tbuckley/cabot-search huggingface dataset:
Abstract 1653: Genetic variation in the vitamin D pathway and risk for colorectal cancer in African Americans
Authors: Fabio Pibiri, Rick A. Kittles, Robert S. Sandler, Temitope O. Keku, Sonia S. Kupfer, Xavier LLor, Nathan A. Ellis
Journal: Cancer Research (2012)

Abstract Background: Colorectal cancer (CRC) is the third leading cause of cancer-related death in both sexes in the United States. There is a large disparity in both CRC incidence and survival between African Americans (AAs) and all other US racial groups. Differences in serum vitamin D levels could contribute to this disparity because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels. In addition, genetic variants in vitamin D-related genes could modify the association between vitamin D levels and CRC risk. Methods: We tested for associations between CRC and 39 single nucleotide polymorphisms (SNPs) in vitamin D-related genes (CYP27A1, GC, CYP3A4, CYP2R1, DHCR7/NADSYN1, VDR, CYP27B1 and CYP24A1). We genotyped 357 AAs cases and 443 AA controls from the North Carolina Colorectal Cancer Study. We calculated odds ratios (OR) using logistic regression, assuming an additive genetic model and controlling for age, gender, and ancestry. We also analyzed SNP associations for colon and rectal cancer cases separately. We analyzed linkage disequilibrium and haplotype association using Haploview. Results: Associations (p&amp;lt;0.05) were detected between CRC and two SNPs in the vitamin D binding protein gene GC, rs3755967 (OR, 0.69; P = .039,) and rs16847024 (OR, 1.50; P = .047,). We also detected an association with a SNP in the 24-hydroxylase gene CYP24A1, rs73913755 (OR, 0.75; P = .034,), which degrades vitamin D. A trend for association was detected in the 25-hydroxylase gene CYP2R1, rs10741657 (OR, 0.79; P = .051), which converts cholecalciferol into calcidiol. When we analyzed colon and rectal cancers separately, only one SNP was associated with colon cancer whereas 9 SNPs were associated with rectal cancer. In particular, rs73913755 (OR, 0.39; P = 3 x 10-7) was statistically significant even after adjustment for multiple testing. Conclusion: We tested vitamin D-related SNPs and found suggestive evidence that they influence the risk of developing CRC in AAs, with differences in risk between the colon and rectum. Comparison of these data with data from US whites could shed light on disparities in these different US populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1653. doi:1538-7445.AM2012-1653
Dr. Love's reply follows
Authors: J. Grafton Love
Journal: JAMA (1962)

<h3>To the Editor:—</h3> There are several articles which might be considered pertinent that Norstrom, Kernohan, and Love did not refer to. One, of course, cannot refer to all articles which might be related to a given subject about which he is writing. We, too, as many other neurosurgeons of considerable experience, have operated for tumors as high as the first cervical segment in patients whose chief complaint was sciatic pain. I fully agree with Dr. Scott, and it has been the practice of the neurologists and the neurosurgeons of the Mayo Clinic for many years, that all patients should have careful physical, neurological, and other pertinent examinations before carrying out a myelogram and operating for an intraspinal lesion. We have observed and operated on many patients with the so-called disk syndrome due to lesions other than those found within the spinal canal. Suffice it to mention twisted ovarian cysts, glomus
Disruption of a regulatory loop between DUSP1 and p53 contributes to hepatocellular carcinoma development and progression
Authors: Pei-Pei Hao, Hua Li, Mi-Jin Lee, Yun-Peng Wang, Jong-Hyun Kim, Goung-Ran Yu, Sang-Yeop Lee, Sun-Hee Leem, Kyu-Yun Jang, Dae-Ghon Kim
Journal: Journal of Hepatology (2015)
Is evidence based medicine neglected by royal college examinations? A descriptive study of their syllabuses
Authors: W.-C. Leung
Journal: BMJ (2000)

style attributes or a combination of both.Numerous studies in the disciplines of epidemiology, work physiology, psychology, and biochemistry have all pointed towards a beneficial effect of physical activity on health, but the optimal intensity, frequency, and duration of physical activity has yet to be established.Although our study was observational, the men were randomly selected from a general population.The estimated effect of jogging did not depend on the inclusion of intermediate variables, supporting the association of jogging with lower mortality.Whether light, moderate, or vigorous exercise should be recommended to the public has changed through the years.Although light exercise has some value, moderate and vigorous exercise is now considered more favourable for health. 3 4Our study supports this by showing that even a vigorous activity such as jogging is associated with a beneficial effect on mortality.
A radioimmune microfilter plate assay for the detection of anti‐granulocyte antibodies
Authors: Ann Marie Braman, Kenneth A. Schwartz
Journal: American Journal of Hematology (1992)

