tbuckley/cabot-search huggingface dataset:
Abstract 5536: <i>TP53</i> and <i>MED12</i> mutations in uterine smooth muscle tumors
Authors: Elisabetta Kuhn, Anna Yemelyanova, Tian-Li Wang, Robert Kurman, Ie-Ming Shih
Journal: Cancer Research (2012)

Abstract Most uterine smooth muscle tumors can be broadly subdivided into two groups: benign leiomyoma (including variant subtypes) and leiomyosarcoma based on cytologic atypia, mitotic activity and coagulative tumor cell necrosis. A small number defies classification into unequivocally benign and unequivocally malignant categories. These tumors, classified as “atypical leiomyoma” and “STUMP” (Smooth muscle Tumors of Uncertain Malignant Potential), generally behave in a benign fashion. Although p53 overexpression, as determined by immunohistochemical staining, has been reported in the atypical group and the leiomyosarcomas, it is uncertain whether they harbor TP53 mutations. In addition, a recent study has reported mutations in the mediator complex 12 (MED12) gene in the majority of benign uterine leiomyomas. We therefore performed a mutational analysis of uterine smooth muscle tumors to determine their TP53 and MED12 mutation status, in order to better understand their molecular genetic characteristics. A total of 9 uterine conventional leiomyomas, 27 atypical leiomyomas and 12 leiomyosarcomas from 40 patients were analyzed. DNA samples were sequenced and TP53 (from exons 4 to 9) and MED12 (exon 2) mutations were analyzed. Clinico-pathological data were collected. TP53 mutations were detected in 17 (63%) of 27 atypical leiomyomas and 8 (67%) of 12 leiomyosarcomas. MED12 mutations were identified in 6 (67%) of 9 conventional leiomyomas, 7 (26%) of 27 atypical leiomyomas and 1 (8%) of 12 leiomyosarcomas. Follow-up was available in 30 patients. None of the patients with atypical leiomyoma had recurrence or died of her disease (average follow-up 23 months). Seven patients with leiomyosarcoma, 4 of whom had TP53 mutations, died of their disease (average follow-up 42 months). The preliminary findings of this study indicate that the presence of TP53 mutations in uterine smooth muscle tumors is not sufficient to drive malignant behavior. Moreover, based on the presence of a MED12 mutation in one case of leiomyosarcoma, we postulate that at least some leiomyosarcomas develop from benign leiomyomas. Future correlated molecular genetic and clinicopathologic studies with a larger number of cases and long-term follow-up information are necessary to confirm this important finding. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5536. doi:1538-7445.AM2012-5536
Abstract 3693: Small molecule microarray screens for inhibitors of oncogenic ETS factors
Authors: Marius Pop, Katie Doug, James Bradner, Angela Koehler, Levi Garraway
Journal: Cancer Research (2010)

Abstract Members of the ETS transcription factors family are involved in many cancers and are often targeted by translocation events that result in oncogenic gene fusions or dysregulated ETS factor expression. For example, the vast majority of prostate cancers harbor translocations involving the ETS factors ERG, ETV1 and ETV4 (most commonly, these are fused to the TMPRSS2 androgen-regulated gene or other house keeping genes). Overexpression of ETS factor gene fusions can induce or sustain malignant characteristics of cancer cells such as survival or invasiveness. However transcription factors have often been deemed “undruggable” by conventional approaches. The focus of this project is to employ novel screening approaches to identify and characterize small molecules that are able to bind and modulate the biological function of oncogenic ETS factors. Toward this end, we have performed Small Molecule Microarray (SMM) screens that involve a total of 80,000 distinct small molecules spanning several categories, including diversity-oriented synthesis (DOS) products, natural products, and other biologically active chemotypes. The SMM screens identified six compound that selectively bind the ETS factor ETV1 with a stringent Zscore. Two of these compounds have shown inhibitory activity in an ETV1-specific promoter-induced luciferase system. Surface Plasmon Resonance analysis has confirmed that each of the two lead compounds binds ETV1 directly, with one compound showing submicromolar binding kinetics. This compound in particular was able to reduce the expression of several ETV1 downstream targets such as MMP1 and MMP7. These efforts suggest that we have identified novel small molecule “perturbagens” of ETV1, an oncogenic ETS transcription factor. More generally, our results suggest that SMM-based screens may offer a robust approach to identify novel compounds that bind and perturb the function of cancer-associated proteins deemed poorly “druggable” by conventional methods. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3693.
Methodology issues in risk assessment for radon.
Authors: N H Harley
Journal: Environmental Health Perspectives (1991)

