tbuckley/cabot-search huggingface dataset:
Abstract 2213: Uncommon <i>CHEK2</i> missense variant and reduced risk of pancreatic cancer
Authors: Ghislaine Scelo, James McKay, Ivana Holcatova, Vladimir Janout, Lenka Foretova, Eleonora Fabianova, Amelie Chabrier, Valerie Gaborieau, Paul Brennan
Journal: Cancer Research (2014)

Abstract CHEK2 is a cell cycle control gene encoding for checkpoint kinase 2, which acts as a tumor suppressor by causing arrest or apoptosis in response to unrepaired DNA damage. Inherited mutations in the CHEK2 gene have been reported to increase the risk of several cancers, although a paradoxical decrease in risk of tobacco-related lung and head and neck cancers was reported. An association between CHEK2 mutations and pancreatic cancer risk has not been reported. Missense variant rs17879961 (replacement of T by C, resulting in the change of Isoleucine by Threonine at position 157 of the protein [I157T]) has been shown to be very rare in the US and western Europe populations (&amp;lt;1%) while more common in central Europe countries (∼5%). We genotyped 585 pancreatic cancer cases and 664 controls recruited in central Europe (Czech Republic and Slovakia). The heterozygous (T/C) genotype was observed in 2.1% of cases and 4.4% of controls. After adjustment for age, sex, and center of recruitment, T/C genotype was associated with a significantly lower incidence of pancreatic cancer than the common T/T genotype (odds ratio [OR]=0.41, 95% confidence interval [CI] 0.20-0.83, p=0.0132). ORs were of similar magnitude by smoking status, diabetes history, and body mass index categories, while an apparent difference by drinking status with observed: OR=0.24 (95% CI 0.09-0.64) for non-drinkers versus OR=0.88 (95%CI 0.31-2.53), p for heterogeneity=0.078. This counter-intuitive halving of the pancreatic cancer risk for CHEK2 rs17879961 T/C carriers warrants replication and functional studies to elucidate mechanisms involved. Citation Format: Ghislaine Scelo, James McKay, Ivana Holcatova, Vladimir Janout, Lenka Foretova, Eleonora Fabianova, Amelie Chabrier, Valerie Gaborieau, Paul Brennan. Uncommon CHEK2 missense variant and reduced risk of pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2213. doi:10.1158/1538-7445.AM2014-2213
Fatal methadone overdose
Authors: E. W Benbow, I. S D Roberts, A. Cairns
Journal: BMJ (1997)

Editor–We had grandiose plans for our study of methadone related deaths1–until we realised that the local drug rehabilitation community was more interested in bidding for a forthcoming contract to provide a methadone maintenance programme to Manchester Health Authority. Our most informative contact refused to be acknowledged in print for fear of dismissal for revealing “commercially sensitive” information about the nature of certain bids. For these reasons, we limited ourselves to studying coroners' records. We freely admit that this approach has drawbacks: for …
SUPPURATIVE APPENDICITIS IN A PATIENT WITH TRANSPOSED VISCERA
Authors: H. Hebblethwaite
Journal: BMJ (1907)

ouAL 1579 determination of a. Thus a specimen which has a true freezing point, -0 61°C., indicating an advanced state of disease, may appear to bave a value a = 0.580 C., a normal value, if the zero has shifted 0.03°C, a by no means unlikely amount in warm weather.
Book Review Letting Go: Death, Dying, and the Law By Melvin I. Urofsky. 204 pp., New York, Charles Scribner's Sons, 1993. $22.50. 0-684-19344-2 Advance Directives and the Pursuit of Death with Dignity By Norman L. Cantor. 209 pp. Bloomington, Indiana University Press, 1993. $24.95. 0-253-31304-X
Authors: Marshall B. Kapp
Journal: New England Journal of Medicine (1994)
Manic Syndrome Associated With Zidovudine
Authors: Mary Alice O'Dowd, F. Patrick McKegney
Journal: JAMA (1988)

