tbuckley/cabot-search huggingface dataset:
TWIST1 promotes invasion through mesenchymal change in human glioblastoma
Authors: Svetlana A Mikheeva, Andrei M Mikheev, Audrey Petit, Richard Beyer, Robert G Oxford, Leila Khorasani, John-Patrick Maxwell, Carlotta A Glackin, Hiroaki Wakimoto, Inés González-Herrero, Isidro Sánchez-García, John R Silber, Philip J Horner, Robert C Rostomily
Journal: Molecular Cancer (2010)

Abstract Background Tumor cell invasion into adjacent normal brain is a mesenchymal feature of GBM and a major factor contributing to their dismal outcomes. Therefore, better understandings of mechanisms that promote mesenchymal change in GBM are of great clinical importance to address invasion. We previously showed that the bHLH transcription factor TWIST1 which orchestrates carcinoma metastasis through an epithelial mesenchymal transition (EMT) is upregulated in GBM and promotes invasion of the SF767 GBM cell line in vitro . Results To further define TWIST1 functions in GBM we tested the impact of TWIST1 over-expression on invasion in vivo and its impact on gene expression. We found that TWIST1 significantly increased SNB19 and T98G cell line invasion in orthotopic xenotransplants and increased expression of genes in functional categories associated with adhesion, extracellular matrix proteins, cell motility and locomotion, cell migration and actin cytoskeleton organization. Consistent with this TWIST1 reduced cell aggregation, promoted actin cytoskeletal re-organization and enhanced migration and adhesion to fibronectin substrates. Individual genes upregulated by TWIST1 known to promote EMT and/or GBM invasion included SNAI2, MMP2, HGF, FAP and FN1. Distinct from carcinoma EMT, TWIST1 did not generate an E- to N-cadherin "switch" in GBM cell lines. The clinical relevance of putative TWIST target genes SNAI2 and fibroblast activation protein alpha (FAP) identified in vitro was confirmed by their highly correlated expression with TWIST1 in 39 human tumors. The potential therapeutic importance of inhibiting TWIST1 was also shown through a decrease in cell invasion in vitro and growth of GBM stem cells. Conclusions Together these studies demonstrated that TWIST1 enhances GBM invasion in concert with mesenchymal change not involving the canonical cadherin switch of carcinoma EMT. Given the recent recognition that mesenchymal change in GBMs is associated with increased malignancy, these findings support the potential therapeutic importance of strategies to subvert TWIST1-mediated mesenchymal change.
Epidemiology of Health Effects of Radiofrequency Exposure
Authors: Anders Ahlbom, Adele Green, Leeka Kheifets, David Savitz, Anthony Swerdlow
Journal: Environmental Health Perspectives (2004)

We have undertaken a comprehensive review of epidemiologic studies about the effects of radiofrequency fields (RFs) on human health in order to summarize the current state of knowledge, explain the methodologic issues that are involved, and aid in the planning of future studies. There have been a large number of occupational studies over several decades, particularly on cancer, cardiovascular disease, adverse reproductive outcome, and cataract, in relation to RF exposure. More recently, there have been studies of residential exposure, mainly from radio and television transmitters, and especially focusing on leukemia. There have also been studies of mobile telephone users, particularly on brain tumors and less often on other cancers and on symptoms. Results of these studies to date give no consistent or convincing evidence of a causal relation between RF exposure and any adverse health effect. On the other hand, the studies have too many deficiencies to rule out an association. A key concern across all studies is the quality of assessment of RF exposure. Despite the ubiquity of new technologies using RFs, little is known about population exposure from RF sources and even less about the relative importance of different sources. Other cautions are that mobile phone studies to date have been able to address only relatively short lag periods, that almost no data are available on the consequences of childhood exposure, and that published data largely concentrate on a small number of outcomes, especially brain tumor and leukemia.
MPs criticise department’s handling of Modernising Medical Careers
Authors: Lynn Eaton
Journal: BMJ (2008)

The Department of Health’s handling of the problems with the Modernising Medical Careers (MMC) programme last year was “inept,” and the leadership it showed was “totally inadequate,” according to a report published by the House of Commons’ Health Select Committee.

The damning report from a cross party group of MPs comes days after a House of Lords judgment that ruled that the Department of Health had acted illegally in restricting the right of medical graduates from outside the European Economic Area (EEA) to work as doctors in the United Kingdom ( BMJ 2008;336:1037; doi: 10.1136/bmj.39574.363924.DB).

