tbuckley/cabot-search huggingface dataset:
Epidemiological studies supports an occupational etiology for nonalcoholic steatohepatitis among petrochemical workers from Bahia, Brazil
Authors: F.M. Carvalho, A.M. Silvany-Neto, H.P. Cotrim, J.L.B. Mendes, J.F. Gidi, F. Guedes, R. Oliveira
Journal: Journal of Hepatology (2001)
Students' use of psychiatric services: the Columbia experience
Authors: B. A. Lerner
Journal: JAMA (1995)

Medical students spend almost a decade learning how to take good care of their patients. No less time and effort should be spent in learning how to take good care of themselves. When students find themselves needing assistance in sorting out their problems, we are available to help them conceptualize their difficulties and carry out an appropriate treatment regimen in a fully confidential matter.
Alpha2-adrenergic receptor-mediated release of lysophosphatidic acid by adipocytes. A paracrine signal for preadipocyte growth.
Authors: P Valet, C Pagès, O Jeanneton, D Daviaud, P Barbe, M Record, J S Saulnier-Blache, M Lafontan
Journal: Journal of Clinical Investigation (1998)

In the search for the existence of adrenergic regulation of the autocrine/paracrine function of the white adipose tissue, it was observed that conditioned media from isolated adipocytes or dialysates obtained by in situ microdialysis of human subcutaneous adipose tissue increased spreading and proliferation of 3T3F442A preadipocytes. These effects were amplified when an alpha2-adrenergic agonist was present during the obtention of conditioned media and microdialysates. This alpha2-adrenergic-dependent trophic activity was completely abolished by pretreatment of the conditioned media or microdialysates with the lysophospholipase, phospholipase B. Among the different lysophospholipids tested only lysophosphatidic acid (LPA) was able to induce spreading and proliferation of 3T3F442A preadipocytes. Moreover, previous chronic treatment of 3T3F442A preadipocytes with LPA which led to a specific desensitization of LPA responsiveness, abolished the alpha2-adrenergic-dependent trophic activities of the conditioned media and microdialysates. Finally, alpha2-adrenergic stimulation led to a rapid, sustained, and pertussis toxin-dependent release of [32P]LPA from [32P]-labeled adipocytes. Based upon these results it was proposed that in vitro and in situ stimulation of adipocyte alpha2-adrenergic receptors provokes the extracellular release of LPA leading, in turn, to regulation of preadipocyte growth.
Genetic Susceptibility to Stuttering
Authors: Simon E. Fisher
Journal: New England Journal of Medicine (2010)

Disorders that disrupt the development of speech, language, or reading have substantial effects on social function. Researchers have implicated specific genetic variants in monogenic speech disorder,1 common language impairments,2,3 and dyslexia.4 With the report by Kang and colleagues in this issue of the Journal, 5 stuttering joins the fray.Stuttering is a disorder in which speech fluency can be severely compromised. It is characterized by the involuntary repetition or prolongation of sounds, syllables, words, or phrases, as well as frequent pauses, impeding the rhythmic flow of speech. Onset is typically between 3 and 6 years of age, and approximately 5% . . .
Abstract LB-107: Inhibiting TNKS sensitizes KRAS mutant cancer cells to MEK inhibitors by suppressing FGFR2 feedback signaling
Authors: Wenlin Shao, Marie Schoumacher, Kristen Hurov, Joseph Lehar, Yan Yan-Neale, Yuji Mishina, Dmitriy Sonkin, Joshua Korn, Daisy Flemming, Michael Jones, Brandon Antonakos, Vessilina Cooke, Mark Stump, Nika Danial, William Sellers
Journal: Cancer Research (2014)