<h3>To the Editor. —</h3> A recent Letter to the Editor<sup>1</sup>reported two cases of manic syndrome associated with zidovudine. In both cases, zidovudine therapy was resumed, but only with maintenance lithium and antipsychotic therapy. We wish to report an additional case of manic syndrome associated with zidovudine therapy in which therapy was resumed without the need for antipsychotics or lithium. <h3>Report of a Case.—</h3> A 36-year-old homosexual man with no psychiatric history was diagnosed as having acquired immunodeficiency syndrome— related complex in 1986. Zidovudine therapy (100 mg/4 h) was started in September 1987. He was also receiving aerosolized pentamidine twice weekly. After seven months of treatment with zidovudine, he was noted by his family to be increasingly irritable and shortly thereafter became frankly delusional. He was admitted to a medical unit, where he was found to be grandiose and hypersexual. His affect was preponderately euphoric and showed an impairment
Histocompatibility antigens controlled by the I region of the murine H-2 complex. I. Mapping of H-2A and H-2C loci.
Authors: J Klein, R Geib, C Chiang, V Hauptfeld
Journal: The Journal of Experimental Medicine (1976)

Skin grafts were reciprocally exchanged in pairs of congenic lines identical in all genes except those located in the central portion of the H-2 complex. Seven such lines were tested: 6R, B10.AQR, A.TL, A.TH, 7R, 9R, and B10.HTT. In all donor-recipient combinations at least some grafts were rejected. In combinations differing at the IA subregion (and other central H-2 regions or subregions), all first-set grafts were rejected within 3 wk after transplantation, and all second-set grafts were rejected within 10 days. In combinations differing at the IC subregion (and other central regions, but not at the IA subregion) between 60 and 100% of first-set grafts were rejected, but some grafts survived for over 100 days. Most of the second-set grafts were rejected within 1 mo after grafting. This behavior of skin grafts indicated the presence of two histocompatibility loci in the I region, a strong one and a weak one. This conclusion was confirmed by genetic mapping which placed the strong locus in the IA subregion and the weak locus in the IC subregion. We designate the former locus H-2A and the latter H-2C. The same strain combinations used for the skin grafting were also used for determination of the capacity of I-region antigens to function as targets in the in vitro cell-mediated lymphocytotoxicity (CML) assay. Spleen cells from mice presensitized in vivo by skin grafting were restimulated in vitro and tested against 51Cr-labeled concanavalin A or lipopolysaccharide blasts. The testing revealed the presence in the I region of two loci coding for CML-target antigens. The two loci comapped with the H-2A and H-2C loci and were most likely identical to them. As in the skin grafting test, in the CML test, the H-2A antigens evoked stronger response than the H-2C antigens. Rejection of skin grafts across the H-2A and H-2C loci was accompanied by the production of Ia antibodies. Direct cytotoxic and absorption tests with Ia antibodies directed against antigens coded for by the IC subregion revealed the presence of IaC antigens on epidermal cells. We suggest that the products of Ia loci might function as transplantation antigens.
Burkitt's Lymphoma in an Arid Part of Texas
Authors: Jeremiah J. Twomey
Journal: JAMA (1966)

BURKITT, in 1958, drew attention to the high incidence of an unusual type of lymphoma in Uganda.<sup>1</sup>It occurs largely in children and involves the retroperitoneal space, facial bones, and ovaries in females.<sup>2</sup>The peripheral lymph nodes are usually spared. These lymphomas are uniformly immature lymphoreticular tumors with prominent histiocytic phagocytosis giving a characteristic microscopic "starry sky" appearance.<sup>3</sup>This histiocytic phagocytosis is not restricted to the Burkitt type of lymphoma,<sup>4</sup>which is best recognized by its anatomical distribution. The epidemiology of Burkitt's tumor in Africa<sup>5,6</sup>suggests that its incidence is influenced by environmental factors. These include a warm climate throughout the year<sup>5</sup>and a heavy annual rainfall.<sup>6</sup>Cases have been observed only occasionally at altitudes higher than 5,000 feet.<sup>6,7</sup>This may be related to lower prevailing temperatures at higher altitudes. Its geographical distribution has been suggested as evidence that the tumor may be
Scalp cyst with heterotopic brain tissue
Authors: D.W. PRYCE, M. KHINE, J.L. VERBOV, D. VELZEN
Journal: British Journal of Dermatology (1993)

