tbuckley/cabot-search huggingface dataset:
All-trans retinoic acid induces p62DOK1 and p56DOK2 expression which enhances induced differentiation and G0 arrest of HL-60 leukemia cells
Authors: Thomas J. Lamkin, Vivian Chin, Andrew Yen
Journal: American Journal of Hematology (2006)

p62 DOK1 (DOK1) and p56 DOK2 (DOK2) are sequence homologs that act as docking proteins downstream of receptor or nonreceptor tyrosine kinases.Originally identified in chronic myelogenous leukemia cells as a highly phosphorylated substrate for the chimeric p210 bcr-abl protein, DOK1 was suspected to play a role in leukemogenesis.However, p62 DOK1À/À fibroblast knockout cells were found to have enhanced MAPK signaling and proliferation due to growth factors, suggesting negative regulatory capabilities for DOK1.The role of DOK1 and DOK2 in leukemogeneis thus is enigmatic.The data in this report show that both the DOK1 and the DOK2 adaptor proteins are constitutively expressed in the myelomonoblastic leukemia cell line, HL-60, and that expression of both proteins is induced by the chemotherapeutic differentiation causing agents, all-trans retinoic acid (atRA) and 1,25-dihydroxyvitamin D3 (VD3).Ectopic expression of either protein enhances atRA-or VD3-induced growth arrest, differentiation, and G 0 /G 1 cell cycle arrest and results in increased ERK1/2 phosphorylation.DOK1 and DOK2 are similarly effective in these capabilities.The data provide evidence that DOK1 and DOK2 proteins have a similar role in regulating cell proliferation and differentiation and are positive regulators of the MAPK signaling pathway in this context.
Small Colorectal Serrated Adenomas: Endoscopic Findings
Authors: E. Jaramillo, M. Watanabe, C. Rubio, P. Slezak
Journal: Endoscopy (1997)

Serrated adenomas are a distinct form of colorectal neoplasia. Several reports have indicated that serrated adenomas may give rise to invasive adenocarcinoma. The present study describes the endoscopic findings in 54 colorectal serrated adenomas detected in 35 patients.Thirty-five of 1225 patients (2.9%) who underwent colonoscopy during 1993 in the gastrointestinal endoscopy section at Karolinska Hospital (22 men, 13 women; mean age 68 years, range 49-84 years) were found to have a total of 182 polyps, including 118 adenomas and 64 hyperplastic polyps at histopathology. Fifty-four of the 118 adenomas (46%) were of the serrated type. In two of the 35 patients, two large exophytic colorectal adenocarcinomas were also present.Twenty-nine of the serrated adenomas (53.5%) were flat, 23 were sessile (42.5%), and two were pedunculated (4%). The mean sizes of the flat and sessile lesions were 3.5 mm (range 2-10 mm) and 5.9 mm (range 2-20 mm), respectively. The endoscopic appearance of serrated adenomas of 5 mm or less (n = 39, 72%) was similar to that of hyperplastic polyps. Forty-two (78%) of the lesions were located in the sigmoid and rectum. Fifty-one lesions showed low-grade dysplasia (including one with microinvasive carcinoma), and the remaining three had high-grade dysplasia.The study suggests that small polyps with a hyperplastic appearance should not be regarded as innocuous, since they may represent serrated adenomas carrying a malignant potential.
Abstract 3515: Increased TSH signaling by overexpressed thyrotrophin receptor is essential for B-RafV600E induced thyroid carcinogenesis
Authors: Young Hwa Kim, Yong Won Choi, Jang-Hee Kim, Tae Jun Park
Journal: Cancer Research (2014)

