tbuckley/cabot-search huggingface dataset:
Duodenal intramural hematoma and delayed perforation: rare but fatal complication of endoscopic therapy for a bleeding duodenal ulcer
Authors: H. Yen, Y. Chen
Journal: Endoscopy (2009)

A 57-year-old woman was admitted with drug-induced hepatitis. An episode of tarry stool passage occurred on the third day in hospital and was treated using a proton pump inhibitor. The bleeding reoccurred on the fourteenth day and upper gastrointestinal endoscopy revealed an actively bleeding duodenal ulcer ([Fig. 1]). Initial hemostasis was achieved with an injection of diluted epinephrine and application of two hemoclips. In the mean time, the patient’s hepatitis resolved. Three days after endoscopy, the patient had vomiting and upper abdominal pain. An abdominal computed tomography (CT) scan disclosed a hyperdense mass over the duodenum. Repeat endoscopy revealed a duodenal intramural hematoma (DIH) with a severe luminal obstruction ([Fig. 2]), and conservative management was started. One week later, the patient experienced a sudden onset of upper abdominal pain. A repeat CT scan revealed duodenal perforation ([Fig. 3]), which was surgically repaired. However, on day 56 in hospital, the patient died of postoperative complications.
Epidermal architecture, growth, and metabolism in acromegaly.
Authors: P J Holt, R Marks
Journal: BMJ (1976)

Epidermal architecture, replication, and anabolic activity were studied in six patients with acromegaly. Patients with acromegaly had significant larger viable epidermal cells than controls. The rates of incorporation of tritiated thymidine, proline, and histidine into skin slices in vitro was also significantly increased in acromegalic patients. The mean autoradiographic labelling indices after intracutaneous injection of triated thymidine were 8.4% in the acromegalic patients and 5.1% in the control group. None of the changes observed could be closely correlated with levels of serum growth hormone.
Comparing the neural blackboard and the temporal synchrony-based SHRUTI architectures
Authors: Lokendra Shastri
Journal: Behavioral and Brain Sciences (2006)

Contrary to the assertions made in the target article, temporal synchrony, coupled with an appropriate choice of representational primitives, leads to a functionally adequate and neurally plausible architecture that addresses the massiveness of the binding problem, the problem of 2, the problem of variables, and the transformation of activity-based transient representations of events and situations into structure-based persistent encodings of the same.
SP0030 Type I Interferonopathies
Authors: L. Rönnblom
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> A number of autoimmune diseases have an increased expression of type I interferon regulated genes in cells from peripheral blood and tissues. This so called interferon signature has been found in patients with SLE, primary Sjögrens syndrome, systemic sclerosis, myositis and a subset of patients with rheumatoid arthritis. The reasons behind the continuous activation of the type I interferon system in patients with these diseases are presence of self-derived inducers of type I interferon production by plasmacytoid dendritic cells (pDCs), lack of proper regulation of cells in the type I interferon system and a genetic predisposition to an enhanced type I interferon response. In fact, a large proportion of the genes predisposing to autoimmunity are involved in the type I interferon signaling pathway, either the production of type I interferon or the response downstream the type I interferon receptor. This has been extensively studied in SLE and among lupus risk genes involved in the production of type I interferon are interferon regulatory factor 5 (<i>IRF5</i>), <i>IRF7</i> and interleukin-1 receptor associated kinase (<i>IRAK1</i>). SLE susceptibility genes important for the type I interferon response are tyrosine kinase 2 (<i>Tyk2</i>), Signal Transducer and Activator of Transcription 4 (<i>STAT4</i>) and interferon induced with helicase C domain 1 (<i>Ifih1</i>). Several of these genes are in addition risk genes for autoimmune diseases beside SLE. Rare mutations of a number of genes, for instance <i>TREX1</i> and <i>ACP5</i>, also cause an increased expression of type I interferon stimulated genes and an autoimmune disease resembling SLE. There are several mechanism by which the increased activation of the type I interferon system can contribute to loss of tolerance and an autoimmune disease process. Thus, type I interferon is an immune adjuvant and stimulate cells in both the innate and adaptive immune system, but can also increase the expression of autoantigens. A major challenge in these so called type I interferonopathies is to down regulated the type I interferon system without increasing the risk for severe infections. <h3>Disclosure of Interest</h3> None Declared
From Molecular Biology to the Bedside
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (1984)

