tbuckley/cabot-search huggingface dataset:
Testing the environment for dispersed mutagens: use of plant bioconcentrators coupled with microbial mutagen assays.
Authors: W S Barnes, E J Klekowski
Journal: Environmental Health Perspectives (1978)

Mutagens dispersed in ecosystems are usually in low concentration and episodic in occurrence. The possibility of detecting such dispersed mutagens by utilizing indigenous bioconcentrator organisms coupled with a microbial mutagen assay offer a useful screening protocol. There are numerous examples of plant and animal species which concentrate toxic substances from the environment. Body extracts of these bioconcentrators can be suitably fractioned and tested for mutagens with various microbial mutagen assays. The fractions may be tested with a broad range of microbial assays covering numerous genetic end points as well as both with and without mammalian microsomal activation. This kind of environmental screening has an advantage over physicochemical techniques, in that sampling techniques are simpler and a wider chemical spectrum can be screened. There are problems inherent with testing a complex biological extract, however. If a reversion assay is used, the metabolite necessary for growth may be present. Toxins may be introduced, either concentrated from the environment in the same way as the mutagen, or produced by the concentrator itself. Finally, the concentrator may also produce an endogenous mutagen which will give spuriously active extracts. Methods for minimizing some of these difficulties are discussed.
An abnormality at the hepatic flexure
Authors: J. Naqvi, G. Watts, V. Rudralingham, S. Duff
Journal: BMJ (2012)

A 92 year old woman presented to the emergency department after collapsing at home. She recalled standing from her chair, feeling lightheaded, and then collapsing. She had felt generally weak for more than a year, with weight loss of 56 lb (25.2 kg) but no change in bowel habit, dysphagia, or gastrointestinal bleeding. Her medical history included hypertension, hypothyroidism, and anaemia (which was currently being investigated by her general practitioner). Among other drugs, she was taking lisinopril, bendroflumethiazide, and levothyroxine. Her son had died at 60 years of age from large bowel obstruction and perforation secondary to colon cancer.

On examination she appeared cachectic with evidence of conjunctival pallor. Her blood pressure was 117/54 mm Hg when lying and 52/31 mm Hg when standing. No masses were palpable on abdominal examination.

Blood tests showed iron deficiency anaemia and hyponatraemia (haemoglobin 75 g/L (normal range 115-165), mean corpuscular volume 78 fL (80-97), iron 2 µmol/L (12-26), total iron binding capacity 42 µmol/L (45-70; 1 µmol/L=5.59 µg/dL), transferrin saturation (ratio of iron to total iron binding capacity) 4.76% (15-50), sodium 130 mmol/L (135-145; 1 mmol/L=1 mEq/L)). Lisinopril and bendroflumethiazide were stopped and the postural hypotension and hyponatraemia resolved. Oesophagogastroduodenoscopy showed no cause for the anaemia. Computed tomography of the abdomen showed an abnormality at the hepatic flexure (fig 1⇓).



Fig 1 Axial computed tomogram of the abdomen 





### 1 What does the scan show and what is the most likely underlying diagnosis?

#### Short answer

A large bowel stricture with shouldering at the hepatic flexure consistent with colonic carcinoma.

#### Long answer

The axial abdominal computed tomogram shows a shouldered colonic stricture at …
Consumption of Added Sugars and Indicators of Cardiovascular Disease Risk Among US Adolescents
Authors: Jean A. Welsh, Andrea Sharma, Solveig A. Cunningham, Miriam B. Vos
Journal: Circulation (2011)