Journal Article Scalp cyst with heterotopic brain tissue Get access D.W. PRYCE, D.W. PRYCE Department of Dermatology, Royal Liverpool Children's Hospital Myrtle Street, Liverpool, U.K Dr D.W. Pryce, Dermatology Department. Royal Liverpool University Hospital. Prescot Street. Liverpool L7 8XP, U.K. Search for other works by this author on: Oxford Academic Google Scholar M. KHINE, M. KHINE Department of Pathology, Royal Liverpool Children's Hospital Myrtle Street, Liverpool, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.L. VERBOV, J.L. VERBOV Department of Dermatology, Royal Liverpool Children's Hospital Myrtle Street, Liverpool, U.K Search for other works by this author on: Oxford Academic Google Scholar D. VAN VELZEN D. VAN VELZEN Department of Pathology, Royal Liverpool Children's Hospital Myrtle Street, Liverpool, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 2, 1 August 1993, Pages 183–185, https://doi.org/10.1111/j.1365-2133.1993.tb03525.x Published: 01 August 1993 Article history Accepted: 15 February 1993 Published: 01 August 1993
Sheep lung cytochrome P4501A1 (CYP1A1): cDNA cloning and transcriptional regulation by oxygen tension.
Authors: T A Hazinski, E Noisin, I Hamon, A DeMatteo
Journal: Journal of Clinical Investigation (1995)

Lung cytochrome P450 activity has been linked to neoplasia and may produce reactive oxidant species and potent arachidonic acid metabolites. In lamb lung, oxygen breathing increases lung P450 activity, and inhibition of lung cytochrome P450 activity reduces oxygen-induced lung injury. The P4501A1 (CYP1A1) isozyme is present in many lung cells, including endothelial cells, and may therefore be involved in the pathogenesis of hyperoxic injury to microvascular endothelium. Therefore, to test the hypothesis that oxygen regulates P4501A1 gene expression in the lung, we cloned the sheep P4501A1 cDNA, and examined its regulation by oxygen breathing significantly increased lung P4501A1 RNA levels and that this increase preceded the increase in isozyme activity. Oxygen exposure also promptly increased P4501A1 RNA levels in cultured lamb lung microvascular endothelial cells but not in endothelial cells isolated from the main pulmonary artery or in lung smooth muscle cells. The oxygen-stimulated increase in P4501A1 RNA levels was not serum dependent, was unaffected by cycloheximide treatment, and could not be mimicked by treatment of the cells with oxygenated medium, conditioned medium, or by chemical oxidants. By nuclear run-on assay in cultured lung endothelial cells, oxygen increased the transcription rate of P4501A1 by almost fourfold after 90 min of oxygen exposure but had no significant effect on P4501A1 RNA stability. We conclude that oxygen tension, but not chemical oxidants, increases P4501A1 gene expression pretranslationally in lung microvascular endothelial cells. We speculate that oxygen induction of P450 activity in these cells may contribute to microvascular injury during oxygen breathing.
European Medicines Agency is accused of weakening its conflict of interest policy
Authors: R. Watson
Journal: BMJ (2014)

Critics have claimed that the European Medicines Agency has watered down its rules on conflicts of interest among committee members and experts, under a new policy that is due to come into effect at the end of January.

The EMA said that the revised policy, which was endorsed by its management board in March 2014, was designed to ensure a more balanced approach than its earlier stance and to ensure that it had access to the best possible expertise.1

Noel Wathion, the agency’s chief policy adviser, explained that past experience had shown that an …
Bronchoconstrictor effect of deep inspiration in asthma
Authors: G M Sterling
Journal: Thorax (2002)

IL-5 in asthmaWe have recently published two manuscripts on the effects of interleukin (IL)-5 administration to patients with mild asthma in the American Journal of Respiratory & Critical Care Medicine 1 and in Thorax. 2 We are addressing this letter to the Editors of both journals.The data described in both papers have been obtained from one experiment performed in the same group of patients with mild asthma.While the paper in the American Journal of Respiratory & Critical Care Medicine reports primarily on the phenotypic changes in circulating blood eosinophils and CD34+ cells, the Thorax paper describes the changes in the airways with measurements of bronchial responsiveness and of eosinophil counts in sputum, together with eotaxin levels in the serum.Both manuscripts, however, detail the changes in blood eosinophil counts and serum
Immunohistochemical study of α1-5 chains of type IV collagen in hereditary nephritis
Authors: Koichi Nakanishi, Norishige Yoshikawa, Kazumoto Iijima, Kosaku Kitagawa, Hajime Nakamura, Hiroshi Ito, Kazuo Yoshioka, Megumi Kagawa, Yoshikazu Sado
Journal: Kidney International (1994)
RENAL FUNCTION DURING GENERAL ANESTHESIA AND OPERATION
Authors: E. M. Papper
Journal: JAMA (1953)

