tbuckley/cabot-search huggingface dataset:
NOTCH pathway inactivation promotes bladder cancer progression
Authors: Antonio Maraver, Pablo J. Fernandez-Marcos, Timothy P. Cash, Marinela Mendez-Pertuz, Marta Dueñas, Paolo Maietta, Paola Martinelli, Maribel Muñoz-Martin, Mónica Martínez-Fernández, Marta Cañamero, Giovanna Roncador, Jorge L. Martinez-Torrecuadrada, Dimitrios Grivas, Jose Luis de la Pompa, Alfonso Valencia, Jesús M. Paramio, Francisco X. Real, Manuel Serrano
Journal: Journal of Clinical Investigation (2015)

NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features. Using bladder cancer cells, we determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition. Evaluation of human bladder cancer samples revealed that tumors with low levels of HES1 present mesenchymal features and are more aggressive. Together, our results indicate that NOTCH serves as a tumor suppressor in the bladder and that loss of this pathway promotes mesenchymal and invasive features.
Truncation of C-mip (Tc-mip), a New Proximal Signaling Protein, Induces c-maf Th2 Transcription Factor and Cytoskeleton Reorganization
Authors: Philippe Grimbert, Asta Valanciute, Vincent Audard, André Pawlak, Sabine Le gouvelo, Philippe Lang, Patrick Niaudet, Albert Bensman, Georges Guellaën, Djillali Sahali
Journal: The Journal of Experimental Medicine (2003)

Several arguments suggest that minimal change nephrotic syndrome (MCNS) results from yet unknown systemic disorder of T cell function. By screening a cDNA library from T cell relapse, we identified a new pleckstrin homology (PH) domain-containing protein encoded by a gene located on chromosome 16q24. Two alternative transcripts were identified. The first species (c-mip) was expressed in fetal liver, kidney, and peripheral blood mononuclear cells (PBMCs), but weakly detected in PBMCs from MCNS patients. The second form (Tc-mip, standing for truncated c-maf inducing protein), corresponds to subtracted transcript and lacks the NH2-terminal PH domain. The expression of Tc-mip was restricted to fetal liver, thymus, and MCNS PBMCs where it was specifically recruited in CD4+ T cells subset. Overexpression of Tc-mip in T cell Jurkat induced c-maf, transactivated the interleukin 4 gene and down-regulated the interferon γ expression, characteristic of a Th2 commitment. Moreover, the overexpression of Tc-mip induced Src phosphorylation, T cell clustering, and a cellular redistribution of the cytoskeleton-associated L-plastin, by a PI3 kinase independent pathway. Tc-mip represents therefore the first identified protein, which links proximal signaling to c-maf induction.
Appropriateness of Hypnoanesthesia
Authors: Robert E. McKlveen
Journal: JAMA (1986)

To the Editor.—  In their report of the use of hypnoanesthesia for the removal of a very large mass from the thigh of a morbidly obese woman, Morris et al 1 state that their patient could not be managed safely by conventional anesthetic techniques and infer that the technique described, using hypnosis, fentanyl, and diazepam, was safe. I believe that both of those claims are subject to challenge.  I agree with the authors that a regional anesthetic is the technique of choice in the morbidly obese patient undergoing surgery of the lower extremities. Their attempts at needle placement were unsuccessful, but those attempts are not described adequately, and leave the following questions: (1) How long a needle was available? It would be very unusual, even in the obese patient, to be unable to reach the lumbar epidural space with a 6-in Touhy needle. (2) Why was the patient unable to
Near drowning: self therapy in situ
Authors: G. Ness, N. Macaskill
Journal: BMJ (2000)

Post-traumatic stress disorder is a common problem, developing in 15-24% of people who are exposed to traumatic events. 1 2 General population surveys have suggested that 1 in 12 adults has experienced post-traumatic stress disorder, the commonest causes being violence (39.5%) and an unexpected bereavement (31.3%).3 Control studies have shown that cognitive behavioural interventions and antidepressant drugs are moderately effective treatments for fully developed post-traumatic stress disorder.4 Early psychological debriefing to prevent the development of post-traumatic stress disorder has had mixed results.5

Previous stress inoculation training might help in such situations that might cause post-traumatic stress,6 but little work has been done to evaluate the effectiveness of teaching cognitive behavioural coping strategies to people at risk of trauma. In this brief paper we report the experience of a trained cognitive behaviour therapist working in a post-traumatic stress clinic who was exposed to the trauma of being trapped underwater and near drowning. During this experience he was able to use a variety of cognitive coping strategies. He did not later develop post-traumatic stress disorder but did experience an alteration of his assumptions about risks of trauma in general and an increase in the strength of his spiritual values.