Abstract Tankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis and mitosis, and are therefore considered as attractive targets for anti-cancer treatment. Using unbiased combination screens in a large panel of cancer cell lines, we have identified a strong synergy between TNKS and MEK inhibitors in KRAS mutant cancer cells. Our study uncovers a novel function of TNKS in the relief of a feedback loop induced by MEK inhibition on FGFR2 signaling pathway. Moreover, dual inhibition of TNKS and MEK leads to more robust apoptosis and anti-tumor activity both in vitro and in vivo than effects observed by previously reported MEK inhibitor combinations. Altogether, our data provides a strong rationale for combined targeting of TNKS and MEK in KRAS mutant cancers. Citation Format: Wenlin Shao, Marie Schoumacher, Kristen Hurov, Joseph Lehar, Yan Yan-Neale, Yuji Mishina, Dmitriy Sonkin, Joshua Korn, Daisy Flemming, Michael Jones, Brandon Antonakos, Vessilina Cooke, Mark Stump, Nika Danial, William Sellers. Inhibiting TNKS sensitizes KRAS mutant cancer cells to MEK inhibitors by suppressing FGFR2 feedback signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-107. doi:10.1158/1538-7445.AM2014-LB-107
Effect of IL-13 and IL-13 Mutant (IL-13E13K) on Airway Hyperresponsiveness (AHR) and Airway Smooth Muscle (ASM) In Mice
Authors: P.R. Gendapodi, M. Kioi, R.K. Puri, P. Abel, R.G. Townley
Journal: Journal of Allergy and Clinical Immunology (2007)
Atherosclerosis Drug Development in Jeopardy: The Need for Predictive Biomarkers of Treatment Response
Authors: David A. Fryburg, Maria T. Vassileva
Journal: Science Translational Medicine (2011)

The limited predictability of phase II biomarkers for atherosclerosis outcomes in phase III studies stands in contrast to the number and varied types of biomarkers--soluble, imaging, and functional--that have been used in a diverse array of trials. Although collectively abundant, these biomarker data exist in a fragmented state. Most biomarkers are studied one at a time, only measure a specific aspect of atherosclerosis, are not integrated in a substantive way, and compete with one another for validation; in the end, progress is slow. The proposed solution from the Atherosclerosis Working Group, a committee of experts from academia, the pharmaceutical industry, government, and the nonprofit sector and managed by the Foundation for the National Institutes of Health Biomarkers Consortium, is to integrate these different measures into an in silico model of atherosclerosis. Through integration of diverse biomarker measurements and outcomes in silico, we may be able to improve trial design as well as the predictive power of short-term markers for longer-term outcomes.
Effect of NOx on the somatic chromosomes of goldsmiths.
Authors: J S Yadav, N Seth
Journal: Environmental Health Perspectives (1998)

The genotoxic effect of NOx was investigated on somatic human chromosomes obtained from lymphocytes of 45 goldsmiths exposed to 1770.5 mg/m3 NOx in ambient air at normal temperature and pressure and compared to an equal number of matched controls breathing air containing 50 microgram/m3 NOx. Short-term lymphocyte cultures were set up from blood collected from both exposed and control individuals by venipuncture in heparinized sterile syringes. Mitotic index (MI), chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and satellite associations (SAs) were analyzed. All the parameters showed a significant increase (p&lt;0.01 and p&lt;0.05) in the exposed individuals as compared to the controls: MI (9.57 vs. 5.01), CAs (3. 48 vs. 0.711), SCEs (10.56 vs. 7.02), and SAs (25.97 vs. 12.84), respectively. Occurrence of DG-type SAs (one D-group chromosome and one G-group chromosome) was highest and 3 D-type (three D-group chromosomes) lowest. NOx was thus found to be genotoxic for humans.
Competing Oscillators in Cardiac Pacemaking
Authors: Denis Noble, Penelope J. Noble, Martin Fink
Journal: Circulation Research (2010)

Interaction between a membrane oscillator generated by voltage-dependent ion channels and an intracellular calcium signal oscillator was present in the earliest models (1984 to 1985) using representations of the sarcoplasmic reticulum. Oscillatory release of calcium is inherent in the calcium-induced calcium release process. Those historical results fully support the synthesis proposed in the articles in this review series. The oscillator mechanisms do not primarily compete with each; they entrain each other. However, there is some asymmetry: the membrane oscillator can continue indefinitely in the absence of the calcium oscillator. The reverse seems to be true only in pathological conditions. Studies from tissue-level work and on the development of the heart also provide valuable insights into the integrative action of the cardiac pacemaker.
The Myofascial Pain Dysfunction: Dental Symptoms and Psychological and Muscular Function
Authors: Astrid Nøklebye Heiberg, Berit Helöe, Berit Schie Krogstad
Journal: Psychotherapy and Psychosomatics (1978)

