tbuckley/cabot-search huggingface dataset:
Drosophila and mammalian models uncover a role for the myoblast fusion gene TANC1 in rhabdomyosarcoma
Authors: Usha Avirneni-Vadlamudi, Kathleen A. Galindo, Tiana R. Endicott, Vera Paulson, Scott Cameron, Rene L. Galindo
Journal: Journal of Clinical Investigation (2011)

Rhabdomyosarcoma (RMS) is a malignancy of muscle myoblasts, which fail to exit the cell cycle, resist terminal differentiation, and are blocked from fusing into syncytial skeletal muscle. In some patients, RMS is caused by a translocation that generates the fusion oncoprotein PAX-FOXO1, but the underlying RMS pathogenetic mechanisms that impede differentiation and promote neoplastic transformation remain unclear. Using a Drosophila model of PAX-FOXO1–mediated transformation, we show here that mutation in the myoblast fusion gene rolling pebbles (rols) dominantly suppresses PAX-FOXO1 lethality. Further analysis indicated that PAX-FOXO1 expression caused upregulation of rols, which suggests that Rols acts downstream of PAX-FOXO1. In mammalian myoblasts, gene silencing of Tanc1, an ortholog of rols, revealed that it is essential for myoblast fusion, but is dispensable for terminal differentiation. Misexpression of PAX-FOXO1 in myoblasts upregulated Tanc1 and blocked differentiation, whereas subsequent reduction of Tanc1 expression to native levels by RNAi restored both fusion and differentiation. Furthermore, decreasing human TANC1 gene expression caused RMS cancer cells to lose their neoplastic state, undergo fusion, and form differentiated syncytial muscle. Taken together, these findings identify misregulated myoblast fusion caused by ectopic TANC1 expression as a RMS neoplasia mechanism and suggest fusion molecules as candidates for targeted RMS therapy.
Characteristics and Prognosis of Never-Smokers and Smokers with Asthma in the Copenhagen General Population Study. A Prospective Cohort Study
Authors: Yunus Çolak, Shoaib Afzal, Børge G. Nordestgaard, Peter Lange
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Asthma is associated with complications, cardiovascular comorbidities, and higher mortality in some individuals.To test the hypothesis that, among individuals with asthma, never-smokers have different characteristics and a better prognosis than smokers.We recruited 94,079 individuals aged 20-100 years from the Copenhagen General Population Study, a prospective cohort study. Among these individuals, 5,691 (6%) had self-reported asthma (2,304 never-smokers, 2,467 former smokers, and 920 current smokers). We examined respiratory symptoms, lung function, and levels of inflammatory and allergic biomarkers in systemic circulation. Furthermore, we assessed prospectively the risk of asthma or chronic obstructive pulmonary disease (COPD) exacerbations, pneumonias, lung cancer, ischemic heart disease, ischemic stroke, and all-cause mortality during 4.5 years of follow-up.Compared with never-smokers without asthma, individuals with asthma had more respiratory symptoms and airflow limitation and higher levels of inflammatory and allergic biomarkers, which were most pronounced in smokers. Among individuals with asthma compared with never-smokers without asthma, multivariable adjusted hazard ratios for asthma exacerbations were 11 (95% confidence interval: 5.8-22) in never-smokers, 13 (6.2-29) in former smokers, and 18 (8.2-39) in current smokers. The corresponding values for other endpoints were, respectively, 8.9 (2.1-38), 23 (8.8-58), and 36 (12-105) for COPD exacerbations; 1.5 (0.9-2.2), 1.6 (1.0-2.4), and 2.4 (1.6-3.7) for pneumonias; 0.6 (0.1-5.1), 4.0 (1.3-12), and 13 (4.3-41) for lung cancer; 1.2 (0.9-1.6), 1.5 (1.2-2.0), and 2.0 (1.4-2.9) for ischemic heart disease; 1.4 (0.9-2.1), 1.2 (0.8-1.9), and 3.0 (1.7-5.3) for ischemic stroke; and 0.9 (0.6-1.3), 1.5 (1.1-2.0), and 2.7 (1.9-3.7) for all-cause mortality.Never-smokers with asthma had an increased risk of asthma and COPD exacerbations, and possibly pneumonias. Importantly, the risks for lung cancer, cardiovascular comorbidities, and death were restricted to smokers with asthma. Thus, tobacco smoking was the main explanation for poor prognosis in asthma.
Indigenous by definition, experience, or world view
Authors: C. Cunningham
Journal: BMJ (2003)

