tbuckley/cabot-search huggingface dataset:
Activation of mesangial cells by the phosphatase inhibitor vanadate. Potential implications for diabetic nephropathy.
Authors: U O Wenzel, B Fouqueray, P Biswas, G Grandaliano, G G Choudhury, H E Abboud
Journal: Journal of Clinical Investigation (1995)

The metalion vanadate has insulin-like effects and has been advocated for use in humans as a therapeutic modality for diabetes mellitus. However, since vanadate is a tyrosine phosphatase inhibitor, it may result in undesirable activation of target cells. We studied the effect of vanadate on human mesangial cells, an important target in diabetic nephropathy. Vanadate stimulated DNA synthesis and PDGF B chain gene expression. Vanadate also inhibited total tyrosine phosphatase activity and stimulated tyrosine phosphorylation of a set of cellular proteins. Two chemically and mechanistically dissimilar tyrosine kinase inhibitors, genistein and herbimycin A, blocked DNA synthesis induced by vanadate. Vanadate also stimulated phospholipase C and protein kinase C. Downregulation of protein kinase C abolished vanadate-induced DNA synthesis. Thus, vanadate-induced mitogenesis is dependent on tyrosine kinases and protein kinase C activation. The most likely mechanism for the effect of vanadate on these diverse processes involves the inhibition of cellular phosphotyrosine phosphatases. These studies demonstrating that vanadate activates mesangial cells may have major implications for the therapeutic potential of vanadate administration in diabetes. Although vanadate exerts beneficial insulin-like effects and potentiates the effect of insulin in sensitive tissue, it may result in undesirable activation of other target cells, such as mesangial cells.
High serum B cell activating factor predicts good clinical response to rituximab in RA: pilot data
Authors: E M Vital, R Cuthbert, E Hensor, R Parmar, S Dass, D Corscadden, K Henshaw, A Rawstron, F Ponchel, P Emery
Journal: Annals of the Rheumatic Diseases (2010)

Rituximab treats rheumatoid arthritis (RA) by temporarily depleting B cells. Initial clinical response and time to relapse after B cell repopulation are variable. Using highly sensitive flow cytometry we have shown that good clinical response is predicted by rapid complete B cell depletion (below 0.0001 cells × 109/l) and lower levels of memory and preplasma cells at baseline. There remains a need for more practically applicable biomarkers predicting response. B cell activating factor (BAFF) promotes the differentiation, activation and …
BMA demands ban on smoking in enclosed workplaces in the United Kingdom
Authors: Annabel Ferriman
Journal: BMJ (2004)

Body set up to increase numbers taking part in trials 365, 149 A new body was launched last week to get the NHS and industry working more closely together to increase the number of patients taking part in clinical trials.The UK Clinical Research Collaboration will bring together key players to speed up the development of medicines in five areas-Alzheimer's disease, stroke, diabetes, mental health, and children's medicine.Representatives from the NHS, industry, the Medical Research Council and other funding bodies, medical charities, and the National Institute for Clinical Excellence (NICE) will make up the new body.Using the successful National Cancer Research Networks organisation as a model, the collaboration will use an initial £24m ($44m; €36m) to set up similar research networks in the five new areas.
THE INFLUENCE OF THE CEREBRAL CORTEX ON GASTRO-INTESTINAL MOVEMENTS
Authors: JAMES W. WATTS
Journal: JAMA (1935)

After the publication of Cushing's<sup>1</sup>address on peptic ulcers and the interbrain and Keller's<sup>2</sup>paper on ulceration of the digestive tract following experimental lesions of the hypothalamus, it seemed desirable to study the effects of hypothalamic lesions on the gastro-intestinal tract of monkeys. Since monkeys had not previously been used in such experiments it was essential that a careful study be made of their gastro-intestinal tracts under laboratory conditions as a basis for interpreting changes that might follow hypothalamic lesions. For this purpose complete autopsies were performed on all animals (eighty in number) that died or were killed during the year 1932-1933 (at the Laboratory of Physiology at Yale University School of Medicine),<sup>3</sup>attention being directed particularly to the intestine. In the course of these autopsies, intussusception with intestinal obstruction was found to be the cause of death in three otherwise healthy animals; all three intussusceptions occurred in
Application of Screening Principles to the Reconstructed Breast
Authors: Jennifer Zakhireh, Barbara Fowble, Laura J. Esserman
Journal: Journal of Clinical Oncology (2009)

