tbuckley/cabot-search huggingface dataset:
Abstract 2149: Novel compound 1, 3-bis (3, 5-dichlorophenyl) urea inhibits lung cancer progression
Authors: Sharad S. Singhal, James Figarola, Jyotsana Singhal, Lokesh Nagaprashantha, David Berz, Samuel Rahbar, Sanjay Awasthi
Journal: Cancer Research (2014)

Abstract The successful clinical management of lung cancer is limited by frequent loss-of-function mutations in p53 which cooperates with chronic oxidant-stress induced adaptations in mercapturic acid pathway (MAP) which in turn regulates critical intracellular signaling cascades that determine therapeutic refractoriness. Hence, we investigated the anti-cancer effects and mechanisms of action of a novel compound called 1, 3 bis (3, 5-dichlorophenyl) urea (COH-SR4) in lung cancer. Treatment with COH-SR4 effectively inhibited the survival and clonogenic potential along with inducing apoptosis in lung cancer cells. COH-SR4 treatment caused the inhibition of GST activity and G0/G1 cell cycle arrest and inhibited the expression of cell cycle regulatory proteins CDK2, CDK4, cyclin A, cyclin B1, cyclin E1, and p27. The COH-SR4 activated AMPK pathway and knock-down of AMPK partially reversed the cytotoxic effects of COH-SR4 in lung cancer. COH-SR4 treatment lead to regression of established xenografts of H358 lung cancer cells without any overt toxicity. The histopathology of resected tumor sections revealed an increase in pAMPK, a decrease in the nuclear proliferative marker Ki67 and angiogenesis marker CD31. Western-blot analyses of resected tumor lysates revealed a decrease in pAkt and anti-apoptotic protein Bcl2 along with an increase in pAMPK, pro-apoptotic protein Bax and cleaved PARP levels. Importantly, COH-SR4 lead to decrease in the mesenchymal marker vimentin and increase in the normal epithelial marker E-cadherin. The results from our in-vitro and in-vivo studies reveal that COH-SR4 represents a novel candidate with strong mechanistic relevance to target aggressive and drug-resistant lung tumors (Supported by NIH grant CA 77495 and Beckman Research Institute of the City of Hope). Note: This abstract was not presented at the meeting. Citation Format: Sharad S. Singhal, James Figarola, Jyotsana Singhal, Lokesh Nagaprashantha, David Berz, Samuel Rahbar, Sanjay Awasthi. Novel compound 1, 3-bis (3, 5-dichlorophenyl) urea inhibits lung cancer progression. [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 2149. doi:10.1158/1538-7445.AM2014-2149
Transplantation of PC1/3-Expressing α-cells Improves Glucose Handling and Cold Tolerance in Leptin-resistant Mice
Authors: Rhonda D Wideman, Sarah L Gray, Scott D Covey, Gene C Webb, Timothy J Kieffer
Journal: Molecular Therapy (2008)

Type 2 diabetes (T2D) is characterized by elevated blood glucose levels owing to insufficient secretion and/or activity of the glucose-lowering hormone insulin. Glucagon-like peptide-1 (GLP-1) has received much attention as a new treatment for diabetes because of its multiple blood glucose-lowering effects, including glucose-dependent enhancement of insulin secretion, inhibition of gastric emptying, and promotion of the survival and growth of insulin-producing beta-cells. GLP-1, along with GLP-2 and oxyntomodulin, is produced in the intestinal L-cell via processing of proglucagon by prohormone convertase 1/3 (PC1/3), while in the pancreatic alpha-cell, coexpression of proglucagon and the alternate enzyme PC2 typically results in differential processing of proglucagon to yield glucagon. We used alginate-encapsulated alpha-cells as a model to evaluate continuous delivery of PC1/3- or PC2-derived proglucagon products. In high fat-fed and db/db mice, PC1/3-, but not PC2-expressing alpha-cells improved glucose handling and transiently lowered fasting glucose levels, suggesting that continuous delivery of PC1/3-derived proglucagon products via cell therapy may be useful for diabetes treatment. In addition, we show that long-term treatment with PC1/3-expressing, but not PC2-expressing, alpha-cells improved cold-induced thermogenesis in db/db mice, demonstrating a previously unappreciated effect of one or more PC1/3-derived alpha-cell products.
ICU Access and Prospective Payment-Reply
Authors: S. Allison Mayer-Oakes
Journal: JAMA (1989)

