A Lown, J B Morganti, C H Stineman, R B D'Agostino, E J Massaro
Journal: Environmental Health Perspectives (1980)

Platinum sulfate was administered intragastrically (IG) to adult male Swiss mice in a single dose at the 7 day LD5 or LD25 level. Control groups received 0.25M H2SO4 (pH 0.85) or 0.14M NaCl. Open field behavior (ambulations, rearings) was measured, and tissue/organ Pt levels determined at 4 hr, or 1, 3, or 7 days post administration. At all times, the LD25 depressed ambulations significantly and rearings marginally. It did not effect exploratory ("hole-in-board") behavior. The LD25 resulted in disproportionately high tissue Pt levels relateive to the LD5. There were significant inverse correlations between behavior and tissue Pt levels for most tissues, but not for brain. In related experiments, adult male mice were subjected to repeated IG administration of Pt(SO4)2 at the LD1 level (one dose every 72 hr for up to 10 doses). Three days after administration of the final dose of each series, open-field and exploratory performance were measured and tissue/organ Pt levels determined. Tissue/organ Pt levels were variable but generally increased with dose number. No Pt was detected in the brain. Activity and explorations were marginally depressed. Only rearings correlated significantly with tissue Pt levels.
When Religious Freedom Clashes with Access to Care
Authors: I. Glenn Cohen, Holly Fernandez Lynch, Gregory D. Curfman
Journal: New England Journal of Medicine (2014)

Interview with Prof. George Annas on the Supreme Court’s Hobby Lobby decision and its context and implications. (11:10)Download At the tail end of this year's Supreme Court term, religious freedom came into sharp conflict with the government's interest in providing affordable access to health care. In a consolidated opinion in Burwell v. Hobby Lobby Stores and Conestoga Wood Specialties Corp. v. Burwell (collectively known as Hobby Lobby) delivered on June 30, the Court sided with religious freedom, highlighting the limitations of our employment-based health insurance system.Hobby Lobby centered on the contraceptives-coverage mandate, which derived from the Affordable Care Act (ACA) mandate that many employers offer insurance coverage of certain “essential” health benefits, including coverage of “preventive” . . .
Abstract 2293: ZEB1 and ZEB2 promote EMT and invasion in esophageal squamous cell carcinoma
Authors: Seiji Naganuma, Shinya Ohashi, Sotai Kimura, Mitsuteru Natsuizaka, Phyllis Gimotty, Andres J. Klein-Szanto, Hiroshi Itoh, Hiroshi Nakagawa
Journal: Cancer Research (2010)

Abstract Introduction: Epithelial-mesenchymal transition (EMT) promotes tumor invasion and metastasis. Amongst transcription factors essential in EMT, zinc finger E-box binding proteins ZEB1 and ZEB2 (ZEB) are upregulated in several tumor types due to loss of the miR-200 family. However, the role of ZEB in esophageal squamous cell carcinoma (ESCC) remains to be elucidated. Methods: ESCC cell lines were grown. Immortalized human esophageal cells EPC2-hTERT were retrovirally co-transduced with EGFR and mutant p53 (p53R175H), early genetic lesions common in ESCC, leading to transformation as described previously (Genes Dev. 2007; 21:2788). Short hairpin RNA was expressed by lentivirus to knockdown ZEB1 and ZEB2. Epithelial cells were grown in organotypic 3-D culture, a form of tissue engineering. Laser capture microdissection (LCM) was performed to isolate RNA for gene expression profiling in the invasive cells in 3-D culture as well as microRNA determination in archived paraffin embedded primary ESCC tissue samples. Real-time RT-PCR, Western blotting and immunohistochemistry were done to determine gene expression. Senescence-associated β-galactosidase activity was determined. Results: In primary ESCC, ZEB expression was found upregulated in tumor cells at the invasive front with increased Vimentin and decreased E-cadherin expressions. Moreover, LCM documented a significant downregulation of the miR-200 family in the invasive tumor cells consistent with EMT. ZEB upregulation and concomitant loss of the miR-200 family were also found in two out of 11 ESCC cell lines, exhibiting EMT corroborated by spindle-shaped cell morphology as well as an E-cadherin to N-cadherin class switch. EGFR overexpression and p53 mutation in EPC2-hTERT cells resulted in ZEB upregulation and a significantly augmented susceptibility to EMT, where robust induction of ZEB and suppression of the miR-200 family were observed upon TGF-β treatment. In 3-D culture, the cells co-transduced with EGFR and mutant p53 markedly invaded into the underlying stroma compartment. The invasive cells had a gene signature compatible with EMT along with ZEB upregulation. Finally, knockdown of either ZEB1 or ZEB2 not only prevented TGF-β from inducing EMT, but also TGF-β-mediated massive senescence in EPC2-hTERT cells transformed by EGFR and mutant p53. Conclusions: Our data indicate that ZEB1 and ZEB2 are negatively regulated by the miR-200 family and induced upon invasion in ESCC. ZEB may regulate senescence and EMT in concert with TGF-β signaling, thus contributing to esophageal carcinogenesis and tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2293.
Coffee Consumption and the Incidence of Type 2 Diabetes
Authors: Aramesh Saremi, Marshall Tulloch-Reid, William C. Knowler
Journal: Diabetes Care (2003)