A significant number of women choose mastectomy for the treatment of early and locally advanced breast cancer. Advances in reconstruction techniques and greater awareness of options have led to an increased use of immediate breast reconstruction, which has resulted in uncertainty for the management of surveillance for local recurrence. In this article, we review mastectomy and reconstruction trends and how these techniques affect the frequency and location of local recurrence. The data on surveillance imaging of the reconstructed breast are extremely limited. However, by assessing the potential role for imaging in this setting and applying the principles of screening, we have identified that there is a potential theoretic advantage of surveillance imaging in a very small subset of women: those with autologous tissue reconstructions and moderate to high risk of recurrence. A prospective registry study of surveillance imaging in this target population would be the appropriate way to determine its benefit and its impact on survival outcomes. In this review article, we will detail the reasons that should allow clinicians to forego routine surveillance imaging in the majority of women who undergo mastectomy and reconstruction.
Familial abnormality of erythrocyte cation transport in essential hypertension.
Authors: K L Woods, D G Beevers, M West
Journal: BMJ (1981)

Cation transport across the red-cell membrane was studied in subjects with essential hypertension and their relatives using rubidium-86 as an analogue of potassium. The activity of the ouabain-sensitive sodium-potassium pump was significantly greater in patients with untreated essential hypertension than in controls (p less than 0.001). No clear separation was seen between normotensive and hypertensive subjects. Activity of the sodium-potassium pump was also increased in a proportion of normotensive relatives of subjects with essential hypertension. Rubidium uptake was significantly lower in normotensive black subjects than in normotensive whites, the difference being in a ouabain-resistant pathway of cation transport. These results provide further evidence that a defect in membrane cation transport contributes to the pathogenesis of essential hypertension.
Three-dimensional co-culture models to study prostate cancer growth, progression, and metastasis to bone
Authors: Ruoxiang Wang, Jianchun Xu, Lisa Juliette, Agapito Castilleja, John Love, Shian-Ying Sung, Haiyen E. Zhau, Thomas J. Goodwin, Leland W.K. Chung
Journal: Seminars in Cancer Biology (2005)
Cystinosis and Its Therapy
Authors: Stanton Segal
Journal: New England Journal of Medicine (1979)

The nature of cystine storage disease remains an enigma despite a concerted effort by investigators over the past decade to delineate its underlying biochemical basis. Normally, the principal intracellular sulfur-containing amino acid is cysteine, which can be synthesized from methionine and which all cell systems are geared up to deal with. Cystine is the disulfide, or oxidized, form of cysteine, and when it passes into the cell, it is reduced to cysteine (the thiol form) by a potent cytoplasmic system that involves the cysteine-containing compound reduced glutathione. Large amounts of glutathione are present in cells, in both oxidized and reduced . . .
Unknown primary Merkel cell carcinoma: 23 new cases and a review
Authors: Tina I. Tarantola, Laura A. Vallow, Michele Y. Halyard, Roger H. Weenig, Karen E. Warschaw, Amy L. Weaver, Randall K. Roenigk, Jerry D. Brewer, Clark C. Otley
Journal: Journal of the American Academy of Dermatology (2012)
MicroRNA expression in Sézary syndrome: identification, function, and diagnostic potential
Authors: Erica Ballabio, Tracey Mitchell, Marloes S. van Kester, Stephen Taylor, Heather M. Dunlop, Jianxiang Chi, Isabella Tosi, Maarten H. Vermeer, Daniela Tramonti, Nigel J. Saunders, Jacqueline Boultwood, James S. Wainscoat, Francesco Pezzella, Sean J. Whittaker, Cornelius P. Tensen, Christian S. R. Hatton, Charles H. Lawrie
Journal: Blood (2010)
Schedule-dependent cytotoxicity of methotrexate and 5-fluorouracil in human colon and breast tumor cell lines.
Authors: C Benz, M Schoenberg, M Choti, E Cadman
Journal: Journal of Clinical Investigation (1980)