Abstract A radioimmune assay (RIA) for IgG anti‐granulocyte antibodies (AGA) was developed which utilized 96 well microfilter plates, required less than 50 μI plasma, and yielded reproducible autologous determinations on patients with absolute granulocyte counts as low as 300 cells/μI. Granulocytes were isolated by a single density ficoll‐hypaque gradient procedure with red blood cell (RBC) removal by lysis and washing. Anti‐granulocyte IgG coating the cells was detected by the addition of 125 I labeled anti‐human IgG. Six patients with autoimmune granulocytopenia and three multiply transfused patients with febrile transfusion reactions believed to be secondary to allogeneic granulocyte antibodies had increased granulocyte IgG. Plasma containing anti‐a and/or anti‐B titers greater than or equal to 512 gave positive results when tested against ABO incompatible granulocytes. This technique was capable of detecting antibodies which were reactive in granulocyte agglutination and immunofluorescence tests as demonstrated with known anti‐NA‐1, anti‐NB‐1, and anti‐Mart sera. Comparison with granulocyte agglutination test (GAT) using clinical criteria for immune granulocytopenia demonstrated concordance with 19 negative samples and 8 positive samples, 1 false negative and 3 false positives were observed using the agglutination method. The multimeric and monomeric IgG fractions of G200 purified Cohn Fraction II were nonreactive by both RIA and GAT methods. However, granulocyte activation by phorbol myristate acetate (PMA) produced false positives in 5 out of 5 cases by GAT but 0 out of 4 by RIA. This RIA assay is not effected by nonimmune granulocyte activation and is more reproducible when compared to existing techniques.
Abstract 4187: A novel genome-wide assay identifies chromatin domains involved in stem cell behavior
Authors: Steven T. Okino, Michelle Kong, Yan Wang
Journal: Cancer Research (2012)

Abstract The activity of DNA regulatory elements are often controlled by chromatin structure. Active regulatory elements are located within “open” or “accessible” chromatin. If a regulatory element is in a “closed” or “inaccessible” chromatin environment it is functionally silenced. We find that when permeabilized cells are treated with nuclease in situ, small DNA fragments, corresponding to accessible chromatin, can be readily isolated. These small DNA fragments, when analyzed by next-generation sequencing, provide a global map of active genomic regulatory domains. We used this technology to identify chromatin domains involved in stem cell behavior using NTera2 cells as a model system. By comparing differentiated and undifferentiated NTera2 cells we identified more than 500 genomic regions that are accessible only in undifferentiated cells. We then used these results, together with ENCODE data analyzing human embryonic stem cells and human cancer cells, to identify genomic regulatory regions that are active only in stem cells. Importantly, many of these regions are proximal to genes that are associated with cell “stemness” (NANOG and LIN28 are examples). In addition, several uncharacterized genes that have RNA expression characteristics similar to NANOG and LIN28 were identified. Interestingly, several stem-cell specific active regulatory domains were found adjacent to previously uncharacterized, stem-cell specific non-coding RNA transcript regions. These findings demonstrate that this approach can serve as a new discovery tool to identify chromatin regions that control stem cell behavior. In addition, chromatin regions associated with other biological or pathological states could also be identified using this approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4187. doi:1538-7445.AM2012-4187
Long-term use of depot tetracosactrin.
Authors: W J Irvine, D R Cullen, S A Khan, I W Percy-Robb, J Ratcliffe
Journal: BMJ (1970)

