tbuckley/cabot-search huggingface dataset:
Targeted loss of E-cadherin is sufficient to induce dedifferentiation, loss of intercellular junctions, and increased invasive potential of colorectal cancer cells
Authors: Allison R. Hatmaker, Young Jin Gi, Carl R. Schmidt, R. Daniel Beauchamp, Robert J. Coffey, A. Scott Pearson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

2486 

Abstract Background. Alterations in the organization of cellular architecture, intercellular adhesion, and adhesion-mediated signaling through loss of junctional proteins are believed to play a critical role in the epithelial-to-mesenchymal transition of cells and acquisition of invasive phenotype during cellular transformation. The purpose of our study is to determine the effects of targeted E-cadherin knockdown on the morphology and invasive potential of human colorectal cancer cell lines. Methods. SW480 and CaCo2 human colorectal carcinoma cell lines were transfected with siRNA to human E-cadherin. RNA and protein expression were measured using RT-PCR and Western blot analyses, respectively. Cell morphology was examined using light microscopy. Protein expression patterns were examined using immunofluoresence. Cellular motility and invasive potential were studied through wound healing assays and invasion assays. Results. RT-PCR and western blot analyses demonstrated knockdown of E-cadherin transcript and protein levels, respectively, in both cell lines. After siRNA knockdown of E-cadherin, SW480 cell lines demonstrated a morphologic epithelial-to-mesenchymal transition and both cell lines demonstrated a loss of membranous localization and intercellular adhesions. Both cell lines demonstrated increased motility and invasive potential after the knockdown of E-cadherin. Conclusion. The above data support a role of E-cadherin in suppressing transformation and invasion through cellular adhesion, maintenance of epithelial differentiation, and possibly adhesion-mediated signaling. This system provides a model to study the effects of E-cadherin knockdown on downstream adhesion-mediated signaling.
Preliminary findings on psychiatric patients as research participants: a population at risk?
Authors: B Stanley, M Stanley, A Lautin, J Kane, N Schwartz
Journal: American Journal of Psychiatry (1981)

To determine whether hospitalized mentally ill patients expose themselves to research with high risks more often than hospitalized nonpsychiatric patients, the authors asked patients from both groups if they would be willing to participate in a series of hypothetical research studies. The mentally ill patients did not agree to participate in studies of either high or low risk more frequently than nonpsychiatric patients. Both groups tended to agree to low-risk/high-benefit studies more often than high-risk/low-benefit studies. Although Brief Psychiatric Rating Scale scores clearly differentiated between psychiatric and nonpsychiatric patients, psychopathology did not correlate with willingness to participate in any of the studies.
Abstract 9602: Serum Proteomic Profiles Predict Coronary Artery Disease in Symptomatic Patients Referred for Coronary Angiography
Authors: William A LaFramboise, Rajiv Dhir, Robert Masterson, Oscar C Marroquin, Suresh R Mulukutla, Dennis M McNamara
Journal: Circulation (2011)

Coronary angiography is a definitive assay for coronary artery disease (CAD). However, high rates of normals and exposure to ionizing radiation warrant development of tests to identify patients lacking significant CAD without cardiac catheterization. We hypothesized that combinatorial proteomic changes in patient sera correlated with coronary artery disease status. Methods: We performed targeted immunoassay profiling of serum from 359 symptomatic patients undergoing coronary angiography. A cohort of 208 patients required stent, angioplasty or bypass graft for hemodynamically significant CAD based on angiography while 151 had no significant disease (No CAD). Both cohorts were comparable in gender, BSA, cholesterol, LDL, creatinine, hypertension and clinical symptoms with a slight difference in age (No CAD: 58+/-10; CAD: 63 +/-11 years, p&lt;0.001). Forty one target proteins implicated in atherogenesis were tested across the 2 groups. Thirty-three proteins were screened among 56 samples, 24 analytes were tested across a 239 sample training set and 12 analytes were validated in 120 additional serum samples. Results: Highly significant increases were detected (false detection level=0.018) in patients with CAD for Apo-B100, fibrinogen, VCAM-1, myeloperoxidase, CRP, resistin, osteopontin, IL-6, IL-1b, IL-10 and NT-pBNP. Apo-A1 fell significantly in this group. A scoring algorithm was derived for patient classification (CAD vs. No CAD) using signatures of 2 to 5 analytes from the 239 patient study. Discrimination of patients without CAD was achieved (86% Negative Predictive Value: NPV) while correctly classifying 95% (PPV) of patients with CAD. Osteopontin, resistin, MMP7 and interferon-g were the most frequent classification biomarkers among diagnostic signatures. Validation studies (120 samples) confirmed this signature plus ACRP30 as the strongest multiplex classifier. Conclusions: A non-invasive serum biomarker test has been developed to discriminate between patients with angiographically-confirmed, significant CAD and those without it. The ability to exempt even a small percentage of patients from cardiac catheterization provides significant medical and economic benefits given the growing epidemic of coronary artery disease.
Psychiatric resident suicide: an analysis of five cases
Authors: R O Pasnau, A T Russell
Journal: American Journal of Psychiatry (1975)

