tbuckley/cabot-search huggingface dataset:
Abstract 132: Divergent estrogen receptor positive and negative breast cancer trends and etiologic heterogeneity in Denmark .
Authors: William F. Anderson, Philip Rosenberg, Lucia Petito, Hormuzd A. Katki, Bent Ejlertsen, Marianne Ewertz, Birgitte B. Rasmussen, Maj-Britt Jensen, Niels Kroman
Journal: Cancer Research (2013)

Abstract Background: Long-term breast cancer trends in incidence in the United States (US) show rising ER positive rates and falling ER negative rates. We hypothesized that these divergent trends reflect etiologic heterogeneity and that comparable trends should be observed in other countries with similar risk factor profiles. Methods: We analyzed invasive female breast cancers in Denmark from 1993-2010. We summarized the overall trend in age-standardized rates with the estimated annual percentage change (EAPC) statistic, and used age-period-cohort models to estimate age-specific EAPCs, cohort rate ratios (CRRs), and projections for future time periods (2011-2018). Results: In Denmark, the overall rate of ER positive cancers rose between 1993 and 2010 by 3·0%/year (95% CI: 2·8 to 3·3%/yr) while the overall rate of ER negative cancers fell by 2·1%/year (95% CI: -2·5 to -1·6%/yr). The ER positive rate increased fastest among postmenopausal women and the ER negative rate decreased fastest among premenopausal women, reflecting that cohorts born after 1944 were at relatively higher risk of ER positive tumors and lower risk of ER negative tumors. If current trends continue, ER positive cancers will increase at least 13% and ER negative cancers will fall as much as 15% by 2018. Conclusion: Divergent ER-specific trends are consistent with distinct etiologic pathways. If trends in known risk factors are responsible, the Danish and US experience may foreshadow a common pattern worldwide. Citation Format: William F. Anderson, Philip Rosenberg, Lucia Petito, Hormuzd A. Katki, Bent Ejlertsen, Marianne Ewertz, Birgitte B. Rasmussen, Maj-Britt Jensen, Niels Kroman. Divergent estrogen receptor positive and negative breast cancer trends and etiologic heterogeneity in Denmark . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 132. doi:10.1158/1538-7445.AM2013-132
The Effect of Cerebral Ischemia on Learning and Retention in Dogs
Authors: Jack M. Zimmerman, Harold C. Nielson, Thomas C. King, Jerry C. Colliver
Journal: JAMA (1966)

With available techniques of cardiac resuscitation it is often possible to restore spontaneous cardiac action in patients with cardiac arrest. However, many patients in whom cardiac activity is restored have neurological sequelae as a consequence of the arrest. It has been demonstrated that hypothermia,<sup>1,2</sup>and possibly the osmotic diuretics,<sup>3</sup>used after a period of total cerebral ischemia, modify the severity of neurological damage. Investigation of agents which might be useful for this purpose has been hampered by the fact that it is difficult to detect less than massive brain damage in the dog. Brockman and Jude<sup>4</sup>have shown that dogs subjected to ten minutes of complete cerebral ischemia by cross clamping the ascending aorta reveal no neurological deficit on gross examination whereas animals subjected to longer periods of occlusion died without awakening from anesthesia. The present report describes a means by which subtle changes in neurological status
Asymptomatic Bacteriuria and Hemoglobin A1
Authors: J K Schmitt, C J Fawcett, G Gullickson
Journal: Diabetes Care (1986)

We measured hemoglobin A1 (HbA1 and performed clean-catch urine cultures in 752 patients (411 men and 341 women) with non-insulin-dependent diabetes mellitus (NIDDM) attending an outpatient diabetes clinic. Prevalence of bacteriuria was significantly greater in diabetic women than in controls (9.1 vs. 5.0%, P &amp;lt; .001) but not in diabetic men. Risk of bacteriuria was not related to level of HbA1 at the time of urine culture. However, mean duration of diabetes mellitus was significantly greater in diabetic women with bacteriuria than in those without infection (9.9 ± 1.5 vs. 5.4 ± 0.4 yr, P &amp;lt; .025), and the prevalence of bacteriuria was significantly greater in patients with complications of long-standing diabetes mellitus than in those without complications (P &amp;lt; .005).
Radiology of the crystal-associated arthritides.
Authors: I Watt
Journal: Annals of the Rheumatic Diseases (1983)