Interest in renal function during anesthesia and operation and in the postoperative period has increased greatly in recent years. There has been an intensive effort to gain further knowledge about renal activity in surgical patients, with a greater appreciation of the subtle physiological changes that occur during and after operation. Renal function was not previously emphasized in care of surgical patients because of pressing demands for study of cardiovascular function and respiration, which are immediate problems in every surgical patient. Although not so apparent, the influence of the kidney on the ultimate success of surgical procedures is no less striking. This paper reviews briefly some of the aspects of renal function during anesthesia and surgery. Perhaps it is not generally realized that the kidney is a circulatory organ of considerable importance; it normally accommodates approximately 25% of the total cardiac output. The kidney undoubtedly has an important role in circulatory
Organochlorines in the environment and breast cancer
Authors: T Key, G Reeves
Journal: BMJ (1994)

of datasets for secondary analysis that maintain the con- fidentiality of subjects.Adequate documentation should accompany such datasets, and the costs of producing the material should be covered by the initial grants-in which case funding agencies would have to provide the necessary finance-or costs should be covered by the secondary analysts.Clearing houses for shared data would reduce the burden on primary researchers.After providing a documented dataset to the central archive once, researchers need not repeatedly answer requests, as the archive takes on this task.The Economic and Social Research Council has established such an archive,24 and other topic based databanks exist.6Journals also have a role in encouraging the sharing of data.For example, the American Journal of Public Health stipulates that data are, in principle, available to the editors and to interested researchers.6If papers
Multiple nuclear dots antinuclear antibodies are not specific for primary biliary cirrhosis
Authors: Jean-Michel Pawlotsky, Chantal Andre, Jean-Michel Metreau, Michel Beaugrand, Elie-Serge Zafrani, Daniel Dhumeaux
Journal: Hepatology (1992)

Multiple nuclear dots antinuclear antibodies display a specific immunofluorescence pattern on HEp-2 cells. They have been reported to be strongly associated with primary biliary cirrhosis, especially when sicca syndrome was present. To determine whether multiple nuclear dots antinuclear antibodies are specific for primary biliary cirrhosis, we studied the clinical, biochemical, immunological and morphological features of 38 patients between December 1983 and September 1990 who had serum multiple nuclear dots antinuclear antibodies detected in an immunology laboratory of a large medical center. Sufficient information was reliable in 36 patients; the group included 31 women and 5 men (mean age = 57.6 +/- 14.5, range = 30 to 87). Fifteen patients (42%) had primary biliary cirrhosis, 5 patients (14%) had type 1 autoimmune chronic active hepatitis, 4 patients (11%) had liver disease of unknown cause and 12 patients (33%) had various immunological disorders but no liver disease. Two of the patients with primary biliary cirrhosis (13%) had clinical sicca syndrome. Our study demonstrates the following: (a) serum multiple nuclear dots antinuclear antibodies are not specific for liver disease because they can be observed in one third of patients with various immunological disorders without liver involvement, and (b) serum multiple nuclear dots antinuclear antibodies are not specific for PBC because they can also be observed in type 1 autoimmune chronic active hepatitis. Our results also suggest that patent sicca syndrome is abnormally present in patients with primary biliary cirrhosis and multiple nuclear dots antinuclear antibodies.
Induction of Serum<i>Haemophilus influenzae</i>Type B Capsular Antibodies in Adult Volunteers Fed Cross-Reacting<i>Escherichia coli</i>075:K100:H5
Authors: Rachel Schneerson, John B. Robbins
Journal: New England Journal of Medicine (1975)

Serum Haemophilus influenzae Type b (HITB) anticapsular antibodies were induced in adult volunteers by feeding of either of two strains of a cross-reacting Escherichia coli 075:K100:H5. In all the fed volunteers colonization for a finite period lasting up to eight weeks occurred, without adventitious reactions. Nine of 14 normal volunteers and one of two volunteers previously immunized with the Type 6 H.influenzae polysaccharide responded with a greater than twofold increase in serum Type 6H. influenzae antibodies. These antibodies induced by Esch. coli were specific for the capsular polysaccharide and had bactericidal activity. The safety of this procedure, the comparable results in laboratory animals and the identification of other cross-reacting strains of Esch. coli with meningococcal and pneumococcal capsular polysaccharides suggest that colonization with these nonpathogenic organisms at birth may provide a general method of preventive immunization to diseases caused by encapsulated bacteria.
Supreme Court case could upend Affordable Care Act
Authors: M. McCarthy
Journal: BMJ (2015)

The US Supreme Court will hear oral arguments on Wednesday 4 March in a case that, should the justices decide for the plaintiffs, could potentially eviscerate the 2010 Affordable Care Act.

