tbuckley/cabot-search huggingface dataset:
Polyphenon E Inhibits the Growth of Human Barrett's and Aerodigestive Adenocarcinoma Cells by Suppressing Cyclin D1 Expression
Authors: Shumei Song, Koyamangalath Krishnan, Kaifeng Liu, Robert S. Bresalier
Journal: Clinical Cancer Research (2009)

Green tea consumption has been shown to exhibit cancer-preventive activities in preclinical studies. Polyphenon E (Poly E) is a well-defined green tea-derived catechin mixture. This study was designed to determine the effects of Poly E on the growth of human Barrett's and aerodigestive adenocarcinoma cells and the mechanisms involved in growth regulation by this agent.Human adenocarcinoma cells and immortalized Barrett's epithelial cells were used as model systems.Poly E inhibited the proliferation of immortalized Barrett's cells as well as various adenocarcinoma cells, and this was associated with the down-regulation of cyclin D1 protein expression. Inhibition of cyclin D1 led to dephosphorylation of the retinoblastoma protein in a dose-dependent manner; these changes were associated with G(1) cell cycle arrest. Poly E down-regulated cyclin D1 promoter activity and mRNA expression, suggesting transcriptional repression, and this correlated with decreased nuclear beta-catenin and beta-catenin/TCF4 transcriptional activity. MG132, an inhibitor of 26S proteosome, blocked the Poly E-induced down-regulation of cyclin D1, and Poly E promoted cyclin D1 polyubiquitination, suggesting that Poly E also inhibits cyclin D1 expression by promoting its degradation.Poly E inhibits growth of transformed aerodigestive epithelial cells by suppressing cyclin D1 expression through both transcriptional and posttranslational mechanisms. These results provide insight into the mechanisms by which Poly E inhibits growth of Barrett's and adenocarcinoma cells, and provides a rationale for using this agent as a potential chemopreventive and therapeutic strategy for esophageal adenocarcinoma and its precursor, Barrett's esophagus.
Skeletal brucellosis in Iraqi patients.
Authors: T I al-Rawi, A J Thewaini, A R Shawket, G M Ahmed
Journal: Annals of the Rheumatic Diseases (1989)

The clinical features of 21 episodes of skeletal brucellosis in 17 Iraqi patients are reported. Six had monarthritis of a large joint, six had spondylitis, and five had spondarthritis. Brucellosis remains a major health problem in Iraq. The disease is transmitted to man through the ingestion of unpasteurised milk or milk products but can also be acquired through physical contact.
Pharmacologic modification of myocardial ischemia.
Authors: L Wetstein, M B Simson, P D Feldman, A H Harken
Journal: Circulation (1982)

The value of three agents in reducing the area of myocardial ischemia in rabbit hearts perfused with crystalloid solution was examined. Ten hearts received crystalloid solution with methylprednisolone (M), 0.25 mg/ml; 18 with hyaluronidase (H), 4 U/ml; and 10 with propranolol (P), 1 microgram/ml. Thirty-six hearts served as controls. The mitral valves were excised, the hearts were paced at 240 beats/min and a coronary artery was ligated. The ischemic area was evaluated by nicotinamide adenine dinucleotide autofluorescence photography, an intrinsic, high-resolution display of anoxic tissue. The ischemic area was determined by computer from standardized photographs. Myocardial oxygen consumption (MVO2) was determined and photographs were taken before and at 10-minute intervals after ligation. At 60 minutes, each heart was perfused with rhodamine dye and quick-frozen. In hearts treated with M and H, coronary blood flow increased by 151% (51.7 +/- 3 to 77.9 +/- 3 ml/min) and 150% (48.3 +/- 2 to 72.3 +/- 2 ml/min), respectively (p less than 0.001), whereas in hearts treated with U and P, coronary flow decreased at 60 minutes. In the control hearts, the ischemic area did not change between 5 and 40 minutes of ischemia. The ischemic area of H-treated hearts decreased from 136 +/- 4 mm2 to 110 +/- 9 mm2 between the postligation control and the end of the experiment (p less than 0.01). The ischemic area of M-treated hearts decreased from 131 +/- 5 mm2 to 113 +/- 5 mm2 (p less than 0.05). P produced no change in ischemic area (p greater than 0.4). There was no change in the oxygen-diffusion zone of P-treated or control hearts (439 +/- 13 vs 383 +/- 12 mu, p greater than 0.1). The oxygen-diffusion zone between perfused and anoxic tissue in the M and H hearts increased from 383 +/- 12 mu to 861 +/- 76 mu and 681 +/- 62 mu, respectively (p less than 0.001). We conclude that significant volumes of myocardium remain normoxic within nonperfused areas of M-, P- and H-treated hearts.
Outbreak of Salmonella Serotype Hartford Infections Associated With Unpasteurized Orange Juice
Authors: Kim A. Cook, Thomas E. Dobbs, W. Gary Hlady, Joy G. Wells, Timothy J. Barrett, Nancy D. Puhr, Gayle A. Lancette, Dean W. Bodager, Bill L. Toth, Carol A. Genese, Anita K. Highsmith, Keith E. Pilot, Lyn Finelli, David L. Swerdlow
Journal: JAMA (1998)

