tbuckley/cabot-search huggingface dataset:
Assessment of the role of activin A and transforming growth factor ? in the regulation of AML12 cell growth
Authors: Y Zhang, H Mashima, M Kanzaki, H Shibata, I Kojima
Journal: Hepatology (1997)

The present study was conducted to determine the role of two autocrine factors, activin A and transforming growth factor β (TGF-β), in the growth regulation of AML12 hepatocytes. We overexpressed truncated type II activin and/or TGF-β receptors in AML12 cells. In AML12 cells overexpressing truncated type II activin receptors (AML-tAR cells), the inhibitory effect of activin A on DNA synthesis was completely blocked. AML-tAR cells proliferated faster than parental cells, both in the presence and absence of epidermal growth factor (EGF). However, AML-tAR cells could not grow in soft agar. Follistatin augmented EGF-induced DNA synthesis in AML12 cells, whereas it was ineffective in AML-tAR cells. In AML12 cells overexpressing truncated type II TGF-β receptor (AML-tTR cells), the inhibitory effect of TGF-β on DNA synthesis was blocked. AML-tTR cells proliferated faster than parental cells, both in the presence and absence of EGF, but at a slower rate than that of AML-tAR cells. AML-tTR cells did not grow in soft agar. The growth rate of cells overexpressing both types of truncated receptors was identical to that of AML-tAR cells, and these cells did not grow in soft agar. These results indicate that both activin A and TGF-β act as autocrine inhibitors of DNA synthesis in AML12 cells, and that the blocking of the actions of two factors does not lead to transformation. Activin A is a predominant autocrine factor in these cells.
Being creative about rationing
Authors: R. Smith
Journal: BMJ (1996)

An innovatory theory helps clearer thinking

Two of the biggest questions in health care are “How much money should we spend?” and “What should we spend it on?” We don't have adequate methods for answering either question, but Ronald Dworkin, professor of law in both Oxford and New York and one of the world's leading thinkers on medical ethics, has developed a theory that provides a means to begin to answer both questions. Last week he presented his “prudent insurance principle” at a meeting in London organised by the Institute for Public Policy Research.

Current practice with health care expenditure is based—more implicitly than explicitly—on what Professor Dworkin calls “the insulation model.” This postulates that health care is fundamentally different from other goods, that equality of access is essential for health care because it is so different, and that when something can be done acutely to avoid death it should be done (“the rescue principle”). In the United States this principle has led to such inappropriate actions as huge sums being spent to separate Siamese twins joined at the heart even though one will inevitably die and the other has only a tiny chance of surviving and no chance of living a normal life. In Britain large sums of money have been spent to give the teenager Jaymee Bowen further treatment for her leukaemia even though the discomfort to her is high, …
Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris results of the international multicenter angina exercise (IMAGE) study
Authors: Stefano Savonitto, Diego Ardissino, Kenneth Egstrup, Klaus Rasmussen, Erling A. Bae, Tor Omland, Per M. Schjelderup-mathiesen, Paolo Marraccini, Inger Wahlqvist, Piera Angelica Merlini, Nina Rehnqvist
Journal: Journal of the American College of Cardiology (1996)
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 44: Table 1
Authors: D S Senchina, S J Stear, L M Burke, L M Castell
Journal: British Journal of Sports Medicine (2013)

Part 44 is dedicated to a review on supplements used in the sport and exercise arena for weight loss, with a particular focus, including a utilitarian and novel classification, on the wide assortment of herbs used as the active ingredient(s), particularly in the seemingly fashionable supplements marketed as having ‘thermogenic’ properties.

### S J Stear

Without doubt, physique, including body mass or composition, size and shape, has an important role to play in optimising sports performance. Size does matter! Consequently, various strategies, including dietary intervention, are employed in an effort to influence physique. Fundamentally, body weight (body mass) is lost when dietary energy (energy intake) is consumed at a level less than daily requirements (energy expenditure), with an energy deficit ∼10–20% being both effective in producing loss and being tolerated over the longer term. However, although any strategy, including popular/fad diets, that reduces energy intake below expenditure will result in weight loss, most athletes need to achieve a more specific goal of promoting loss of body fat while maintaining lean body mass and optimising sports performance. Therefore, athletes embarking on an energy-reduction programme should do so only under the guidance of a sports nutrition professional. This will ensure that the intakes of important macronutrients and micronutrients are not detrimentally compromised and that the energy intake is sufficient to support their training/competition needs. Although there is growing evidence of a positive role for dairy/calcium intake in assisting weight/fat loss, this has not yet been extensively studied in the athletic population.