I was pleased to be getting a day off to go on a “boys'” sailing adventure on Lake Windermere. My previous experience of the lake had been of visiting lakeside cake and gift shops with my wife and 2 year old daughter, but now I was going sailing with a general practitioner friend of similar age (39), Peter.

Though the wind seemed disappointingly light, I was excited to be on an 18 foot yacht, having sailed before only in dinghies. I love water, being a strong swimmer and a sports diver. We made slow progress down the lake because …
Tc-99m ECD Neuro-SPECT and Diffusion Weighted MRI in the Detection of the Anatomical Extent of Subacute Stroke
Authors: Ruben Krishnananthan, Satoshi Minoshima, David Lewis
Journal: Clinical Nuclear Medicine (2007)

We present a case of subacute middle cerebral artery infarct, which demonstrates restricted diffusion on MRI and reperfusion hyperemia in the posterior half of the lesion on angiography. Tc-99m ethyl cysteinate dimer (ECD) SPECT obtained shortly after the MRI failed to demonstrate perfusion defects in the regions demonstrating reperfusion hyperemia on angiography, underestimating the true size of the infarct. Crossed cerebellar diaschisis is, however, present. SPECT studies obtained over the following weeks demonstrated gradual enlargement of the lesion to approximate the MRI signal changes over a 19-day period. The case presented demonstrates retention of ECD in the infarcted brain. Several studies have demonstrated that Tc-99m ECD uptake is dependent on preserved brain tissue function because tracer retention requires enzymatic esterase activity, rather than the passive, nonenergy dependent trapping of Tc-99m hexamethylpropyleneamine oxime. Hence, infarcted areas undergoing reperfusion hyperemia are unlikely to demonstrate ECD uptake. This report illustrates that MRI diffusion weighted imaging may be more accurate in demonstrating the full extent of reperfused infarcts earlier than Tc-99m ECD SPECT. SPECT in this case failed to demonstrate reduced uptake in reperfused regions of the infarct. Also, crossed cerebellar diaschisis may serve as an early marker of extensive neuronal dysfunction.
Pancreatic Neuroendocrinology: Peripheral Neural Mechanisms in the Regulation of the Islets of Langerhans*
Authors: RALPH E. MILLER
Journal: Endocrine Reviews (1981)

The islets of Langerhans are richly vascularized and both the islet cells and blood vessels are intimately associated with a variety of autonomic nerves. Direct electrical stimulation of the nerves in vivo or pharmacological stimulation of the islets with neurotransmitters in vitro results in changes in the rate of release of islet hormones. The purpose of this paper is to describe the anatomy of the islet in relation to its vascular supply and both motor and sensory autonomic nerves, which may play a role in altering the secretion rate of islet hormones. Evidence for catecholaminergic, cholinergic, and peptidergic nerves as well as possible peptide neurotransmitters in the pancreas is examined. Secondly, physiological and pharmacological studies are reviewed that reveal how efferent autonomic neural activity leads to altered islet secretion rates. Third, because the complex structure of the islet is supplied with a variety of autonomic nerves, the evidence for excitation of these nerves via reflex activation is examined.
Multiple Pathologies Seen on a Single Contrast-Enhanced 18F-FDG PET/CT
Authors: Punit Sharma, Chung Marangmei
Journal: Clinical Nuclear Medicine (2015)