The authors present case histories of five psychiatric residents in a large metropolitan area who committed suicide during an 11-year period. Although they found no single precipitant or predictor, they noted striking similarities in the cases, including a high incidence of psychopathology manifested in marital problems, absence of close personal relationships, previous psychotherapy, drug and/or alcohol abuse, etc. The authors suggest an interaction of personal, peer, and institutional factors as casual in all of these suicides and recommend such improvements in residency programs as providing individual faculty preceptors for each resident and facilitating psychotherapy for troubled residents.
The thalamus as a site of action of antipsychotic drugs
Authors: B M Cohen, W Wan
Journal: American Journal of Psychiatry (1996)

Because recent data suggest that there are abnormalities of the thalamus in schizophrenia, the authors tested the effects of antipsychotic drugs on thalamic sites.Nine rats were given acute doses of the typical neuroleptic haloperidol (N = 3), the atypical neuroleptic clozapine (N = 3), or a drug-free vehicle (N = 3). Cellular activation was assessed by using immunohistochemistry to determine expression of the immediate response gene c-fos.Both antipsychotic drugs induced increased Fos immunoreactivity, suggesting increased activity in cells of the midline nuclei of the thalamus.The shared clinical effects of antipsychotic drugs may be mediated in part through actions on the thalamus.
Developing the BMJ's coverage of basic science
Authors: A. Berger, R. Smith
Journal: BMJ (1998)

Paper p 1275 

The BMJ wants to do a better job of informing readers about developments in basic science. One of several ways in which we are trying to do this is by including with some research papers a brief commentary on the science underlying the clinical phenomenon described in the paper. The first of these science commentaries, on peanut allergy, appears on p 1275.1 …
Abstract 186: Coronary Angiographic Findings in Patients with or Without ST-Segment Elevation Resuscitated After Out-of-Hospital Cardiac Arrest
Authors: Ziaullah Kamal, Geir Oystein Andersen, Jan Eritsland, Tomas Draegni, Kjetil Sunde, Arild Mangschau
Journal: Circulation (2011)

Background: Long-term survival after out-of-hospital cardiac arrest (OHCA) has improved in the last decade with special focus on the post cardiac arrest syndrome. Therapeutic hypothermia and percutaneous coronary intervention (PCI) are the two most important in-hospital interventions. International guidelines recommend aggressive use of coronary angiography in patients with ST segment elevation myocardial infarction (STEMI), but it is not clear if also patients without ST elevation should undergo early coronary angiography (ECA). The aim of the study was to document outcome in all OHCA patients of cardiac etiology, with special focus on angiographic findings and survival among patients with or without ST segment elevation. Methods: All patients admitted to our hospital after primary resuscitated OHCA are registered in our Post-resuscitation care registry. Electrocardiogram (ECG), coronary angiographic findings and overall survival of patients admitted in 2008 with cardiac etiology were investigated retrospectively by reviewing medical charts. Patients were classified according to the presence of ST segment elevation on post-resuscitation ECG or not. Results: Altogether 62 patients were included. ST elevation was present in 33 (53%) patients in whom all underwent ECA, 24 (73%) had an acute coronary occlusion, 5 (15%) had old occlusions, 17 (51%) had multivessel disease, and 29 (88%) received PCI. Among the 29 (47%) patients without ST elevation, 24 (83%) underwent ECA, of whom 5 (17%) had an acute coronary occlusion, 12 (50%) had old occlusions, 18 (75%) had multivessel disease, and 12 (38%) received PCI. In total, 60% of the patients were treated with therapeutic hypothermia with no difference between the two groups. Overall survival was 64% and 59% in patients with and without ST elevation, respectively (ns). Conclusion: Overall survival after OHCA of cardiac etiology was good, with no difference between patients with or without ST segment elevation. The presence of ST elevation on ECG was highly associated with the presence of an acute coronary occlusion, but a substantial proportion of patients without ST elevation also had coronary occlusions treated by PCI and more studies are warranted to determine whether all patients should undergo ECA.
Delayed Effect of Genetic Segregation on the Transmission of the Mammary-Tumor Agent in Mice
Authors: W. E. Heston, George Vlahakis, Margaret K. Deringer
Journal: JNCI Journal of the National Cancer Institute (1960)