Links between people, their land, and culture need to be acknowledged 

“Indigenous” has a number of usages that differ from “to be born in a specific place,” which is how the Concise Oxford Dictionary defines it.1 These usages tend to define indigenous by the experiences shared by a group of people who have inhabited a country for thousands of years, which often contrast with those of other groups of people who reside in the same country for a few hundred years. A number of alternative terms are preferred to indigenous. For example, in Australia, Aboriginal and Torres Strait Islander is appropriate and acceptable. In Canada and the United States, the term First Nations is used to describe the Indian, Metis, and Inuit populations, whereas in Hawaii, native Hawaiian finds favour. Many groups prefer their own language. The Maori of New Zealand use “Tangata Whenua” or “people of the land” in preference to Maori used by the colonising Victorian English who, unaware of its meaning (ordinary or common), ironically deemed the indigenous population to be the ordinary inhabitants, rendering themselves extraordinary in the process.2

Te Ahukaramu Charles Royal, a recent Maori recipient of the Churchill fellowship for overseas study, offers an attractive definition of indigenous based on what he calls …
PARALDEHYDE OR BENZYL ALCOHOL AS CAUSE OF FATALITY
Authors: Harold Speert
Journal: JAMA (1942)

<h3>To the Editor:—</h3> Since its introduction in obstetrics, paraldehyde has proved to be a valuable analgesic agent in labor. In addition to its excellent analgesic and amnesic properties, its usefulness has been greatly enhanced by the relaxation and sleep it affords the parturient patient between pains. Most physicians who have used this drug have been impressed with the wide margin of safety it enjoys over other commonly employed analgesics. In the hands of different obstetricians, and with varying technics of administration, it has been found to possess a high degree of safety for both mother and child. Hanson (<i>California &amp; West. Med.</i><b>47</b>:191 [Sept.] 1937) has reported a case in which an overdose (120 cc.) of paraldehyde was given rectally during labor, with complete recovery of the mother and the delivery of a normal infant in good condition. Yet reports of 4 cases have appeared in the literature incriminating
A1.40 Adiponektin and resistin levels in pregnant patients with rheumatoid arthritis
Authors: Eva Akermann, Manuela Tham, Frauke Forger
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Pregnancy induces a modulation of the maternal immune system in order to install tolerance towards the semiallogeneic fetus. This change of the maternal immune systems influences some autoimmune diseases such as rheumatoid arthritis (RA) in a positive way. Our previous study showed that genes of the adipocytokine pathway were differently regulated by pregnancy as well as by RA. The objective of this study was to analyse the association between pregnancy induced improvement of RA and changes of adipocytokine levels. <h3>Material and Methods</h3> Adiponectin and resistin levels were measured in sera of pregnant (n = 29) and non-pregnant (n = 24) RA patients as well as in pregnant (n = 26) and non-pregnant (n = 9) healthy controls by ELISA. Pregnant RA patients were analysed before conception, once at each trimester and 8 weeks postpartum. Disease activity was measured by CRP and DAS28-CRP. <h3>Results</h3> Resistin levels were higher in non-pregnant RA patients than in healthy controls. Resistin levels increased during pregnancy and decreased postpartum in both healthy subjects and RA patients. However, RA patients with active disease during pregnancy showed higher resistin levels at the third trimester than healthy women. There was a positive correlation between resistin levels and CRP. Adiponektin levels increased at the second trimester of pregnancy and decreased thereafter in both healthy subject and RA patients. There was no difference between patients and healthy subjects. Adiponektin levels of RA patients negatively correlated with CRP. <h3>Conclusion</h3> Pregnancy induces an increase of both the resistin and the adiponectin levels. Resistin levels are further influenced by active disease. By contrast, the increase of the adiponectin levels at the second trimester might play a role in the modulation of disease activity of RA.
Vascular Abnormalities in Children With Diabetes Mellitus
Authors: Arthur W. Feinberg
Journal: JAMA (1967)

The arterial pulse wave was recorded in 907 diabetic and 203 normal subjects between 10 and 19 years of age. The technique involves the application of a cuff about the finger and does not require intra-arterial puncture. A 73% prevalence of abnormalities was found in the arterial pulse wave of the diabetic children, none of whom had overt, clinical evidence of vascular disease. Only 7% of the nondiabetic children had arterial pulse wave abnormalities. The exact nature of the vascular abnormality reflected by the pulse wave is unknown. However, arterial pulse tracings would seem to provide a convenient and accurate means of evaluating early vascular disease before the onset of clinical symptoms. Studies are currently in progress to determine the clinical applicability of this procedure to large population groups.
Breast Cancer Treated with Stilboestrol
Authors: W. D. Hasler
Journal: BMJ (1946)