Acidic foods such as orange juice have been thought to be unlikely vehicles of foodborne illness.To investigate an outbreak of Salmonella enterica serotype Hartford (Salmonella Hartford) infections among persons visiting a theme park in Orlando, Fla, in 1995.Review of surveillance data, matched case-control study, laboratory investigation, and environmental studies.General community.The surveillance case definition was Salmonella Hartford or Salmonella serogroup C1 infection in a resident of or a visitor to Orlando in May or June 1995. In the case-control study, case patients were limited to theme park hotel visitors and controls were matched to case patients by age group and hotel check-in date.Risk factors for infection and source of implicated food.Sixty-two case patients from 21 states were identified. Both Salmonella Hartford and Salmonella enterica serotype Gaminara (Salmonella Gaminara) were isolated from stool samples of 1 ill person. Thirty-two case patients and 83 controls were enrolled in the case-control study. Ninety-seven percent of case patients had drunk orange juice in the theme park vs 54% of controls (matched odds ratio, undefined; 95% confidence interval, 5.2 to undefined). The orange juice was unpasteurized and locally produced. Salmonella Gaminara was isolated from 10 of 12 containers of orange juice produced during May and July, indicating ongoing contamination of juice probably because of inadequately sanitized processing equipment.Unpasteurized orange juice caused an outbreak of salmonellosis in a large Florida theme park. All orange juice was recalled and the processing plant closed. Pasteurization or other equally effective risk-management strategies should be used in the production of all juices.
AMA promotes benefits of “genetically improved” foods
Authors: Janice Hopkins
Journal: BMJ (2001)

Although biotechnology has produced greatly improved, widely accepted drugs, there is still enormous controversy over the development of genetically modified crops that increase yields, lower costs, and offer better ways to feed the world, the director of science policy at the American Medical Association has said.

Speaking at a New York press briefing last week, Dr Barry David Dickinson, director of science policy for the American Medical Association, said that biotechnological advances had improved human insulin, growth hormone, monoclonal antibodies, tissue plasminogen activator (TPA), and more.

“Why, then, is there controversy over genetically modified crops?” he asked.

The seminar was funded by an unrestricted grant from the Council for Biotechnology Information, a group of six biotechnology firms and two trade associations. They included Aventis …
TREATMENT IN ALCOHOLISM
Authors: JACKSON A. SMITH, W. T. BROWN
Journal: American Journal of Psychiatry (1952)

1. In 7 of the 8 patients ACE in the dosage given did not obviate the need for sedation. 2. In this series, ACE failed to decrease significantly the morbidity. 3. ACE in large doses should be considered as a means of sedation in an alcoholic with cirrhosis in whom barbiturates are poorly tolerated. 4. The administration of ACE to chronic alcoholics failed to alter their drinking pattern after they recovered from the delirium.
Salt-split human skin substrate for the immunofluorescent screening of serum from patients with cicatricial pemphigoid and a new method of immunoprecipitation with IgA antibodies
Authors: Yves Sarret, Russell Hall, L. Michael Cobo, Jean Thivolet, Dorothy L. Patton, David T. Woodley
Journal: Journal of the American Academy of Dermatology (1991)

