tbuckley/cabot-search huggingface dataset:
Hypoxic human cancer cells are sensitized to BH-3 mimetic–induced apoptosis via downregulation of the Bcl-2 protein Mcl-1
Authors: Luke R.E. Harrison, Dimitra Micha, Martin Brandenburg, Kathryn L. Simpson, Christopher J. Morrow, Olive Denneny, Cassandra Hodgkinson, Zaira Yunus, Clare Dempsey, Darren Roberts, Fiona Blackhall, Guy Makin, Caroline Dive
Journal: Journal of Clinical Investigation (2011)

Solid tumors contain hypoxic regions in which cancer cells are often resistant to chemotherapy-induced apoptotic cell death. Therapeutic strategies that specifically target hypoxic cells and promote apoptosis are particularly appealing, as few normal tissues experience hypoxia. We have found that the compound ABT-737, a Bcl-2 homology domain 3 (BH-3) mimetic, promotes apoptotic cell death in human colorectal carcinoma and small cell lung cancer cell lines exposed to hypoxia. This hypoxic induction of apoptosis was mediated through downregulation of myeloid cell leukemia sequence 1 (Mcl-1), a Bcl-2 family protein that serves as a biomarker for ABT-737 resistance. Downregulation of Mcl-1 in hypoxia was independent of hypoxia-inducible factor 1 (HIF-1) activity and was consistent with decreased global protein translation. In addition, ABT-737 induced apoptosis deep within tumor spheroids, consistent with an optimal hypoxic oxygen tension being necessary to promote ABT-737–induced cell death. Tumor xenografts in ABT-737–treated mice also displayed significantly more apoptotic cells within hypoxic regions relative to normoxic regions. Synergies between ABT-737 and other cytotoxic drugs were maintained in hypoxia, suggesting that this drug may be useful in combination with chemotherapeutic agents. Taken together, these findings suggest that Mcl-1–sparing BH-3 mimetics may induce apoptosis in hypoxic tumor cells that are resistant to other chemotherapeutic agents and may have a role in combinatorial chemotherapeutic regimens for treatment of solid tumors.
Prevention of steatohepatitis by pioglitazone: Implication of adiponectin-dependent inhibition of SREBP-1c and inflammation
Authors: Alain Da Silva Morais, Valérie Lebrun, Jorge Abarca-Quinones, Sonia Brichard, Louis Hue, Bruno Guigas, Benoit Viollet, Isabelle A. Leclercq
Journal: Journal of Hepatology (2008)
Histochemical changes in mucus in duodenal ulceration.
Authors: S M Morrissey, P M Ward, A P Jayaraj, F I Tovey, C G Clark
Journal: Gut (1983)

In duodenal ulceration the Alcian blue staining acid mucosubstances in goblet cells are reduced and the goblet cells themselves disappear. At the same time periodic acid-Schiff (PAS) staining neutral mucosubstances appear in the cells of the surface epithelium. These changes have been measured quantitatively with the help of a Vickers M86/0010 Scanning and Integrated Microdensitometer. During healing the changes are reversed. It is suggested that these changes suggest a metaplasia towards a gastric type mucosa as a protective response to the presence of ulceration.
Suicide and Affective Disorder Among the Old Order Amish-Reply
Authors: Janice A. Egeland
Journal: JAMA (1986)

<h3>In Reply.—</h3> We appreciate Dr deGruy's raising a point we could not cover in our article. His salient observation is that our published pedigrees show instances of intermarriage between those with a positive family history for affective disorders. In response to the first question, the frequency of assortative mating (homogamy) between spouses both having a psychiatric illness does not appear greater than would be predicted by random selection. Even though the spouse may be well, over half of our bipolar pedigrees have a positive family history on both sides of the family.<sup>1</sup>Whether this assortative mating increases the suicidal potential has not been well investigated in studies. Research does show that a systematic assortative mating does increase the transmission of major affective disorders.<sup>2-4</sup>Our data (unpublished) would support this finding of higher morbid risk as well as greater comorbidity in the extended families on both sides. Furthermore, recent
Relative roles of cardiac receptors and arterial baroreceptors during hemorrhage in conscious dogs.
Authors: Y T Shen, D R Knight, J X Thomas, S F Vatner
Journal: Circulation Research (1990)