The alpha dose per unit radon daughter exposure in mines and homes is comparable at about 5 mGy/WLM. This means that excess lung cancer risk determined in follow-up studies of miners should be valid to extrapolating to environmental populations. There are several models currently used for risk projection to estimate lung cancer in the U.S. from indoor radon exposure. The accuracy of the estimates depends upon the quality of the exposure data and the models. Recent miner epidemiology confirms that excess lung cancer risk decreases with time subsequent to cessation of exposure. The most rigorous ecological study, to date, shows a persistent negative relationship between average measured indoor radon in U.S. counties and lung cancer mortality. A model for lung cancer risk is proposed that includes smoking, urbanization, and radon exposure. The model helps to explain the difficulties in observing the direct effects of indoor radon in the environment.
Topiramate in the treatment of psoriasis: a pilot study
Authors: R. Ryback
Journal: British Journal of Dermatology (2002)

This study was initiated following a serendipitous finding in which a patient who presented with both a mood disorder and psoriasis experienced significant improvement of her psoriasis following treatment with topiramate.To determine the efficacy of topiramate for the treatment of psoriasis.Seven other patients, six of whom presented with both mood disorders and psoriasis and one with psoriasis only, were treated in an open-label fashion with topiramate. Topiramate therapy was usually initiated at 15 mg day-1 and gradually titrated by 15 mg week-1 to an average final dose of 56 mg day-1. Patients were treated for a minimum of 4 months. Psoriasis severity was measured using the psoriasis area and severity index (PASI).For all patients, the mean PASI score decreased from 16.1 before treatment to 7.1. For patients exhibiting improvement, the mean PASI score decreased from 14.3 to 3.9.These results represent the first known report of the efficacy of topiramate in the treatment of psoriasis.
Grannloma annulare and sarcoidosis
Authors: Philip Harrison, Sam Shuster
Journal: British Journal of Dermatology (1979)

Journal Article Grannloma annulare and sarcoidosis Get access Philip Harrison, Philip Harrison Department of Dermatology, Royal Victoria Infirmary, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar Sam Shuster Sam Shuster Department of Dermatology, Royal Victoria Infirmary, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 100, Issue 2, 1 February 1979, Page 231, https://doi.org/10.1111/j.1365-2133.1979.tb05569.x Published: 01 February 1979
How to undermine general practice
Authors: M. McCartney
Journal: BMJ (2014)

The destabilisation of general practice is underway. Most general practices in England are not paid a regular amount but make their money through the contract negotiated in 2004. Core funding includes the “global sum,” which makes up about half of a practice’s income 1 and now amounts to £66.25 for each patient every year2—cheaper than the cost of health insurance for a pet dog.3

The rest of a practice’s income is earned in bits, bobs, and from ticking the boxes of the quality and outcomes framework. It was anticipated that the 2004 contract would leave some practices vastly worse off, and so the “minimum practice income …
Innate immunity in the central nervous system
Authors: Richard M. Ransohoff, Melissa A. Brown
Journal: Journal of Clinical Investigation (2012)

Immune responses in the CNS are common, despite its perception as a site of immune privilege. These responses can be mediated by resident microglia and astrocytes, which are innate immune cells without direct counterparts in the periphery. Furthermore, CNS immune reactions often take place in virtual isolation from the innate/adaptive immune interplay that characterizes peripheral immunity. However, microglia and astrocytes also engage in significant cross-talk with CNS-infiltrating T cells and other components of the innate immune system. Here we review the cellular and molecular basis of innate immunity in the CNS and discuss what is known about how outcomes of these interactions can lead to resolution of infection, neurodegeneration, or neural repair depending on the context.
Thrombosis and Anticoagulants
Authors: J. Marshall
Journal: BMJ (1965)

Keepingthe Heart Going" (19 June, p. 1566) we believe that incorrect emphasis has been placed upon the risks of the production of ventricular fibrillation by pacing on the T wave in patients who have returned to sinus rhythm.All proved instances of ventricular fibrilla- tion, in our experience, have occurred only with the epicardial system of pacing, and only in the immediate post-thoracotomy period.'It seems that the risk of ventricular fibrillation is highest when the threshold for the production of ventricular fibrillation is lowered from superficial myocardial damage caused by stitching the electrode on to the epicardium and from alterations in pul- monary ventilation due to the thoracotomy.Another facotor was probably the unnecessarily high power of the earlier units.Now that we use endocardial jugular sys- tems for long-term pacing, thereby avoiding a thoracotomy, the risk of ventricular fibrillation must be greatly reduced, and we have never seen it in our experience of over 100 patients treated by endocardial pacing.-We
Occurrence of different cancers in patients with Parkinson's disease
Authors: H. Moller, L. Mellemkjaer, J. K McLaughlin, J. H Olsen
Journal: BMJ (1995)