In the multibillion dollar supplement industry, ‘weight loss’ supplements contribute a significant proportion. A huge range of supplements claims to enhance sports performance by affecting body composition—either by increasing muscle mass and/or reducing body fat. Supplements in the broad ‘weight loss’ category include caffeine, l-carnitine, chromium picolinate, CLA (conjugated linoleic acid), dairy/calcium supplements, HMB …
Prospective Relation of C-Reactive Protein With Type 2 Diabetes
Authors: Marieke B. Snijder, Jacqueline M. Dekker, Marjolein Visser, Coen D.A. Stehouwer, John S. Yudkin, Lex M. Bouter, Robert J. Heine, Giel Nijpels, Jacob C. Seidell
Journal: Diabetes Care (2003)

We read with great interest the article by Han et al., which was recently published in Diabetes Care (1). The authors studied the association between baseline levels of C-reactive protein (CRP) and the 6-year incidence of the metabolic syndrome and type 2 diabetes in Mexican subjects. They found an odds ratio (OR) of 4.1 (95% CI 2.1–8.0) for developing the metabolic syndrome and an OR of 5.4 (2.2–13.4) for incident type 2 diabetes among women in the highest compared with the lowest tertile of CRP. ORs were adjusted for age, smoking, physical activity, and alcohol intake. In men, no such association was found. Additional adjustment for BMI slightly lowered the ORs; adjustment for waist-to-hip …
STUDIES ON TYPHUS FEVER
Authors: Hans Zinsser, M. Ruiz Castaneda
Journal: The Journal of Experimental Medicine (1933)

The experiments recorded above demonstrate that the systematic treatment of a horse with formalin- and phenol-killed Rickettsiae obtained from the Mexican virus by our X-ray rat technique induces the development of properties in the horse's serum which may be described as follows: 1. An original agglutinating potency for Proteus X-19 (Weil-Felix reaction) not exceeding dilutions of 1-40 was enhanced to a potency of 1-160 and, feebly, 1-320. 2. The horse's serum, after immunization, exerts distinct protective action against the Mexican virus, whether mixed with the virus before injection, administered 1 week or somewhat longer before the virus or given 24, 48 or 72 hours after infection with virus. Experiments of the last category have been most successful when the serum was given subcutaneously. 3. The serum of the immunized horse agglutinates the Weigl louse vaccines, containing Rickettsia prowazeki of the European disease in dilutions comparable in potency to the Weil-Felix reaction. Since the serum described exerted protective effects when given 7 and 13 days before infection with the virus, there is some prospect of prophylactic usefulness on the part of this serum. Since the serum also protected when subcutaneously administered 24, 48 and 72 hours after intraperitoneal infection of guinea pigs, and somewhat modified the disease even when given 96 hours after infection-that is 1 day before the control came down with a typical reaction-, it is at least logical to investigate its possible therapeutic value by early administration in the human disease of the New World or Mexican type. The time intervals governing the experiments of the last two categories in guinea pigs were of course dependent upon the balance between the amounts of virus and of serum used. The failure of similar effects upon the European virus is not easily explained. This is especially difficult to understand in view of the unquestionable agglutinating potency of the serum for the Weigl vaccines. Whether this difficulty is purely a quantitative one, or depends upon other factors, can be determined only by further investigation.
Maternal testosterone in pregnancy and atopic outcomes in childhood
Authors: S. O. Shaheen, M. Hines, R. B. Newson, M. Wheeler, D. R. M. Herrick, D. P. Strachan, R. W. Jones, P. G. J. Burney, A. J. Henderson
Journal: Allergy (2006)