The select committee questions the role of the chief medical officer (CMO) in a situation in which junior doctors struggled with a poorly tested computer based application system and faced unprecedented uncertainty about their career.

“The management of the introduction of the MMC reforms . . .was inept,” says the report. “Project management . . . was equally poor.”

Decisions took little account of the needs and concerns of …
Are Short Telomeres Hallmarks of Cancer Recurrence?
Authors: Jerry W. Shay
Journal: Clinical Cancer Research (2013)

Abstract Exposure to radiation and some chemotherapeutic agents is associated with an increased risk of developing second cancers. Short telomeres are almost universally associated with malignant cancer progression. An unanswered question is whether inherited short telomeres or therapy-related telomere shortening is a biomarker of the development of second malignant neoplasms. Clin Cancer Res; 20(4); 779–81. ©2013 AACR.
Case of Cut-Throat: Recovery
Authors: W. Thurnall
Journal: BMJ (1857)

A few wor(ds as to tlhe treatment.In mentioning this case to one or twvo professionial friends, I was told that a crucial incision wi-ould liaxlla 1'en bess, as tlhe approved practice in obstructed menses, etc.; but from tbis I dissent.In primiparie, where the os is like "a minuite cicatrix", " a small crowquill", " a sliglht indleittation", or is " impervious, hard, and circular", the crucial incMision may be thoe very best; but vhere the known recently existing state of parts was that of ample development after repeated child-hearing, and wlhere, tlherefore, the new formation-miiust exten(d, lengtlhwvise, fioma side to side, and be comporatitvelv narrow from-1 back to front, such incision was neith?er required nor applicable.Bleeding, large or small, was never thougiht of.It startles one to read of the.Ciosarean operation having been performed "in a case of this kind"; and as for destrctio)n of thle child in Mr. Hatton's case, this was resorted to on other grouinds than the occlusion, and which were deemed sufficient to dlemuand so serious an expedient.
Ulcerative colitis in the tropics.
Authors: H K Chuttani, S P Nigam, S K Sama, P C Dhanda, P S Gupta
Journal: BMJ (1967)

Ulcerative colitis as a separate entity was first described by Wilks and Moxan (1875).Idiopathic ulcerative colitis has been defined as an acute and chronic inflammatory and ulcerative disease of the rectum and colon of unknown aetiology (Kirsner, 1959).Many reports on various aspects of the disease have appeared in the Western literature (Bargen, 1930 ; Felsen and
Ejection Time by Ear Densitogram and Its Derivative
Authors: VERONICA QUARRY-PIGOTT, RAUL CHIRIFE, DAVID H. SPODICK
Journal: Circulation (1973)

Ear densitographic ejection times (EDET) and first derivative ear densitogram ejection times (dEDET) were studied to determine whether their reliability and validity justify their substitution for ejection times derived from the far less stable carotid pulse tracing. Inter- and intra-subject comparisons were made on thirty individuals under a wide variety of disease and challenge states. Statistical analysis of the data-which had been obtained through a blinded procedure-showed an overall correlation ( r ) of .98 for carotid vs EDET and .99 for carotid vs dEDET. The t -test demonstrated no significant differences among ejection times derived from the three methods. Moreover, the close tracking at rest and during challenges of ejection times derived from these curves with those from the carotid indicate that either method may be substituted for standard carotid curves without sacrificing reliability or validity of the measure. Both ear curves offer distinct advantages over carotid pulse curves because their sensor is self-retaining and they remain stable during exercise and other body and respiratory movements. The additional feature of simplicity in reading the first derivative of the ear densitogram over its undifferentiated curve makes dEDET the preferred method.
UK government vows to monitor waiting times for mental health services in new strategy
Authors: G. Iacobucci
Journal: BMJ (2014)

The coalition government has set out its priorities for improving mental health services in England by eliminating the variability and “discrimination” in the current system.

A new action plan outlines 25 pledges for improving services in the short term,1 to support its longer term mental health strategy2 and its mandate to the NHS for 2013-14, which focused on mental health and dementia.3

In a speech delivered at the launch of the document, the deputy prime minister, Nick Clegg, said it was time to bring mental health “out of the shadows” and ensure that it was treated with equal importance as physical health.