To determine the relative roles of cardiac receptors and arterial baroreceptors during blood loss, the effects of acute hemorrhage on measurements of mean arterial pressure, cardiac output, stroke volume, total peripheral resistance, and heart rate were examined in chronically instrumented, conscious dogs with all nerves intact (n = 15) and following either cardiac denervation (CD, n = 14), sinoaortic denervation alone (SAD, n = 11), or combined sinoaortic denervation plus cardiac denervation (SAD + CD, n = 8). Hemorrhage at a constant rate (0.5 ml/kg/min) was continued until mean arterial pressure fell to 40 mm Hg or 30 ml/kg of blood was withdrawn. Hemorrhage (20 ml/kg) decreased mean arterial pressure similarly in the intact group (-15 +/- 3.3 mm Hg) and CD group (-17 +/- 3.2 mm Hg), but to a greater extent in the SAD (-53 +/- 3.4 mm Hg) and SAD + CD (-49 +/- 2.9 mm Hg) groups. Total peripheral resistance increased similarly in the intact (20.4 +/- 3.0 mm Hg/l/min) and CD (22.4 +/- 2.4 mm Hg/l/min) groups, but did not increase in SAD and SAD + CD groups. Acute cardiac denervation induced with intrapericardial lidocaine in either the intact or SAD groups resulted in similar responses of mean arterial pressure to hemorrhage as those observed in the chronic CD and chronic SAD + CD groups, respectively. Thus, dogs with cardiac denervation withstand hemorrhage and increase total peripheral resistance to a similar extent as intact dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Sickling tests. Pitfalls in performance and interpretation
Authors: Rose G. Schneider, Jack B. Alperin, Hermann Lehmann
Journal: JAMA (1967)

Testing for erythrocyte sickling is a common procedure in many laboratories, and it is generally considered simple to perform and interpret. Nevertheless, we frequently receive reports which are found to be falsely positive or falsely negative, and such incorrect data have even been recorded in connection with investigations on the abnormal hemoglobins.<sup>1</sup>Recent discoveries of the existence of several dozen hereditary hemoglobin variants and the development of methods for their identification have made possible the recognition of many previously unknown hemoglobinopathies. Although such recognition depends largely on electrophoretic and genetic data, sickling tests often provide a valuable rapid diagnostic aid. The purpose of this paper is to describe conditions under which the reliability of these tests is frequently impaired. <h3>Precautions for Accuracy.—</h3> Obviously, the blood sample for testing must be the patient's own, unmixed with that of a donor. Yet, we receive a surprising number of samples which were
Electrophoresis of proteins and nucleic acids: I--Theory.
Authors: J. D. Hayes, P. K. Stockman
Journal: BMJ (1989)

Electrophoresis is used extensively in both routine clinical chemistry and biomedical research as a rapid method to separate macromolecules.The high reso- lution of proteins or nucleic acids that can be achieved by electrophoresis makes it an indispensable tool in the research laboratory.The separation of complex mix- tures of either protein or nucleic acid polymers is most conveniently achieved with electrophoresis; indeed, often the separations obtained by electrophoresis can- not be achieved by any other method.By contrast, the separation of smaller molecules such as amino acids, nucleotides, sugars, or drugs is best achieved by high performance liquid chromatography.Hence electro- phoresis and high performance liquid chromatography are generally considered to be complementary in their applications.Electrophoretic techniques have revolutionised the study of pathophysiological processes at a molecular level for reasons that include the following: * Methods of high resolving power have been developed * Methods are easily manipulated and optimised for any application * Many samples can be processed simultaneously, thereby allowing direct comparisons between stan- dards, controls, and unknown samples * Most methods are quick to perform * Sensitive detection methods have been described * Suitable equipment is available commercially and is inexpensive * All methods can be used for analytical or preparative purposes.In this article we discuss the theory of electrophoresis, and in our next article we will consider in detail the more powerful techniques available and their clinical applications.
Landmark article Feb 25, 1939: Surgical ligation of a patent ductus arteriosus. Report of first successful case. By Robert E. Gross and John P. Hubbard
Authors: R. E. Gross
Journal: JAMA (1984)