Signaling through the IL-4R α-chain (IL-4Rα) is crucial for the development of Th2 cells, central effectors in atopic disease. Alleles of the IL-4Rα have been identified that have been variably associated with increased incidence of allergic disease, but there is little direct evidence that any variant is sufficient to alter a target that determines allergic pathophysiology or susceptibility. Variants of IL-4Rα encoding isoleucine instead of valine at position 50 (I50 vs V50, respectively) can signal increased Stat6-dependent transcriptional activity, whether in an I50, Q551 or I50, R551 haplotype. Strikingly, signaling through these receptors did not increase the efficiency of Th2 development or the IL-4 mediated repression of Th1 development or a target gene, IL-18Rα. Further, IL-4-induced proliferation was similar for Th2 cells independent of the variant expressed. Together these findings indicate that IL-4Rα variants that exhibit gain-of-function with respect to Stat6 do not act directly through alterations in Th2/Th1 induction after Ag exposure. The data further suggest that for such variants, any mechanistic involvement is based on a role in cellular targets of Th2 cytokines.
THE INTERRELATION OF THE SURVIVING HEART AND PANCREAS OF THE DOG IN SUGAR METABOLISM
Authors: Admont H. Clark
Journal: The Journal of Experimental Medicine (1916)

The experiments indicate that the pancreas, when perfused aseptically with Locke's solution containing physiological concentrations of dextrose, does not alter the reducing properties of the perfused solution. The pancreas, however, seems to supply something to the Locke's solution circulating through its arteries which in some way brings about a utilization of sugar by the living heart to an extent that does not occur with the heart alone. This pancreatic substance possesses some of the characteristics of an enzyme. It is inactivated by boiling; it is unstable, rapidly becoming inactive on standing; it acts in small amounts; it causes a great acceleration in the rate of a reaction which otherwise proceeds slowly, and the rate of reaction diminishes as the reaction proceeds. Thus this substance has more of the characteristics of an enzyme than of a stable internal secretion like that of the adrenal glands. The disappearance of sugar was dependent upon the presence of living heart tissue, and it ceased as soon as the perfusate was removed from the heart-pancreas circulation and did not occur at all when a pancreatic perfusate was passed through a non-beating heart. This result indicates that the reaction is not similar to that obtained when muscle and pancreas extracts act on more concentrated solutions of dextrose. The living heart in the presence of the pancreatic factor and dextrose, is responsible for two effects. First, a condensation of the sugar to a non-reducing form that yields again a simple sugar on hydrolysis or by simply standing, with a preservative, at 37 degrees C. for 24 hours. Second, a disappearance of sugar which is probably due to its destruction by hydrolysis or oxidation. After deducting the reducing sugar in the heart-pancreas perfusions which could be recovered by hydrolysis, the amount of sugar which had actually disappeared exceeded that which was used by the heart when perfused with dextrose alone. As to the fate of this portion of the sugar, no definite evidence was obtained. The question arises as to whether this substance obtained from the perfused pancreas is identical with the hypothetical internal secretion of the pancreas so essential in sugar metabolism. That there is an internal secretion of the pancreas which can be obtained by this method, and that in some way it accelerates the utilization of sugar by the living heart, seems evident. Though the conclusions are based on the heart and pancreas isolated from the numerous interrelating factors occurring in the body, the evidence suggests, at least, that the substance or substances obtained by perfusing the pancreas may be concerned in the normal activity of the pancreas upon sugar metabolism.
Predictive Factors of Malignancy in Thyroid Nodules with a Cytological Diagnosis of Follicular Neoplasm
Authors: Seong Hyeon Lee, Jeong Su Baek, Joo Young Lee, Jung Ah Lim, Soo Youn Cho, Tae Hyun Lee, Yun Hyi Ku, Hong Il Kim, Min Joo Kim
Journal: Endocrine Pathology (2013)
Evolution of anti-DNA autoantibodies by somatic hypermutation: evidence for postmutational B cell tolerance
Authors: Kristin Schroeder, Ute Wellmann, Thomas H Winkler, Martin Herrmann
Journal: Annals of the Rheumatic Diseases (2012)