The ability of the immune system to generate innumerable variants of the immunoglobulin structure that binds to antigen — the antibody variable region — sets it apart from all other biologic systems. How that unique diversity originates has challenged immunologists for over 50 years, but an explanation has at last been found. Its solution is a triumph of molecular biology.1 Not only is the mechanism intellectually satisfying but, as we shall see, it is clinically important.Let us consider how immunoglobulin diversity develops, by imagining that antibodies constitute the language of lymphocytes. The words of the language are the variable . . .
α2-Macroglobulin Inhibits the Malignant Properties of Astrocytoma Cells by Impeding β-Catenin Signaling
Authors: Inge Lindner, Nasr Y.A. Hemdan, Martin Buchold, Klaus Huse, Marina Bigl, Ilka Oerlecke, Albert Ricken, Frank Gaunitz, Ulrich Sack, Andreas Naumann, Margrit Hollborn, Dietmar Thal, Rolf Gebhardt, Gerd Birkenmeier
Journal: Cancer Research (2010)

Abstract Targets that could improve the treatment of brain tumors remain important to define. This study of a transformation-associated isoform of α2-macroglobulin (A2M*) and its interaction with the low-density lipoprotein receptor-related protein-1 (LRP1) suggests a new mechanism for abrogating the malignant potential of astrocytoma cells. LRP1 bound A2M* found to be associated with an inhibition of tumor cell proliferation, migration, invasion, spheroid formation, and anchorage-independent growth. Transcriptional studies implicated effects on the Wnt/β-catenin signaling pathway. Notably, LRP1 antibodies could phenocopy the effects of A2M*. Our findings suggest a pathway of tumor suppression in astrocytoma that might be tractable to therapeutic exploitation. Cancer Res; 70(1); 277–87
INHIBITION OF LIPOPROTEIN LIPASE ACTIVITY FOLLOWING INJECTION OF PITUITARY EXTRACTS INTO RABBITS
Authors: Aaron Kellner, Robert L. Hirsch, Elizabeth B. Freeman
Journal: The Journal of Experimental Medicine (1960)

Rabbits given a single subcutaneous injection of an alkaline extract of hog, bovine, or human anterior pituitary glands developed marked hyperlipemia within 12 to 24 hours. The injections in some instances were followed by sickening and death of the animal, though no anatomical changes responsible for these consequences could be determined. No such sequelae were observed in animals given much larger injections of comparable extracts made from other tissues. An inhibitor to lipoprotein lipase appeared regularly in the serum of the injected animals in association with the hyperlipemia. The injection of heparin into such animals failed to result in the elaboration of clearing factor, and serum from these animals inhibited in vitro the hydrolysis of lipid emulsions by active lipoprotein lipase obtained from normal rabbits or human beings. The inhibitor was produced only in vitro by the pituitary extracts. It did not antagonize the anticoagulant action of heparin, and is probably a lipoprotein.
Comparison of Bombyx mori and Helicoverpa armigera cytoplasmic actin genes provides clues to the evolution of actin genes in insects
Authors: A. Mange, J. C. Prudhomme
Journal: Molecular Biology and Evolution (1999)