Background: In mice, androgens downregulate Th2 cytokine responses, but whether androgen levels during pregnancy might influence the development of allergy in the offspring has not been studied. Methods: In the Avon Longitudinal Study of Parents and Children (ALSPAC), a population‐based birth cohort of 14 541 pregnancies, we related maternal blood total testosterone during pregnancy, measured in a subset of the cohort, to allergic outcomes in the offspring, including asthma, hayfever, eczema ( n = 543) and wheezing ( n = 532) at 69–81 months, and atopy (positive skin prick test to Dermatophagoides pteronyssinus , cat or grass, n = 386) and blood total immunoglobulin E (IgE; n = 314) at 7 years. We used logistic and linear regression to analyse binary outcomes and log‐transformed IgE, respectively, controlling for potential confounders. Results: Maternal testosterone was negatively associated with total IgE in boys [adjusted geometric mean ratio (GMR), per doubling of testosterone, 0.33 (0.20–0.55), P = 0.000038 ( n = 168)], but not in girls [GMR 1.04 (0.53–2.06), P = 0.91 ( n = 146)], P ‐value interaction 0.0086. The effect in boys was even stronger in the absence of maternal atopic disease. Testosterone was not associated with skin test positivity or atopic disease in either sex. Conclusions: Higher testosterone levels in pregnancy are associated with lower IgE production in boys.
Polymorphism of lymphocyte function-associated antigen-1 demonstrated by a lupus patient's alloantiserum.
Authors: K D Pischel, S D Marlin, T A Springer, V L Woods, H G Bluestein
Journal: Journal of Clinical Investigation (1987)

We have found a human serum, E27, obtained from a multiply transfused patient with systemic lupus erythematosus, which immunoprecipitates the lymphocyte function associated antigen-1 (LFA-1). The immunoprecipitated molecules were identified as the LFA-1 alpha and beta chains by their comigration on SDS-PAGE, two-dimensional SDS-PAGE, and by sequential clearance experiments. Serum E27 did not immunoprecipitate LFA-1 from autologous cells, though LFA-1 molecules were present. In contrast, serum E27 immunoprecipitated LFA-1 from most but not all normal donor lymphocytes. Thus, serum E27 defines two serological phenotypes of LFA-1. 95% of normal individuals tested exhibited the LFA-1 phenotype precipitated by serum E27. Serum E27 appears to be directed at determinants of the LFA-1 alpha-chain and not the beta-chain since it immunoprecipitated LFA-1 molecules but not the Mac-1 molecules. Additional evidence for the alpha chain specificity was provided by immunoprecipitation of mouse-human heterohybridoma cells. LFA-1 was immunoprecipitated by serum E27 from mouse-human heterohybridoma cells expressing the human alpha-chain, not from a hybrid cell line expressing the human beta-chain. Together these findings demonstrate an antigenic polymorphism of the human LFA-1 alpha-chain molecule.
Discordance for childhood coeliac disease in monozygotic twins
Authors: J. A. Walker-Smith
Journal: Gut (1973)

Discordance for childhood coeliac disease in monozygotic twin boys is reported. The diagnosis of coeliac disease in the second-born twin was established by demonstration of a flat small intestinal mucosa on biopsy and a clinical response to a gluten-free diet. The first-born twin had a normal small intestinal mucosa. Phenotypic, genotypic, and dermatoglyphic observations as well as gross observation of the placenta and membranes provided strong evidence that these twin boys were monozygotic.
Birth‐related increase in intracolonic hydrogen gas and nitric oxide as indicator of host–microbial interactions
Authors: T. Sobko, M. Norman, E. Norin, L. E. Gustafsson, J. O. Lundberg
Journal: Allergy (2005)

Background: Bacterial colonization of the intestine early in life might have implications for allergy development. We studied early host–bacterial interactions in the gut by simultaneous measurements of hydrogen gas (H 2 ) and faecal short chain fatty acid pattern (SCFAs), i.e. bacterial products, as well as of nitric oxide (NO), a marker of mucosal immune activation. Methods: A novel minimally invasive technique was used for repeated measurements of luminal colonic H 2 and NO in 32 healthy newborn infants delivered vaginally or by Caesarean section. Luminal gas was sampled and analysed at five occasions: immediately after birth, day 1, days 3–5, 1 and 5–6 months after birth. Results: Colonic H 2 , NO and faecal SCFAs were undetectable at birth. The H 2 and SCFAs appeared within 24 h and continued to increase during the 6 months follow‐up. Nitric oxide remained very low until 3–5 days after birth at which time it markedly increased. In some apparently healthy infants NO transiently reached levels similar to those seen in adults with inflammatory bowel disease. Conclusion: Intracolonic measurements of H 2 and NO may be useful to monitor the developmental colonization process as well as mucosal responses.
Ye olde guide to healthy living
Authors: W. Moore
Journal: BMJ (2008)