Abstract B-RafV600E oncogene mutation occurs most commonly in papillary thyroid cancer (PTC), and is associated with tumor initiation. However, a genetic modification by B-RafV600E in the thyrocytes results in oncogene induced senescence (OIS). In the present study, therefore, we attempted to evaluate the factors involved in the senescence overcome program in PTC. First of all, we observed downregulation of p-Erk1/2 and upregulation of dual specific phosphatase 6 (DUSP6) in the PTC with B-RafV600E mutation. In B-RafV600E expressing thyrocytes, although DUSP6 mRNA was upregulated, its protein and phosphatase activity were similar to those of normal thyrocytes. However, DUSP6 activity was reactivated when ROS was downregulated by thyroid stimulating hormone (TSH). Moreover, upregulation of MnSOD by TSH was observed in thyrocytes and PTC. Although serum TSH was not increased, its receptor was markedly upregulated in PTC with B-RafV600E. TSH together with DUSP6 inhibited B-RafV600E induced senescence in the thyrocytes, and reactivated Ras/Akt/GSK3β resulted in c-Myc protein stabilization by inhibition of its degradation. These observations led us to conclude that increased TSH signaling by overexpression of TSH receptor is essential for B-RafV600E induced papillary thyroid carcinogenesis. Citation Format: Young Hwa Kim, Yong Won Choi, Jang-Hee Kim, Tae Jun Park. Increased TSH signaling by overexpressed thyrotrophin receptor is essential for B-RafV600E induced thyroid carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3515. doi:10.1158/1538-7445.AM2014-3515
London's catch-up vaccination campaign against measles, mumps, and rubella reaches less than a quarter of children who were unvaccinated
Authors: L. Hitchen
Journal: BMJ (2008)

A catch-up campaign managed to vaccinate only a quarter of London children who had missed out on vaccinations against measles, mumps, and rubella (MMR) when they were young, the annual meeting of the Health Protection Agency heard last week. 

Lessons learnt could help to inform plans for the country-wide campaign, which is due to start shortly, the audience heard. All primary care trusts in England were sent a letter last month asking them to reduce the risk of a measles epidemic by offering the MMR vaccine to every unvaccinated child younger than 18.

In the catch-up campaign in London parents of less than half the children returned consent forms, 80% of children whose forms were returned had already been vaccinated, and only 70% of the rest received the jab.

Immunisation coordinators from the London campaign thought that there had been too little time to plan the scheme, with most saying that they had had been given than six weeks. …
Comparison of coronary hemodynamics in patients with internal mammary artery and saphenous vein coronary artery bypass grafts: A noninvasive approach using combined two-dimensional and Doppler echocardiography
Authors: Kenji Fusejima, Yoshiharu Takahara, Yoshio Sudo, Hirokazu Murayama, Yoshiaki Masuda, Yoshiaki Inagaki
Journal: Journal of the American College of Cardiology (1990)
David Bartlett Bower
Authors: Beresford Crook, Maureen Sands, J Richard Smith
Journal: BMJ (2007)

David studied medicine at Trinity College, Cambridge, and St Bartholomew's Hospital, London. During his medical training he also qualified as a barrister but soon decided that his future lay in the field of medicine, and surgery in particular. After obtaining his FRCS he developed an interest in obstetrics and gynaecology and …
Photosensitivity reaction associated with use of the combined oral contraceptive
Authors: S.M. Cooper, S. George
Journal: British Journal of Dermatology (2001)

Sir, The combined oral contraceptive pill is a rarely reported cause of photosensitivity. Most of the reported cases were not formally phototested and therefore the precise nature of the photoreaction is not characterized. Oestrogen, rather than progesterone, in the combined oral contraceptive pill has been implicated most frequently in the induction of photosensitivity. We report a case of photosensitivity induced by the oral contraceptive pill, proven by phototesting, where the abnormalities in both symptoms and phototesting resolved after stopping the pill. A 24‐year‐old woman reported a 6‐year history of diffuse, prickly erythema developing in an exposed site distribution less than 20 min after sun exposure. The rash was erythematous, nonpapular and confluent, lasted approximately 24 h, and resolved without residual bruising or scarring. She experienced a prickling sensation but no rash from light transmitted through window‐glass. There was no history of tolerance, in fact the rash worsened through the summer months and was progressively worse year on year. Her skin was completely clear in winter. She was in good health with no family history of photosensitivity. Her only medication was the combined oral contraceptive Marvelon (ethinyloestradiol 30 micrograms, desogestrel 150 micrograms) which she had taken for 7 years.
Vemurafenib for Melanoma Metastases to the Brain
Authors: Nicole M. Rochet, Lisa A. Kottschade, Svetomir N. Markovic
Journal: New England Journal of Medicine (2011)