The cytoplasmic actin genes BmA3 and BmA4 of Bombyx mori were found clustered in a single genomic clone in the same orientation. As a similar clustering of the two cytoplasmic actin genes Ha3a and Ha3b also occurs in another lepidopteran, Helicoverpa armigera, we analyzed the sequence of the pair of genes from each species. Due to the high conservation of cytoplasmic actins, the coding sequence of the four genes was easily aligned, allowing the detection of similarities in noncoding exon and intron sequences as well as in flanking sequences. All four genes exhibited a conserved intron inserted in codon 117, an original position not encountered in other species. It can thus be postulated that all of these genes derived from a common ancestral gene carrying this intron after a single event of insertion. The comparison of the four genes revealed that the genes of B. mori and H. armigera are related in two different ways: the coding sequence and the intron that interrupts it are more similar between paralogous genes within each species than between orthologous genes of the two species. In contrast, the other (noncoding) regions exhibited the greatest similarity between a gene of one species and a gene of the other species, defining two pairs of orthologous genes, BmA3 and HaA3a on one hand and BmA4 and HaA3b on the other. However, in each species, the very high similarities of the coding sequence and of the single intron that interrupts it strongly suggest that gene conversion events have homogenized this part of the sequence. As the divergence of the B. mori genes was higher than that of the H. armigera genes, we postulated that the gene conversion occurred earlier in the B. mori lineage. This leads us to hypothesize that gene conversion could also be responsible for the original transfer of the common intron to the second gene copy before the divergence of the B. mori and H. armigera lineages.
Stress and illness: call to action
Authors: Woody Caan
Journal: BMJ (2006)

One-time general consent for research on biological samples Opt out system for patients is optimal and endorsed in many countriesEditor-Wendler's valuable overview of empirical studies of patients' preferences about the use of residual (leftover) tissue for research is not complete. 1 The discussion has already been settled by legislation in many countries.In 2004 the Danish act on patient rights was amended with an opt out system for using residual tissue for research.In 2004 the US Office for Human Research Protections (OHRP) issued guidance that research on residual tissue which is anonymous to the researcher is not human subject research and therefore the tissue can be used without consent. 2Earlier the Dutch Federation of Medical Research Societies' code of conduct on research with residual tissue drafted with patients' organisations had an opt out system for research on samples anonymous to the researcher. 3 In the recent UK Human Tissue Act no form of consent is needed for the use of fully anonymous or coded (or linked) residual tissue that is anonymous to the researcher, provided that an ethical review board has permitted the study.The more restrictive provisions in the original bill were amended also because of pressure from patient groups afraid that research to their benefit would be hampered by the proposed consent system.Wendler emphasises autonomy and argues that one-time consent protects the autonomy of individuals and protects them from serious risks.There are two major arguments against this.Firstly, autonomy should be balanced against other values such as the interests of patients who might benefit from this research. 4 Secondly, autonomy as such cannot protect individuals from risks but only from risks they do want to carry.Research on residual tissue, whether anonymous or anonymously used and being coded, does not carry any risks to individuals.Ethical review boards should oversee that sufficient measures have been taken to ensure that the samples used in research remain anonymously used.It should be possible to enrich data from tissue research with patient data.Fully anonymising samples, as suggested by Wendler, is a waste of valuable information.
Human Cloning and the Challenge of Regulation
Authors: John A. Robertson
Journal: New England Journal of Medicine (1998)

The birth of Dolly, the sheep cloned from a mammary cell of an adult ewe, has initiated a public debate about human cloning. Although cloning of humans may never be clinically feasible, discussion of the ethical, legal, and social issues raised is important. Cloning is just one of several techniques potentially available to select, control, or alter the genome of offspring.13 The development of such technology poses an important social challenge: how to ensure that the technology is used to enhance, rather than limit, individual freedom and welfare.A key ethical question is whether a responsible couple, interested in . . .
Ross Meuros Paxton
Authors: R. Parrish
Journal: BMJ (2010)

<h3>Summary</h3> 1.Clinical, laboratory and pathologic data on the course of tularemia in normal and vaccinated <i>Macacus mulatta</i> are presented. 2.The disease in monkeys has many similarities to the disease in man. 3.Vaccination did not protect immature monkeys against large infective doses and only partially protected young adult monkeys against small infective doses. 4.An improved vaccine described by Foshay was the most effective of the four vaccines tested.
Molecular genetics of heart, lung, and blood diseases. The shape of things to come.
Authors: C Lenfant
Journal: Circulation (1993)