The effect of sequential methotrexate and 5-fluorouracil on the clonal growth of the human colon adenocarcinoma cell, HCT-8, and the hormone-dependent human breast carcinoma cell, 47-DN, was examined. In both cell lines, when 5-fluorouracil was given during the last 6 h of a 24 h methotrexate exposure period, there was marked synergistic inhibition of clonal growth. Shorter intervals or the reverse sequence of drugs were either additive or antagonistic. These results indicate the importance of the drug sequence and time interval between drug administration for optimal cytotoxicity in these human cell lines. This information suggests that the administration of methotrexate 18 h before 5-fluorouracil may have potential application in the design of clinical trials for these malignancies.
P246Cystatin C and hemorheological parameters in the essential hypertension patients
Authors: E Oschepkova, N Ageeva, V Dmitriev, A Rogoza, V Titov
Journal: Cardiovascular Research (2014)

Objective: Cystatin C, an endogenous marker for glomerular filtration rate - kidney function, also correlates with cardiovascular risk factors. At the same time changes of blood fluidity are also one of main risk factors of cardiovascular disorders. The aim of our study was to investigate if it is association Cystatin C with hemorheological parameters of blood in the essential hypertensive patients (EH pts). Design and Methods: 26 EH pts (18M, 8F) grade 1 or 2, av. age 48,4±2,4 years with short duration EH (no more 5 years) and without chronic kidney disease (Creatinine level: 84,7±1,9 μmol/L, GFR: 114,9±5,4 ml/min), 24-h SBP was 140,8±2,7 mm.Hg., 24-h DBP was 86,0 ±2,6 mm Hg. Cystatin C was defined by a method of turbidimetry on the Architect C 8000 analyzer (Abbot, USA). Whole blood viscosity of native blood and at standard hematocrit =30 at high (128c-1) ν1 and low (0,95c-1) ν2 shear rates, plasma viscosity (νpl) were measured by a rotational viscometer (Low Shear 30 “Contraverse”, Switzerland). Hematocrit (Ht) and aggregation of erythrocytes (ν2/ ν1) were studied also. 24 hour blood pressure monitoring (24-h BPM) was carried out by BPlab (Russia).The statistical analysis was carried out by nonparametric method of Spearman with STATISTICA 6. The data is presented as M±SE. Results: In the whole group EH pts Cystatin C level was 1,00±0,02 μg/L, Ht=49,7±0,8%, ν1=5,05±0,10sPs, ν2=26,5±1,2sPs, νpl=1,51±0,01 sPs, at standard hematocrit ν1st= 3,18±0,02, ν2st 8,2±0,4, ν2/ ν1=5,2±0,1. Significant association Cystatin C with platelet aggregation (r=0,49; p<0,05) and plasma viscosity ν2 (r=0,46; p<0,05) were found. We didn't find significant association Cystatin C with other hemorheological parameters. Conclusion: our results confirm a hypothesis of significant influence of Cystatin C on hemorheological properties of blood in EH pts, what can be an additional risk factor for cardiovascular negative events.
Barrie Patrick Marmion
Authors: J. Ayres
Journal: BMJ (2014)

Barrie Patrick Marmion excelled as a clinical microbiologist, medical researcher and academic, mentor to many younger colleagues, and outstanding human being. His professional life and activity stretched more than 70 years, from the era when smallpox, typhoid, and diphtheria were encountered regularly, through to times of gene therapy and routine molecular diagnostics. His contributions to microbiology were considerable, including his last paper, which is about to be published.

Barrie was born the son of Joseph and Melita (“Millie”) Marmion in Alverstoke in Hampshire. The family subsequently moved to Kent, where his father became the county pharmacist and where his two sisters were born. His warm, supportive, and happy family background was reflected in his personality. He started his medical studies at University College London in 1939, with a brief interlude during which he was seconded to the Welsh National School of Medicine in Cardiff for his preclinical studies because of the outbreak of war, after which he returned to UCH for his clinical studies. The latter were conditioned by the reduced senior staff away in the forces and having to undertake some air raid duties. He had clinical, preregistration experience at Great Ormond Street Hospital and graduated …
Remove isolated vomiting as an automatic indication for computed tomography in children with head injury
Authors: J. Fryer, E. Abrahamson
Journal: BMJ (2014)

We welcome the changes in the 2014 National Institute for Health and Care Excellence (NICE) head injury guidelines that downgrade vomiting in children as an indicator for computed tomography (CT) of the head,1 but we feel that they do not go far enough.