The plan proposes a series of actions for increasing access to mental health services, and it challenges healthcare …
Points: Cardiac catheterisation: here today, where tomorrow?
Authors: D. Krikler
Journal: BMJ (1982)

A Ledermann and colleagues (12 June, p 1784) reporting thrombocytopenia following benoxaprofen therapy.They state that thrombocytopenia associated with benoxaprofen has not been reported before.We reported thrombocytopenia in association with leucopenia and toxic epidermal necrolysis in a 62- year-old woman after only nine days' treatment with benoxaprofen, and this was published in May 1982.
Hyperinsulinemia cluster predicts the development of type 2 diabetes independently of family history of diabetes.
Authors: P Kekäläinen, H Sarlund, K Pyörälä, M Laakso
Journal: Diabetes Care (1999)

OBJECTIVE: The aim of this prospective study was to determine risk factor clusters predicting type 2 diabetes in subjects with and without family history of diabetes by applying factor analyses. RESEARCH DESIGN AND METHODS: The study population consisted of 309 siblings of diabetic (DM+) or nondiabetic (DM-) probands. Risk factors, including lipids, lipoproteins, blood pressure, and glucose tolerance status, were measured at the baseline study and 8 years later. RESULTS: Siblings in the DM+ group had a significantly higher risk of diabetes (odds ratio [OR] = 3.25; P = 0.002) than siblings in the DM- group. Altogether, factor analyses revealed four significant factors in both the DM+ and DM- groups (the percentage of cumulative variance explained 62-66%). Of these, factor 1 (percentage of variance, 27-29%) was characterized by high loadings for BMI, hypertension, glucose area, insulin area (the highest loading), and triglycerides in both the DM+ and DM- groups; therefore, factor 1 can be interpreted as a hyperinsulinemia factor. Also, other factors were essentially similar in both groups. Hyperinsulinemia factor was similarly associated with the risk of developing diabetes in the DM+ group (OR = 4.33, 95% CI 2.29-8.19; P &amp;lt; 0.001) and the DM- group (OR = 4.22, 95% CI 2.02-8.81; P &amp;lt; 0.001) in logistic regression analyses. CONCLUSIONS: Our results indicate that a cluster of cardiovascular risk factors around hyperinsulinemia is an important predictor of diabetes in 8-year follow-up independent of family history of diabetes.
Second vCJD patient to receive experimental treatment
Authors: C. Dyer
Journal: BMJ (2003)

Doctors treating an 18 year old girl in the north of England with variant Creutzfeldt-Jakob disease (vCJD) were given the go-ahead last week to inject her brain with pentosan polysulphate, an experimental treatment tried earlier this year on a Belfast teenager with the disease.

Dame Elizabeth Butler-Sloss, president of the High Court's family division, who gave the green light last December for 19 year old Jonathan Simms to have the treatment ( BMJ 2003;326: 8), …
Recommended guidelines for training in adult clinical cardiac electrophysiology
Authors: Nancy C. Flowers, J.A. Abildskov, William F. Armstrong, Anne B. Curtis, Jonathan L. Elion, Paul C. Gillette, Jerry C. Griffin, Mark E. Josephson, Harold L. Kennedy, Costas T. Lambrew, Jay W. Mason, Gerald V. Naccarelli, L.Thomas Sheffield
Journal: Journal of the American College of Cardiology (1991)
Cantharidin-induced acantholysis: adhesion molecules, proteases, and related proteins
Authors: J.A. YELL, S.M. BURGE, D. DEAN
Journal: British Journal of Dermatology (1994)

Acantholysis is a feature of disorders such as Hailey‐Hailey disease and Darier's disease. Immunocytochemical studies have shown internalization of desmosomal components after acantholysis. Basal cytokeratins show suprabasal expression in lesional Darier's disease. The exact mechanisms of acantholysis are still unclear. Cantharidin induces blistering, with suprabasal keratinocyte acantholysis, possibly by protease activation. Plasmin has been implicated in the pathogenesis of acantholysis in Darier's disease and Hailey‐Hailey disease. We examined the distribution of desmosomal components, proteases and cytokeratins in cantharidin blisters, to compare them with those previously found in Darier's disease and Hailey‐Hailey disease. Two drops of cantharidin collodion were applied to the skin of five normal volunteers. A 4‐mm punch biopsy of the blister was taken, and snap frozen. Sections were stained with antibodies to desmosomal proteins (dp) 1/2, dp 3, desmosomal glycoproteins (dg) 1, 2/3, extracellular carbohydrate residues, using the lectins peanut agglutinin (PNA) and soybean agglutinin (SBA), proteases and cytokeratins. Acantholytic cells were stained diffusely with dp l/2: there was markedly reduced or absent peripheral staining for dp 3, dg l, dg 2/3, PNA and SBA. There was no clumping of stain. Plasminogen, fibrinogen and urokinase were expressed in some acantholytic cells. Basal keratin markers were expressed suprabasally in acantholytic cells. These results are similar to those previously obtained in Darier's disease, but different from the staining obtained in Hailey‐Hailey disease. Extracellular glycosylated portions of adhesion molecules may be lost after acantholysis, perhaps as a result of conformational changes, internalization of extracellular domains, or proteolysis. The changes in the expression of plasminogen, fibrinogen, urokinase and cytokeratins in acantholytic cells in cantharidin‐induced blisters are, as in Darier's disease and Hailey‐Hailey disease, probably secondary to acantholysis, and changes in the shape of cells. We conclude that cantharidin blisters may be a useful model for the study of acantholysis in Darier's disease.
Unusual Complications of Labour
Authors: H. Burt-White
Journal: BMJ (1938)

