tbuckley/cabot-search huggingface dataset:
Association of C1 Esterase-Inhibitor Functional Activity and Treatment Response With C1 Esterase-Inhibitor Concentrate (Berinert®) for Acute Attacks of Hereditary Angioedema
Authors: A.K. Bewtra, D.S. Hurewitz, J.A. Bernstein, T. Machnig, H. Keinecke, T.J. Craig
Journal: Journal of Allergy and Clinical Immunology (2012)
Identification of Potential Human Oncogenes by Mapping the Common Viral Integration Sites in Avian Nephroblastoma
Authors: Petr Pajer, Vladimír Pečenka, Jarmila Králová, Vít Karafiát, Dana Průková, Zdena Zemanová, Roman Kodet, Michal Dvořák
Journal: Cancer Research (2006)

Abstract Gene deregulation is a frequent cause of malignant transformation. Alteration of the gene structure and/or expression leading to cellular transformation and tumor growth can be experimentally achieved by insertion of the retroviral genome into the host DNA. Retrovirus-containing host loci found repeatedly in clonal tumors are called common viral integration sites (cVIS). cVIS are located in genes or chromosomal regions whose alterations participate in cellular transformation. Here, we present the chicken model for the identification of oncogenes and tumor suppressor genes in solid tumors by mapping the cVIS. Using the combination of inverse PCR and long terminal repeat-rapid amplification of cDNA ends technique, we have analyzed 93 myeloblastosis-associated virus type 2–induced clonal nephroblastoma tumors in detail, and mapped &amp;gt;500 independent retroviral integration sites. Eighteen genomic loci were hit repeatedly and thus classified as cVIS, five of these genomic loci have previously been shown to be involved in malignant transformation of different human cell types. The expression levels of selected genes and their human orthologues have been assayed in chicken and selected human renal tumor samples, and their possible correlation with tumor development, has been suggested. We have found that genes associated with cVIS are frequently, but not in all cases, deregulated at the mRNA level as a result of proviral integration. Furthermore, the deregulation of their human orthologues has been observed in the samples of human pediatric renal tumors. Thus, the avian nephroblastoma is a valid source of cancer-associated genes. Moreover, the results bring deeper insight into the molecular background of tumorigenesis in distant species. (Cancer Res 2006; 66(1): 78-86)
Prospective study of change in patellar tendon abnormality on imaging and pain over a volleyball season
Authors: P Malliaras, J Cook, R Ptasznik, S Thomas
Journal: British Journal of Sports Medicine (2006)

Patellar tendon injury, defined by tendon abnormality (TA) on imaging and by pain, is common among volleyball players, but little is known about change in this injury over a volleyball season. Increased activity in the season compared with the off season may result in the development of TA and/or pain. This study investigated the behaviour of TA and pain over a competitive volleyball season.Tendon abnormality and pain were measured in 101 volleyball players at the beginning and end of a season. Pain was measured with the single leg decline squat test, which loads the patellar tendon, and TA was detected with ultrasound imaging. Hours of weekly activity were measured and compared during the season and the off season. The proportion of tendons that underwent development and resolution in TA and/or pain over the season was investigated.Hours of weekly activity was greater during the season than in the off season. Most of the tendons investigated (66.3%) did not undergo a change in TA or pain over the season. Tendon abnormality and/or pain developed in 16.6% of tendons and resolved in 11.2%.The tendons of volleyball players respond variably to the increased load over the season. Change in TA and pain does not appear to be entirely dependent upon load.
Abstract B15: Immunochemotherapy with 5-fluorouracil and interferon-enhances innate and adoptive immune responses against pancreatic cancer <i>in vivo</i>
Authors: Hadeel Khallouf, Susanne Serba, Dirk Jäger, Jan Schmidt
Journal: Clinical Cancer Research (2010)