In patients with cicatricial pemphigoid, immunoglobulins (usually IgG) and complement are deposited within the dermoepidermal junction and are detected by direct immunofluorescent staining of perilesional mucous membrane and/or skin with fluorescein-labeled antibodies to human immunoglobulins. Although rare, some patients also have circulating low-titer, anti-basement membrane zone autoantibodies. In this study, we report 11 patients with the clinical, histologic, and immunologic criteria for cicatricial pemphigoid who had circulating an-ti-BMZ autoantibodies as demonstrated by positive indirect staining of a normal human skin that had been fractured through the dermoepidermal junction by prolonged incubation in a cold, 1 mol/L sodium chloride solution. On this salt-split human skin substrate, 9 of the 11 patients (82%) had autoantibodies that bound to the epidermal roof, one serum stained only the dermal floor, and one serum stained both sides of the separation. The predominant class of immunoglobulin in the patients' sera that bound to the substrate was IgA; IgA was the single immunoglobulin in 55% and was associated with IgG in 18%. IgG was the only immunoglobulin detected in 27% of the cases. No specific protein was detected by either Western immunoblot or a new IgA immunoprecipitation procedure. In patients with cicatricial pemphigoid, immunoglobulins (usually IgG) and complement are deposited within the dermoepidermal junction and are detected by direct immunofluorescent staining of perilesional mucous membrane and/or skin with fluorescein-labeled antibodies to human immunoglobulins. Although rare, some patients also have circulating low-titer, anti-basement membrane zone autoantibodies. In this study, we report 11 patients with the clinical, histologic, and immunologic criteria for cicatricial pemphigoid who had circulating an-ti-BMZ autoantibodies as demonstrated by positive indirect staining of a normal human skin that had been fractured through the dermoepidermal junction by prolonged incubation in a cold, 1 mol/L sodium chloride solution. On this salt-split human skin substrate, 9 of the 11 patients (82%) had autoantibodies that bound to the epidermal roof, one serum stained only the dermal floor, and one serum stained both sides of the separation. The predominant class of immunoglobulin in the patients' sera that bound to the substrate was IgA; IgA was the single immunoglobulin in 55% and was associated with IgG in 18%. IgG was the only immunoglobulin detected in 27% of the cases. No specific protein was detected by either Western immunoblot or a new IgA immunoprecipitation procedure.
Activation of Sympathetic Vasodilator and Vasoconstrictor Neurons by Electric Stimulation in the Medulla of the Dog and Cat
Authors: PERCY LINDGREN, BÖRJE UVNÄS
Journal: Circulation Research (1953)

Electric stimulation in the ventrolateral area of the medulla elicited vasodilation in skeletal muscles, and vasoconstriction in the skin and intestines. The vasodilation was accredited to activity in the cholinergic sympathetic vasodilator outflow previously shown to originate in the motor cortex of the dog. The possible functional significance of the vasodilator fibers in regulating muscle blood flow during exercise is discussed.
MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death
Authors: Arin B. Aurora, Ahmed I. Mahmoud, Xiang Luo, Brett A. Johnson, Eva van Rooij, Satoshi Matsuzaki, Kenneth M. Humphries, Joseph A. Hill, Rhonda Bassel-Duby, Hesham A. Sadek, Eric N. Olson
Journal: Journal of Clinical Investigation (2012)

Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abnormal increases in intracellular Ca²⁺ during myocardial reperfusion can cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Therapeutic modulation of Ca²⁺ handling provides some cardioprotection against the paradoxical effects of restoring blood flow to the heart, highlighting the significance of Ca²⁺ overload to IR injury. Cardiac IR is also accompanied by dynamic changes in the expression of microRNAs (miRNAs); for example, miR-214 is upregulated during ischemic injury and heart failure, but its potential role in these processes is unknown. Here, we show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The cardioprotective roles of miR-214 during IR injury were attributed to repression of the mRNA encoding sodium/calcium exchanger 1 (Ncx1), a key regulator of Ca²⁺ influx; and to repression of several downstream effectors of Ca²⁺ signaling that mediate cell death. These findings reveal a pivotal role for miR-214 as a regulator of cardiomyocyte Ca²⁺ homeostasis and survival during cardiac injury.
Recurrent T cell receptor rearrangements in the cytotoxic T lymphocyte response in vivo against the p815 murine tumor.
Authors: J P Levraud, C Pannetier, P Langlade-Demoyen, V Brichard, P Kourilsky
Journal: The Journal of Experimental Medicine (1996)