Case IA boy, aged 14, was admitted to hospital on FebruLary 19, 1937, having been ill for the past week with headache, general irritability, and vomiting.There was definite head retraction and rigidity of neck, and Kernig's sign was present.He was noTnially conscious.TIhe cerebrospinal fluid was under pressure and was turbid.Pathological Report, Februiary 22.-" Turbid xanthochromic fluid with a heavy deposit of pus.Chlorides 0.680 per cent.; sugar absent; albumin 0.3 per cent.Films show large numbers of polymorphonuclears and a very occasional Gram- negative diplococcus, probably meningococcus."The patient was treated by anti-meningococcal serum- intramuscular on February 19, intramuscular and intravenous on February 20; and by prontosil, two tablets (0.6 gramme) every four hours-that is, 3.6 grammes (about 60 grains) each twenty-four hours-commencing February 21 and continued for one month.He rapidly improved.Lumbar puncture on February 19, 20, 2 1, and 22, and again on March 17, showed that the fluid was clear, and the pathologist reported it to be normal.Before the end of the first week the headache and neck re- traction had entirely disappeared.He looked well, and said that he felt well.He continued to have a slight pyrexia, which in the third and fourth weeks sometimes reached 100' F., but remained in good health and without symptoms.Case II A youth, aged 17, was admitted on April 26, 1937, with four days' history of headache and pain in the back and limbs, with vomiting for the last two days.He was quite conscious.Head retraction and neck rigidity were present.Kernig's sign was positive, and the cerebrospinal fluid was turbid and its pressure mtuch increased.Pathological Report, April 29.-" Turbid xanthochromic fluid, with a large coagulum and heavy deposit of pus.Chlorides 0.720 per cent.; sugar absent; albumin 0.2 per cent.Films show large numbers of polymorphonuclears and a very occasional Gram-negative diplococcus-probably meningo- coccus."Trertament.-He was given 10 c.cm. of serum intramuscularly and 10 c.cm. intrathecally on April 26; 10 c.cm. intrathecally and 10 c.cm. intravenously on April 27; prontosil on April 26-two tablets (each 0.3 gramme) four-hourly, increased to twenty tablets in the twenty-four hours on April 29, reduced again to twelve in twenty-four hours on May 2, and stopped on May 10.The patient made a rapid recovery. Case II1A youth, aged 17, was admitted on May 7, 1937.Four days earlier his illness had begun with headache, vomiting, and stiffness in the neck.He was conscious.His head was retracted and his neck rigid.Kernig's sign was positive.The cerebrospinal fluid was under increased pressure and was turbid.
Review: Statins reduce mortality and cardiovascular events in adults at risk for cardiovascular disease
Authors: Richard A. Davidson, Eric Rosenberg
Journal: Annals of Internal Medicine (2009)

Source Citation Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009;338:b2376. 19567909
Functionally Enhanced siRNA Targeting TNFα Attenuates DSS-induced Colitis and TLR-mediated Immunostimulation in Mice
Authors: Sandra M Ocampo, Carolina Romero, Anna Aviñó, Joan Burgueño, Miguel A Gassull, Jordi Bermúdez, Ramon Eritja, Ester Fernandez, Jose C Perales
Journal: Molecular Therapy (2011)