There have been few reports of associations between coffee consumption and diabetes. In healthy subjects given an oral glucose tolerance test (OGTT), the 1-h glucose concentration was lower when the glucose load was given with coffee (1). There were no significant differences in the other time points in the test, nor in serum insulin concentration at any time point. In contrast, others have reported a deterioration of glucose tolerance after coffee ingestion (2,3). In healthy subjects a rise in blood glucose levels after caffeine intake was detected at the 2nd, 3rd, and 4th hours in comparison to …
Allergic Rhinitis and Onset of Bronchial Hyperresponsiveness
Authors: Rafea Shaaban, Mahmoud Zureik, David Soussan, Josep M. Antó, Joachim Heinrich, Christer Janson, Nino Künzli, Jordi Sunyer, Matthias Wjst, Peter G. Burney, Françoise Neukirch, Bénédicte Leynaert
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Patients with allergic rhinitis have more frequent bronchial hyperresponsiveness (BHR) in cross-sectional studies.Objectives: To estimate the changes in BHR in nonasthmatic subjects with and without allergic rhinitis during a 9-year period.Methods: BHR onset was studied in 3,719 subjects without BHR at baseline, who participated in the follow-up of the European Community Respiratory Health Survey.Measurements and Main Results: BHR was defined as a ⩾20% decrease in FEV1 for a maximum dose of 1 mg of methacholine. Allergic rhinitis was defined as having a history of nasal allergy and positive specific IgE (≥0.35 IU/ml) to pollen, cat, mites, or Cladosporium. The cumulative incidence of BHR was 9.7% in subjects with allergic rhinitis and 7.0% in subjects with atopy but no rhinitis, compared with 5.5% in subjects without allergic rhinitis and atopy (respective odds ratios [OR] and their 95% confidence intervals [95% CI] for BHR onset, 2.44 [1.73–3.45]; and 1.35 [0.86–2.11], after adjustment for potential confounders including sex, smoking, body mass index and FEV1). Subjects with rhinitis sensitized exclusively to cat or to mites were particularly at increased risk of developing BHR (ORs [95% CI], 7.90 [3.48–17.93] and 2.84 [1.36–5.93], respectively). Conversely, in subjects with BHR at baseline (n = 372), 35.3% of those with allergic rhinitis, compared with 51.8% of those without rhinitis had no more BHR at follow-up (OR [95% CI], 0.51 [0.33–0.78]). BHR "remission" was more frequent in patients with rhinitis treated by nasal steroids than in those not treated (OR [95% CI], 0.33 [0.14–0.75]).Conclusions: Allergic rhinitis was associated with increased onset of BHR, and less chance for remission except in those treated for rhinitis.
A radical approach to the pathogenesis of diabetic complications
Authors: Ann Marie Schmidt, David Stern
Journal: Trends in Pharmacological Sciences (2000)

Diabetes is by far the most common metabolic disorder that is associated with significant morbidity and mortality, with an estimated worldwide prevalence of between 1% and 5% (Ref. 1). All forms of diabetes, both inherited and acquired, are typified by hyperglycemia, a relative or absolute lack of insulin, and the development of diabetes-specific microvascular pathology in the retina, renal glomerulus and peripheral nerve. As a consequence of microvascular pathology, diabetes is now the leading cause of new blindness in persons aged 20–74 years and end-stage renal failure1. Persons with diabetes are the fastest-growing group of patients undergoing renal dialysis and transplantation. Indeed, by the time diabetic subjects begin dialysis, their life expectancy is dramatically reduced to only three or four years. Long-term, over 60% of persons with diabetes develop neuropathy, which includes distal symmetrical polyneuropathy, mononeuropathies and a variety of autonomic neuropathies causing erectile dysfunction, urinary incontinence, gastroparesis and nocturnal diarrhea1. Overall, life expectancy for patients with diabetes is ∼7–10 years shorter than for people without diabetes1.
Bowel screening has long term benefits, research shows
Authors: J. Wise
Journal: BMJ (2013)

Bowel cancer screening with faecal occult blood testing reduces the risk of dying from bowel cancer, and this effect lasts as long as 30 years, a new long term study has shown. However, bowel cancer screening does not influence all cause mortality, so patients won’t necessarily live longer.