Every newborn baby in Britain is subjected to several painful procedures * Little is done to minimise the discomfort of these procedures * Placing 2 ml of a 25% or 50% sucrose solution on the tongue before heel prick significantly reduces crying time * There is a dose-response effect in the reduction of crying with increasing concentrations of sucrose * Sucrose on the tongue may be a useful and safe form of analgesia in newborn infants lifted its paw off a hotplate.6This effect was completely reversed by naltrexone.Blass and Hoffmeyer subsequently showed that 2 ml of 12% intraoral sucrose significantly reduced the duration of cry in newborn babies subjected to heel prick or circumcision.'Our group repeated that study with 7 5% sucrose and found no difference in the duration of crying.8However, we remained intrigued by the reports of Blass et al and undertook this study with different sucrose concen- trations.We conclude that in our first study we used a sucrose solution too weak to induce a measurable analgesic effect.Non-sucrose sweet substances such as saccharin also seem to increase pain latency in animals.9Other substances such as milk and in particular milk fat seem to have a similar effect through the endogenous opiate pathways.'0We do not know whether simply cuddling an infant after heel prick is as effective in reducing crying as 50% sucrose.We are undertaking further clinical studies to evaluate the effect of sucrose and other substances in pain prevention in immature babies and older children.
Disseminated Mycobacterium bovis Infection From BCG Vaccination and HIV Infection
Authors: Pol Boudes
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Dr Reichman<sup>1</sup>recently declared that he was concerned about the role of BCG vaccine in individuals at risk of human immunodeficiency virus (HIV) infection. Because we too think that this vaccination is dangerous, we report herein on a healthy individual who was given BCG vacine and later developed acquired immunodeficiency syndrome and also disseminated<i>Mycobacterium bovis</i>infection related to his previous vaccination. <h3>Report of a Case.—</h3> A 32-year-old Algerian man, living in France since the age of 12 years, presented in April 1988 because of chronic diarrhea. Crohn's disease was suspected. He was successfully treated with 1 mg/kg per day of prednisone and 1.5 g/d of metronidazole. At that time, an extensive search for microorganisms was unsuccessful. Prednisone therapy was slowly tapered to 5 mg/d in November 1988, when severe bilateral<i>Pneumocystis carinii</i>pneumonia developed. He was successfully treated with sulfamethoxazole and trimethoprim. No other microorganisms,
Independent and incremental prognostic value of tests performed in hierarchical order to evaluate patients with suspected coronary artery disease. Validation of models based on these tests.
Authors: S G Pollock, R D Abbott, C A Boucher, G A Beller, S Kaul
Journal: Circulation (1992)

BACKGROUND The additive prognostic value of tests done in a hierarchical order for the detection of coronary artery disease (CAD) is not always known. The principal goal of this study, therefore, was to assess the incremental prognostic value of data obtained in succession (clinical, exercise stress testing, 201Tl imaging, and coronary angiography) in patients with suspected CAD. A second goal was to develop models for determining prognosis based on results of these tests and to test the clinical validity of these models in unrelated patients. METHODS AND RESULTS Data from two groups of patients who had undergone such evaluation and had been followed for a mean of 4.4 years were analyzed. There were 204 patients from Massachusetts General Hospital (MGH) and 299 from the University of Virginia (UVA). There were 20 deaths and 21 nonfatal infarctions in the MGH group and 41 deaths and nine infarctions in the UVA group. Both univariate and multivariate Cox regression analyses were performed to assess the individual and incremental prognostic value of these tests. In both groups, 201Tl imaging provided significant additional prognostic information compared with clinical and exercise stress test data (p less than 0.05). At MGH, where the lung/heart 201Tl ratio had been analyzed, coronary angiography did not provide additional prognostic information. In this group of patients, the combination of clinical and exercise 201Tl variables provided greater prognostic information than the combination of clinical and angiographic data (p less than 0.001). In the UVA cohort, in which the lung/heart ratio had not been analyzed, coronary angiography provided incremental prognostic information compared with clinical and exercise 201Tl data alone (p less than 0.05). When models developed using data from either sample were applied to the other unrelated sample, there was often close agreement between the overall observed rates and those predicted by the models. This was also true for the low-risk and high-risk subgroups. Some models, however, did not perform as well as other models, which suggests that models that do well in one sample may not always be generalized to other groups. CONCLUSIONS Tests performed in hierarchical order for the evaluation of suspected CAD provide additional prognostic information. Models developed using clinically relevant combinations of test results obtained from different patient populations are frequently able to predict absolute levels of survival in unrelated but similar samples.
Exfoliative cytology as a diagnostic test for basal cell carcinoma: a meta-analysis
Authors: S. Bakis, L. Irwig, G. Wood, D. Wong
Journal: British Journal of Dermatology (2004)