Evidence is presented for gene control over the propagation of the mammary-tumor agent in mice. The segregation data do not support an interpretation of single-gene control, but they suggest that the agent can be propagated in the presence of one or more of several genes. It appears that females lacking any of the genes for propagating the agent do not eliminate it through production of antibodies against it, but apparently the agent is lost in subsequent generations through dilution. There is evidence that females that can propagate the agent vary in the quantity or quality of agent produced, presumably owing to the number they possess of the several genes for the propagation of the agent. The mammary tumors observed in the study are classified as to histologic type, and the other neoplasms of many kinds that were observed are listed.
Abstract 12527: Adiponectin Protects Against Doxorubicin-induced Cardiomyopathy Through An Akt Dependent Mechanism
Authors: Sonomi Maruyama, Rei Shibata, Taiki Ohashi, Koji Ohashi, Hiroyuki Daida, Kenneth Walsh, Noriyuki Ouchi, Toyoaki Murohara
Journal: Circulation (2010)

Background: Although accumulating evidence suggests that an adipocyte-derived plasma protein adiponectin protects against the development of various heart disorders, its role in doxorubicin (DOX)-i...
TV: Curing the incurable
Authors: C. Martyn
Journal: BMJ (1999)

Baby making is supposed to be fun and-judging from this overpopulated planet-straightforward.Not so for the one in six infertile couples, an estimated 80 million worldwide.Their devastation may be like that of Rachel, the barren biblical character, who said: "Give me a child else I die."Enter the baby makers;
Angiogenesic profile in sporadic and NF2-related schwannomas
Authors: Emmanuelle di Tomaso, Anat Stemmer-Rachamimov, Andrew Potts, Rakesh Jain, Scott Plotkin
Journal: Cancer Research (2008)