Cocaine exhibits high liability for inducing addictive behaviors, but the mechanisms of neuroplasticity underlying the behavioral effects remain unclear. As a crucial mediator of neuroplasticity in diverse functional models, brain-derived neurotrophic factor (BDNF) could contribute to the mechanisms of addiction-related neuroplasticity. Here, we addressed the hypothesis that cocaine increases synaptic dopamine which induces BDNF protein expression to initiate addiction-related behavior in the rat. Enzyme-linked immunosorbent assay was used to measure BDNF protein expression in rat striatal tissues. For behavioral readout, we used the Metris Sonotrack system to measure the emission of 50-KHz ultrasonic vocalization (USV), a response that correlates with electrical brain stimulation and conditioned place-preference behavior in rodents. A single injection of cocaine significantly increased BDNF protein expression, but this effect was not further augmented by repeated cocaine administration. A single administration of cocaine elicited significant and dose-related USV responses, and the magnitude of the behavior increased with repeated drug administration. SCH23390, but not raclopride, significantly attenuated cocaine-induced BDNF protein expression, whereas either the D<sub>1</sub>-like or D<sub>2</sub>-like receptor antagonist blocked cocaine-induced USV behavior. Furthermore, significant USV behavior was elicited by the nonselective dopamine agonist, apomorphine, but not by agonists that are selective for D<sub>1</sub>-like or D<sub>2</sub>-like receptors. Intracerebroventricular injection of the neurotrophin TrkB receptor inhibitor, K252a, blocked cocaine-induced USV behavior, but not locomotor activity. These results suggest that neurotrophin signaling downstream of dopamine receptor function probably constitutes a crucial link in cocaine induction of USV behavior, and may contribute to the mechanisms underlying the development of addiction-related behaviors.
Altered fractal behavior and heart rate variability in daily life in neurally mediated syncope
Authors: Bonpei Takase, Haruhiko Hosaka, Yoshihiro Matsushima, Takashi Akima, Syuuichi Katsushika, Toshihiko Nishioka, Fumitaka Ohsuzu, Akira Kurita
Journal: Journal of the American College of Cardiology (2002)
Psychiatry and religion – not such an obscure parallel
Authors: Alex E Jewkes
Journal: Journal of the Royal Society of Medicine (2009)

I applaud R Whitley for his thought-provoking essay.1

Such comparisons are not so hard to understand as they may appear at first glance. All religions aim to help individuals at times of need, to act as comfort in good times and bad, and provide guidance (if not always direct help). A role not unfamiliar to patients' expectations of the modern medic, I think many would agree.

Just like religion, medicine has changed through the ages. Just like religion, it shall continue to do so.

The important realization for us professionals is the responsibility bestowed upon us by being held in such esteem. When religious leaders are caught in the wrong, much questioning and anger tends to follow.

Many patients have similar expectations of doctors. Psychiatry stands at an extreme end of the spectrum – here patients may be deemed ‘hopeless’ and ‘rejected by all’. Their ailments baffle many people – we cannot see and many cannot understand what is wrong. Science provides relatively few easy answers.

It is not so hard to understand the parallels drawn between ‘psychiatrists’ and ‘priests’ – patients turning to them for help at the time of their greatest need.

Yet with such responsibility comes great demands – on all medics, especially psychiatrists, must try their upmost to uphold.
Paget's disease of bone: the Lancashire focus.
Authors: D J Barker, A T Chamberlain, P B Guyer, M J Gardner
Journal: BMJ (1980)

The radiological prevalence of Paget's disease of bone has been studied in 31 towns in Britain. A remarkably localised area of high prevalence has been shown in Lancashire. Although environmental influences seem dominant in the aetiology of the disease, no hypothesis about the environmental cause of the Lancashire focus can be advanced.
RECANALIZATION WITHIN 90 MINUTES OF SYMPTOM ONSET CRITICALLY DETERMINES CORONARY MICROVASCULAR INTEGRITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION ACHIEVING TIMI GRADE 3 FLOW
Authors: Atsushi Yamamuro, Shuichiro Kaji, Koichi Tamita, Kite Kim, Yoshimori An, Syunsuke Funakoshi, Noriyuki Kimura, Tomohiro Nishino, Satoshi Honda, Takeshi Kitai, Natsuhiko Ehara, Atsushi Kobori, Makoto Kinoshita, Tomoko Tani, Shigefumi Morioka, Toru Kita, Yutaka Furukawa
Journal: Journal of the American College of Cardiology (2010)
High water intake ameliorates tubulointerstitial injury in rats with subtotal nephrectomy: Possible role of TGF-β
Authors: Toshihiro Sugiura, Atsushi Yamauchi, Hiroshi Kitamura, Yasuko Matsuoka, Masaru Horio, Enyu Imai, Masatsugu Hori
Journal: Kidney International (1999)
The Fatty Tumors
Authors: Raffaele Lattes
Journal: JAMA (1968)