The study, published in the New England Journal of Medicine ,1 is a long term follow-up to the Minnesota Colon Cancer Control Study, which began in 1975 and included 46 551 participants …
Molecular studies of ceruloplasmin deficiency in Wilson's disease.
Authors: M J Czaja, F R Weiner, S J Schwarzenberg, I Sternlieb, I H Scheinberg, D H Van Thiel, N F LaRusso, M A Giambrone, R Kirschner, M L Koschinsky
Journal: Journal of Clinical Investigation (1987)

Deficiency of serum ceruloplasmin is a characteristic biochemical abnormality of Wilson's disease, although the mechanism of this finding is unknown. Ceruloplasmin messenger RNA (mRNA) levels were therefore examined in five patients with Wilson's disease and five controls with other types of hepatic disease. Northern and dot blot hybridizations showed that detectable ceruloplasmin mRNA was present in all of the patients with Wilson's disease, including one patient with no detectable serum ceruloplasmin. However, the ceruloplasmin mRNA levels in the Wilson's disease patients were only 33% that of controls (P less than 0.001). In contrast, albumin mRNA levels in the Wilson's disease patients averaged 161% that of controls. In an attempt to better delineate the level of gene expression responsible for this decrease in ceruloplasmin mRNA, the nuclear run-on assay was used to analyze transcriptional rates. The amount of ceruloplasmin gene transcription in four Wilson's patients was decreased to 44% that of three controls. These results indicate that the diminished serum ceruloplasmin levels in patients with Wilson's disease are due at least in part to a decrease in ceruloplasmin gene transcription.
The role of the bile acid receptor FXR in determining ATP-binding cassette (ABC) transporter expression and liver injury in common bile duct-ligated (CBDL) mice
Authors: M. Wagner, P. Fickert, G. Zollner, A. Fuchsbichter, D. Silbert, H.U. Marschall, F.J. Gonzalez, K. Zatloukal, H. Denk, M. Trauner
Journal: Journal of Hepatology (2003)
Selective Coronary Arteriography in Young Men A Follow-Up of 449 Patients
Authors: JUAN S. LIM, WILLIAM L. PROUDFIT, F. MASON SONES
Journal: Circulation (1974)

The prognosis for 449 young men with normal, mildly abnormal, and obstructive arteriograms with and without internal mammary artery implants was studied. Prognosis for patients with normal arteriograms was good in regard to incidence of infarction and mortality. In 30 patients with mildly abnormal arteriograms there appeared to be a relatively higher incidence of myocardial infarction, although the total number of patients in this category was small. In 116 young men with obstructive coronary disease the 5-year survival rate was 66.8%. The 5-year mortality in patients with single vessel involvement was 8.8% and in those with multiple vessel disease mortality was 37%. The mortality was 6.8% each year among survivors in this group of patients with both single and multiple vessel disease. The prognosis was worse when there was multiple vessel involvement, when there was generalized decrease in contractility shown by the left ventriculogram, or when the electrocardiogram showed evidence of myocardial infarction. The influence of internal mammary artery implantation could not be accurately assessed because of the small number of cases and the substantial number of patients who did not have postoperative internal mammary arteriography.
A CASE OF SUPPOSED MALIGNANT DISEASE OF THE UTERUS TREATED BY IODOFORM.
Authors: I. W. FISKE
Journal: JAMA (1884)

[Read before the Kalamazoo Academy of Medicine, January 29, 1884.] About three and a half years since I was called to see Mrs. H., who had been suffering for some time with some uterine trouble. She came here from Ionia, where she had had removed some time previous a portion of the external os uteri for supposed malignant disease. I found the uterus somewhat enlarged, with the inside roughened and uneven. She was suffering from considerable pain at this time. Some physician in Grand Rapids had applied pure nitric acid to the internal part of the organ. I applied iodized phenol to the inside and hot water injections, and also used electricity, passing the current through the pelvis, and also applying one pole to the os and the other to the lower part of the spine, and always with relief. After about two months' treatment the inside became smooth, pain
Factors in the Survival of Patients with Insulin-Requiring Diabetes for 50 Years
Authors: Harry A Cochran, Alexander Marble, John A Galloway
Journal: Diabetes Care (1979)