<h3>In Reply. —</h3> We agree with Drs Franklin and Rackow that access to ICU care before and after the introduction of the Prospective Payment System and outcomes of "ward" patients must also be evaluated. A clinically based national study that is designed to accomplish that purpose is nearing completion.<sup>1</sup>We agree that the results of our study should be cautiously interpreted until additional data are available. Further monitoring of the Prospective Payment System should continue in order to assess its impact fully.
Glyceryl trinitrate in angina pectoris: tablet or aerosol?
Authors: G Sandler, G A Clayton
Journal: BMJ (1967)

Rheumatoid Arthritis-Boardman and Hart ft=OURNiL The patient's preference and grip strength indicate improvement on drugs which are anti-inflammatory or analgesic agents; under defined conditions joint size is an index of specific antiinflammatory effect.The reduction of joint size by, prednisone, an anti- inflammatory agent, is contrasted with the absence of change on paracetamol.High dosage of salicylate, unlike low dosage, is associated with reduction in joint size.There is no detectable difference between low dosage of salicylate and placebo in their effect on joint size.It is suggested that high dosage of salicylate, unlike low dosage, has a clinically measurable anti-inflammatory effect.If suppression of inflammation is desirable in rheumatoid arthritis high dosage of salicylate is indicated independently of symptoms.Unlimited use of high dosage of salicylate in trials may affect the findings.Low dosage modifies the response if given in combination.Salicylate intake should be eliminated from comparative trials of anti-inflammatory agents.It is suggested that the plan of this trial provides a simple method for the clinical assessment of the anti-inflammatory properties of a rapidly acting drug.We wish to thank Dr. Peter Fowler for providing the millimetre gauge for the measurement of joint size; Dr. E. Lewis-Faning for statistical advice; and Mr. J. A. Baker, chief pharmacist at the hospital, for organizing the provision of tablets suitable for the trials.Our thanks are also due
Rapid onset of bloating and early satiety: an unusual cause with positive histology
Authors: A R Tanner, I Cook, S McGee, B Bentley, R Frost, D Finnis
Journal: Gut (2008)

A 65-year-old man presented with a 4-week history of early satiety, upper abdominal distension and rapid loss of weight. Three years previously he had undergone a radical cystectomy for familial bladder cancer, otherwise he was a completely fit …
p53 mutations in BRCA1-associated familial breast cancer
Authors: Beata Schlichtholz, Brigitte Bouchind'homme, Sabinne Pagés, Emmanuel Martin, Stéphane Liva, Henri Magdelenat, Xavier Sastre-Garau, Dominique Stoppa-Lyonnet, Thierry Soussi
Journal: The Lancet (1998)
Effect of AIC (Amb a 1 immunostimulatory oligonucleotide conjugate) on nasal allergen challenge and clinical response to seasonal ragweed exposure
Authors: Martin Y Desrosiers, Francois Lavigne, Martin Blaquiere, Normand Dube, Joseph Eiden, Qutayba A Hamid
Journal: Journal of Allergy and Clinical Immunology (2002)
NARCOTICS IN THE TREATMENT OF COUGHING
Authors: Percy Fridenberg
Journal: JAMA (1931)

<h3>To the Editor:</h3> —Apropos of Dr. Hatcher's instructive article (The Journal, April 25, p. 1383), irritation of Arnold's branch to the ear is by no means a rare cause of obstinate coughing. Aside from disorders of the external ear, such as eczema (which does not often elicit coughing) and impacted cerumen, instrumentation of the canal or region of the drum usually brings on a cough response. The most common cause of obstinate coughing as an aura reflex is a foreign body, and this should always be suspected in case of a stubborn, useless, cough in children who have the common and playful habit of putting beads, small beans or peas into the ear or nose. The danger of postoperative coughing or, in fact, any expulsive effort (sneezing, vomiting, hiccuping) is particularly grave in the case of ophthalmic patients and after cataract or glaucoma operations may burst open the operative wound,
Doctors must work in partnership with patients, says GMC
Authors: Peter Moszynski
Journal: BMJ (2006)