Background— Whereas increased carbohydrate and sugar consumption has been associated with higher cardiovascular disease risk among adults, little is known about the impact of high consumption of added sugars (caloric sweeteners) among US adolescents. Methods and Results— In a cross-sectional study of 2157 US adolescents in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004, dietary data from one 24-hour recall were merged with added sugar content data from the US Department of Agriculture MyPyramid Equivalents databases. Measures of cardiovascular disease risk were estimated by added sugar consumption level (&lt;10%, 10 to &lt;15%, 15 to &lt;20%, 20 to &lt;25%, 25 to &lt;30%, and ≥30% of total energy). Multivariable means were weighted to be representative of US adolescents and variances adjusted for the complex sampling methods. Daily consumption of added sugars averaged 21.4% of total energy. Added sugars intake was inversely correlated with mean high-density lipoprotein cholesterol levels (mmol/L) which were 1.40 (95% confidence interval [CI] 1.36 to 1.44) among the lowest consumers and 1.28 (95% CI 1.23 to 1.33) among the highest ( P trend =0.001). Added sugars were positively correlated with low-density lipoproteins ( P trend =0.01) and geometric mean triglycerides ( P trend =0.05). Among the lowest and highest consumers, respectively, low-density lipoproteins (mmol/L) were 2.24 (95% CI 2.12 to 2.37) and 2.44 (95% CI 2.34 to 2.53), and triglycerides (mmol/L) were 0.81 (95% CI 0.74, 0.88) and 0.89 (95% CI 0.83 to 0.96). Among those overweight/obese (≥85th percentile body-mass-index), added sugars were positively correlated with the homeostasis model assessment ( P linear trend =0.004). Conclusion— Consumption of added sugars among US adolescents is positively associated with multiple measures known to increase cardiovascular disease risk.
Treatment of Pain
Authors: Seymour Diamond
Journal: JAMA (1976)

The treatment of the patient with intractable pain has been an enigma to the practicing physician. This monograph, which records a symposium, will be of primary interest to neurosurgeons and those physicians concentrating their practice on pain problems. The book contains 14 loosely organized chapters, nine of which are written by proponents of different specific neurosurgical procedures for pain relief. The indications, contraindications, suitable choice of patients, and description of techniques are discussed. Specifically, there are chapters on injection of the Gasserian ganglion, percutaneous cordotomy, controlled thermocoagulation of the trigeminal ganglion and rootlets, posterior spinal rhizotomy, sympathectomy, mesencephalotomy, thalamotomy, and cingulotomy. Recent work in transcutaneous, peripheral nerve, and dorsal column stimulation is presented by C. Norman Shealy. A highlight in the chapter on sympathectomy is the discussion on the effectiveness of high thoracic sympathectomy for the patient with intractable angina in whom coronary bypass is contraindicated or ineffective. It is
Molecular biology and biochemistry of differentiation.
Authors: S E Harris
Journal: Environmental Health Perspectives (1976)

Recent work in the field of molecular biology and differentiation has been directed towards an assessment of the number of different genes involved in the development and differentiation process. By the techniques of RNA-DNA hybridization to single copy DNA, it appears that some 60,000-200,000 different RNA sequences are expressed during embryonic development in the mouse. The differentiating brain shows the highest degree RNA transcription diversity. The new technique of cDNA-poly(A)-containing RNA hybridization is described. The nuclear poly(A)-containing RNA appears to reflect the high complexity of sequences as determined in RNA-DNA experiments described above. The cytoplasmic poly(A)-containing RNA or messenger RNA appears to represent a subset of approximately 10-20% of the information in the nuclear poly (A)-RNA. Also, the major portion of frequency class of messenger RNA in different organs such as kidney, spleen, and liver are common to these different organs. However, brain, although containing many of the cytoplasmic messenger RNA sequences found in liver, kidney, and spleen, has a large class of messenger RNA sequences which are specific to the nervous system.
Reassessing the need for sport diving medicals
Authors: P Smith
Journal: British Journal of Sports Medicine (2001)