Tumor necrosis factor (TNFα) is a proinflammatory cytokine involved in the pathogenesis of inflammatory bowel disease (IBD). Although TNFα has been extensively targeted using systemic drugs, the use of antisense and small interfering RNA (siRNA) to drive down its expression at the site of inflammation should provide important advantages. In this study, native and chemically modified siRNA against TNFα was developed and characterized using a murine model of IBD. siRNA with 2'-O-methyl and propanediol modifications (siTNF-OMe-P) were resistant to nuclease degradation and provided better silencing efficacy in vitro as compared to unmodified siRNA. Every modification reduced nonspecific Toll-like receptor (TLR)-mediated immunomodulation in human peripheral blood mononuclear cells (PBMC) cells. Intrarectal administration of siTNF-OMe-P significantly ameliorated the clinical endpoints and histopathological severity in 5% dextran sulphate sodium (DSS)-treated mice as compared to unmodified and other chemically modified siRNAs. Differential gene expression assessed in siTNF-OMe-P-treated animals correlated with improved colon integrity and reduced TLR activation as compared to all treatment groups. All in all, this study demonstrates that propanediol and 2'-O-methyl modifications have profound functional consequences for siRNA efficacy in vivo. Consequently, this strategy has potential implications for therapeutic intervention in IBD and other diseases.
CARDIAC RESYNCHRONIZATION THERAPY: EFFECT OF OPTIMIZING THE V-V INTERVAL IN HEART FAILURE
Authors: Susan M. Ellery, Lynne K. Williams, Francisco Leyva-Leon, Kiran C. Patel, Robert A. Bleasdale, Berthold Stegemann, Vince Paul, Paul Steendijk, Michael P. Frenneaux
Journal: Journal of the American College of Cardiology (2011)
Vitamin supplements do not cut risk of gastrointestinal cancer
Authors: Susan Mayor
Journal: BMJ (2004)

Supplements of antioxidant vitamins do not reduce the risk of gastrointestinal cancers, and some may be associated with an increased risk of death, concluded a systematic review published last week.

The Cochrane Hepato-Biliary Group reviewed all randomised trials that compared antioxidant supplements with placebo for the prevention of gastrointestinal cancers. The group assessed the incidence of gastrointestinal cancers, overall mortality, and adverse effects in 14 randomised trials, which comprised a total of 170 525 participants ( Lancet 2004;364: 1219-28).

Vitamins A, C, and E; β …
CXCR1/2 inhibition enhances pancreatic islet survival after transplantation
Authors: Antonio Citro, Elisa Cantarelli, Paola Maffi, Rita Nano, Raffaella Melzi, Alessia Mercalli, Erica Dugnani, Valeria Sordi, Paola Magistretti, Luisa Daffonchio, Pier Adelchi Ruffini, Marcello Allegretti, Antonio Secchi, Ezio Bonifacio, Lorenzo Piemonti
Journal: Journal of Clinical Investigation (2012)

Although long considered a promising treatment option for type 1 diabetes, pancreatic islet cell transformation has been hindered by immune system rejection of engrafted tissue. The identification of pathways that regulate post-transplant detrimental inflammatory events would improve management and outcome of transplanted patients. Here, we found that CXCR1/2 chemokine receptors and their ligands are crucial negative determinants for islet survival after transplantation. Pancreatic islets released abundant CXCR1/2 ligands (CXCL1 and CXCL8). Accordingly, intrahepatic CXCL1 and circulating CXCL1 and CXCL8 were strongly induced shortly after islet infusion. Genetic and pharmacological blockade of the CXCL1-CXCR1/2 axis in mice improved intrahepatic islet engraftment and reduced intrahepatic recruitment of polymorphonuclear leukocytes and NKT cells after islet infusion. In humans, the CXCR1/2 allosteric inhibitor reparixin improved outcome in a phase 2 randomized, open-label pilot study with a single infusion of allogeneic islets. These findings indicate that the CXCR1/2-mediated pathway is a regulator of islet damage and should be a target for intervention to improve the efficacy of transplantation.
Immunologic effects of rituximab on the human spleen in immune thrombocytopenia
Authors: Sylvain Audia, Maxime Samson, Julien Guy, Nona Janikashvili, Jennifer Fraszczak, Malika Trad, Marion Ciudad, Vanessa Leguy, Sabine Berthier, Tony Petrella, Serge Aho-Glélé, Laurent Martin, Marc Maynadié, Bernard Lorcerie, Patrick Rat, Nicolas Cheynel, Emmanuel Katsanis, Nicolas Larmonier, Bernard Bonnotte
Journal: Blood (2011)