To the Editor:—  I am writing about the editorial,  Unpredictable Fatty Tumors, ( 204 :923 1968).  The statement that in one series liposarcomas... constituted 20% of malignant  should be modified to the effect that they constituted 20% of malignant mesenchymal tumors or sarcomas .  The survey by Stout was not made at the Armed Forces Institute of Pathology but was based on the records of the Division of Surgical Pathology at Columbia University College of Physicians and Surgeons. The AFIP published Stout's monograph. There is what is probably an obvious misprint: It is stated that  in any part of the body, etc. Instead of angiosarcoma the text should read liposarcoma.  I believe these comments are necessary to put back the difficult problem of liposarcoma in its proper perspective.
Metered dose inhalers: Authors' reply
Authors: D J Williams, A C Williams, D G Kruchek
Journal: BMJ (1993)

EDrrOR,-Some of the issues raised by Bonneux and Barendregt have already been addressed in the discussion section of our paper.There is a fundamental misapprehension contained in Bonneux and Barendregt's second paragraph.Their argument is valid only if this department is assumed to have been responsible for all the cases of gastric cancer from a defined population.
Ascites from cirrhotic patients induces angiogenesis through the phosphoinositide 3-kinase/Akt signaling pathway
Authors: Manuel Morales-Ruiz, Sònia Tugues, Pilar Cejudo-Martín, Josefa Ros, Pedro Melgar-Lesmes, Patricia Fernández-Llama, Vicente Arroyo, Juan Rodés, Wladimiro Jiménez
Journal: Journal of Hepatology (2005)
Effect of Soy Protein Containing Isoflavones on Cognitive Function, Bone Mineral Density, and Plasma Lipids in Postmenopausal Women
Authors: Sanne Kreijkamp-Kaspers, Linda Kok, Diederick E. Grobbee, Edward H. F. de Haan, André Aleman, Johanna W. Lampe, Yvonne T. van der Schouw
Journal: JAMA (2004)

Postmenopausal estrogen therapy has been posited to have some beneficial effects on aging processes, but its use has risks. Isoflavones, estrogenlike compounds naturally occurring in plant foods, might confer positive effects with fewer adverse effects.To investigate whether soy protein with isoflavones improves cognitive function, bone mineral density, and plasma lipids in postmenopausal women.Double-blind, randomized, placebo-controlled trial of 202 healthy postmenopausal women aged 60 to 75 years, recruited from a population-based sample in the Netherlands, conducted between April 2000 and September 2001.Participants were randomly assigned to receive 25.6 g of soy protein containing 99 mg of isoflavones (52 mg genistein, 41 mg daidzein, and 6 mg glycetein or total milk protein as a powder on a daily basis for 12 months.Cognitive function was assessed using the following instruments: dementia, Mini-Mental State Examination; memory, Rey Auditory Verbal Learning Test, immediate recall, delayed recall, and recognition, the Digit Span forward and reversed, and the Doors test; complex attention tasks, Digit Symbol Substitution and Trailmaking, A1, A2, and B; and verbal skills, Verbal Fluency A and N, animals and occupations, and the Boston Naming Task. Bone mineral density of the hip and lumbar spine was assessed using dual-energy x-ray absorptiometry scanning. Lipid assessment included lipoprotein(a), total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides.A total of 175 women completed the baseline and at least 1 postintervention analysis and were included in the modified intent-to-treat analysis. Adherence was good (median plasma genistein levels, 17.2 and 615.1 nmol/L for placebo and soy group, respectively). Cognitive function, bone mineral density, or plasma lipids did not differ significantly between the groups after a year.This double-blind randomized trial does not support the hypothesis that the use of soy protein supplement containing isoflavones improves cognitive function, bone mineral density, or plasma lipids in healthy postmenopausal women when started at the age of 60 years or later.
Sumoylation of Corepressor SAFB1 – Mechanism of Action and Biological Relevance in Breast Cancer.
Authors: J. Garee, R. Meyer, S. Oesterreich
Journal: Cancer Research (2009)