The production of autoantibodies against nuclear antigens is a hallmark of systemic lupus erythematosus (SLE). The 33.C9 anti-dsDNA antibody is of immunoglobulin G (IgG) isotype and derived from a SLE patient. Three somatic mutations of the 33.C9gl antibody are necessary and sufficient for the binding to DNA, nucleosomes and histones as the reversion of the somatic mutations to germline sequence abolished binding to all of these antigens. The same somatic mutations that generate dsDNA binding also led to binding of apoptotic cells. The authors propose that the nuclear material from apoptotic cells accumulates in the germinal centre due to a phagocytosis defect of macrophages and selects anti-DNA B cells. These data led us to the hypothesis that autoreactive B cells are generated from non-autoreactive B cells during germinal centre reactions. Then the newly generated autoreactive B cells are positively selected on nucleosomes on follicular dentritic cells. The authors want to test this hypothesis in mice, which express the 33.C9 germline variant antibody as B cell receptor (BCR) (33.C9 gl mice). To obtain mice, which express the 33.C9 germline variant antibody as BCR the authors targeted the BCR heavy- and light chain loci to obtain 33.C9gl heavy chain and 33.C9gl light chain double knockin mice. As expected, B cells expressing the revertant BCR are developing normally and show no evidence for tolerisation. Upon immunisation with a surrogate phage antigen the transgenic B cells form germinal centres and undergo somatic hyper mutation. The three critical somatic hyper mutations, which are necessary and sufficient for the acquisition of high affinity anti-dsDNA binding, were not observed in a large collection of sequences analysed. In accordance with this, anti-DNA autoantibodies do not develop, even after repetitive immunisations and when Follicular dendritic cells were MFG-E8 deficient. These results strongly suggest a self-tolerance checkpoint by deletion of autoreactive clones during or after the germinal centre reaction.
PRESENCE OF NON-CALCIFIED PLAQUES ON CORONARY CT IN SUBJECTS WITH DIABETES MELLITUS CAUSED A HIGHER RISK PROGNOSIS FOR MAJOR CARDIAC EVENTS OVER A MEDIAN OF 74 MONTHS
Authors: Hiroyuki Takaoka, Nobusada Funabashi, Masae Uehara, Koya Ozawa, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2013)
Influenza: Response of T-Cell Lymphopenia to Thymosin
Authors: Morton A. Scheinberg, Neil R. Blacklow, Allan L. Goldstein, Thomas A. Parrino, Frederick B. Rose, Edgar S. Cathcart
Journal: New England Journal of Medicine (1976)

Eighteen volunteers in tow study groups were inoculated with influenza A (H3N2) and their peripheral blood T, B and null cells enumerated at subsequent intervals. Infection with wild-type virus or with a live, attenuated virus vaccine markedly reduced the proportion and absolute number of T-cell rosettes 24 hours after inoculation. T-Cell depression preceded the onset of clinical illness in symptomatic subjects, continued during illness, and returned to normal with recovery. T-cell lymphopenia was most pronounced in volunteers infected with wild-type virus and was accompanied by an increase in null cells. Lymphocytes from six wild-virus recipients with T-cell leukopenia were incubated in vitro with a calfthymus extract (thymosin), significantly increasing the percentage of T rosettes in all six subjects (P less than 0.0001). These data indicate that influenza is accompanied by pronounced quantitative and functional changes in T cells.
Mimotopes of the hepatitis C virus hypervariable region 1, but not the natural sequences, induce cross-reactive antibody response by genetic immunization
Authors: Silvia Zucchelli, RosaMaria Roccasecca, Annalisa Meola, Bruno Bruni Ercole, Rosalba Tafi, Jean Dubuisson, Giovanni Galfré, Riccardo Cortese, Alfredo Nicosia
Journal: Hepatology (2001)

The hypervariable region 1 (HVR1) of the putative envelope protein E2 of hepatitis C virus (HCV) contains a principal neutralization epitope, and anti-HVR1 antibodies have been shown to possess protective activity in ex vivo neutralization experiments. However, the high rate of variability of this antigenic fragment may play a major role in the mechanism of escape from host immune response and might represent a major obstacle to developing an HCV vaccine. Thus, even if direct experimental evidence of the neutralizing potential of anti-HVR1 antibodies by active immunization is still missing, the generation of a vaccine candidate with a cross-reactive potential would be highly desirable. To overcome the problem of HVR1 variability, we have engineered cross-reactive HVR1 peptide mimics (mimotopes) at the N terminus of the E2 ectodomain in plasmid vectors suitable for genetic immunization. High levels of secreted and biologically active mimotope/E2 chimeras were obtained by transient transfection of these plasmids in cultured cells. All plasmids elicited anti-HVR1 antibodies in mice and rabbits with some of them leading to a cross-reacting response against many HVR1 variants from natural isolates. Epitope mapping revealed a pattern of reactivity similar to that induced by HCV infection. In contrast, plasmids encoding naturally occurring HVR1 sequences displayed either on full-length E2 in the context of the whole HCV structural region, or on a soluble, secreted E2 ectodomain, did not induce a cross-reacting anti-HVR1 response.
Abrupt condylar destruction of the mandibula in juvenile idiopathic arthritis
Authors: M Twilt
Journal: Annals of the Rheumatic Diseases (2003)