A 16-year-old girl had melanoma with the BRAF V600E mutation that metastasized to the brain. The response to vemurafenib was dramatic, and the patient continues to improve 6 months after starting therapy.
HLA-B27-Associated Cardiac Disease
Authors: Lennart Bergfeldt
Journal: Annals of Internal Medicine (1997)

Purpose: To review the available information about cardiac disease in relation to the immunogenetic marker HLA-B27 and the inflammatory disorders associated with it (seronegative spondyloarthropathies). Data Sources: English-language clinical studies, case reports, and reviews published in 1995 or earlier were identified from a search of the MEDLINE database. These papers, textbooks, and other bibliographic sources were used to identify other relevant publications, enabling collection of references from 1936 through 1995 in a stepwise manner. Study Selection: Clinical studies, case reports, and topical reviews on the HLA-B27 histocompatibility locus, seronegative spondyloarthropathies, and cardiac disease were selected. Data Extraction: Information from systematic or hypothesis-driven studies, including those showing clinically and statistically meaningful associations between disorders, and additional relevant information from case reports and reviews is presented. Data Synthesis: Immunogenetic, histopathologic, clinical, and electrophysiologic evidence was examined to explore the concept of HLA-B27-associated cardiac disease. Results: Relative to the general population (in which the frequency is 6% to 8%), men (but not women) with pace-makers have a significantly increased frequency of HLA-B27. Furthermore, a cardiac syndrome that consists of severe conduction system abnormalities plus aortic regurgitation is associated with HLA-B27, which was present in 67% to 88% of the patients with both of these clinical findings. This proportion of HLA-B27 is similar to that found in patients with ankylosing spondylitis and Reiter disease. Cardiac and aortic tissue both show intimal proliferation of small arteries (obliterative endarteritis) and fibrosis, as seen in tissues adjacent to afflicted joints. Both cardiac conduction abnormalities and aortic regurgitation occur in patients with various HLA-B27-related extracardiac disorders, regardless of the severity of the latter; in about 50% of patients with these cardiac findings, a diagnosis of an HLA-B27-related rheumatic disease has not previously been made. Third-degree (complete) atrioventricular block related to HLA-B27 is located within the atrioventricular node in 95% rather than the expected 20% of cases. Conclusions: The heart and the joints are both of major importance as targets for the HLA-B27-associated disease process. HLA-B27-related cardiac lesions may be found in the absence of other rheumatologic manifestations. Furthermore, a genetically linked cardiac syndrome has been defined: the combination of conduction system abnormalities and aortic regurgitation.
Spectrum of Appearance of Hyperostosis Frontalis Interna on ln-111 Leukocyte Scans
Authors: ELIZABETH OATES
Journal: Clinical Nuclear Medicine (1988)

It is important to differentiate cerebral uptake of ln-111 labeled leukocytes in abscess, metastasis, infarct, hemorrhage, subdural hematoma, and meningitis from marrow accumulation in hyperostosis frontalis interna, a relatively common benign disorder. The intensity of activity can vary from faint to minimal, moderate to intense, but the pattern of symmetrical frontal uptake sparing the midline is a consistent finding. As illustrated here, findings may be confirmed by bone scans and CT scans.
Positive Differential Heterophile Antibody Test
Authors: Clifford Askinazi, F. Sessions Cole, John L. Brusch
Journal: JAMA (1976)

A patient who had documented mononucleosis in June 1971 has been persistently symptomatic since that time, with easy fatigability and weight loss. He has also had a positive differential heterophile antibody test for mononucleosis for 14 months. Although no evidence for active Epstein-Barr virus (EBV) infection was discovered, the possibility of a chronic EBV infection is discussed. (<i>JAMA</i>236:1492-1493, 1976)
Uric Acid Excretion: Quantitative Assessment from Spot, Midmorning Serum and Urine Samples
Authors: PETER A. SIMKIN
Journal: Annals of Internal Medicine (1979)