The football club doctor system EDITOR,-I read with interest the paper by Waddington et al 1 highlighting the inadequacies of the football club doctor system in Britain.This paper confirms the situation that many people already knew to exist.Advertisements for club doctors are rarely published in medical journals, doctors normally being appointed on a "who you know" basis.It is also particularly disappointing that, at a time when the specialty of sports and exercise medicine is being established in this country, the majority of doctors working with professional footballers have no qualifications or little experience in the specialty.However, this is not confined to football clubs and probably also applies to rugby clubs and many other sporting associations.One aspect not mentioned in the paper is medical litigation.It is to be hoped that doctors involved with football clubs have arranged medical defence cover, because, if a situation arises in which a player's sporting career is threatened by medical mismanagement and the doctor involved has no professionally recognised sports medicine qualification, he or she could be found guilty of medical negligence.With the amount of money involved in professional football, this could lead to dire consequences for the medical career of the practitioner involved.From a report commissioned by the Football League on the Hillsborough tragedy, the concept of the "crowd doctor" was introduced, meaning that any doctor involved in the medical care of the crowd at a football stadium would be required to possess at least the Diploma in Immediate Medical Care. 2 Before that, the situation was similar to that of the present club doctor system, and few doctors held any recognisable qualifications or training in medical emergencies and resuscitation.A similar recommendation by sports medicine authorities is required to enhance the quality of service provided to football clubs and increase the stature of the specialty.However, it is not a one sided situation.Football clubs must realise the importance of a medical team in looking after their prime assets, the players.Advertising of jobs in medical journals, insisting on experience and qualifications, adequate remuneration, and the provision of job descriptions and contracts should all be implemented.By working together to improve the current situation, a service can be provided in which both professional football players and the medical profession can have confidence.
Vitamin D Receptor Gene Polymorphisms and Breast Cancer Risk
Authors: Michelle Guy, Lorraine C. Lowe, Deborah Bretherton-Watt, Janine L. Mansi, Clare Peckitt, Judith Bliss, Rosalind Given Wilson, Valerie Thomas, Kay W. Colston
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The steroid hormone 1,25-dihydroxyvitamin D3 is thought to protect against breast cancer. The actions of 1,25-dihydroxyvitamin D3 are mediated via the vitamin D receptor (VDR), and a number of polymorphisms in the VDR gene have been identified. These result in distinct genotypes, some of which may alter susceptibility to breast cancer. We have investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in a United Kingdom Caucasian population. Experimental Design: In a retrospective case-control study, female breast cancer patients (n = 398) and control women (n = 427) were recruited, and three VDR polymorphisms were determined. Results: The 3′ VDR polymorphisms BsmI and variable-length poly(adenylate) sequence were both significantly associated with breast cancer risk; odds ratios (adjusted for age menopausal status and hormone replacement therapy usage) for bb genotype versus BB genotype = 1.92 (95% confidence interval, 1.20–3.10; P &amp;lt; 0.01) and for LL versus SS = 1.94 (95% confidence interval, 1.20–3.14; P &amp;lt; 0.01). A 5′ VDR gene variant, FokI, was not associated with breast cancer risk when analyzed in isolation (P &amp;gt; 0.05). However, FokI did modulate the increased risk associated with the bb/LL genotype such that possession of one or more F alleles together with the bb/LL genotype augmented breast cancer risk. Furthermore, the highest proportion of bb and FFLL/FfLL genotypes occurred in women with metastatic breast cancer. Conclusions: VDR polymorphisms are associated with breast cancer risk and may be associated with disease progression. Additional investigations into how different genotypes may affect the functional mechanisms of the VDR will provide a better strategy for identifying women at risk of breast cancer and for developing improved treatments.
Magnetic resonance imaging and spectroscopy accurately estimate the severity of steatosis provided the stage of fibrosis is considered
Authors: Stuart McPherson, Julie R. Jonsson, Gary J. Cowin, Peter O’Rourke, Andrew D. Clouston, Andrew Volp, Leigh Horsfall, Dinesh Jothimani, Jonathan Fawcett, Graham J. Galloway, Mark Benson, Elizabeth E. Powell
Journal: Journal of Hepatology (2009)
Phacomatosis spilorosea associated with lymphoedema
Authors: H.F. Jordaan, R. Happle
Journal: British Journal of Dermatology (2008)

Journal Article Phacomatosis spilorosea associated with lymphoedema Get access H.F. Jordaan, H.F. Jordaan Department of Dermatology, University of Stellenbosch and Tygerberg Hospital, Stellenbosch, South Africa Search for other works by this author on: Oxford Academic Google Scholar R. Happle R. Happle Department of Dermatology, Philipp University of Marburg, Deutschhausstrasse 9, 35033 Marburg, Germany Correspondence: Rudolf Happle. E‐mail: happle@med.uni‐marburg.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 2, 1 August 2008, Pages 489–491, https://doi.org/10.1111/j.1365-2133.2008.08640.x Published: 01 August 2008
S56 Unravelling VEGF165 Signalling in the Lung
Authors: K Ourradi, C Jarrett, T Blythe, SL Barratt, GI Welsh, AB Millar
Journal: Thorax (2012)