The evidence linking vomiting and clinically important traumatic head injury in children is poor. …
Pathology of the defunctioned rectum in ulcerative colitis.
Authors: B F Warren, N A Shepherd, D C Bartolo, J W Bradfield
Journal: Gut (1993)

Faecal stream diversion may induce inflammatory changes in the defunctioned segment of the large intestine. These changes are predominantly mucosal, although confusing histological features including granulomas may be present. The pathology of 15 defunctioned rectal stumps has been studied. All patients had previously undergone urgent total colectomy for ulcerative colitis and rectal stumps had been left in situ while they awaited pelvic ileal reservoir construction. All rectal stumps showed predominantly mucosal disease but there were additional features such as florid lymphoid follicular hyperplasia (12 cases), transmural inflammation (nine cases), granulomas (four cases), fissures (eight cases), and changes akin to ischaemia or to pseudomembraneous colitis (four cases). These changes may result from a combination of defunctioning and of active ulcerative proctitis. Some induce a histological appearance that may mimic Crohn's disease. Nevertheless review of all 15 colectomy specimens showed unequivocal ulcerative colitis and none of the patients has subsequently shown any clinical, radiological, or pathological evidence to support a diagnosis of Crohn's disease. Histology of the rectal stump in ulcerative colitis may lead to an erroneous diagnosis of Crohn's disease and the patient may subsequently be denied the advantage of a pelvic ileal reservoir.
"Absolute" is inappropriate for quantitative risk estimation
Authors: H. Tunstall-Pedoe
Journal: BMJ (2000)

Risk prediction, risk management, and risk avoidance are in fashion and invading medical practice, but current terminology is unfortunate and tendentious in a clinical context. Gambling and life insurance led to the first mathematics of risk. Individual outcomes were unpredictable, but if the circumstances and rules of the game did not change, the long run odds could be estimated from previous experience.

Longitudinal studies, of which the Framingham study was a pioneer, identified human risk factors which, when measured at the start of observation, correlated with the subsequently recorded risk. Risk is recorded as an event rate having numerator, denominator, and time period, but problems arose in how to portray different levels of risk at different levels of risk factors.

> “Absolute” risk…has misleading medicolegal and ethical implications

For half a century relative risk was king. Dividing high risk by low produced a simple multiple with no units—relative risk of smoking = 2.5. Relative …
Reduction in Risk of Progression of Diabetic Retinopathy
Authors: Barbara E.K. Klein
Journal: New England Journal of Medicine (2010)

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (ClinicalTrials.gov number, NCT00000620) was designed primarily to study the effects of intensive glycemic control on cardiovascular events in persons with type 2 diabetes. The ACCORD Eye study (NCT00542178), described by the ACCORD Study Group and ACCORD Eye Study Group in this issue of the Journal, 1 is a subgroup study of the larger ACCORD trial, designed to examine effects of several medical interventions on the progression of diabetic retinopathy. A sample of 4065 of the 10,251 participants in ACCORD was targeted for the eye study; complete data were obtained for 2856 . . .
Importance of repeat testing in the diagnosis of penicillin allergy
Authors: V. Matheu, E. Perez-Rodriguez, I. Sanchez-Machin, J.C. Garcia-Robaina, F. De La Torre Morin
Journal: British Journal of Dermatology (2005)

Conflicts of interest: none declared. Sir, In the May 2005 issue of this Journal Lammintausta and Kortekangas‐Savolainen1 presented an interesting article about the usefulness of skin tests in determining drug hypersensitivity. We have found the results to be very helpful as there are only few reported works about the prevalence of positive skin tests in the context of allergic reactions. However, we have some points of contention. Although both patch tests (PTs) and intradermal tests (IDTs) are used for the diagnosis of nonimmediate reactions to aminopenicillins, and both tests appear to be valuable, delayed‐reading IDTs appear to be somewhat more sensitive2 than PTs, but also less specific.3 In the report by Lammintausta and Kortekangas‐Savolainen, beta‐lactam antibiotics were the drugs more often suspected and tested. However, IDTs with major and minor determinants were carried out only in 31 of 342 patients with suspected penicillin allergy and none of them elicited a positive reaction. The European Network for Drug Allergy (ENDA) recommends testing in most patients in whom penicillin allergy is suspected.4 In fact, most diagnoses of penicillin allergy have recently been reported to be obtained by means of the IDT.5, 6 Between January 2002 and June 2005 we evaluated 604 patients with suspected beta‐lactam allergy. In all of them, after written informed consent, skin prick tests and IDTs were performed with benzylpenicilloyl polylysine (PPL), minor determinants mixture (MDM; including benzylpenicillin, benzylpenicilloic acid and sodium benzylpenicilloate), penicillin G and the suspect drug if it was other than penicillin. PPL and MDM were purchased from two different companies (Allergopen®; Allergopharma, Reinbeck, Germany and Diater SA, Madrid, Spain). If the skin tests were negative, controlled drug challenge was performed under strict supervision. After 15 days the skin tests and drug challenge were repeated, as recommended by ENDA.4 After completing the study, 66 patients were diagnosed with beta‐lactam allergy, 60 by skin testing and 10 of those in the repeat tests. From 1108 challenges with beta‐lactams in 554 patients, there were only six positives following a previously negative skin test.
Evaluating complementary and alternative therapies for cancer patients
Authors: B. R. Cassileth
Journal: CA A Cancer Journal for Clinicians (1999)