Abstract Scaffold attachment factor B1 (SAFB1) was originally isolated due to its ability to bind Scaffold/Matrix attachment regions of genomic DNA. Subsequently, SAFB1 has also been shown to be involved in RNA processing, chromatin organization and stress response. Work from our laboratory has shown that SAFB1 can bind and modulate transcription of the HSP-27 promoter and repress activity of ERα. Repression of ERα occurs through an independent and transferable c-terminal repression domain. Further work has indicated that SAFB1 can interact with and repress transactivation of a host of nuclear receptors including PPARg and FXR, suggesting a general role for SAFB1 in transcriptional repression.Many proteins associated with transcriptional regulation are post translationally modified by small ubiquitin like modifier (SUMO). SUMO is a 98 amino acid mature polypeptide that is added post translationally to target proteins usually within a consensus sumoylation motif, ΨKXE (where Ψ is a large hydrophobic residue, K-lysine of modification and X any residue). The process of sumoylation is analogous to ubiquitination. SUMO modification of proteins associated with transcription has generally been associated with transcriptional repression. The mechanism by which this modification leads to transcriptional repression has yet to be defined.Work by our laboratory has indicated that SAFB1 is modified by sumoylation. In silico analysis indicated two consensus sumoylation motifs within SAFB1. Immunoprecipitation studies revealed SUMO modified forms of SAFB1. Mutating the lysine's within the sumoylation motifs to arginine (K231,294R) lead to a loss of sumo modified SAFB1 indicating these as the sites of modification. Transient ERE-Tk-Luciferase assays showed a loss of transcriptional repression with over expression of SAFB1 K231,294R compared to SAFB1 wildtype. Loss of transcriptional repression was also seen utilizing transient Gal4DBD reporter assays indicating an effect of sumoylation on SAFB1's intrinsic repressive function. Co-immunopreciptation studies have indicated interaction between SAFB1 and SUMO E3 ligases suggesting these may be important for modifying SAFB1. Additionally, over expression of members of the sumoylation machinery can enhance SAFB1 repressive activity indicating this modification is important for SAFB1 transcriptional repression. Loss of SAFB1 sumoylation does not alter protein half life indicating the loss of transcriptional repression is not through this mechanism.Our studied have indicated that sumoylation of SAFB1 is important for its repressive activity. Additional studies within the lab are aimed at addressing the mechanism and the complete extent of functional consequences of sumoylation of SAFB1. A better understanding of post translational modification of SAFB1 may provide additional insights into the diverse functions of SAFB1 and its role in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4142.
Abstract A72: TGF-β2 underpins CD44-promoted breast tumor cell invasion
Authors: Allal Ouhtit, Samineh Madani, Ishita Gupta, Somya Shanmuganathan, Hamad Al-Riyami, Yahya Al-Farsi
Journal: Cancer Research (2013)

Abstract Hyaluronan (HA) mediates communication between cancer cells and the environment via interactions with the cell surface receptor CD44. The long-term objective of this study is to increase our understanding of the mechanisms by which CD44-HA interaction promotes BC metastasis, and further identify and validate CD44-downstream transcriptional targets for anti-metastatic therapy. Here, we have developed a tetracycline (tet)-regulated expression of CD44 gene in the BC cell line MCF-7 (B5 clone) and identified TGF-beta2 (Transforming Growth Factor beta-2; 3 fold induction) as a potential CD44s-downstream transcriptional target by microarray analysis. The same RNA samples, used for microarray analysis and their corresponding protein lysates, were examined for CD44 expression by RT-PCR and western-Blot methods, respectively. TGF-beta2 mRNA levels were significantly elevated following the removal of tet at 18, 24, and 48 h post-HA stimulation compared to controls. Furthermore, the TGF-beta2 precursor protein increased in a time-dependent pattern upon HA-stimulation and in the absence of tet. Inhibition of CD44 gene by RNAi method decreased TGF-beta2 expression upon HA-stimulation and in the absence of tet. Our data put together strongly support the hypothesis that TGF-beta2 is a potential target of HA/CD44-downstream-signaling mediating BC cell invasion. Finally, CREB might be the transcription factor linking CD44 to TGF-beta2 transcription. Citation Format: Allal Ouhtit, Samineh Madani, Ishita Gupta, Somya Shanmuganathan, Hamad Al-Riyami, Yahya Al-Farsi. TGF-β2 underpins CD44-promoted breast tumor cell invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A72.