The health services watchdog, the Healthcare Commission, has scored most NHS trusts in England as weak for elements of their children's services.Although the overall standard of services was "fair," the commission found outpatient care, day care, and emergency care were singled out as the areas of greatest concern.The lack of training in surgical and anaesthetist staff working on emergencies and elective surgery in children also gave cause for concern.The commission assessed 157 NHS trusts against standards set out in the National Service Framework for children and young people, which was launched in 2003 as part of its new system for assessing NHS performance-the annual health check.Key standards in the framework include the treatment of children in child specific and child friendly environments and the provision of sufficient numbers of appropriately trained staff.
Malaria in the U.K.
Authors: C V Foll
Journal: BMJ (1972)

Unquiet Rest SIR,-Chauvinism in medical research is to be deplored, but your leading article on unquiet rest (23 September, p. 715) does less than justice to the pioneering British work of Masterton& on sleep patterns of junior medical staff.As early as 1965 he drew attention to both the lack of sleep obtained by busy residents on a surgical service and the effects this could have on the feelings they had about themselves and their work.The experiments of Friedman and his col- leagues2 referred to in your leading artie now confirm objectively for medical per- formance what has been known for some time in other fields-namely, that in pro- longed intellectual tasks ability declines with acute sleep lack.3However, doctors are not yet sufficiently impressed with this to order their lives properly and, as Masterton showed, the pressure of extenal affairs in a hospital environment may be the overriding factor which produces the sleep lack state.The lack of sleep in intensive care units has also been recognized since 1964, when Edgerton and Kay4 and Kornfield, Zimberg, and Malm5 first postulated that it might be of importance in the acute delirium-like states that can occur during incarceration in the intensive care environment.This hypothesis, which was extended by one of us (Dudley6) to include other problems of sensory barrage and deprivation, has proved somewhat too simplistic.While by definition we can regard sleep lack as bad and from observation recognize that it may contribute to the patient's disturbed convalescence, its aetiological im- portance in delirium and its influence on the physiology of recovery require much further study.-Weare, etc.,
Flea-Collar Dermatitis
Authors: Paul C. Cronce
Journal: JAMA (1968)

An insecticide (2,2-dichlorovinyl dimethyl phosphate and related compounds) in antiflea dog collars caused primary irritant contact dermatitis in four patients who handled dogs wearing these collars. This dermatitis probably will occur with increased frequency and could be confused with mild poison ivy dermatitis.
Assessment of the lactulose-mannitol test in Crohn's disease.
Authors: F Andre, C Andre, Y Emery, J Forichon, L Descos, Y Minaire
Journal: Gut (1988)

The mannitol-lactulose intestinal permeability test was evaluated in 100 healthy controls and 47 patients with Crohn9s disease. These patients were further separated into three subgroups of increased activity (Harvey-Bradshaw index) and in two subgroups, with elective colonic lesions and associated ileal and colonic lesions. Results were given as percentages of urinary recoveries for mannitol (M), lactulose (L), and L/M ratio. As a whole, patients with Crohn9s disease have lower mean M and higher mean L and mean L/M ratios than controls. The magnitude of alterations in M, L, and L/M increased with activity. The sensitivity of the test, however, reached interesting figures (67%:L and 86%:L/M) only in subgroup III which was composed of relapsing patients. Mean M was lower in patients with associated ileal lesion but, whatever the criterion (M, L, or L/M), the test does not provide any clue for the detection of a possible infraclinical associated ileal localisation.
Abstract 4775: HPV16-E2/E4, -E6 and -E7 genes and HPV-disrupted human genes show large variation in expression levels in OSCC independent of the viral physical status.
Authors: Jens P. Klussmann, Nadine C. Olthof, Christian U. Huebbers, Jutta Kolligs, Frans CS Ramaekers, Simon Preuss, Uta Drebber, Emily Vucic, Wan Lam, Bernd Kremer, Ernst Jan Speel
Journal: Cancer Research (2013)