Patients with myofascial pain dysfunction (MPD) are traditionally seen by dentists. No organic lesions are found, and there is accumulating evidence that psychological factors influence both the onset and the development of the disorder, thus calling for a multiprofessional investigation approach. This report presents a preliminary study by a team consisting of a psychiatrist, a dentist and a physiotherapist. 25 patients with MPD diagnosis were examined. Almost all of the patients had tense muscles in neck and back, indicating that muscular tension is not a local phenomenon in the masticatory muscles. It was possible to distinguish two main categories of MPD patients, the 'typical MPD patients' and the 'multiproblem patients'. Problems that need further investigation are pointed to.
1043. In Vivo Gene Transfer into Rat Hematopoietic Stem Cells Using rSV40 Viral Vectors
Authors: Bianling Liu, Jean-Pierre Louboutin, Judy Daviau, David S. Strayer
Journal: Molecular Therapy (2005)

Hematopoietic stem cell (HSC) gene transfer has been attempted almost entirely ex vivo, and has been limited by cytokine-induced loss of self-renewal capacity and transplantation-related defects in homing and engraftment. We tried to circumvent such limitations by injecting vectors directly into the bone marrow (BM), in order to transduce HSC in their native environment. SV40-derived gene delivery vectors were used because they transduce resting CD34+ cells very efficiently. Rats received SV(Nef-FLAG), carrying FLAG epitope as a marker - or a control rSV40- directly into the BM cavity of each femur. Intracellular transgene expression was detected by cytofluorimetry of peripheral blood (PB) or BM cells. An average of 5.3% of PB leukocytes expressed FLAG for the entire study, 56 weeks. Transgene expression was sustained in multiple cell lineages, including granulocytes (average, 3.3%), CD3+ T lymphocytes (average, 0.53%) and CD45R+ B lymphocytes, indicating gene transfer to long-lived progenitor cells with multilineage capacity. An average of 15% of femoral marrow cells expressed the transgene >= 16.5 months after transduction. Thus, direct intramarrow administration of rSV40s yields efficient gene transfer to rat BM progenitor cells, and may be worthy of further investigation.
INJURIES TO THE CHILD'S HEAD DURING LABOR.
Authors: B. SACHS
Journal: JAMA (1906)

For many years I have been anxious to enlist the interest of the obstetrician and of the general practitioner in the injuries which the child's brain is apt to sustain during parturition. The general opinion prevails, and it is not wholly wrong, that the child's head is wonderfully tolerant and that the child is none the worse for prolonged labor and for instrumental delivery. The physician who has delivered a woman of a living child without seriously injuring the mother and without leaving on the child the outward mark of difficult labor feels proud of his achievement, and if the child has no convulsions during the first 24 or 48 hours of life, if it appears to move all its limbs, the physician walks away with pride and an easy conscience. He has done his duty according to his own best light and in accordance with the best teachings of
Alcohol and the fetus in the west of Scotland.
Authors: J O Beattie, R E Day, F Cockburn, R A Garg
Journal: BMJ (1983)

Forty children with the fetal alcohol syndrome were identified in the west of Scotland. All were growth retarded and had abnormal facial features, and all those who were tested were found to have neurological or developmental abnormalities. Two children died of associated physical defects. Most of the mothers were socially deprived, and all had drunk heavily while pregnant. Three women had subsequently died. These findings provide clear evidence that in the west of Scotland maternal alcohol abuse during pregnancy is a significant cause of morbidity and mortality in children.
Exposure to house dust endotoxin and allergic sensitization in adults
Authors: U. Gehring, W. Bischof, G. Schlenvoigt, K. Richter, B. Fahlbusch, H.‐E. Wichmann, J. Heinrich
Journal: Allergy (2004)