Background Exfoliative cytology is only occasionally used in clinical practice to diagnose basal cell carcinoma (BCC). Objectives To systematically review the literature examining exfoliative cytology as a diagnostic tool for BCC and to meta-analytically summarize the accuracy of this test. Methods Diagnostic test meta-analysis. A computerized database search was made of MEDLINE (1966–2000) and EMBASE (1950–2000) using appropriately indexed terms. Hand searches of relevant journals were made. Bibliographies of relevant articles were further explored. Histopathology was used as the reference standard. A summary receiver–operating characteristic curve analysis was performed using the statistical package Meta-Test version 0·6 (J. Lau, New England Medical Center, Boston, MA, U.S.A., 1997). Results Eight primary studies (seven English language and one Italian language) fulfilled the inclusion criteria. The pooled sample included 1261 BCCs. These studies varied greatly in methodological quality and were, in general, poor. A meta-analysis showed the pooled sensitivity to be high at 97%[95% confidence interval (CI) 94–99]. Consequently, only 3% of BCCs included were misdiagnosed as non-BCC by cytology. The corresponding pooled specificity was 86% (95% CI 80–91). Conclusions Exfoliative cytology probably has a high diagnostic accuracy for BCC. However, large, better designed and better reported studies are needed to ascertain the true accuracy of this technique. In the interim, this test should be considered in specific subgroups of patients in whom even a 2-mm punch biopsy may be considered inappropriate, e.g. a cosmetically sensitive site in a young person. Similarly, it should be considered when a BCC is to be treated without a diagnostic biopsy being taken, e.g. with cryotherapy.
Demonstration of active potassium transport in the mammalian colon.
Authors: A S Kliger, H J Binder, C Bastl, J P Hayslett
Journal: Journal of Clinical Investigation (1981)

The mechanism responsible for K transport in the mammalian colon is controversial. Experiments were performed to determine whether K secretion involves active as well as passive driving forces in controls and in animals with a marked increase in K secretion. In these experiments a steady-state solution was established in proximal and distal colon of both control rats and animals fed a K-enriched diet during in vivo luminal perfusion, to compare the observed luminal [K] with predicted equilibrium [K] when net water and electrolyte movement approached zero. Transmural potential difference was measured simultaneously. A difference between the predicted equilibrium and observed luminal [K] under this condition indicates active transport. In controls the observed [K] of 20 mmol/liter in proximal colon markedly exceeded the predicted value of 6.2 +/- 0.3, mean +/- SE, indicating active secretion. In contrast, the observed [K] in distal colon of 5 mmol/liter was less than predicted (10.0 +/- 1.0), suggesting active absorption. In K-loaded animals active K secretion was demonstrable and increase above control in both segments of colon. In proximal colon the observed [K] rose to 40 mmol/liter, compared to a predicted value of 7.2 +/- 0.3, whereas in distal colon the observed [K] was 50 mmol/liter vs. a predicted value of 7.0 +/- 0.8. These studies suggest active K secretion in proximal, but not in distal colon of control animals. Further, these data suggest that the increase in the capacity for K secretion that occurs in response to chronic K loading involves stimulation of an active mechanism in both proximal and distal colon.
SERUM LIPOIDS IN MALNUTRITION 1
Authors: Evelyn B. Man, Edwin F. Gildea
Journal: Journal of Clinical Investigation (1936)

In previous studies of the blood lipoids in relation to various disease syndromes most authors have not considered the role which malnutrition in itself may play in determining the amount of these substances.For example, patients with hyperthyroidism usually lose a great deal of weight and may develop an extreme degree of malnutrition.The fall in the cholesterol and fatty acids that frequently occurs may be related to the general effect of the malnutrition and not to any direct action of the thyroid principles on lipoid metab- olism.There is some experimental work on animals which indicates that malnutrition may reduce the level of blood lipoids.In the present paper the relationship between malnutrition and the serum lipoids in patients with a variety of dis- eases is presented.The disease syndromes that are suspected of directly disturbing fat metabolism, and particularly the blood lipoids, have been avoided. MATERIALS AND METHODSCholesterolemia and lipemia have been studied in 31 emaciated patients with or without an au- thentic history of weight loss and in 5 patients who appeared well nourished in spite of recent weight loss.The lipoids have also been followed in 10 subjects while they were undergoing marked changes in nutritional status.The subjects stud- ied were patients with diabetes, tuberculosis, arteriosclerosis, carcinoma and abnormalities of the gastro-intestinal tract.Patients with nephritis, nephrosis, liver cirrhosis, hyperthyroidism, hypothyroidism or manic-depressive psychosis are omitted.Serum from venous blood taken from patients in a postabsorptive state was analyzed by methods previously described (3, 10, 12) for cholesterol, fatty acids, lipoid phosphorus, protein, albumin and globulin.The errors of these methods and the range of normal values have been discussed (10, 11, 12, 13, 17).