The continued patency of a ductus arteriosus for more than the first few years of life has long been known to be a potential source of danger to a patient for two reasons: First, the additional work of the left ventricle in maintaining the peripheral blood pressure in the presence of a large arteriovenous communication may lead eventually to cardiac decompensation of severe degree. Second, the presence of a patent ductus arteriosus makes the possessor peculiarly subject to fatal bacterial endarteritis. While it is true that some persons have been known to live to old age with a patent ductus of Botalli, statistics have shown that the majority die relatively young because of complications arising from this congenital abnormality. Dr. Maude Abbott<sup>1</sup>presented a series of ninety-two cases which came to autopsy in which it was shown that the patient had had a patent ductus arteriosus without any other
Generalists and Specialists
Authors: Richard K. Williams
Journal: JAMA (1984)

To the Editor.—  Dr Davidson1may be correct in his thoughts concerning the strengths of medical generalists, but his evolutionary analogies lend little credence to his argument.  To suggest that fish are specialists is a gross misstatement. The teleost fishes make up without a doubt the greatest radiation of vertebrate evolution that exists today andprobably ever existed. The number of species and individuals occupying every conceivable habitat of fresh and marine waters and the diversity of this group far exceed those of all other vertebrates.2While it is true that they spend their time under water, there is, after all, generally more water than land.  It is also difficult to leave unchallenged the fanciful Lamarckian scenario of avian evolution apparently seriously offered as a caveat to subspecialization. The birds whose beaks became so heavy that they were unable to fly and then drowned in rising waters are entirely
F-18 FDG Uptake in Benign Esophageal Disease
Authors: SIEMA M. BAKHEET, TARIQ AMIN, ABDUL-GHAFFAR ALIA, RONALD KUZO, JOHN POWE
Journal: Clinical Nuclear Medicine (1999)

We describe three patients who had obstructive esophageal symptoms and conventional radiologic examinations strongly suggesting the presence of esophageal cancer. Whole-body PET scans showed variable degrees of F-18 fluorodeoxyglucose (FDG) uptake in the involved esophagus that supported this diagnosis. In two patients, additional intense focal uptake was apparent in the hilum, mediastinum, and the supraclavicular area, consistent with lymph node metastases. One patient had intense F-18 FDG linear uptake secondary to bacterial esophagitis in an esophageal stricture that cleared after a course of antibiotic treatment. The second patient had moderate uptake in association with a stricture in the lower one third of the esophagus that was histologically proved to be Barrett’s esophagus. The third patient had mild uptake related to esophageal spasm and gastroesophageal reflux.
Transmembrane signaling of interleukin 2 receptor. Conformation and function of human interleukin 2 receptor (p55)/insulin receptor chimeric molecules.
Authors: M Hatakeyama, T Doi, T Kono, M Maruyama, S Minamoto, H Mori, M Kobayashi, T Uchiyama, T Taniguchi
Journal: The Journal of Experimental Medicine (1987)

Chimeric genes were constructed which gave rise to the expression of novel receptor molecules consisting of the extracellular domain of the human interleukin 2 receptor (IL-2-R; p55 or Tac antigen) joined to the transmembrane domain and either full-length or truncated cytoplasmic domain of the human insulin receptor (Ins-R). Expression studies using mouse T cell line EL-4 revealed that the chimeric receptors are able to manifest properties indistinguishable from the authentic IL-2-R. On the other hand, stimulation of the tyrosine kinase activity by IL-2 was not observed in the chimeric receptor with the entire cytoplasmic domain of the Ins-R. These findings thus shed light on the structural conformation and functioning of the IL-2-R complex.
Solitary Peutz–Jeghers-type hamartomatous polyp as a cause of recurrent acute pancreatitis
Authors: M. Kantarcioglu, G. Kilciler, I. Turan, C. Ercin, Y. Karslioglu, I. Guvenc, Z. Polat, S. Bagci
Journal: Endoscopy (2009)

A 28-year-old man was referred to us with a diagnosis of acute pancreatitis. The patient had experienced abdominal pain, nausea, and vomiting. In the 2 months prior to admission, he had been admitted and treated for acute pancreatitis twice in another hospital. He had no history of alcohol intake or habitual drug use. The physical examination was unremarkable except for epigastric tenderness, but his amylase level was markedly raised (2461 IU/L [normal range < 480 IU/L]). Abdominal ultrasonography and computed tomography (CT) revealed mild edematous acute pancreatitis without gallstones. The CT scan also showed a large (2.5 cm × 1.5 cm), well-circumscribed mass in the second part of the duodenum ([Fig. 1]). Magnetic resonance cholangiopancreatography demonstrated normal common bile duct and pancreatic duct.
Chlorinated and brominated dioxins and dibenzofurans in human tissue following exposure.
Authors: A Schecter, J J Ryan, Y Masuda, P Brandt-Rauf, J Constable, D C Hoang, C D Le, T Q Hoang, T N Nguyen, H P Pham
Journal: Environmental Health Perspectives (1994)