We here present the staging contrast-enhanced 18F-FDG PET/CT images of a 53-year-old woman with right breast cancer. Apart from the 18F-FDG avid primary breast tumor, 18F-FDG avid thyroiditis, 18F-FDG avid right paratracheal tubercular lymphadenitis, and non-18F-FDG avid pancreatic neuroendocrine tumor were seen on PET/CT. All the lesions were confirmed with fine-needle aspiration cytology. This interesting case demonstrates a spectrum of true-positive, false-positive, and false-negative lesions on a single 18F-FDG PET/CT examination.
Abstract 995: Transient low doses of DNA demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells
Authors: Hsing-Chen Tsai, Huili Li, Leander Van Neste, Yi Cai, Carine Robert, Feyruz V. Rassool, James J. Shin, Kirsten M. Harbom, Robert Beaty, Emmanouil Pappou, James Harris, Ray-Whay Chiu Yen, Nita Ahuja, Malcolm V. Brock, Vered Stearns, David Feller-Kopman, Yi-Chun Lin, Alana L. Welm, Jean-Pierre Issa, Il Minn, William Matsui, Yoon-Young Jang, Saul J. Sharkis, Stephen B. Baylin, Cynthia A. Zahnow
Journal: Cancer Research (2012)

Abstract Reversal of gene promoter DNA hypermethylation and associated abnormal gene silencing is an attractive approach to cancer therapy. The DNA methylation inhibitors, decitabine (5-aza-2′-deoxycytidine) and azacitidine (5-azacytidine) are proving efficacious clinically for hematological neoplasms, especially at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, but these may not explain the prolonged time to response often seen in patients. We now show that transient exposure of cultured and primary leukemic and epithelial tumor cells to decitabine or azacitidine at clinically-relevant nanomolar doses, without causing immediate cytotoxicity, produces a “memory” for anti-tumor responses, including potent inhibition of subpopulations of cancer, stem-like cells which often resist other therapies. These inhibitory effects are accompanied by sustained decreases in genome-wide promoter DNA methylation with associated gene re-expression, and anti-tumor changes in multiple key cellular regulatory pathways, such as cell cycle events mediated through FOXM1, cell invasion and motility, and granulocyte and breast cancer cell maturation. Notably, most of the key pathways altered by decitabine or azacitidine involve high priority targets for pharmacologic anti-cancer strategies, which provides molecular basis for possible combination therapies. Thus, low dose decitabine and azacitidine regimens may potentially have broad applicability for cancer management. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 995. doi:1538-7445.AM2012-995
Identification of conduction block in cardiac muscle: in vitro observations in canine epicardium
Authors: A. Kadish, J. Spear
Journal: Cardiovascular Research (1994)

Objective: The aim was to examine the ability of several previously proposed criteria and of "vector mapping" to distinguish slow conduction from conduction block in canine myocardium. Methods: Two different in vitro preparations of canine epicardium were used. In 10 tissues, an anatomical barrier was simulated by a cut (five longitudinal and five transverse to fibre orientation). Eleven tissues removed two weeks after occlusion-reperfusion infarction were also studied. Isochronal activation maps were constructed from extracellular and intracellular recordings and vector loops formed by summing two orthogonally recorded bipolar electrograms were used to indicate the direction of cardiac activation. Results: In the cut model, electrograms recorded from over the anatomical barrier were usually normal or showed double potentials but could occasionally be fractionated. Isochronal activation maps obtained from extracellular recordings were able to identify five of five anatomical barriers transverse to, but only one of five barriers longitudinal to, fibre orientation. The direction of cardiac activation indicated by vector loops identified conduction block in all 10 preparations. In 11 tissues removed from canine ventricles with experimental myocardial infarction, microelectrode recordings were used to characterise regions as either slow conduction or conduction block. Isochronal activation patterns obtained from extracellular recordings generally showed impulses proceeding through zones of conduction and around zones of conduction block but disagreed with the results of microelectrode impalements in two of 11 cases. Electrogram morphology was also not always able to distinguish slow conduction from block. The direction of cardiac activation determined by vector mapping accurately characterised all regions of tissue as showing either slow conduction or conduction block. Conclusions: Limited regions of conduction block or slow conduction are frequently present in epicardial tissues removed from experimental myocardial infarction. The morphology of extracellular electrograms and isochronal activation mapping performed from extracellular recordings is often but not always able to distinguish slow conduction from conduction block. Vector mapping is useful in distinguishing slow conduction from conduction block in these situations and may help evaluate myocardial conduction patterns. Cardiovascular Research 1994;28:259-269
Occult Streptococcus pyogenes in cellulitis: demonstration by immunofluorescence
Authors: W.B. SHELLEY, N. TALANIN, E. DORINDA SHELLEY, E.H. FREIMER
Journal: British Journal of Dermatology (2010)