<h3>Introduction</h3> Vascular endothelial growth factor (VEGF) is a potent mitogenic, angiogenic and permeability factor that has been implicated in the development of lung injury and repair in a number of respiratory diseases such as ARDS and IPF VEGF<sub>165</sub>a functions via VEGF receptors in particular VEGFR-2, leading to a diverse and complex network of signalling pathways including activation of both the MAPK pathway and eNOS This results in changes to cell permeability, migration and proliferation. We have investigated the downstream signalling mechanisms regulated by VEGF<sub>165</sub>a in pulmonary and systemic endothelial cells. Understanding the signalling pathway used by VEGF<sub>165</sub>a to regulate lung biology is critical to preferentially induce specific beneficial effects. <h3>Methods</h3> Human Umbilical Vein Endothelial Cells (HUVEC) and Human Lung Microvascular Endothelial Cells (HUMVEC-L) were treated with 20ng/ml of VEGF165a lysed and studied using phosphospecific antibodies which measure the phosphorylation/activation of key signalling molecules. Phosphorylation of VEGFR-2 was measured using phosphotyrosine-specific antibody to tyr1175 and tyr1214. Phosphorylation and hence activation of MEK, MAPK and eNOS were also measured. The effects of VEGF isoforms on cell permeability in a time and dose dependent manner were measured by using a transwell system and “Electrical Cell-Substrate Impedance Sensor” (ECIS). Changes in the cellular distribution of VE-cadherin a protein known to be involved in the regulation of cell permeability was assessed by immunofluorescent labelling and confocal microscopy. <h3>Results</h3> Phosphorylation of VEGFR-2 at tyr1175 and tyr1214was induced between 5 and 10min (n=4; &gt;5 fold increase). Activation of MEK and p44/42 MAPK (members of the MAPK pathway which regulates cell proliferation) were seen over a similar time course to that of VEGFR-2 (n=4; &gt;5 fold increase) (Figs 1A, B). Phosphorylation of eNOS which regulates cell permeability was also observed (n=3; &gt;2 fold) and indeed VEGF165a increased permeability in both HUVEC and HUMVEC-L (Huvec p&lt;0.001); (Humvec-l p&lt;0.01) (Fig 1). Finally we showed that in both cell types VEGF induced changes in the cellular distribution of VE-cadherin. <h3>Conclusion</h3> These results demonstrate that signalling pathways, previously suggested to induce mitogenesis or permeability are activated by VEGF 165a in HUVEC and HMVEC-l cells, identifying potential future therapeutic targets.
The perils of unmasking scientific truths
Authors: Felix I D Konotey-Ahulu
Journal: BMJ (2007)

To be chosen to deliver the keynote address at the Martin Luther King Jr Foundation's award banquet took me completely by surprise—and to find that four bodyguards had been assigned me shook me rigid. Nobel laureates Linus Pauling and Max Perutz, along with Hermann Lehmann, Roland Scott, A C Allison, Graham Serjeant, and I, were among a select few invited to Philadelphia to receive an award “for outstanding research in sickle cell anaemia.” But why was I asked to deliver the keynote address, with Pauling and other abnormal haemoglobin heavyweights on the platform?

Was it, perhaps, because a foundation commemorating a black person wanted to “show off” the only black African among those receiving the award? Was it, perhaps, because I was then director of the largest sickle cell disease clinic in the world? Or was it because I was the only person to have traced hereditary disease in his forebears, …
Stress in Middle-Aged Women: Influence of Type A Behavior and Narcissism
Authors: Isao Fukunishi, Takashi Moroji, Shohei Okabe
Journal: Psychotherapy and Psychosomatics (1995)

The authors examined (1) strength of stress, (2) awareness of stress, and (3) influence of type A behavior and narcissistic personality on stress and its related factors in a sample of 500 middle-aged women. Compared to 400 middle-aged working men, the women scored lower on the type A and coping scales, suggesting the possibility that women with high scores on type A behavior cope better with stress. Moreover, type A behavior in women was related to narcissistic personality. The strength of stressors and stress coping in type A women are affected by the severity of narcissism.
Campaigners win ruling that antiretroviral drugs order be enforced
Authors: P. Sidley
Journal: BMJ (2002)

The Pretoria High Court has ordered South Africa's health minister, Manto Tshabalala-Msimang, and seven of nine provincial health authorities to provide antiretroviral drugs for HIV positive pregnant women to reduce transmission of the virus to their babies.