Abstract Pancreatic cancer has the poorest prognosis of all cancers urging the necessity of new therapeutic approaches. Recent clinical data show encouraging results for combining Interferon-α (IFN-α) immunotherapy with 5-Fluorouacil (5-FU) chemotherapy. However, the role of IFN-α in this immunochemotherapy scheme is still elusive. Here we investigate in vivo the relevance of different immune subpopulations in the anti-cancer immune response mediated by IFN-α in combination with 5-FU. Luciferase-transfected Panc02 cells were implanted in the pancreas of C57BL/6 mice. Five days later, mice were treated with 5-FU alone, 5-FU + IFN-α or with a vehicle control. In parallel, CD4+ T cells, CD8+ T cells, and NK cells were depleted by neutralizing antibodies. Depletion of CD11c+ dendritic cells (DCs) was performed using transgenic CD11c.DTR mice. On day 21, tumor volume was measured and NK cells were isolated and enriched from spleens of mice then used as effectors against Panc02 cells in a standard chromium release assay. Tumors were frozen for further immunohistochemistry analysis to evaluate the immune cells infiltration. In parallel, we performed flow cytometry analysis to evaluate the effects of different treatments on the expression of MHC-I and NKG2D ligands (MULT-1 and Rae-1) on Panc02 cells. Our data show that treatment with IFN-α + 5-FU has significantly decreased tumor volume in comparison with control or 5-FU treatments. This decrease in tumor volume was remarkably abolished by depleting CD8+ T cells or NK cells. Furthermore, NK cells isolated from spleens of IFN-α + 5-FU treated mice showed enhanced cytotoxicity towards Panc02 cells. Moreover, IFN-α + 5-FU treatment enhances the expression of MHC-I and NKG2D-ligand MULT-1 on Panc02 cells which could be the possible key for the enhanced recognition and per se killing by CD8+ T cells and NK cells respectively. To conclude, this study gives more insight about the mechanism of action of INF-α in combination with 5-FU and introduces CD8+ T cells and NK cells as main players in the observed anti-cancer immune response. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B15
Increased risk of irritable bowel syndrome after bacterial gastroenteritis: cohort study
Authors: L. A G. Rodriguez, A. Ruigomez
Journal: BMJ (1999)

Evidence exists of an increased risk of irritable bowel syndrome after an episode of bacterial gastroenteritis. 1 2 In one study, 12out of 38patients presented with bowel dysfunction 1year after salmonella gastroenteritis.1 In another study, 386patients with bacterial gastroenteritis were surveyed by questionnaire 6months after infection, and 27(7%) had developed irritable bowel syndrome.2 Both studies, however, lacked a control group.3

Our source population came from the General Practice Research Database, which contains clinicalinformation on patients recorded by general practitioners in the United Kingdom.4

We identified patients aged 25to 74with a bacteriologically confirmed first episode of gastroenteritis, from a recent study that examined the association between acid suppressing drugs and the development of gastroenteritis.5 We excluded all patients with a history of irritable bowel syndrome, cancer, or alcoholism. We sampled a comparison cohort from the source population from which patients …
Peripheral artery occlusive disease in chronic phase chronic myeloid leukemia patients treated with nilotinib or imatinib
Authors: T D Kim, D Rea, M Schwarz, P Grille, F E Nicolini, G Rosti, L Levato, F J Giles, H Dombret, T Mirault, H Labussière, R Lindhorst, W Haverkamp, I Buschmann, B Dörken, P D le Coutre
Journal: Leukemia (2013)
Impaired glucose tolerance and height.
Authors: D R Williams, P M Clark, N E Day, T Wang, C Byrne, L Cox, C N Hales
Journal: BMJ (1991)

The Association of British Insurers has placed on record its statement of practice regarding HIV testing.This confirms the non-prejudicial stance taken by insurers when medically assessing applicants for insurance.The association is actively redressing misleading and emotive statements with specific leaflets and other appropriate measures.
Human Genetics Commission develops framework for direct to consumer genetic tests
Authors: S. Mayor
Journal: BMJ (2009)

Genetic tests for which the results are likely to have a big impact on the person being tested should be provided to the public only within the framework of a consultation with a medical practitioner, recommend draft principles for direct to consumer genetic tests.