Abstract Infection with high-risk human papillomavirus (HPV) type 16 is an independent risk factor for the development of oropharyngeal squamous cell carcinomas (OSCC). However, it is unclear whether viral integration is an essential hallmark in the carcinogenic process of OSCC and whether HPV integration correlates to the level of viral gene transcription and influences the expression of disrupted genes. HPV16 integration sites were assessed in 75 patients with HPV16-DNA- and p16INK4A-positive OSCC using Detection of Integrated Papillomavirus Sequences (DIPS)- as well as Amplification of Papillomavirus Oncogene Transcripts (APOT)-PCR. Quantitative RT-PCR assays were carried out to determine the viral E2/E4, E6 and E7 gene expression levels. Expression levels of 7 human genes disrupted by the virus were extracted from mRNA expression profiling data of 32 OSCC. Nuclear localization of HPV16 was visualized using Fluorescence In Situ Hybridization (FISH) in 59 OSCC, and corresponding viral copy numbers were assessed by quantitative RT-PCR in 61 tumors. We identified 37 HPV16-human fusion products indicating viral integration in 29 (39%) OSCC. In the remaining tumors (61%) only episome-derived PCR products were detected. When comparing OSCC with or without an integration-derived fusion product, we neither found significant differences in the mean expression of the viral genes E2/E4, E6 and E7, the nuclear FISH staining patters nor the viral copy numbers per cell. The expression of the HPV-invaded genes also did not significantly differ when comparing the expression in the affected tumor with the expression of that gene in either group of OSCC. In conclusion, our data do not support the hypothesis that integration affects the levels of viral and/or HPV-disrupted human gene transcripts. Thus constitutive, rather than a high level, of expression of oncogene transcripts appears to be required in HPV-related OSCC. Citation Format: Jens P. Klussmann, Nadine C. Olthof, Christian U. Huebbers, Jutta Kolligs, Frans CS Ramaekers, Simon Preuss, Uta Drebber, Emily Vucic, Wan Lam, Bernd Kremer, Ernst Jan Speel. HPV16-E2/E4, -E6 and -E7 genes and HPV-disrupted human genes show large variation in expression levels in OSCC independent of the viral physical status. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4775. doi:10.1158/1538-7445.AM2013-4775
Markers of Dysglycaemia and Risk of Coronary Heart Disease in People without Diabetes: Reykjavik Prospective Study and Systematic Review
Authors: Nadeem Sarwar, Thor Aspelund, Gudny Eiriksdottir, Reeta Gobin, Sreenivasa Rao Kondapally Seshasai, Nita G. Forouhi, Gunnar Sigurdsson, John Danesh, Vilmundur Gudnason
Journal: PLoS Medicine (2010)

Sarwar and colleagues report data from a prospective cohort in Iceland, and carry out a meta-analysis to evaluate the association between blood sugar levels and risk of coronary heart disease in people who do not have diabetes. Strong evidence for an increase in risk was not found.
Influence of Ambient Fungal Spores on Emergency Visits for Asthma to a Regional Children's Hospital
Authors: ROBERT E. DALES, SABIT CAKMAK, RICHARD T. BURNETT, STAN JUDEK, FRANCES COATES, JEFFREY R. BROOK
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The impact of ambient aeroallergens on morbidity from childhood asthma is largely unknown. To address this issue, we studied the association between daily emergency department visits for asthma to a children's hospital, and daily concentrations of both pollen grains and fungal spores during a 5-yr period between 1993 and 1997. Air pollution and meteorological data accounted for in the analyses included ozone, nitrogen dioxide, sulfur dioxide, sulfates, temperature, barometric pressure, and relative humidity. The daily number of asthma visits ranged from 0 to 36 per day with an average of 7.5. Fungal spores, but not pollen grains, were associated with visits (p < 0.05). The percentage increase associated with each group, independent of the others, was 1.9% (SE 0.9) for deuteromycetes, 4.1% (1.6) for basidiomycetes, 2.8% (1.0) for ascomycetes, and 8.8% for these spores combined. In summary, fungal spores account for a significant proportion of the asthma exacerbations in children that prompt an emergency department visit.
Chromium Supplementation Does Not Improve Glucose Tolerance, Insulin Sensitivity, or Lipid Profile
Authors: Jenny E. Gunton, N. Wah Cheung, Rosemary Hitchman, Graham Hams, Christine O’Sullivan, Kaye Foster-Powell, Aidan McElduff
Journal: Diabetes Care (2005)

Chromium supplements are thought to be the second most commonly taken nutritional supplement, used by an estimated 10 million Americans (1). Chromium is an essential element in humans, and deficiency is associated with the development of diabetes, which was first noted in patients receiving long-term parenteral nutrition before the advent of routine chromium supplementation (2,3). In these patients, diabetes resolved following chromium replacement (2–4).