With substantial improvements in analytic techniques over the past decade, it has become possible to measure polychlorinated dioxins (PCDDs) and dibenzofurans (PCDFs) in human tissue in a congener-specific fashion down to the low parts per trillion level. This paper reviews findings using these new techniques from a number of recent medical and environmental case studies. These studies include those of workers exposed to a polychlorinated biphenyl (PCB) transformer fire in the United States, German chemical workers exposed to 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD) while cleaning up after an explosion, workers at a municipal incinerator in New York City, a chemist exposed to brominated and chlorinated dioxins, U.S. veterans and also Vietnamese civilians exposed to Agent Orange contaminated with TCDD in Vietnam, and victims of the polychlorinated dibenzofuran and PCB contaminated rice oil (Yusho) incident in Japan.
Prevention of Rhesus Immunization. A Controlled Clinical Trial with a Comparatively Low Dose of Anti-D Immunoglobulin
Authors: C. D. De Wit, E. Borst-Eilers, Ch.M. v. d. Weerdt, G. J. Kloosterman
Journal: BMJ (1968)

A controlled clinical trial was carried out to test the effectiveness of a comparatively low dose of anti-D immunoglobulin (250 μg) in preventing rhesus immunization. In the control group 17 out of 329 women (5%) formed rhesus antibodies, whereas in the treated group only 3 out of 333 women (0.9%) showed active immunization, all three of whom had an exceptionally large transplacental bleeding.
Oral Lignocaine. Its Absorption and Effectiveness in Ventricular Arrhythmia Control
Authors: P. I. Parkinson, L. Margolin, D. S. P. Dickson
Journal: BMJ (1970)

A preliminary study suggests that the gastrointestinal absorption of lignocaine is predictable and that adequate antiarrhythmic blood concentrations are maintained for four to five hours when 500 mg. is taken with food and for two hours if the drug is taken without food. Ventricular arrhythmias were successfully treated with oral lignocaine in four patients.
Control of Hypertension
Authors: John S. Loder
Journal: JAMA (1977)

To the Editor.—  I write in immediate reference to Dr Kochar's comments on hypertension screening (236:2551) but also regarding the larger issue of what is to be done with the newly found hypertensive person. Dr Kochar says, For treatment of hypertension, a 'step care' approach is advised. Therapy in almost all instances begins with a diuretic.  To a fairly freshly discovered hypertensive person such as myself, it seems that the first and most important therapeutic step in a steppedcare program has been missed in this review and seriously slighted in other reviews.1This missed step is to work with the patient to change his or her life-style.  In my own case, the change needed was to turn from an exceptionally sedentary life to regular daily exercise—swimming about one-half kilometer per day—coupled with some dietary self-restraint. These measures led to modest (6%) weight reduction but substantial blood pressure control (162/102
Abstract B37: Prognostic analysis of primary hepatic carcinoma with cancer embolus of biliary duct
Authors: Bao Tian Zhou
Journal: Clinical Cancer Research (2010)