The number of genetic tests available on the open market has increased in the past few years and will continue to grow as the technology develops. The Human Genetics Commission, the UK government’s advisory body on developments in human genetics, set up a working group with expertise in regulation, clinical, and molecular genetics and genetic counselling. The group includes representatives from the genetic testing industry and will develop a framework of “high level principles” to promote consistency in the provision of direct to …
Effects of Diet and Physical Activity Interventions on Weight Loss and Cardiometabolic Risk Factors in Severely Obese Adults
Authors: Bret H. Goodpaster, James P. DeLany, Amy D. Otto, Lewis Kuller, Jerry Vockley, Jeannette E. South-Paul, Stephen B. Thomas, Jolene Brown, Kathleen McTigue, Kazanna C. Hames, Wei Lang, John M. Jakicic
Journal: JAMA (2010)

The prevalence of severe obesity is increasing markedly, as is prevalence of comorbid conditions such as hypertension and type 2 diabetes mellitus; however, apart from bariatric surgery and pharmacotherapy, few clinical trials have evaluated the treatment of severe obesity.To determine the efficacy of a weight loss and physical activity intervention on the adverse health risks of severe obesity.Single-blind randomized trial conducted from February 2007 through April 2010 at the University of Pittsburgh. Participants were 130 (37% African American) severely obese (class II or III) adult participants without diabetes recruited from the community.One-year intensive lifestyle intervention consisting of diet and physical activity. One group (initial physical activity) was randomized to diet and physical activity for the entire 12 months; the other group (delayed physical activity) had the identical dietary intervention but with physical activity delayed for 6 months.Changes in weight. Secondary outcomes were additional components comprising cardiometabolic risk, including waist circumference, abdominal adipose tissue, and hepatic fat content.Of 130 participants randomized, 101 (78%) completed the 12-month follow-up assessments. Although both intervention groups lost a significant amount of weight at 6 months, the initial-activity group lost significantly more weight in the first 6 months compared with the delayed-activity group (10.9 kg [95% confidence interval {CI}, 9.1-12.7] vs 8.2 kg [95% CI, 6.4-9.9], P = .02 for group × time interaction). Weight loss at 12 months, however, was similar in the 2 groups (12.1 kg [95% CI, 10.0-14.2] vs 9.9 kg [95% CI, 8.0-11.7], P = .25 for group × time interaction). Waist circumference, visceral abdominal fat, hepatic fat content, blood pressure, and insulin resistance were all reduced in both groups. The addition of physical activity promoted greater reductions in waist circumference and hepatic fat content.Among patients with severe obesity, a lifestyle intervention involving diet combined with initial or delayed initiation of physical activity resulted in clinically significant weight loss and favorable changes in cardiometabolic risk factors.clinicaltrials.gov Identifier: NCT00712127.
APLASTIC ANEMIA ASSOCIATED WITH ADMINISTRATION OF CHLORAMPHENICOL
Authors: Malcolm M. Hargraves
Journal: JAMA (1952)

One of the most frustrating of the problems that confront the hematologist always has been aplastic anemia. He thinks that somewhere in the patient's environment may be an agent responsible for the suppression or failure of the bone marrow and that, if the agent could but be found and removed, recovery might result. Seldom is such an agent found although occasionally some new commercial solvent, some new commercial process using old solvents, or some new drugs introduced into the therapeutic field prove to have toxic effect. Individual idiosyncrasy for many of these agents, however, complicates the problem tremendously. General experience in the past has shown that even though newly introduced drugs are stated, on the basis of careful experimental and clinical study, to have no injurious effect on hematopoietic tissues, long and extensive clinical administration may be required before possible sensitivity reactions are demonstrated. This is probably best shown by
Nurses as leaders in chronic care
Authors: Thomas Bodenheimer, Kate MacGregor, Nancy Stothart
Journal: BMJ (2005)

Their role is pivotal in improving care for chronic diseases 

T he chronic care model is widely accepted as a standard for improving care for people with chronic conditions.1 In the United States, projects to put the chronic care model into practice often centre around doctors. Yet the healthcare literature and the experience of many efforts to improve chronic care indicate that nurses, not doctors, are the key to implementing the chronic care model in a patient centred care team. By nature of their education and role, nurses are in a position to champion transformation of chronic care. In many nations, but not in the United States, nurses have been taking this central role for decades.w1

The essence of the chronic care model is the interaction between an informed, activated patient and a prepared, proactive practice team.w2 Indeed, such a team is nearly always needed to enable patients to become adequately informed and activated. What is the record of …
Periderm prevents pathological epithelial adhesions during embryogenesis
Authors: Rebecca J. Richardson, Nigel L. Hammond, Pierre A. Coulombe, Carola Saloranta, Heidi O. Nousiainen, Riitta Salonen, Andrew Berry, Neil Hanley, Denis Headon, Riitta Karikoski, Michael J. Dixon
Journal: Journal of Clinical Investigation (2014)