Background: It has been suggested that exposure to elevated levels of endotoxin decreases the risk of allergic sensitization. Objective: To examine the associations between current exposure to bacterial endotoxin in house dust and allergic sensitization in adults. Methods: In 1995–1996, we conducted a nested case–control study following a cross‐sectional study performed within the European Community Respiratory Health Survey (ECRHS). Data of 350 adults aged 25–50 years was analysed. Allergic sensitization was assessed by measurement of specific immunoglobulin E (IgE) against several inhalant allergens. Living room floor dust samples were taken. The endotoxin content was quantified using a chromogenic kinetic Limulus amoebocyte lysate test. Results: Multiple logistic regression analysis showed a negative association between exposure to house dust endotoxin and severe allergic sensitization. Odds ratios (95% CI) adjusted for place of residence, gender, age, and ‘caseness’ were 0.80 (0.64–1.00) for sensitization to ≥1 allergen and 0.72 (0.56, 0.92) for sensitization to ≥2 allergens using 3.5 kU/l as a cut‐off value for sensitization. With regard to single allergens, the protective effect of endotoxin was strongest for pollen sensitization [aOR (95% CI) = 0.74 (0.58, 0.93)]. Conclusion: Our results indicate that current exposure to higher levels of house dust endotoxin might be associated with a decreased odds of allergic sensitization in adults.
Effects of Proteasome Inhibition on the Kidney in Experimental Hypercholesterolemia
Authors: Alejandro R. Chade, Joerg Herrmann, Xiangyang Zhu, James D. Krier, Amir Lerman, Lilach O. Lerman
Journal: Journal of the American Society of Nephrology (2005)

Hypercholesterolemia (HC) and atherosclerosis often accompany and aggravate renal disease. Proteasome inhibitors (PSI) can decrease proliferation and inflammation, likely by reducing activation of the proinflammatory NF-κB. However, chronic proteasome inhibition has never been demonstrated in the HC kidney. Four groups of pigs (<i>n</i> = 7 each) were studied after a 12-wk normal (N) or 2% HC diet alone or supplemented (N+PSI and HC+PSI) with MLN-273 (0.08 mg/kg subcutaneously twice weekly). Renal hemodynamics and function were quantified <i>in vivo</i> using electron-beam computed tomography at baseline and after vasodilator challenge using acetylcholine. Renal tissue was studied <i>ex vivo</i> using immunoblotting, PCR, and immunohistochemistry. Serum cholesterol was similarly elevated in HC and HC+PSI. Basal renal blood flow was similar among the groups, whereas GFR was decreased in both N+PSI and HC+PSI. The blunted renovascular and functional responses to acetylcholine in HC were normalized in HC+PSI (suggesting renal endothelial function improvement), which was accompanied by decreased renal endothelin, NF-κB, and augmented endothelial nitric oxide synthase expression. In parallel, HC+PSI animals also showed elevated NAD(P)H oxidase expression and circulating oxidized LDL, suggesting a potential for increased oxidative stress. This study shows that chronic PSI intervention in HC improves renal endothelial functional responses to challenge, possibly by modulating nitric oxide availability and endothelin. Furthermore, PSI may decrease intrarenal inflammation through modulation of the NF-κB pathway but may potentially increase oxidative stress, which warrants further investigation. This study may support a role for the ubiquitin/proteasome system in the kidney in HC and early atherosclerosis.
War on the roads
Authors: I. Roberts
Journal: BMJ (2002)

The public health community must intervene T he last thing the world needs is another war.Nevertheless, this week the BMJ exposes one more-the war on the world's roads.But to what extent can the global road trauma epidemic be likened to war?War is often waged by the powerful on the weak.In this case, the interests of pedestrians, cyclists, and other vulnerable road users are pitted against the powers that stand to profit from increasing global motorisation.And there are many millions of casualties.Every day about 3000 people die and 30 000 people are seriously injured on the world's roads. 1 In this issue Nantulya and Reich point out that over 85% of the deaths and 90% of disability adjusted life years lost from road traffic injuries are in low and middle income countries, with pedestrians, cyclists, and bus passengers bearing most of the burden. 2Most of the victims will never own a car, and many are children.Even in the high income countries, poor children are at greatest risk.The existence of a steep social class gradient in mortality in child pedestrians is well documented, but the evidence about socioeconomic gradients in morbidity due to injury has been conflicting. 3 This week Hippisley-Cox and colleagues report a study of over 56 000 admissions of injured children to hospitals in Trent that provides clear evidence of a social class gradient in morbidity from injury, and which is steepest for injuries in pedestrians. 4 Nevertheless, the prevention of traffic crashes is low on the list of public health priorities both in the United Kingdom and internationally, with record low levels of funding in research and development. 5 As in other wars, propaganda is an important weapon.It is not in the interests of those who sell road transport to allow the private trouble of road death and injury to become a public issue.The idea that governments and the motor manufacturing industry have a major responsibility is not for public consumption.It is much more acceptable that the victims are held responsible.In this issue, Roger Browning, a trustee of the victims' charity RoadPeace, writes about the loss of his daughter in a road crash and his frustration at the absence of an appropriate response from the relevant authorities, including the medical profession. 6 According to Marcel Haegi, the president of the European Federation of Road Traffic Victims, the failure of governments to properly enforce road safety laws, and to investigate road deaths as they would other situations involving the taking of life, is commonplace. 7
All-cause mortality in males with sleep apnoea syndrome: declining mortality rates with age
Authors: P. Lavie, L. Lavie, P. Herer
Journal: European Respiratory Journal (2005)