Uric acid excretion can be measured in milligrams of urinary uric acid per decilitre of glomerular filtrate by obtaining the product of urinary uric acid and serum creatinine concentrations and dividing by the urine creatinine (all concentrations in mg/dL). In 29 normal adult men, the excretion rate in spot, midmorning samples was 0.4 ± 0.1 (SD) mg of uric acid per decilitre of glomerular filtrate. Eight of 36 untreated gouty men excreted uric acid at a rate more than three standard deviations above normal. Excretion of uric acid is conveniently and physiologically assessed by this simple method.
Age and bone mass as predictors of fracture in a prospective study.
Authors: S L Hui, C W Slemenda, C C Johnston
Journal: Journal of Clinical Investigation (1988)

To study the effect of bone mass on the risk of fracture, we followed 521 Caucasian women over an average of 6.5 yr and took repeated bone mass measurements at the radius. We observed 138 nonspinal fractures in 3,388 person-yr. The person-years of follow-up and the incident fractures were cross-classified by age and bone mass. The incidence of fracture was then fitted to a log-linear model in age and bone mass. It was found that incidence of fracture increased with both increasing age and decreasing radius bone mass. When subsets of fractures were examined it was found that age was a stronger predictor of hip fractures, whereas midshaft radius bone mass was a stronger predictor of fractures at the distal forearm. We concluded that bone mass is a useful predictor of fractures but that other age-related factors associated with fractures need to be identified.
Early Adult to Midlife Cardiovascular Risk Factors and Cognitive Function
Authors: Kristine Yaffe, Eric Vittinghoff, Mark J. Pletcher, Tina D. Hoang, Lenore J. Launer, Rachel A. Whitmer, Laura H. Coker, Stephen Sidney
Journal: Circulation (2014)

Background— Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife. Methods and Results— In a prospective study of 3381 adults (age, 18–30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010–2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized z scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test z scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education ( P &lt;0.05 for all). Fewer significant associations were observed for cholesterol. Conclusions— Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation.
Psychogenic Encopresis Treated With Imipramine
Authors: V. Siomopoulos
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In their list of therapeutic indications of imipramine hydrochloride (Tofranil, Presamine), the companies' package inserts include psychogenic enuresis but not the related condition of psychogenic encopresis. I know of only two reports<sup>1,2</sup>and of no controlled studies concerning the use of imipramine in the treatment of psychogenic encopresis. Both reports suggest that imipramine can be of value in the treatment of this condition. Recently, I treated a child with chronic, continuous, nonretentive psychogenic encopresis, which subsided rapidly after imipramine treatment. <h3>Report of a Case.—</h3> A 9-year-old boy was referred for psychiatric evaluation because of chronic fecal soiling, after a thorough medical work-up on two different occasions did not show any organic illness responsible for this condition. The soiling began at the age of 3 1/2 years, a few months after the family emigrated from Greece to the United States and at about the time that his
Comment on: Singer et al. Adiponectin and All-Cause Mortality in Elderly People With Type 2 Diabetes. Diabetes Care 2012;35:1858–1863
Authors: Jian-Jun Liu, Subramania Tavintharan, Chee Fang Sum, Su Chi Lim
Journal: Diabetes Care (2013)

The article in Diabetes Care by Singer et al. (1) elegantly showed that higher adiponectin was independently associated with increased all-cause mortality in elderly subjects with type 2 diabetes mellitus (T2DM). This was in contrary to the authors’ hypothesis that higher adiponectin level would be associated with lower all-cause mortality given the anti-inflammation, antiatherogenic, and insulin-sensitizing properties of adiponectin. The authors alluded to the important association between elevated adiponectin and chronic kidney disease, which could have contributed to increased mortality. However, they conceded that …
The Curability of Phthisis
Authors: T. Harris
Journal: BMJ (1889)

cease to be "fashionable" or reliable if they did not give due weight to those facts of climate which the intelligent and educated portion of the public are quite capable of ascertaining for themselves; and that, by setting up pretentious claims which are inconsistent with observed facts, we run the risk of incurring suspicion and mistrust.We surely cannot desire in this matter to deceive ourselves or to mislead others.
Deletion of the Proline-Rich Region of the Murine Metastasis Susceptibility Gene Brd4 Promotes Epithelial-to-Mesenchymal Transition- and Stem Cell-Like Conversion
Authors: Jude Alsarraj, Renard C. Walker, Joshua D. Webster, Thomas R. Geiger, Nigel P.S. Crawford, R. Mark Simpson, Keiko Ozato, Kent W. Hunter
Journal: Cancer Research (2011)