Appropriate development of stratified, squamous, keratinizing epithelia, such as the epidermis and oral epithelia, generates an outer protective permeability barrier that prevents water loss, entry of toxins, and microbial invasion. During embryogenesis, the immature ectoderm initially consists of a single layer of undifferentiated, cuboidal epithelial cells that stratifies to produce an outer layer of flattened periderm cells of unknown function. Here, we determined that periderm cells form in a distinct pattern early in embryogenesis, exhibit highly polarized expression of adhesion complexes, and are shed from the outer surface of the embryo late in development. Mice carrying loss-of-function mutations in the genes encoding IFN regulatory factor 6 (IRF6), IκB kinase-α (IKKα), and stratifin (SFN) exhibit abnormal epidermal development, and we determined that mutant animals exhibit dysfunctional periderm formation, resulting in abnormal intracellular adhesions. Furthermore, tissue from a fetus with cocoon syndrome, a lethal disorder that results from a nonsense mutation in IKKA, revealed an absence of periderm. Together, these data indicate that periderm plays a transient but fundamental role during embryogenesis by acting as a protective barrier that prevents pathological adhesion between immature, adhesion-competent epithelia. Furthermore, this study suggests that failure of periderm formation underlies a series of devastating birth defects, including popliteal pterygium syndrome, cocoon syndrome, and Bartsocas-Papas syndrome.
Growth Suppression of Human Coronary Vascular Smooth Muscle Cells by Gene Transfer of the Transcription Factor E2F-1
Authors: Harnath S. Shelat, Ta-Jen Liu, Diane L. Hickman-Bick, Michael K. Barnhart, Thomas Vida, Patricia M. Dillard, James T. Willerson, Pierre Zoldhelyi
Journal: Circulation (2001)

Background —The transcription factor E2F-1 promotes S-phase entry and death in transformed cells and primary cardiomyocytes. We tested the hypothesis that overexpression of E2F-1 forces growth-arrested human coronary vascular smooth muscle cells (VSMCs) to enter the S phase, undergo apoptosis, and thereby regulate VSMC growth. Methods and Results —Early-passage (≤5 passages) coronary VSMCs were transduced at an MOI of 100 with a recombinant adenovirus encoding human E2F-1. E2F-1 expression was observed by immunohistochemistry as early as 6 to 8 hours after exposure of the VSMCs to Ad.E2F-1 but not to the control vector Ad.RR. When cells were kept in growth-arrest medium, 40% of Ad.E2F-1–treated VSMCs entered the S phase by 96 hours, whereas the percentage remained &lt;5% in Ad.RR-treated cells. Transition to the S phase in the E2F-1–transduced VSMCs was followed by apoptosis, as reflected by chromatin condensation, membrane blebbing, cell detachment, and loss of mitochondrial membrane integrity. E2F-1 overexpression resulted in positive dUTP nick end-labeling mediated by terminal deoxynucleotidyl transferase, associated with a robust increase in caspase 3–like activity. Four days after infection with Ad.E2F-1, the fraction of hypodiploid VSMCs in subG 1 increased to 75%. At 7 days, gene transfer of E2F-1 had completely suppressed the growth of VSMCs, whereas the number of Ad.RR-infected cells had increased &gt;8 times. Conclusions —Overexpression of the transcription factor E2F-1 regulates growth of human coronary VSMCs by forcing the cells to enter the S phase and then to die. Cell death appears to involve caspase 3–like activity, which, in the VSMCs, is markedly increased by overexpression of E2F-1.
CONTACT CASES OF LEPROSY IN THE BRITISH ISLES
Authors: J. M. H. MacLeod
Journal: BMJ (1925)