Faced with today’s baffling profusion of self help advice, ranging from the daft to the downright dangerous, bewildered patients could do worse than return to the wholesome simplicity of Restoration England. Whether disfigured by scurvy, poxed by running sores, or simply a little bit under the weather, the afflicted in the 17th century could rely on eminently sensible advice from no less a reliable quarter than Charles II’s own doctor.

Although he possessed no university medical qualification and incurred the wrath of the College of Physicians for practising unlicensed, John Archer not only enjoyed the title of Chymical Physitian in Ordinary to …
Sailing and swimming
Authors: Matt Wyon
Journal: British Journal of Sports Medicine (2001)

Club doctors and physiotherapistsEDITOR,-Waddington et al 1 are to be congratulated on highlighting the need to provide the best available care to professional footballers.Their paper is, however, inherently biased by factors that detract from the validity of their conclusions.For example, they have provided no evidence for their postulation that non-chartered physiotherapists are more vulnerable to threats to their clinical autonomy than other qualified professionals.Published quotations from the semistructured interviews are of an emotive nature, and the quoted questions posed by the interviewer are clearly leading.It is well recognised that responses in such interviews can be greatly influenced by the manner in which they are posed.The authors make no comparison of methods used by chartered and non-chartered physiotherapists, and their outcomes.Similarly there has been no comparison between the performance of club doctors with or without postgraduate qualifications in sports medicine, and, moreover, no evidence produced of actual harm resulting.Indeed, in recent months in Scottish League football, the Dundee club doctor restored circulation to the foot of a player following a serious ankle injury, and the Dumbarton club doctor restarted the breathing of an apnoeic player.In a recent survey of 15 players in a Scottish football club (unpublished work), 13 stated that they had been discouraged by the (non-chartered) physiotherapist and nine by the (non-specialist) club doctor from training or competing while injured, and none had been encouraged by either to return to playing before complete recovery.Indeed, 10 confessed to concealment of the true severity of injuries, perhaps reflecting the ethos at that particular club.Care oVered to professional footballers merits careful evaluation.However, this should be detailed, methodical, and independent of bias, such as that which can arise when studies are commissioned and funded by interested parties.
Eating disorders in general practice.
Authors: M B King
Journal: BMJ (1986)

A total of 748 patients who attended four south London group practices were screened using the eating attitudes test; 1% of women had bulimia nervosa and a further 3% a partial syndrome eating disorder. Eating and weight control behaviour and psychiatric indicators for an eating disorder were analysed. Patients with bulimia nervosa and partial syndromes were remarkably similar. They were mainly women, from the middle to upper classes, in the normal weight range but having had considerable weight fluctuation in the past, more likely to have had a history of menstrual irregularity, often psychologically troubled, and tended to have more family psychopathology.
98. Stable Lentivirus-Mediated RNA Interference: Comparison of U6 and H1 Promoters in Endothelial Cells and GFP Knockdown in Mouse Brain
Authors: Petri I. Makinen, Jonna K. Koponen, Anna-Mari Turunen, Tarja M. Malm, Jari Koistinaho, Mikko P. Turunen, Seppo Yla-Herttuala
Journal: Molecular Therapy (2005)

RNA interference (RNAi) is a post-transcriptional RNA degradation process, which has become a useful tool in gene function studies and recently in gene therapy applications. Long-term expression of short hairpin RNA molecules (shRNA) required for many gene therapy applications can be achieved by lentiviral vectors (LVs). The two most commonly used promoters to drive the shRNA expression are the human U6 small nuclear promoter (U6) and human H1 promoter (H1). Our goal was to construct an efficient and optimal LV-based shRNA expression system and to explore LV-mediated RNAi for long-term gene silencing. For this purpose, we systematically compared the U6 and H1 promoters for optimal silencing of green fluorescent protein (GFP) in mouse endothelial cells. We show that the U6 promoter is more efficient than H1 in GFP silencing, leading to 80% GFP knockdown at the average of one integrated vector genome per target cell genome. In addition, the silencing was persistent for several months. Finally, as a proof of principle, we demonstrate that the GFP expression is silenced in vivo after stereotactic LV injection into GFP transgenic mice brain. In conclusion, LV-mediated RNAi is a powerful gene silencing method, which is useful for gene therapy applications requiring long-term knockdown of gene functions in vitro and in vivo.
Ga-67 Scintigraphy in a Patient With Adult T-cell Leukemia/Lymphoma
Authors: TOSHIBUMI KINOSHITA, KIYOSHI ISHII, HIROSHI NAGANUMA, FUMIO ENDOH
Journal: Clinical Nuclear Medicine (1995)