Journal Article Occult Streptococcus pyogenes in cellulitis: demonstration by immunofluorescence Get access W.B. SHELLEY, W.B. SHELLEY Division of Dermatology. Department of Medicine, PO Box 10008, Toledo, OH 43699‐0008, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar N. TALANIN, N. TALANIN Division of Dermatology. Department of Medicine, PO Box 10008, Toledo, OH 43699‐0008, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar E. DORINDA SHELLEY, E. DORINDA SHELLEY Division of Dermatology. Department of Medicine, PO Box 10008, Toledo, OH 43699‐0008, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar E.H. FREIMER E.H. FREIMER Department of Microbiology, Medical College of Ohio, PO Box 10008, Toledo, OH 43699‐0008, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 132, Issue 6, 1 June 1995, Pages 989–991, https://doi.org/10.1111/j.1365-2133.1995.tb16961.x Published: 01 June 1995 Article history Accepted: 16 August 1994 Published: 01 June 1995
Persuading Youths That Hops Ain't Hip
Authors: Mike Mitka
Journal: JAMA (1998)

AS SOME HIP-HOPPING young Americans help pack the Safari Club on Tijuana's Avenida Revolución chugging beers, guzzling tequila, and "Gittin' Jiggy Wit' It," one can understand if they forget they're helping advance medical research. But they are.
Household Exposure to Pesticides and Risk of Childhood Hematopoietic Malignancies: The ESCALE Study (SFCE)
Authors: Jérémie Rudant, Florence Menegaux, Guy Leverger, André Baruchel, Brigitte Nelken, Yves Bertrand, Catherine Patte, Hélène Pacquement, Cécile Vérité, Alain Robert, Gérard Michel, Geneviève Margueritte, Virginie Gandemer, Denis Hémon, Jacqueline Clavel
Journal: Environmental Health Perspectives (2007)

We investigated the role of household exposure to pesticides in the etiology of childhood hematopoietic malignancies.The national registry-based case-control study ESCALE (Etude sur les cancers de l'enfant) was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and sex. Maternal household use of pesticides during pregnancy and paternal use during pregnancy or childhood were reported by the mothers in a structured telephone questionnaire. Insecticides (used at home, on pets, or for garden crops), herbicides, and fungicides were distinguished. We estimated odds ratios (ORs) using unconditional regression models closely adjusting for age, sex, degree of urbanization, and type of housing (flat or house).We included a total of 764 cases of acute leukemia (AL), 130 of Hodgkin lymphoma (HL), 166 of non-Hodgkin lymphoma (NHL), and 1,681 controls. Insecticide use during pregnancy was significantly associated with childhood AL [OR = 2.1; 95% confidence interval (CI), 1.7-2.5], both lymphoblastic and myeloblastic, NHL (OR = 1.8; 95% CI, 1.3-2.6), mainly for Burkitt lymphoma (OR = 2.7; 95% CI, 1.6-4.5), and mixed-cell HL (OR = 4.1; 95% CI, 1.4-11.8), but not nodular sclerosis HL (OR = 1.1; 95% CI, 0.6-1.9). Paternal household use of pesticides was also related to AL (OR = 1.5; 95% CI, 1.2-1.8) and NHL (OR = 1.7; 95% CI, 1.2-2.6); but for AL the relationships did not remain after adjustment for maternal pesticide use during pregnancy.The study findings strengthen the hypothesis that domestic use of pesticides may play a role in the etiology of childhood hematopoietic malignancies. The consistency of the findings with those of previous studies on AL raises the question of the advisability of preventing pesticide use by pregnant women.
Up-Regulation of the Peripheral Benzodiazepine Receptor during Human Colorectal Carcinogenesis and Tumor Spread
Authors: Kerstin Maaser, Patricia Grabowski, Yelda Oezdem, Antje Krahn, Bernhard Heine, Harald Stein, Heinz Buhr, Martin Zeitz, Hans Scherübl
Journal: Clinical Cancer Research (2005)