Abstract Background: In China, primary hepatic carcinoma (PHC) is one of the most frequent malignancies, which is more accompanied by cancer embolus of portal vein and is less with cancer embolus of biliary duct (CEBD) clinically. Anterior cases were diagnosed as PHC with CEBD by B ultrasound, CT, MRCP, or ERCP. Hepatectomy and choledochotomy were performed resecting the primary tumor and cleaning the CEBD completely, followed with TACE after operation. Nowaday ultrasound in biliary duct and orthotopic liver transplantation were worth considering as a brand new and extreme diagnose and treat method respectively. The article was intended to evaluate the clinicopathological characteristics and the prognosis of PHC with CEBD by therapeutic effect contrast to PHC with CEBD in different location. Methods: The clinical data of 412 PHC patients with CEBD underwent surgical hepatectomy from 2000 to 2009 in the several hepatobiliary surgery centers of hospitals in China were retrospectively analyzed to research the clinicopathological characteristics and the prognosis. All the patients were divided into three groups based on distribution and location of CEBD. Results: The overall 1 -year, 3-year, and 5-year survival rates from the time of operation were 76.8%, 53.4%, and 40.1 %, respectively. There was no significant difference in the prognosis between PHC patients with or without CEBD (P&amp;gt;0.05). Independent factors affecting the prognosis of PHC patients were infiltration growth and multiple development. CEBD had no contribution in the prognosis of PHC patients. But the prognosis was different in PHC patients with different locations of cancer embolus in the biliary duct (P&amp;lt;0.05). Conclusion: Surgical operation remains the most effective treatment to PHC patients with CEBD. CEBD had no contribution in the prognosis of PHC patients. The location of the cancer embolus in the biliary duct was significant factors affecting the prognosis of PHC patients with CEBD. The prognosis was the worst in those PHC patients with CEBD located in the right hepatic duct. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B37.
QUANTITATIVE ASSESSMENT OF INTRAVENTRICULAR VORTICITY USING CONVENTIONAL COLOR-DOPPLER ULTRASOUND. HEAD TO HEAD CLINICAL VALIDATION AGAINST PHASE-CONTRAST MAGNETIC RESONANCE IMAGING
Authors: Marta Alhama, Javier Bermejo, Raquel Yotti, Esther Perez-David, Yolanda Benito, Ana Gonzalez-Mansilla, Candelas Perez del Villar, Francisco Fernandez-Aviles, Juan del Alamo
Journal: Journal of the American College of Cardiology (2012)
What's the Price of a Research Subject? Approaches to Payment for Research Participation
Authors: N Dickert, C Grady
Journal: New England Journal of Medicine (1999)

Successful clinical research depends on the ability to recruit research subjects. Tension between the need to recruit subjects and the obligation to offer them certain types of protection has made recruitment a persistent ethical challenge. One important and difficult issue involves whom investigators should enroll in research studies. A different but equally crucial issue concerns the types of inducement investigators should use to recruit subjects.For decades, many investigators have paid subjects for participating in research studies, and this practice remains one of the most controversial methods of recruitment.1 Despite discussions over many years, ethical issues about payment remain unresolved. . . .
Postprandial endothelial dysfunction is not apparent in young healthy individuals
Authors: Spyridon Koulouris, Panagiotis Marousis, Ilias Karabinos, Vasiliki Komesidou, Nikolaos Exadaktylos, Christos Pitsavos, Ioannis Lekakis
Journal: Journal of the American College of Cardiology (2003)
Lymphangioma and Arthus' Phenomenon
Authors: Hugh A. Johnson
Journal: JAMA (1965)

<h3>To the Editor:—</h3> Arthus' phenomenon, the local necrosis of tissue after injection of antigen in a sensitized animal, has been used to slough implanted tumors in experimental animals. Because I have had cases of extensive hemangiomas that have sloughed and regressed after partial excision, it occurred to me that the partial excision might have released an antigen that precipitated the process, which itself was perhaps an expression of the auto-immune disease process, destruction of seemingly normal tissue by the immune reaction. I have not had a non-resectable hemangioma on which I could try my thesis. I have had, however, two cases with extensive lymphangioma-hemangioma in which total excision was out of the question. In the first patient an extensive lymphangioma with minimal areas of capillary hemangioma involved the right arm only. In the second patient an extensive lymphangioma with minimal capillary hemangioma involved many areas of the body. On the
Patients aren't accurate at detecting medical errors
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

Patients and families are often seen as valuable collaborators in improving safety by recognising and reporting medical errors, but a recent study says that they often get it wrong—mistaking delays and poor quality of service for errors.

Patients' safety has received prominent attention in the United States since the Institute of Medicine's 1999 study To Err is Human: Building a Safer Health System , which said that almost 100 000 Americans died each year from medical errors ( BMJ 1999;319:1519).

In the latest study researchers from the …
Tumor derived exosome induction of the CD3+CD8+ T cell tolerogenic phenotype
Authors: Brian Maybruck, Brian Gastman
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Traditionally, CD8+ T cells have been defined as being immunogenic; however, they have also been shown to demonstrate a tolerogenic phenotype. One area less studied, regarding the tolerogenic phenotype of CD8+ T cells, is their role in cancer. What has been described is that their