The authors report a case of adult T-cell leukemia/lymphoma (ATLL) involving lymph nodes, skin and spleen. Human T-lymphotropic virus type I (HTLV-I) infection predisposes to the genesis of ATLL. Ga-67 scintigraphy is useful to evaluate the extent and distribution of ATLL in HTLV-I-positive individuals.
Unexpectedly Expected Fetal Thyroid Function on Posttreated Radioiodine (131I) SPECT/CT of a Patient With Differentiated Thyroid Cancer
Authors: Wichana Chamroonrat, Chanika Sritara, Chirawat Utamakul, Arpakorn Kositwattanarerk, Kanungnij Thamnirat, Yoch Anongpornjossakul
Journal: Clinical Nuclear Medicine (2014)

We present a 25-year-old woman who has a diagnosis of differentiated thyroid cancer, a 2.5-cm papillary carcinoma in the right lobe, and presence of minimal extrathyroid invasion. 131I ablation and/or treatment of 150 mCi was given orally 3 months after total thyroidectomy. A fetus with radioiodine uptake in the fetal thyroid was unsuspectedly detected by SPECT/CT after 131I treatment.
Cloning and Characterization of the Novel Chimeric Gene <i>TEL/PTPRR</i> in Acute Myelogenous Leukemia with inv(12)(p13q13)
Authors: Fumihiko Nakamura, Yuichi Nakamura, Kazuhiro Maki, Yuko Sato, Kinuko Mitani
Journal: Cancer Research (2005)

Abstract We have cloned a novel TEL/protein tyrosine phosphatase receptor-type R (PTPRR) chimeric gene generated by inv(12)(p13q13). PTPRR is the first protein tyrosine phosphatase identified as a fusion partner of TEL. The chimeric gene fused exon 4 of the TEL gene with exon 7 of the PTPRR gene, and produced 10 isoforms through alternative splicing. Two isoforms that were expressed at the highest level in the leukemic cells could have been translated into COOH-terminally truncated TEL protein possessing the helix-loop-helix domain (tTEL) and TEL/PTPRR chimeric protein linking the helix-loop-helix domain of TEL to the catalytic domain of PTPRR. These two mutant proteins exerted a dominant-negative effect over transcriptional repression mediated by wild-type TEL, although they themselves did not show any transcriptional activity. Heterodimerization with wild-type TEL might be an underlying mechanism in this effect. TEL/PTPRR did not exhibit any tyrosine phosphatase activity. Importantly, overexpression of TEL/PTPRR in granulocyte macrophage colony-stimulating factor–dependent UT7/GM cells resulted in their factor-independent proliferation, whereas overexpression of tTEL did not. After cytokine depletion, phosphorylated signal transducers and activators of transcription 3 (STAT3) significantly declined in mock cells, but remained in both tTEL- and TEL/PTPRR-overexpressing cells. Loss of tumor suppressive function of wild-type TEL and maintenance of STAT3-mediated signal could at least partly contribute to the leukemogenesis caused by inv(12)(p13q13).
My last choice
Authors: Richard Smith
Journal: BMJ (2004)

Do you need approval from an ethics committee to ring up chief executives of hospitals and ask them questions? As a journalist, a member of parliament, or a confidence trickster you wouldn't, but if you are a researcher who has drawn up a protocol you might. Ethics committees, which were devised to protect vulnerable patients from some abuse, have forgotten why they were created and have begun to equate chief executives with the unconscious or the mentally incompetent. They have, in other words, spun out of control.

No fewer than five sets of researchers describe a series of Kafkaesque experiences with ethics committees …