Abstract The peripheral benzodiazepine receptor (PBR) is overexpressed in a variety of cancers. In Unio Internationale Contra Cancrum (UICC) III colorectal cancers, a high level of PBR overexpression correlates with poor prognosis. However, little is known about the role of PBR in the development and progression of colorectal cancer. This study addresses the up-regulation of PBR during colorectal carcinogenesis and tumor spread. One hundred sixteen consecutive patients undergoing surgery for colorectal cancer with either regional (59 patients) or distant metastases (57 patients) were followed-up for 5 years or until death. Twenty-four of the 59 patients with initial UICC stage III cancers later developed distant metastases. PBR overexpression in tumor specimens was determined by immunohistochemistry. UICC stage III patients with colorectal primaries highly overexpressing PBR developed metastases significantly more often than patients with low PBR overexpression in their primary carcinoma. In 54 of the 116 patients adenomas and/or metastases and/or recurrences were available to be studied for PBR up-regulation during colorectal carcinogenesis and tumor spread. PBR was found to be overexpressed in 86% of early and late adenomas. Furthermore, 85% of primaries and of 86% of metastases displayed PBR overexpression. PBR overexpression was also detected at the mRNA level as revealed by real-time PCR. The extent of PBR protein overexpression was equivalent in colorectal adenomas and carcinomas but slightly increased in metastases. These data suggest a functional role of PBR during colorectal carcinogenesis and tumor spread. Thus, PBR qualifies as a target for innovative diagnostic and therapeutic approaches.
Insulin-like growth factor I stimulates lipid oxidation, reduces protein oxidation, and enhances insulin sensitivity in humans.
Authors: M A Hussain, O Schmitz, A Mengel, A Keller, J S Christiansen, J Zapf, E R Froesch
Journal: Journal of Clinical Investigation (1993)

To elucidate the effects of insulin-like growth factor I (IGF-I) on fuel oxidation and insulin sensitivity, eight healthy subjects were treated with saline and recombinant human (IGF-I (10 micrograms/kg.h) during 5 d in a crossover, randomized fashion, while receiving an isocaloric diet (30 kcal/kg.d) throughout the study period. On the third and fourth treatment days, respectively, an L-arginine stimulation test and an intravenous glucose tolerance test were performed. A euglycemic, hyperinsulinemic clamp combined with indirect calorimetry and a glucose tracer infusion were performed on the fifth treatment day. IGF-I treatment led to reduced fasting and stimulated (glucose and/or L-arginine) insulin and growth hormone secretion. Basal and stimulated glucagon secretion remained unchanged. Intravenous glucose tolerance was unaltered despite reduced insulin secretion. Resting energy expenditure and lipid oxidation were both elevated, while protein oxidation was reduced, and glucose turnover rates were unaltered on the fifth treatment day with IGF-I as compared to the control period. Enhanced lipolysis was reflected by elevated circulating free fatty acids. Moreover, insulin-stimulated oxidative and nonoxidative glucose disposal (i.e., insulin sensitivity) were enhanced during IGF-I treatment. Thus, IGF-I treatment leads to marked changes in lipid and protein oxidation, whereas, at the dose used, carbohydrate metabolism remains unaltered in the face of reduced insulin levels and enhanced insulin sensitivity.
Naturally occurring short splice variant of CYLD positively regulates dendritic cell function
Authors: Cathy Cecilia Srokowski, Joumana Masri, Nadine Hövelmeyer, Anna Katharina Krembel, Christine Tertilt, Dennis Strand, Karsten Mahnke, Ramin Massoumi, Ari Waisman, Hansjörg Schild
Journal: Blood (2009)