P815 is a murine mastocytoma of DBA/2 origin which, although immunogenic, rapidly develops as a tumor in immunocompetent syngeneic hosts. In this report, we have studied, by a molecular approach, the in vivo alpha/beta T cell response to P815. Both situations of tumor growth after engraftment of naive animals or tumor rejection by preimmunized animals have been analyzed. The spectrum of T cell receptor beta chain rearrangements in the tumor-infiltrating lymphocytes was found to be highly variable among individual tumor-bearing mice. However, two rearrangements, one using V(beta)1 and J(beta)1.2 segments and one using the V(beta)1 and J(beta)2.5 segments, with conserved junctional regions, reproducibly emerge in most individuals. These two rearrangements thus correspond to "public" (recurrent) T cell clones, as opposed to "private" ones, which emerge in a seemingly stochastic fashion in immunized animals. Importantly, these public cells are observed in situations of either growth or rejection of the tumor. Quantification provides a clear increase in public T cells in secondary responses, but no obvious correlation provides between their level and primary tumor rejection. The V(beta)1- J(beta)1.2 rearrangement is borne by CTL directed against an antigen derived from P1A, a nonmutated mouse self protein which is expressed in P815 but not in normal mouse tissues except testis. A recurrent, public T cell response can thus be observed to an antigen derived from a self protein expressed by a tumor.
Fifth Pathway in New Jersey
Authors: W. Edward McGough
Journal: JAMA (1975)

The Fifth Channel in New Jersey is a Fifth Pathway program for US foreign medical graduates. In its third year, 83 percent of its 81 graduates are house officers at 18 US medical school-affiliated hospitals. Performance as house officers is characterized as competitive with peers, including US graduates. Positive attitudes toward work load, fellow workers, and patients compared with those of fellow house staff are noted. Quality of performance as house officers correlates most strongly with the change in mean scores of two batteries of clinical National Board examinations taken during the Fifth Pathway and less strongly with mean scores of single batteries of National Boards, Intelligence quotient, Educational Council for Foreign Medical Graduates (ECFMG) examination, ang age. Recommendations concerning the implementing of similar programs in other states are presented.
Reversal of osteopenia with diet in adult coeliac disease.
Authors: T Valdimarsson, O Lofman, G Toss, M Strom
Journal: Gut (1996)

To evaluate the effects of a gluten free diet on bone mineral density in untreated adult patients with coeliac disease, 63 patients (17-79 years, 35 women) were examined at diagnosis and after one year taking a gluten free diet. Bone mineral density was measured in the forearm using single photo absorptiometry and in the lumbar spine, femoral neck, and trochanter using dual energy x ray absorptiometry. The values for each patient were compared with those of 25 healthy controls, matched for sex, age, and menopausal state. Before being given a gluten free diet bone mineral density in the total group was reduced at all sites (p &lt; 0.001). Age adjusted bone mineral density was inversely correlated with age. During the first year taking a gluten free diet bone mineral density increased at all sites (p &lt; 0.01). This was seen in patients of all ages and in patients who were without symptoms of malabsorption (weight loss or diarrhoea) before treatment. Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed. These findings emphasise the importance of early diagnosis and treatment in all patients with coeliac disease.
TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets
Authors: David T. Yeung, Michael P. Osborn, Deborah L. White, Susan Branford, Jodi Braley, Alan Herschtal, Michael Kornhauser, Samar Issa, Devendra K. Hiwase, Mark Hertzberg, Anthony P. Schwarer, Robin Filshie, Christopher K. Arthur, Yiu Lam Kwan, Judith Trotman, Cecily J. Forsyth, John Taper, David M. Ross, Jennifer Beresford, Constantine Tam, Anthony K. Mills, Andrew P. Grigg, Timothy P. Hughes
Journal: Blood (2014)
An Integrated Genomic Screen Identifies LDHB as an Essential Gene for Triple-Negative Breast Cancer
Authors: Mark L. McCleland, Adam S. Adler, Yonglei Shang, Thomas Hunsaker, Tom Truong, David Peterson, Eric Torres, Li Li, Benjamin Haley, Jean-Philippe Stephan, Marcia Belvin, Georgia Hatzivassiliou, Elizabeth M. Blackwood, Laura Corson, Marie Evangelista, Jiping Zha, Ron Firestein
Journal: Cancer Research (2012)