BRITISH ISLES.[TSR BM"1orn 107 tioni owinig to its tenldenlcy to cause vomiting when taken by the miiouth.Large quanitities of fluids slhould be given (water, barley water, etc.).Lactogen, slightly sweetenied, hlas beeni swell tolerated where there has been much niausea, and Benger's food hlas also been easily taken.The patient should be kept in bed for at least fourteeii days even in the mllildest eases.It is owinig to patients failinig to realize the importance of this that thle prognosis of a mild case is so bad. RE,SULTS.Since assunming the post of district suirgeon, Bindura, I have seeni 36 cases of blackwater fever (29 males and(i 7 females); 33 recover-ed anid 3 died.Trhe percentage of mortalitv was tlhus 8.33.All the deaths occurred in males.Only onie was actually dIIe to blackNwater fever, and inl that one my warnillg not to move the patient had been disregarded.Dcatlis.Casf: l.-A middle-aged man, living temporarily in a tent, developed blackwater fever.On t.he day of onset I attended him, and found that he did not present aniy alarming symptoms.He was put on the treatment I have mentioned, and instructions as to diet were given to his wife.She was also warned not to allow him to be mo-ved.On the third day of the dises.seI had a message stating that his water was now quite clear and that he was much better.Oin the morning of the fourth day 1 received a very urgent message saying that the patient had been moved, for better nursing, to a cottage a quarter of a mile away, and was then in an extremely critical condition.I found the patient quite collapsed and very yellow.All attempts to improve matters by the use of hot-water bottles, subcutaneous and rectal saline, injections of camplhor, strychnlinie, and pituitary extract, failed to produce any improvemenet, and he died twenty-seven hours after having been moved.Case 2.-A middle-aged man who had nio blackwater for ten days, and who had a history of a severe kick in the epigastrium from a mule three months before, developed what clinically appeared to be intussusception and died.He had complete stoppage, passed blood per anum, and had a well defined sausage-shaped tumour in the region of the tr-ansverse colon; the diagniosis, therefore, was probably correct.Operation was refused, and I did not urge it owing to the weak state of the patieint; the relatives refused a post-Oiortc?aexaminiation.Case 3.-A young man developed severe blackwater fever, with scanty urine and retention, which niecessitated catheterizationi during the whole of his illness.The urine became clear in two days, when bronchopneumo71ia developed; this cleared up in fouir days and the patient's condition seemed most hopeful.The patient then developed a very severe attack of mumrips, and after aiiotlher twenty-four hours an old appendicitis of five years' standing lit up.The patient was too ill to stand an operation, and died twenty-four hours later.CONCLUSIONS.
Cholestatic Jaundice in Patients Treated with Erythromycin Estolate
Authors: W. Paul Havens
Journal: JAMA (1962)

Cholestatic jaundice occurred in 4 patients who had been treated for variable periods with erythromycin estolate (Ilosone). All of these patients had a history of strong allergies, and the onset of disease was accompanied by itching, anorexia, and nausea, followed by jaundice. Eosinophilia was found in 3 of them. Epigastric distress was common and occasionally severe. The duration of jaundice ranged from 2 weeks to more than 15 weeks, and although complete recovery occurred in 3 patients, 1 still had evidence of hepatic dysfunction with hepatomegaly 6 months after the onset of disease. While it is impossible to prove that they did not have viral hepatitis, the history of multiple allergies, the eosinophilia, and the biochemical alterations in the blood suggest a drug-induced hepatitis due to hypersensitivity.
Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets.
Authors: P Harrison, B Wilbourn, N Debili, W Vainchenker, J Breton-Gorius, A S Lawrie, J M Masse, G F Savidge, E M Cramer
Journal: Journal of Clinical Investigation (1989)

The origin of platelet alpha-granule fibrinogen (Fg), whether from endogeneous synthesis or exogeneous derivation, remains unknown. Although Fg biosynthesis by megakaryocytes (MK) has been suggested, recent studies have demonstrated that certain alpha-granular proteins originate primarily from plasma. To study the origin of alpha-granule Fg, platelet-associated Fg was measured by ELISA and Western blotting, and localized by immunofluorescence and immunoelectron microscopy in a patient with symptomatic congenital afibrinogenemia before and after replacement therapy with cryoprecipitate. alpha-Granule Fg was detected in the majority of platelets as early as 24 h postinfusion, suggesting that direct platelet uptake was occurring. Platelet Fg reached a maximum value of 42.5% of normal values at 3 d postinfusion and was localized in the alpha-granules, while plasma levels followed a typical half-life profile. Significant alpha-granule Fg was still detectable at 13 d postinfusion, with plasma Fg virtually absent. Studies on cultured CFU-MKs from the patient also confirmed that MKs can incorporate exogeneous Fg into alpha-granules. These results indicate that platelet alpha-granule Fg can be derived from the circulating plasma pool and that Fg uptake can occur in both platelets and MKs.