The objective of this study was to assess whether an increasing severity of sleep apnoea is associated with increased all-cause mortality hazards and to assess whether the syndrome is associated with excess mortality, in comparison with the general population. Participants included 14,589 adult males, aged 20–93 yrs, referred to the sleep clinics with suspected sleep apnoea or diagnosed with sleep apnoea. Altogether, 372 deaths were recorded after a median follow-up of 4.6 yrs. The crude all-cause mortality rate was 5.55/1,000 patient yrs, increasing with apnoea severity. Cox proportional analysis revealed that both respiratory disturbance index (RDI) and body mass index significantly influenced all-cause mortality hazard but there was no interaction between them. Males with respiratory disturbance index &gt;30 had a significantly higher mortality hazard rate than the reference group of males with RDI ≤10. Comparing mortality rates of males with moderate/severe sleep apnoea to the general population revealed that only males aged &lt;50 yrs showed an excess mortality rate. The hazard of mortality in sleep apnoea increases with apnoea severity as indexed by respiratory disturbance index. Moderate and severe levels of sleep apnoea are moderately associated with an increased risk of all-cause mortality, in comparison with the general population, particularly in males aged &lt;50 yrs. The lack of information about possible confounders and treatment effects should be taken into consideration in the interpretation of these results.
Razoxane in treatment of acute myeloid leukaemia.
Authors: M Bhavnani, K Dhir, I W Delamore
Journal: BMJ (1978)

Razoxane in treatment of acute myeloid leukaemia Razoxane (ICRF 159; 1,2-Bis (3,5 dioxopiperazin-l-yl) propane, Cl ,H16N404) has been used for treating acute leukaemia.'It is thought to act as an inhibitor of RNA, or more likely of DNA, and to interfere with cell division at the G2/M phase of the cell cycle.2After recent claims of success with razoxane and cystosine in treating acute myeloid leukaemia and the relative absence of side effects, we decided to treat consecutive and unselected patients with acute myeloid leukaemia with this combination.
Presentation on US Hospital Websites of Risks and Benefits of Transcatheter Aortic Valve Replacement Procedures
Authors: Mariah L. Kincaid, Lee A. Fleisher, Mark D. Neuman
Journal: JAMA Internal Medicine (2015)

on specific risks associated with this procedure.Moreover, while websites rarely presented quantitative information about either risks or benefits, benefits were quantified more frequently than risks.Our findings suggest that web-based advertising of TAVR to the public by hospitals may understate the established risks of this procedure and provide little context for the magnitude of those risks to inform patient decision making.Hospitals may promote appropriate use of TAVR by presenting more balanced information regarding TAVR's risks and benefits.
Partial Reversibility of Airflow Limitation and Increased Exhaled NO and Sputum Eosinophilia in Chronic Obstructive Pulmonary Disease
Authors: ALBERTO PAPI, MICAELA ROMAGNOLI, SIMONETTA BARALDO, FAUSTO BRACCIONI, IPPOLITO GUZZINATI, MARINA SAETTA, ADALBERTO CIACCIA, LEONARDO M. FABBRI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV(1) of < 12% and < 200 ml after 200 microg of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV(1) of < 12% but > 200 ml after 200 microg of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.