Breast cancer has been redefined into three clinically relevant subclasses: (i) estrogen/progesterone receptor positive (ER+/PR+), (ii) HER2/ERRB2 positive, and (iii) those lacking expression of all three markers (triple negative or basal-like). While targeted therapies for ER+/PR+ and HER2+ tumors have revolutionized patient treatment and increased lifespan, an urgent need exists for identifying novel targets for triple-negative breast cancers. Here, we used integrative genomic analysis to identify candidate oncogenes in triple-negative breast tumors and assess their function through loss of function screening. Using this approach, we identify lactate dehydrogenase B (LDHB), a component of glycolytic metabolism, as an essential gene in triple-negative breast cancer. Loss of LDHB abrogated cell proliferation in vitro and arrested tumor growth in fully formed tumors in vivo. We find that LDHB and other related glycolysis genes are specifically upregulated in basal-like/triple-negative breast cancers as compared with other subtypes, suggesting that these tumors are distinctly glycolytic. Consistent with this, triple-negative breast cancer cell lines were more dependent on glycolysis for growth than luminal cell lines. Finally, we find that patients with breast cancer and high LDHB expression in their tumors had a poor clinical outcome. While previous studies have focused on the ubiquitous role of LDHA in tumor metabolism and growth, our data reveal that LDHB is upregulated and required only in certain cancer genotypes. These findings suggest that targeting LDHB or other components of lactate metabolism would be of clinical benefit in triple-negative breast cancer.
HYPOMAGNESAEMIA AND CYCLOSPORIN TOXICITY
Authors: ImeldaA. Borland, J.R. Gosney, A.N. Hillis, E.P.M. Williamson, R.A. Sells, Norbert Schmitz, HansHartwig Euler, Helmut Loffler, J.P. O'Connor, D.S. Kleinman, H.E. Kunze
Journal: The Lancet (1985)
Cost-Effectiveness of Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease and Abnormal Fractional Flow Reserve
Authors: William F. Fearon, David Shilane, Nico H.J. Pijls, Derek B. Boothroyd, Pim A.L. Tonino, Emanuele Barbato, Peter Jüni, Bernard De Bruyne, Mark A. Hlatky
Journal: Circulation (2013)

Background— The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial demonstrated a significant reduction in subsequent coronary revascularization among patients with stable angina and at least 1 coronary lesion with a fractional flow reserve ≤0.80 who were randomized to percutaneous coronary intervention (PCI) compared with best medical therapy. The economic and quality-of-life implications of PCI in the setting of an abnormal fractional flow reserve are unknown. Methods and Results— We calculated the cost of the index hospitalization based on initial resource use and follow-up costs based on Medicare reimbursements. We assessed patient utility using the EQ-5D health survey with US weights at baseline and 1 month and projected quality-adjusted life-years assuming a linear decline over 3 years in the 1-month utility improvements. We calculated the incremental cost-effectiveness ratio based on cumulative costs over 12 months. Initial costs were significantly higher for PCI in the setting of an abnormal fractional flow reserve than with medical therapy ($9927 versus $3900, P &lt;0.001), but the $6027 difference narrowed over 1-year follow-up to $2883 ( P &lt;0.001), mostly because of the cost of subsequent revascularization procedures. Patient utility was improved more at 1 month with PCI than with medical therapy (0.054 versus 0.001 units, P &lt;0.001). The incremental cost-effectiveness ratio of PCI was $36 000 per quality-adjusted life-year, which was robust in bootstrap replications and in sensitivity analyses. Conclusions— PCI of coronary lesions with reduced fractional flow reserve improves outcomes and appears economically attractive compared with best medical therapy among patients with stable angina. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01132495.
Increased expression of type VI collagen in lung fibrosis.
Authors: U Specks, A Nerlich, T V Colby, I Wiest, R Timpl
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Pulmonary fibrosis is characterized by disturbances of extracellular matrix protein deposition resulting from fibroblast activation and proliferation. Collagen VI, forming microfibrillar meshworks separate from major fibrillar systems, is thought to serve as an anchoring element between collagen I/III fibrils and basement membranes and as a cell binding substrate. We report on the expression of collagen VI in normal and in fibrotic lungs. Collagen VI is present in vascular and bronchial walls and in the interstitial space of normal lungs. Its turnover is too low to generate a mRNA signal by in situ hybridization. Collagen VI expression is increased in lung fibrosis, and its degree appears independent of the etiology of fibrosis. There was no evidence for differential regulation of gene expression for the alpha 1(VI) and alpha 3(VI) constitutive peptide chains of collagen VI. Collagen VI mRNA is expressed by fibroblasts, mostly with myofibroblast characteristics. Collagen VI was coexpressed with collagen III rather than collagen I in idiopathic bronchiolitis obliterans with organizing pneumonia, acute interstitial pneumonitis of the Hamman-Rich type, and bleomycin-induced fibrosis, but collagen VI overlapped with collagen types I and III in idiopathic pulmonary fibrosis. These coexpression data suggest that collagen VI expression may be an early rather than a late phenomenon in pulmonary fibrosis.