In the case King versus Burwell the plaintiffs argue that federal subsidies that have helped millions of US consumers to purchase health insurance coverage through the federal exchange created by the 2010 act are illegal.1

At issue are five words in the law that state that the subsidies would be made available through an “exchange established by the state.” Unexpectedly, only 13 states and the District of Columbia elected to set up their own exchanges, with the rest opting …
Occupational asthma and rhinoconjunctivitis from inhalation of dried cow's milk caused by sensitization to α‐lactalbumin
Authors: G. Bernaola, S. Echechipía, I. Urrutia, E. Fernández, M. Audícana, L. Fernández de Corres
Journal: Allergy (1994)

A chocolate candy worker was diagnosed as having occupational asthma and rhinoconjunctivitis on the basis of clinical record and methacholine challenge. Positive conjunctival and bronchial challenge tests with lactalbumin showed that this protein was the pathogenetic agent. Type I hypersensitivity mechanism is demonstrated by means of skin prick test and RAST.
ROLE OF NUTRITIONAL INTERVENTION ON REVERSAL OF FETAL DUCTAL CONSTRICTION CAUSED BY MATERNAL INGESTION OF POLYPHENOL-RICH FOODS
Authors: Paulo Zielinsky, Antonio L. Piccoli, João L.L. Manica, Luiz Henrique E. Nicoloso, Izabele Vian, Luciano P. Bender, Patrícia E. Pizzato, Marcelo Pizzato, Fernanda Swarowsky, Carolina W. Barbisan
Journal: Journal of the American College of Cardiology (2011)
Quality Standards of Hospital Care — Who Is Legally Liable?
Authors: William J. Curran
Journal: New England Journal of Medicine (1969)

HOSPITAL personnel have been brought up for many years on the principle that "hospitals do not practice medicine." The law courts have in the past agreed with this proposition, asserting that only physicians can be licensed by law to practice medicine and, therefore, that hospitals can neither practice medicine nor control the actions of physicians. This proposition applies as well to dentists and nurses and other health professionals who are legally licensed. The hospital can no more perform these services than those of physicians, at least from the point of view of a legal authority under license.But the law . . .
1,25-Dihydroxyvitamin D3 induces collagen binding to the human monocyte line U937.
Authors: B S Polla, A M Healy, M Byrne, S M Krane
Journal: Journal of Clinical Investigation (1987)

Interactions of cells with components of the extracellular matrix can modulate cellular functions. We measured binding of a major matrix protein to U937 cells, a human promonocytic line. Radioiodinated type I or type III human collagen was bound only to U937 cells differentiated to a more mature phenotype with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Binding was observed at 4 degrees C and was saturable; Scatchard analysis of the binding to 1,25-(OH)2D3-pretreated U937 cells indicated a single class of high-affinity binding sites. Preincubation of U937 cells with interferon gamma did not induce collagen binding. Collagen binding did not appear to be dependent on fibronectin binding. Surface proteins of U937 cells were 125I labeled and cell membrane proteins resolved by affinity chromatography on collagen-Sepharose. Major specifically labeled bands of 180, 155, and 125 kD were identified in membrane fractions from 1,25-(OH)2D3-pretreated U937 cells only. 1,25-(OH)2D3 appears to specifically regulate collagen binding to monocyte precursors.
Abstract IA4: Designing biological systems to report on disease
Authors: Pamela A. Silver
Journal: Cancer Research (2012)

Abstract Biology presents us with an array of design principles. From studies of both simple and more complex systems, we understand some of the fundamentals of how nature works and what goes wrong in the disease state. We are interested in using the foundations of biology to engineer cells in a logical and predictable way to perform certain functions with relevance to therapeutics and diagnostics. By necessity, the predictable engineering of biology requires knowledge of quantitative behavior of individual cells and communities and the ability to construct reliable models. By building and analyzing synthetic systems, we learn more about the fundamentals of biological design as well as engineer useful living devices with myriad applications. For example, we are interested in building cells that can perform specific tasks, such as remembering past events and thus acting as a biological computer. In particular, we have built genetic circuits whereby cells can ‘remember’ stimuli for many generations including DNA damage and hypoxia. By characterizing these ‘memory’ cells, we can identify key genes that may act as therapeutic targets and explanations for persistence of a subset of cells in tumors. Citation Format: Pamela A. Silver. Designing biological systems to report on disease [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr IA4.