M odern molecular genetics has revolutionized medical research by providing approaches to determine the location of genes that cause disease, even in the absence of knowledge about the underlying biological defects.These new approaches, when combined with innovative techniques derived from such traditional disciplines as physiology and biochemistry, will have far-reaching effects.Potential benefits include improved methods for presymptomatic diagnosis, carrier detection, primary prevention, and treatment.The National Heart, Lung, and Blood Institute (NHLBI) has an established record of encouraging and supporting the development of innovative genetic approaches to study monogenic disorders, including cystic fibrosis, familial hypertrophic cardiomyopathy, hemo- philia, and sickle cell disease.While continuing its commitment to stimulate and support such efforts, the institute is placing a major emphasis on the use of existing knowledge to devise effective methods of genetic therapy for these diseases.One manifestation of that emphasis is the Working Group on Gene Therapy Approaches and Resources for Heart, Lung, and Blood Diseases, convened by the institute in 1992.Its charge was to identify new opportunities and chart a course for future research efforts.The working group recognized that several clinical protocols involving gene transfer were already approved and generating data, but they noted the existence of barriers to the further evolution of human gene therapy.Although genetic interventions for heart, lung, and blood diseases may differ in the specifics of the approach, the working group identified common themes in scientific issues and resources fundamental to facilitat- ing development of gene therapy for these diseases.Two planned NHLBI programs already reflect the influence of the working group's report.Gene Therapy Approaches for Cystic Fibrosis aind Other Heart, Lung, and Blood Diseases will promote collaboration within and between research institutions, develop infrastruc- tural resources, and foster the entry of both young and established investigators into the field of gene therapy research.The other, Gene Therapy for Sickle Cell Disease, is directed toward developing strategies to correct or replace the endogenous, defective gene in sickle cell anemia.
Letter from Chicago: Orphans
Authors: G. Dunea
Journal: BMJ (1991)

In the past orphaned children have often suffered greatly, being abused, neglected, brought up by hand, or denied a second helping of gruel.But orphan drugs have escaped such a cruel fate, at least in recent times.Indeed since 1983 these drugs for rare diseases and with limited commercial potential have prospered.For in that year congress promoted their development by granting the manufacturers several tax incentives as well as a seven year market exclusivity.These arrangements worked well.Even critics of government interference conceded that for once congress had done something right.About 400 new drugs were developed during that period.Some 50 were approved for marketing, notably erythropoetin, synthetic growth hormone, and inhaled pentamidene -some with annual sales exceeding $200 million.But lately the stellar success of these orphans has bred concern and envy.Several lobbies complained that the prices charged were too high and kept the drugs from patients, especially those with AIDS.Drug companies left out in the cold may also have experienced the green eyed passion.To help, last year Democrat Congressman Henry Waxman sponsored a bill revoking the seven year marketing exclusivity once the number of patients needing a drug exceeded 200 000.The bill would have also allowed a second company to market the drug if it could prove it had begun work on it within six months of orphan status being granted to the first company.
EDUCATIONAL NUMBER, SESSION 1934-5: THE TRAINING OF THE MEDICAL PRACTITIONER
Authors: H. Brackenbury
Journal: BMJ (1934)

Medical education, like all other education, is a co- operative businress'.The idea that even the infant mind is a tabula rasa, a clean slate on which the parent, the teacher, environment in general, may write what it will, has long since been discardel.But even the infant mind, conditioned, as to the impressions that may be made upon it, by the biologically inherited number, character, and connexions of the brain cells, is not a passive instrument, but, at least after those first few months of extrauterine life of which we really know so little, progressively takes a larger and larger part in itself' determining wvhat impressions it will receive -and how it will react to them.By the time adolescence is reached nature and nurture, especially the deliberate discipline of the schools, have produced or disclosed limitations, of a greater or less degree of severity, so that, with regard to all subsequent education, whether of a general or of a technical character, the contribution of the student is of at least equal impor- tance to the contribution 'of the teacher.In medical education, as in other spheres, this is sometimes forgotten, or at least not always given its full emphasis, and it is by no means uncommon, when the result is not con- spicuously successful, for the teaching to be blamed when the student is at fault, and vice versa.The considera- tion, therefore, of what these respective contributions o9ght to be should be of substantial value and importance.Though their formulation and definition is not easy, and though others might prefer to set them out quite differently, the attempt may be worth making.The con- tribution of the medical school may be considered first, and then the contributlon of the student.
Treatment of polymyalgia rheumatica and giant cell arteritis. I. Steroid regimens in the first two months.
Authors: V Kyle, B.L Hazleman
Journal: Annals of the Rheumatic Diseases (1989)