travenous pyelography and micturition cys- tography.It is now our routine to wait until the patient has had a course of drug therapy and treatment with the alarm bell before arranging radiological investigations."They do not make other reference to "drug ther- Correspondence *a,. 497sensitivity of the assay (30 picograms/ml.).These results contrast with the failure of the plasma corticosteroid levels to respond to insulin or lysine vasopressin in a patient several months after the withdrawal of long-term prednisolone therapy given two to three times per day, in keeping with the findings of Livanou et al.3The details of these cases will be published in due course.Meanwhile it is clear that the theoretical disadvantage of depot tetracosactrin referred to by Drs.Treadwell and Dennis is not a practical reality, at least when it is used in a dosage of 0.5 mg.intramuscularly twice weekly.-Weare, etc.,
Angiopoietin-Like Protein 2 and Risk of Type 2 Diabetes in a General Japanese Population
Authors: Yasufumi Doi, Toshiharu Ninomiya, Yoichiro Hirakawa, Otowa Takahashi, Naoko Mukai, Jun Hata, Masanori Iwase, Takanari Kitazono, Yuichi Oike, Yutaka Kiyohara
Journal: Diabetes Care (2012)

To examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM).A total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline: <2.15, 2.16-2.71, 2.72-3.40, and ≥3.41 ng/mL. During follow-up, 221 participants developed T2DM.In multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95% CI, 1.14-2.85; P = 0.01).Elevated serum ANGPTL2 levels were positively associated with the development of T2DM in a general population, independent of other risk factors including hs-CRP levels.
“Red flag” techniques in Barrett’s esophagus: minor additional benefit or a waste of time?
Authors: P. Eisendrath, J. Devière
Journal: Endoscopy (2006)

Barrett’s esophagus is associated with an increased risk of adenocarcinoma developing in the distal esophagus [1]; the incidence of this type of tumor is dramatically increasing in Western countries [2]. The multi-step process of malignant transformation of Barrett’s metaplasia means that surveillance should be recommended in patients who have been diagnosed with the condition. However, the value of surveillance programs of this type is still a matter of controversy, as they have little impact on life expectancy and a poor degree of cost-effectiveness [3]. A major reason for this is that since Barrett’s esophagus is often asymptomatic, a large proportion of the patients remain undiagnosed [4]. A surveillance policy is therefore unlikely to have a major impact on deaths related to esophageal adenocarcinoma, except with mass screening programs; however, the costs of the latter may easily be prohibitive. Another issue is the relatively low incidence of high-grade dysplasia and early cancer (HGD/EC), currently estimated at 0.5 % per year, which implies that a large majority of Barrett’s patients will never develop esophageal cancer. Finally, early neoplastic lesions are difficult to identify, and the current “gold standard”, the Seattle protocol, has a poor degree of accuracy, particularly in long-segment Barrett’s esophagus without visible lesions [5]. Moreover, besides being time-consuming and uncomfortable for the patient, this surveillance technique (based on taking random four-quadrant biopsies every 2 cm in the esophagus) is associated with sampling errors and is far from being widely applied in everyday practice.
Rab27a: a new face in β cell metabolism-secretion coupling
Authors: Toru Aizawa, Mitsuhisa Komatsu
Journal: Journal of Clinical Investigation (2005)

In pancreatic β cells, not only insulin exocytosis per se, but translocation of β granules toward the plasma membrane — an event upstream of exocytosis — are under the control of glucose. However, the molecular basis of this translocation has been poorly understood. Rab27a-mediated translocation of glucose-induced β granules is reported in this issue of the JCI. Rab27a or its effector molecule may constitute a novel pharmacological target because potentiation of the Rab27a pathway is expected to restore β cell glucose competency in patients with diabetes mellitus.
Market and Regulatory Influences on the Availability of Coronary Angioplasty and Bypass Surgery in U.S. Hospitals
Authors: James C. Robinson, Deborah W. Garnick, Stephen J. McPhee
Journal: New England Journal of Medicine (1987)