Ninety-seven diabetic patients who had taken insulin for 50 yr and longer were surveyed by questionnaire to identify factors that might explain their unusual longevity. The analysis suggested that the long survival of this group was related to the following: maintenance of normal or near normal body weight, regular contact with a personal physician, periodic blood glucose determinations, frequent urine testing, regular exercise, and longevity of the parents and grandparents. The results support the conclusion that careful management of diabetes favors longevity.
Abstract 1213: EGFR interacts with fatty acid synthase
Authors: Lakshmi Reddy Bollu, Jiangong Ren, Jiangong Wang, Weihua Zhang
Journal: Cancer Research (2012)

Abstract Background: Over expression of the epidermal growth factor receptor (EGFR) and fatty acid synthase (FASN) is common in cancers. It has been found that de novo fatty acid synthesis accounts for &amp;gt;90% of total cellular lipids in cancer cells. In this study, we found that EGFR physically interacts with FASN and this interaction is independent of EGFR kinase activity. Methods: We created fourteen flag tagged domain deleted EGFR, and transfected them with FASN into HEK293T cells, and performed Co-immuno-precipitation (Co-IP) followed by Western blot analysis. Results: We found EGFR interacted with FASN independent of EGFR kinase activity. Fine scale domain mapping revealed that the transmembrane (TM) and intracellular domains of EGFR are necessary for the EGFR-FASN interaction. The extracelluar domains of L1 and LF are also required for a sufficient EGFR-FASN interaction. Conclusions: EGFR interacts with FASN independent of its tyrosine kinase activity and that the transmembrane and intracellular domain of EGFR is critical for the interaction between EGFR and FASN. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1213. doi:1538-7445.AM2012-1213
Surgery for Complications of Acute Myocardial Infarction
Authors: ELDRED D. MUNDTH, MORTIMER J. BUCKLEY, WILLARD M. DAGGETT, CHARLES A. SANDERS, W. GERALD AUSTEN
Journal: Circulation (1972)

THE GREATER availability of well-equipped and well-staffed coro- nary care units, death from arrhythmias complicating myocardial infarction has be- come less common.'This has been a result of improved methods of patient monitoring, earlier diagnosis of arrhythmias, and prompt treatment.2 3Death from myocardial infarc- tion at present is more commonly a result of cardiogenic shock or refractory cardiac fail- ure." 3-5 The mechanical complications of myocardial infarction, including rupture of the interventricular septum, papillary muscle rup- ture, and acute left ventricular aneurysm, although uncommon, are associated wih a high mortality rate.Concomitant with the development of an accurate and safe method of selective cine- coronary arteriography6 for the diagnosis of coronary artery disease, effective surgical procedures for direct coronary arterial revas- cularization have evolved.7-10Despite an impressive volume of patients undergoing elective revascularization, urgent myocardial
ADDRESS ON ORAL AND DENTAL SURGERY
Authors: TRUMAN W. BROPHY
Journal: JAMA (1884)

Chairman of the Section on Oral and Dental Surgery of the American Medical Association, May, 1884. Mr. President and Gentlemen: A rule of this Association requires the chairman of each Section to prepare and read a paper in general session descriptive of what has been accomplished in his respective Section for its advancement during the past year. If I were to follow strictly the rule I should confine myself to a resumé of the<i>discoveries and advances made in oral and dental surgery during</i>the last twelve months. These have been sufficiently numerous and important to furnish material for a far more extended address than I contemplate, and the subjects are especially inviting; nevertheless, I shall venture, with your kind permission, upon rather a wide departure from established custom in this respect, and in place of these matters shall briefly recapitulate the struggles through which this department of medicine has
SOME FURTHER CONSIDERATIONS CONCERNING THE TREATMENT OF NEUROSYPHILIS
Authors: C. EUGENE RIGGS
Journal: JAMA (1918)

While dogmatism has no place in medicine, it is especially unfortunate in the weighing of evidence and the evaluation of data in the tentative endeavor now being made to determine the most efficient form of therapy for the treatment of neurosyphilis. Cotton manifests the true scientific spirit when he says that with a spirit of open-mindedness every method should be given a thorough trial, and that it is only by continual experimenting with new ideas that we can hope for progress in this new line of endeavor. If an apology were necessary because of my selection of this much discussed subject, it were best made in the words of Southard: "That no more important human problem now exists than syphilis, and that neurosyphilis is a highly important fraction of the total problem." The three principal methods of procedure in the treatment of nervous syphilis are intraspinal, intracranial (subdural or intraventricular)