Thirty nine patients with polymyalgia rheumatica (PMR) and 35 with giant cell arteritis (GCA) were treated with high or low dose steroid regimens in a prospective study of the first two months of treatment. Patients with PMR needed 15-20 mg prednisolone initially; 13/20 (65%) relapsed on an initial dose of 10 mg/day. All but two patients with GCA were successfully treated with 40 mg/day prednisolone initially but relapsed on a reduction to 20 mg/day. One patient with GCA receiving 30 mg/day relapsed after four weeks. Six patients with PMR developed GCA during the first two months and required an increased prednisolone dose to control symptoms. The erythrocyte sedimentation rate or C reactive protein did not predict relapse.
Human CD19 and CD40L deficiencies impair antibody selection and differentially affect somatic hypermutation
Authors: Menno C. van Zelm, Sophinus J.W. Bartol, Gertjan J. Driessen, Françoise Mascart, Ismail Reisli, Jose L. Franco, Beata Wolska-Kusnierz, Hirokazu Kanegane, Louis Boon, Jacques J.M. van Dongen, Mirjam van der Burg
Journal: Journal of Allergy and Clinical Immunology (2014)
Clusters of anophthalmia: No link with benomyl in Italy..
Authors: F Bianchi, A Calabro, E Calzolari, P P Mastroiacovo, G Petrelli, A Spagnolo, R Tenconi
Journal: BMJ (1994)

from the syndrome.5Further work is needed on the physiological and behavioural aspects of the parent-infant interaction that occurs among groups in whom bed sharing is common before this practice is implicated in the pathogenesis of the sudden infant death syndrome.
γ-Glutamyltransferase Activity and Development of the Metabolic Syndrome (International Diabetes Federation Definition) in Middle-Aged Men and Women
Authors: Philippe André, Beverley Balkau, Sylviane Vol, Marie Aline Charles, Eveline Eschwège
Journal: Diabetes Care (2007)

OBJECTIVE—Among hepatic enzymes, γ-glutamyltransferase (GGT) is the main predictor of type 2 diabetes incidence, although it has not been shown that GGT predicts pre-diabetes states. Our aim was to study the association of GGT with the development of the metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS—We analyzed the 3-year data from the Data from Epidemiological Study on the Insulin Resistance Syndrome prospective cohort of 1,656 men and 1,889 women without MetS at baseline, according to the International Diabetes Federation definition. RESULTS—Over 3 years, 309 participants developed the MetS. After adjustment for age, alcohol intake, physical activity, smoking habits, and alanine aminotransferase (ALT), the odds ratios for incident MetS increased across baseline GGT quartiles (1, 1.96, 2.25, and 3.81 in men, P &amp;lt; 0.03; and 1, 1.23, 1.80, and 1.58 in women, P &amp;lt; 0.05). After additional adjustment for insulin resistance markers (fasting insulin or homeostasis model assessment of insulin resistance index), the association was attenuated and the linear relation no longer significant in both sexes (P = 0.08, P = 0.16). However, men in the highest in comparison to the lowest quartile of GGT retained a significant risk for incident MetS. In women, there was no longer a significant risk. GGT was significantly associated with the 3-year incidence of individual components of the MetS. The incidence of the MetS also increased with ALT, but after adjustment on GGT this association remained significant only in women. CONCLUSIONS—GGT, a predictor of type 2 diabetes, was associated with a risk of incident MetS. This association was mainly related with insulin resistance but was independent of other confounding factors.