Using 1983 data on 3720 nonfederal short-term hospitals, we analyzed the influence of local market competition and state regulatory programs on the availability of percutaneous transluminal coronary angioplasty and coronary-artery bypass surgery. The degree of competition for patients with heart disease was measured in terms of the number of hospitals in the local market area that maintained a cardiac catheterization laboratory or facility for open-heart surgery. When the patient case mix and the hospital's teaching role were controlled for, institutions with more than 20 competitors in the local area were 166 percent more likely to offer coronary angioplasty (P less than 0.0001) and 147 percent more likely to offer bypass surgery (P less than 0.0001) than hospitals with no competitors in the local market. Four fifths of the hospitals performing bypass surgery whose annual volume was less than 200 had one or more neighboring hospitals with a facility for open-heart surgery. State rate-regulation programs in New York, New Jersey, Connecticut, Massachusetts, and Maryland significantly reduced the availability of both procedures, with the greatest regulatory effects being observed in the most competitive hospital markets. We conclude that in the period under consideration, competition encouraged and regulation discouraged the proliferation of these cardiac services.
TCT-123 Preliminary safety and efficacy results from the REALISE trial: REnAL denervatIon by ultraSound transcatheter Emission
Authors: Gilles Montalescot, Philippe Cluzel, Atul Pathak, Hervé Rousseau, Jérôme Roncalli, Meyer Elbaz, Ghalia Anzaha, Vincent Cabane, Mano Iyer, Xavier Girerd
Journal: Journal of the American College of Cardiology (2013)
Smoking Is Associated With Progression of Diabetic Nephropathy
Authors: Peter T Sawicki, Ulrike Didjurgeit, Ingrid Mühlhauser, Ralf Bender, Lutz Heinemann, Michael Berger
Journal: Diabetes Care (1994)

OBJECTIVE To investigate the association between cigarette smoking and the progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS A prospective, follow-up study over one year was conducted in a sequential sample of 34 smokers, 35 nonsmokers, and 24 ex-smokers with type I diabetes, hypertension, and diabetic nephropathy. Progression of renal disease was defined according to the stage of nephropathy as an increase in proteinuria or serum creatinine or a decrease in the glomerular filtration rate. RESULTS Progression of nephropathy was less common in nonsmokers (11%) than in smokers (53%) and patients who had quit smoking (33%), P &amp;gt; 0.001. In a stepwise logistic regression analysis, cigarette pack years, 24-h sodium excretion, and GHb were independent predictive factors for the progression of diabetic nephropathy. Because blood pressure (BP) was well controlled in these patients and most values were within a normotensive range, neither standing, sitting, nor supine BP values were associated with progression of nephropathy. CONCLUSIONS Cigarette smoking represents an important factor associated with progression of nephropathy in treated hypertensive type I diabetic patients.
ON THE ANTIGENS OF RED BLOOD CORPUSCLES
Authors: K. Landsteiner, James van der Scheer
Journal: The Journal of Experimental Medicine (1925)

Erythrocytes contain more than one substance responsible for the production of lysins and agglutinins. By injections of alcoholic extracts of horse erythrocytes mixed with a foreign serum, hemolysins and agglutinins can be more readily obtained than by the same quantities of extract alone. The immune sera reacted on horse and donkey blood but not on the blood of other species. The antibodies obtained differ from those prepared in the usual way with unchanged red blood corpuscles. The differences involve the ratio lysin: agglutinin, the specificity, the inhibition of hemolysis by alcoholic extracts, and the flocculation of these extracts. Ordinary anti-horse sera give flocculation reactions with emulsions of alcoholic extracts of corpuscles but to a lesser degree and not so regularly as those produced by means of extracts. The specific substances present in alcoholic blood extracts are probably not proteins. According to this view, species specificity in animals depends not alone on proteins but also on another group of substances.
In vitro immunoglobulin synthesis by human intestinal lamina propria lymphocytes.
Authors: P A Drew, J T La Brooy, D J Shearman
Journal: Gut (1984)

The concentration of IgG and IgA was measured in the supernatants of peripheral blood mononuclear cells and of cells harvested from the intestinal lamina propria, which were cultured in vitro in the presence or absence of mitogens. The lamina propria mononuclear cells were harvested by collagenase digestion of macroscopically normal mucosa from 10 fresh surgical resections for carcinoma. Secretion of IgA in cultures of unstimulated lamina propria mononuclear cells greatly exceeded that of IgG. The addition of pokeweed mitogen increased Ig secretion by cultures of peripheral blood mononuclear cells but decreased Ig secretion by lamina propria mononuclear cells. The addition of concanavalin A suppressed Ig synthesis by pokeweed mitogen stimulated cells more in cultures of peripheral blood mononuclear cells than in lamina propria mononuclear cells. Cycloheximide inhibited Ig secretion by more than 90% in cultures of peripheral blood mononuclear cells, but there was less inhibition in cultures of lamina propria mononuclear cells. In the four unstimulated cultures of lamina propria mononuclear cells examined, over 75% of the Ig was secreted in the first three to four days of culture. The results indicate that lamina propria mononuclear cells are refractory to the inductive and suppressive signals of mitogens, and represent an activated cell population which is committed to Ig secretion before being cultured.
ALLERGIC CONTACT DERMATITIS CAUSED BY MELMAC ORTHOPEDIC COMPOSITION
Authors: Adolph H. Conrad
Journal: JAMA (1953)