The bromodomain-containing chromatin-modifying factor BRD4 is an inherited susceptibility gene for breast cancer progression and metastasis, but its functionality in these settings has yet to be explored. Here we show that deletion of either of the BRD4 bromodomains had modest effects on the metastatic suppression ability of BRD4. In contrast, expression of the natural short isoform of BRD4 that truncates the protein after the SEED domain restored progression and metastatic capacity. Unexpectedly, deletion of the proline-rich region induced mesenchymal-like conversion and acquisition of cancer stem cell-like properties, which are mediated by the carboxy-terminal P-TEFb binding domain. Deletion of this proline-rich region also induced a gene expression signature that predicted poor outcome in human breast cancer data sets and that overlapped G3 grade human breast tumors. Thus our findings suggest that BRD4 may be altering the predisposition of tumors to undergo conversion to a more de-differentiated or primitive state during metastatic progression.
Viscosupplementation for Osteoarthritis of the Knee
Authors: Anne W.S. Rutjes, Peter Jüni, Bruno R. da Costa, Sven Trelle, Eveline Nüesch, Stephan Reichenbach
Journal: Annals of Internal Medicine (2012)

Background: Viscosupplementation, the intra-articular injection of hyaluronic acid, is widely used for symptomatic knee osteoarthritis. Purpose: To assess the benefits and risks of viscosupplementation for adults with symptomatic knee osteoarthritis. Data Sources: MEDLINE (1966 to January 2012), EMBASE (1980 to January 2012), the Cochrane Central Register of Controlled Trials (1970 to January 2012), and other sources. Study Selection: Randomized trials in any language that compared viscosupplementation with sham or nonintervention control in adults with knee osteoarthritis. Data Extraction: Primary outcomes were pain intensity and flare-ups. Secondary outcomes included function and serious adverse events. Reviewers used duplicate abstractions, assessed study quality, pooled data by using a random-effects model, examined funnel plots, and explored heterogeneity by using meta-regression. Data Synthesis: Eighty-nine trials involving 12 667 adults met inclusion criteria. Sixty-eight had a sham control, 40 had a follow-up duration greater than 3 months, and 22 used cross-linked forms of hyaluronic acid. Overall, 71 trials (9617 patients) showed that viscosupplementation moderately reduced pain (effect size, −0.37 [95% CI, −0.46 to −0.28]). There was important between-trial heterogeneity and an asymmetrical funnel plot: Trial size, blinded outcome assessment, and publication status were associated with effect size. Five unpublished trials (1149 patients) showed an effect size of −0.03 (CI, −0.14 to 0.09). Eighteen large trials with blinded outcome assessment (5094 patients) showed a clinically irrelevant effect size of −0.11 (CI, −0.18 to −0.04). Six trials (811 patients) showed that viscosupplementation increased, although not statistically significantly, the risk for flare-ups (relative risk, 1.51 [CI, 0.84 to 2.72]). Fourteen trials (3667 patients) showed that viscosupplementation increased the risk for serious adverse events (relative risk, 1.41 [CI, 1.02 to 1.97]). Limitations: Trial quality was generally low. Safety data were often not reported. Conclusion: In patients with knee osteoarthritis, viscosupplementation is associated with a small and clinically irrelevant benefit and an increased risk for serious adverse events. Primary Funding Source: Arco Foundation.
More uninsured Americans, less poverty, and more maternal deaths
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

The number of Americans who have no health insurance rose by 2.2 million last year to 47 million, up from 44.8 million in 2005, according to the US Census Bureau's annual update. Now 15.8% of the population is uninsured. More than 80% of them are employed but almost two thirds have low paid jobs.

The Census Bureau's report comes as Congress is about to discuss expanded health insurance coverage for children in the State Children's Health Insurance Program. Both houses of Congress passed bills to cover more …