"Complementary and alternative" therapies are actually a vast collection of disparate, unrelated regimens and products, ranging from adjunctive modalities that effectively enhance quality of life and promising antitumor herbal remedies now under investigation, to bogus therapies that claim to cure cancer and that harm not only directly, but also indirectly by encouraging patients to avoid or postpone effective cancer care. Complementary therapies such as music and massage, herbal teas to aid digestion and relieve nausea, yoga, tai chi, meditation, and the many other well-documented techniques that relieve stress and enhance well-being should be made available to patients to augment and ease the experience of cancer treatment and recovery. Many time-tested herbal and diet-based remedies are now being studied for their abilities to induce or extend remission without toxicity. At the same time, lack of government regulatory authority leaves consumers at the mercy of those who promote unproved remedies, scores of which line grocery store and pharmacy shelves. Many of these over-the-counter products contain harmful ingredients. Herb-drug interactions, only some of which are documented, occur with frequency and are sufficiently problematic to require that patients stop taking herbal remedies prior to surgery (to prevent interactions with anesthetics and anticoagulant effects); before radiation (due to potential for increased photosensitivity); and during courses of chemotherapy (to prevent product-drug interactions). Moreover, both good information and misinformation that appear in printed materials and on the Internet appeal to better educated consumers, who are, in fact, the most likely to try complementary and alternative methods.
Rich countries dominate cancer league table
Authors: J. Carlowe
Journal: BMJ (2011)

Denmark has the world’s highest incidence of cancer, with 326 new cases each year for every 100 000 people. It is followed by Ireland (317), Australia (314), New Zealand (309), and Belgium (307).

The data, compiled by the World Cancer Research Fund, show that every year 267 in every 100 000 in the United Kingdom develop cancer, putting it in 22nd place. When the data are broken down by sex the UK ranks 33rd in the world for men but 12th for cancers in women and 11th for breast cancer alone.

The fund used statistics compiled by the World Health Organization to compare cancer rates around the world. The ranking shows that rich countries have much higher rates of cancer than poor ones. WHO …
Woman compensated for removal of ovaries
Authors: C. Dyer
Journal: BMJ (1995)

<h3>Abstract</h3> The reproducibility and translation of neuroscience research is assumed to be undermined by introducing environmental complexity and heterogeneity. Rearing laboratory animals with minimal (if any) environmental stimulation is thought to control for biological variability but may not adequately test the robustness of our animal models. Standard laboratory housing is associated with reduced demonstrations of species typical behaviors and changes in neurophysiology that may impact the translation of research results. Modest increases in environmental enrichment (EE) mitigate against insults used to induce animal models of disease, directly calling into question the translatability of our work. This may in part underlie the disconnect between preclinical and clinical research findings. Enhancing environmental stimulation for our model organisms promotes ethological natural behaviors but may simultaneously increase phenotypic trait variability. To test this assumption, we conducted a systematic review and evaluated coefficients of variation (CVs) between EE and standard housed mice and rats. Given findings of suboptimal reporting of animal laboratory housing conditions, we also developed a methodological reporting table for enrichment use in neuroscience research. Our data show that animals housed in EE were not more variable than those in standard housing. Therefore, environmental heterogeneity introduced into the laboratory, in the form of enrichment, does not compromise data integrity. Overall, human life is complicated, and by embracing such nuanced complexity into our laboratories, we may paradoxically improve on the rigor and reproducibility of our research.