We recently encountered two patients who had allergic skin reactions to Melmac Orthopedic Composition. This preparation consists of two powders, a melamine resin (Melmac 405) and ammonium chloride, which acts as a catalyst. For preparation of the plaster bandages, 300 gm. of Melmac 405 is dissolved in 1,000 cc. of water, and just before the plaster bandages are immersed in the solution 30 gm. of ammonium chloride is added. When the plaster is treated with this solution it becomes waterproof and urineproof and appears to be more than twice as strong as plaster of paris; therefore, only about onehalf the usual amount of plaster bandage is required, and the cast produced is lighter and smaller than the ordinary plaster bandage.  REPORT OF CASES  Case1.—A 13-year-old white boy was first seen by one of us (L. T. F.) on Sept. 22, 1952, because of an injury to the right wrist
Comparison of antianginal actions of verapamil and propranolol.
Authors: M J Bowles, V B Subramanian, A B Davies, E B Raftery
Journal: BMJ (1981)

Comparison of antianginal actions of verapamil and propranololVerapamil is a slow calcium channel blocker that has been in clinical use for almost 20 years as an antiarrhythmic agent.It also has an antianginal action,' but inconsistent results have been obtained in clinical trials owing to insufficient dosage.2We found that the drug produced a significant decrease in the number of anginal attacks and the consumption of glyceryl trinitrate with improvement in exercise tolerance and ST changes when used in a dose of 360 mg daily.3We have now compared the potency and mode of action of verapamil with those of propranolol, a standard beta-adrenergic- receptor-blocking drug, using fixed high doses of each.
Relationship between epicardial ST-segment elevation and myocardial ischemic damage after experimental coronary artery occlusion in dogs.
Authors: M K Heng, B N Singh, R M Norris, M B John, R Elliot
Journal: Journal of Clinical Investigation (1976)

The relationship between early and late epicardial electrocardiographic changes as well as those in regional myocardial blood flow (MBF) and the severity of myocardial damage was determined in 12 anesthetized dogs with left anterior descending coronary artery ligation. Radioactive microspheres (15 mum) were used to measure regional MBF at 15 min (early) and 24 h (late) after coronary occlusion. Severity of myocardial damage was assessed by the extent of myocardial creatine phosphokinase depletion 24 h after coronary ligation. There was a close linear correlation between myocardial creatine phosphokinase activity and regional MBF both early (r=0.93, 2P less than 0.001) and late (r=0.88, 2P less than 0.001). An inverse but less precise relationship existed between acute epicardial ST-segment elevation and early (r=-0.41, 2P less than 0.001), or late (r=0.35, 2P less than 0.05) regional MBF. Similarly, a weak correlation was found between myocardial creatine phosphokinase (IU/mg protein) at 24 h and early epicardial ST (millivolt) elevation (r=-0.36, 2P less than 0.02). In the center zones of the infarct with MBF 1/10 of normal, about 35% of the areas with normal QRS width had no epicardial ST-segment elevation 15 min after coronary occlusion. About 44% of the areas which developed pathological Q-waves in the electrocardiogram at 24 h had no ST elevation 15 min after coronary ligation. Late evolution of abnormal Q-waves occurred almost invariably in areas in which the early MBF was reduced to less than 50% of normal and in areas which subsequently had myocardial creatine phosphokinase levels reduced to less than 60% of normal. After coronary occlusion, the severity of the ultimate myocardial damage, which was directly proportional to the degree of reduction in MBF, was therefore not reliably predicted by the early epicardial ST-segment elevation. The data obtained in these studies suggest the need for caution in the use of acute ST-segment elevation as a predictive index of the extent or severity of myocardial ischemic damage.