4434  Vestibular schwannoma (VS) and meningiomas are benign tumors that comprise 35-40% of all brain tumors. Neurofibromatosis 2 (NF2) is characterized by the presence of bilateral VS and multiple meningiomas for which alternative treatments are desperately needed. Currently there are no agents that produce disease stabilization or regression. This lack of active drugs is especially critical for NF2 patients where tumor progression is common. Previous groups have shown VEGF expression in small series of sporadic VS. In this study, we expand these findings to include a larger sample VS that include both sporadic and NF2 tumors. We broadened our study to include 5 parameters commonly used to characterize angiogenesis in tumors: microvascular density (MVD), and immunolabeling for VEGF, VEGFR2, PDGFRalpha and PDGFRbeta. Formalin-fixed, paraffin-embedded specimens were obtained from surgical resections of 22 patients with sporadic VS and from 21 patients with NF2 that underwent surgical resection at MGH. Sections were stained with polyclonal antibodies against VEGF (Santa Cruz Biotechnology), VEGFR2, PDGFRalpha and PDGFRbeta; (Cell Signaling), CD31, and Factor VIII (Dako). Intensity of immunostaining was scored in semi-quantitative fashion (0: no expression, +1: mild expression, +2: moderate expression, +3: strong expression) for VEGF, VEGFR2 and PDGF Receptors. MVD was calculated by averaging the number of CD31-positive vessels in 5-15 fields (10x). Intensity of each parameter was quantified for endothelial and tumor cells respectively. Expression of VEGF was detected in all sporadic and NF2-related VS. Strong (+3) expression of VEGF in tumor cells was more common in sporadic VS (45%) than in NF2-related VS (5%). In contrast, endothelial-bound VEGF was more common in NF2-related VS (75%) than in sporadic VS (45%). There was no difference in mean MVD between sporadic (13.5 vessels/mm2) and NF2-related tumors (12.5 vessels/mm2). The number of vessels expressing VEGFR2 was greater in sporadic (10.7 vessels/mm2) than in NF2 (7.4 vessels/mm2). Similarly the percentage of tumors expressing PDGFRbeta on vessels was greater in sporadic tumors (82%) than in NF2 tumors (55%). VEGF expression in tumor cells was universal in this series of sporadic and NF2-related VS. Although the intensity of VEGF expression appears greater in sporadic lesions, endothelial- bound VEGF is more common in NF2-related lesions and is positively associated with increased MVD. This finding indicates a potential activity of the VEGF angiogenic pathway in this patient population with subtle differences between NF2 and sporadic tumors with respect to the endothelial receptors. Therefore anti-VEGF therapy such as bevacizumab represents a rational approach to treating NF2 patients with VS in which surgery is not possible or has failed. A better understanding of the respective angiogenic mechanisms is necessary prior to using tyrosine kinase inhibitors.
Abstract 14179: Feasibility of Routine Right Heart Catheterization and Doppler Echocardiography to Obtain Measures of Right Ventricular Contractility and Pulmonary Vascular Impedance
Authors: Marc A Simon, Timothy N Bachman, Juliana Bursic, Kathy L Edelman, Hunter C Champion
Journal: Circulation (2011)

Background: Right ventricular (RV) dysfunction confers poor prognosis in pulmonary hypertension (PH). However, predicting which patients will do poorly and when remains difficult. Hemodynamic calcu...
Clinical forms of severe tardive dyskinesia
Authors: G Gardos, J O Cole, M Salomon, S Schniebolk
Journal: American Journal of Psychiatry (1987)

The authors describe 19 patients with severe tardive dyskinesia, 11 of whom had a diagnosis of affective or schizoaffective disorder rather than schizophrenia. Most patients had been receiving long-term neuroleptic treatment with few interruptions and had received only one or two different neuroleptics. Frequent eye blinking was the most prevalent prodromal sign of tardive dyskinesia (in seven patients). Four subtypes of tardive dyskinesia could be distinguished: choreoathetosis, tardive dystonia, blepharospasm, and tardive akathisia. Optimal pharmacotherapy most often consisted of combinations of neuroleptics, lithium carbonate, benzodiazepines, and antiparkinsonian drugs. However, after an average of 62 months, only five patients had markedly improved.
Assessment of dependence and motivation to stop smoking
Authors: Robert West
Journal: BMJ (2004)

Whether a smoker succeeds in stopping smoking depends on the balance between that individual's motivation to stop smoking and his or her degree of dependence on cigarettes. Clinicians must be able to assess both of these characteristics. Motivation is important because “treatments” to assist with smoking cessation will not work in smokers who are not highly motivated. Dependence is especially important in smokers who do want to stop smoking, as it influences the choice of intervention. It is also important to bear in mind that:

### Qualitative methods

The simplest approach to measuring dependence on cigarettes is a basic qualitative approach that uses questions to find out whether the smoker has difficulty in refraining from smoking in circumstances when he or she would normally smoke or whether the smoker has made a serious attempt to stop in the past but failed.