The dietary requirement for chromium is controversial, with the recommended daily intake in the U.S. being 0.05–0.20 μg (5). Chromium is abundant in the environment; however, aside from the extreme situation of unsupplemented parenteral nutrition, it has proven difficult to ascertain any clinical effects, due solely to chromium deficiency. Despite these difficulties, chromium supplements are widely promoted in the complementary health industries.

There are many studies examining the effects of various forms of chromium supplementation (rev. in 6,7). These studies utilized a variety of chromium formulations, varying doses, and patients with normal glucose tolerance, diabetes, or gestational diabetes. The outcomes have been inconsistent. Some studies showed no benefit, and other studies have shown inconsistent improvements in glucose, insulin resistance, and/or lipids. The paucity of data has prompted the National Institutes of Health to release a program announcement to address the issue: “Chromium as an adjuvant therapy …
247. Devising Aβ-Specific Passive Immunization Strategies for Alzheimer's Disease Using rAAV Vector-Mediated scFv Antibody Delivery
Authors: Kelly L. Fowlkes, Michael A. Mastrangelo, Wade C. Narrow, Yona Levites, Todd E. Golde, Howard J. Federoff, William J. Bowers
Journal: Molecular Therapy (2006)

Amyloid beta (Aβ) has been identified as a key pathological component in Alzheimer's disease (AD). The accumulation of intraneuronal and extracellular Aβ coincides with the cognitive deficits associated with disease progression and is believed to underlie these deficits. Significant in vitro and human pathological data suggest that intraneuronal accumulation of Aβ peptides plays an early triggering role in the cascade ultimately leading to AD-related neurodegeneration. Recently, a triple transgenic mouse model of AD (3xTg-AD) that develops both amyloid and tau pathology has been created, which to date is the most disease-relevant model system depicting what occurs in human AD. We and others have observed significant accumulation of intraneuronal Aβ in these mice at 3 months of age, a time point prior to the onset of demonstrable amyloid plaque and tau pathologies, but similar temporally to when synaptic dysfunction is electrophysiologically detectable. Aβ-specific intracellular antibodies (intrabodies) with differing intracellular trafficking characteristics were engineered from a previously obtained secretion-competent single-chain antibody (scFv) to interact with Aβ intracellularly and promote its degradation. Cell lines have been created that harbor a doxycycline-regulated transcription unit expressing the Swedish mutant form of human amyloid precursor protein and in essence, intracellular human Aβ peptides. Intrabody constructs are being assessed in these lines for their abilities to modulate Aβ intracellular localization and half-life. Recombinant adeno-associated virus (rAAV) vectors expressing the parental scFv's and the engineered intrabodies are being administered to 3xTg-AD mice prior to the initial appearance of the intraneuronal Aβ signature. In pilot in vivo studies, soluble and membrane-bound forms of the Aβ-specific scFv were intra-cranially administered to the CA1 region of the hippocampus in 2-month-old 3xTg-AD mice. Mice were sacrificed at 8 months post-injection, and brains were processed for immunohistochemical analyses. Results collected to date strongly suggest that this passive immunotherapeutic modality leads to clearance of Aβ in hippocampal regions. Future work involving rAAV-mediated intrabody expression will provide major insights into the involvement of intraneuronal Aβ accumulation in the temporal and spatial progression of early AD pathogenic events and potentially leading to the development of new anti-Aβ therapeutics. Supported by NIH R01AG020204 to HJF and NIH R01AG023593 to WJB.
The private life of systematic reviews
Authors: I. Roberts, G. Schierhout
Journal: BMJ (1997)

Hardly a month goes by without a report in the medical literature on some aspect of systematic review methodology. The articles address the parts of a systematic review that come under the scientific spotlight in the methods section of a report; they represent the public face of a systematic review.

The conduct of a systematic review, however, depends also on enlisting the cooperation of the trialists who provide the data. In contrast to the public nature of the more technical aspects of a systematic review, details of these interpersonal interchanges are never mentioned in the published report. We argue that a closer look at these interpersonal interactions raises important questions for the evolving science of reviewing the medical literature.

Personal communication with trialists is an important way of ensuring that trials are not missed in a systematic review. Trialists can be sent a list of the trials found to date and asked if they know of any others. Most investigators are pleased to help: “Thank you for your letter …. I enclose a list of relevant studies, some of which are controlled.”

Some investigators, however, recognise that trial identification is the most arduous part of a systematic review and see this as freeloading: “You asked me in your letter whether there are other …