The court action was brought by the AIDS activist group Treatment Action Campaign and hundreds of doctors and nurses employed in public hospitals, to force the government to widen the availability of the drug nevirapine, which was previously restricted to clinical trials.

Although the court gave its ruling in the case at the end of last year, the doctors and the campaign were forced to return to the court to ask for …
Coexistence of antitopoisomerase I and anticentromere antibodies in patients with systemic sclerosis
Authors: T Dick
Journal: Annals of the Rheumatic Diseases (2002)

Background: Antibodies targeting DNA topoisomerase I (ATA) or centromere proteins (ACA) are associated with clinical subsets of patients with systemic sclerosis (SSc). The occurrence of those autoantibodies is considered to be mutually exclusive. Objective: To describe the clinical and immunogenetic data of three patients who are co-expressing both antibodies, and then review previous publications. Methods: Both antibodies were detected by different methods, including indirect immunofluorescence technique, enzyme linked immunosorbent assay, immunodiffusion, and immunoblot. Patients were HLA typed by serological and molecular genetic methods. Data were extracted from published reports for comparison. The search for published studies was through Medline and other database research programmes. Results: During routine laboratory diagnostics over several years three patients with scleroderma and coincidence of ATA and ACA were identified: patient 1 with diffuse SSc, Raynaud9s phenomenon, puffy fingers and fingertip necrosis, contractures, and calcinosis; patient 2 with diffuse SSc, Raynaud9s phenomenon, oedema of the hands, and interstitial calcinosis of hands, knees, and shoulders, and pulmonary fibrosis; patient 3 with scleroderma of hands, forearms, and face, Raynaud9s phenomenon, puffy fingers, finger contractures, fingertip necrosis, and calcinosis. All three patients studied were carriers of HLA alleles known to be associated with these autoantibodies. In serial measurements the concentrations of the two antibodies showed independent or even reverse fluctuations. Screening of 100 patients with ACA for ATA and vice versa disclosed no further patients with coincidence of these antibodies. Twenty eight cases of ACA/ATA coexistence in 5423 patients (0.52%) with SSc or SSc associated symptoms were found in an analysis of published studies. Conclusion: The expression of ATA and ACA is not totally mutually exclusive, but coincidence is rare (&lt;1% of patients with SSc). Patients with both autoantibodies often have diffuse scleroderma and show immunogenetic features of both antibody defined subsets of SSc.
Complete Regression of Established Subcutaneous B16 Murine Melanoma Tumors after Delivery of an HIV-1 Vpr-Expressing Plasmid by in Vivo Electroporation
Authors: Andrea N. McCray, Kenneth E. Ugen, Karuppiah Muthumani, J.J. Kim, David B. Weiner, Richard Heller
Journal: Molecular Therapy (2006)

Novel therapies and delivery methods directed against malignancies such as melanoma, and particularly metastatic melanoma, are needed. The HIV-1 accessory protein Vpr (viral protein R) has previously been demonstrated to induce G2 cell cycle arrest as well as in vitro growth inhibition/killing of a number of tumor cells by apoptosis. In vivo electroporation has been utilized as an effective delivery method for pharmacologic agents and DNA plasmids that express "therapeutic" proteins and has been targeted to various tissues, including malignant tumors. For the study reported here, we hypothesized that intratumoral delivery of a Vpr expression plasmid through in vivo electroporation would induce apoptosis and growth attenuation or regression of melanoma tumors. Established subcutaneous B16.F10 melanoma tumors were injected intratumorally with a Vpr-expressing (either 25 or 100 microg) plasmid, followed by electroporation, on day 0 (i.e., when tumors had attained an appropriate size) and day 4. Treatment with 25 or 100 microg of the Vpr-expressing plasmid resulted in complete tumor regression with long-term survival in 14.3 and 7.1% of the mice, respectively. In addition, electroporative delivery of the Vpr-expressing plasmid was shown to induce apoptosis in tumors after intratumoral injection. This is the first report demonstrating the ability of Vpr, when delivered as a DNA expression plasmid with in vivo electroporation, to attenuate melanoma lesion growth and induce complete tumor regression coupled with long-term survival of mice in a highly aggressive and metastatic solid tumor model.