Clinical intervention goals for smoking according to dependence and …
Insanity defense pleas in Baltimore City: an analysis of outcome
Authors: J S Janofsky, M H Dunn, E J Roskes, J K Briskin, M S Rudolph
Journal: American Journal of Psychiatry (1996)

The authors studied all defendants in Baltimore City's circuit and district courts who pleaded not criminally responsible, Maryland's version of the not guilty by reason of insanity plea, during a 1-year period. The study was designed to compare the perception that the insanity plea is misused to actual outcome data.The cohort of defendants who pleaded not criminally responsible in both the circuit and district courts during calendar year 1991 was identified. Data on demographic characteristics, crimes committed, diagnoses, and psychiatrists' opinions on criminal responsibility were collected. Trial outcome data were obtained through a search of the circuit and district court computer systems.Of the 60,432 indictments filed in the two courts, 190 defendants (0.31 per 100 indictments) entered a plea of not criminally responsible. All but eight defendants (0.013 per 100 indictments) dropped this plea before trial. For these eight cases, both the state and the defense agreed that the defendant should be found not criminally responsible, and the plea was uncontested at trial. The remaining defendants had their charges dropped before trial, remained not competent to stand trial at the time of the study, or withdrew their pleas of not criminally responsible before trial.There were no trials that contested the plea of not criminally responsible. The state and defense agreed with each other for all of the defendants who actually retained the plea at trial. The perception that the insanity defense is overused and misused is not borne out by data.
Abstract 2416: Gender Disparities In Treatment After Coronary Artery Bypass: A New Twist On An Old Problem
Authors: Lynn V Doering, Rebecca L Cross, Michael R Irwin, Marise C Magsarili, Marie J Cowan
Journal: Circulation (2007)

Background: Treatment disparities that disadvantage women following coronary artery bypass graft (CABG) surgery have been reported. However, postoperative treatment of depression has not been assessed in this population. The purpose of this study was to evaluate treatment rates for depression and routine postoperative therapies in men and women after CABG. Methods: Within the first month after post-CABG hospital discharge, 206 patients (age 66 ± 11 years, 99 [48%] men) from three cardiac surgery centers were evaluated for the presence of major depression using structured clinical interviews (Structured Clinical Interview for DSM [SCID] or Diagnostic Interview and Structured Hamilton [DISH]). Medical records were reviewed and patients were queried to identify postoperative use of antidepressants, aspirin, statins, beta blockers and angiotensin converting enzyme inhibitors. Gender comparisons were conducted by t-tests and chi-square. Odds ratios (OR) and confidence intervals (CI) for treatments by gender were generated by multivariate logistic regression. Results: Rates of major depression were similar in men and women (19 [19%] vs. 18 [17%], p = .66), but men were less likely than women to receive antidepressants (3 [3%] vs. 12 [11%], p = .03). Even when antidepressant use was considered together with age, depression status, and other medications, the disparity favoring its use in women remained (OR = 5.87, CI = 1.2 – 29.1, p =.03). Women were less likely than men to receive statins (OR = 0.3, CI = 0.14 – 0.92, p =.03) and aspirin (OR = 0.3, CI = 0.14 – 0.67, p =.003). Conclusion: For both men and women, major depression after CABG is undertreated. While women remain less likely than men to receive standard therapies for coronary artery disease after CABG, men are less likely than women to receive antidepressants. Because depression is associated with increased cardiac mortality and morbidity, these findings emphasize the importance of its identification and treatment in all CABG patients. Clinicians should guard against gender bias in assessing the need for antidepressant treatment, as well as in the application of more routine therapies.
Scottish doctors' input to NHS white paper GMSC will continue to represent all GPs Labour wants low pay rise for doctors
Authors: Linda Beecham
Journal: BMJ (1997)

# Scottish doctors' input to NHS white paper {#article-title-2}

Scottish doctors have called for the forthcoming white paper on the NHS in Scotland to take account of the continued underfunding of the service.

Mr Arthur Morris, chairman of the BMA's Scottish council, told the council last week that the previous administration had locked the Labour government into decreasing public expenditure for at least two years. And Dr Angus Ford, chairman of the Scottish Joint Consultants Committee, said that it was impossible to make further efficiency savings without closing clinical services. “The next crisis,” he warned, “will not be about grannies on trollies; it will be about grannies competing for trollies.”

Representatives of the council were due to meet the Scottish health minister, Mr Sam Galbraith, on 25 September to discuss the implications of the government's intention to abolish the internal market. A separate white paper will cover the health service in England and Wales.

The council decided that its list for the minister should include a request for improved forward planning; a concentration on fewer clinical indicators; an evaluation of the range of commissioning projects; more attention to be paid to clinical support services; and improvements in community …