Unilateral and bilateral involvement of the temporomandibular joint (TMJ) and subsequent growth disturbance of the mandibula is a common feature in juvenile idiopathic arthritis (JIA).1 The prevalence varies between 17% and 87% depending on the subtype of JIA.2–6 No conclusive measures for local disease activity are found. Arthritis of the TMJ is usually not associated with pain, and clinical signals, such as deviation of the jaw, impaired opening of the mouth, absence of translation, crepitation, or clicking during palpation, are usually scarce, which explains the delay in diagnosis.7

The TMJ consists of fibrocartilage, hyaline cartilage, and synovial membrane like other joints. The growth centre of the mandible is located on the articular surface of the condylar caput instead of more distal to the joint,8 therefore the TMJ …
Is saliva serology useful for the diagnosis of Helicobacter pylori?
Authors: J M Christie, C A McNulty, N A Shepherd, R M Valori
Journal: Gut (1996)

BACKGROUND: The Cortecs Diagnostics Helisal Assay test is a quantitative immunoassay for salivary IgG antibodies against Helicobacter pylori. Saliva can be obtained simply with the kit in the general practitioners surgery. AIMS: To compare the new saliva serological test for H pylori with 9gold standard9 evidence of H pylori infection (antral biopsy specimens for histology, culture, and urease test) and a new serum serological test. PATIENTS: Eighty six unselected dyspeptic patients undergoing endoscopy. METHODS: Each patient provided saliva and serum before endoscopy for H pylori serology, which was compared against 9gold standard9 evidence of infection. RESULTS: Thirty two patients were H pylori positive by the 9gold standard9 tests. At a cut off value of 0.15 EU/ml the saliva test had a sensitivity of 88% and a specificity of 71%, with a negative predictive value of 90%. If patients who were taking omeprazole or had recent antibiotics are excluded, the sensitivity is unchanged but the specificity increases to 79%. The serum test had a similar sensitivity of 85% but better specificity of 78%. CONCLUSION: Serum testing remains the best serological test for H pylori in the hospital setting. Saliva testing may have a role in epidemiological studies and in screening dyspeptic patients in general practice, especially in children in whom venesection is more difficult.
Clinical Studies with Carbomycin
Authors: Phil R. Manning, Philip N. Jones, Roy S. Bigham
Journal: New England Journal of Medicine (1953)

CARBOMYCIN, a recent addition to the antibiotic family, is produced by Streptomyces halstedii.1 Studies in vitro and in vivo have shown that the substance is active against gram-positive bacteria but has little or no effect on most pathogenic gram-negative micro-organisms.1 2 3 Early reports indicate that this antibiotic is effective against some gram-positive bacteria that have become resistant to other antibiotics.2 3 4 Carbomycin is primarily a bacteriostatic agent.2 This report describes our experience in the treatment of 30 patients with bacterial infections caused by beta-hemolytic streptococci, coagulase-positive Staphylococcus aureus, pneumococci and Neisseria gonorrhoeae.Methods and MaterialsAll patients were young . . .
Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis
Authors: Irina Pleines, Ina Hagedorn, Shuchi Gupta, Frauke May, Lidija Chakarova, Jolanda van Hengel, Stefan Offermanns, Georg Krohne, Christoph Kleinschnitz, Cord Brakebusch, Bernhard Nieswandt
Journal: Blood (2011)
Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
Authors: Michał Kamiński, Cesare Hassan, Raf Bisschops, Jürgen Pohl, Maria Pellisé, Evelien Dekker, Ana Ignjatovic-Wilson, Arthur Hoffman, Gaius Longcroft-Wheaton, Denis Heresbach, Jean-Marc Dumonceau, James East
Journal: Endoscopy (2014)

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the role of advanced endoscopic imaging for the detection and differentiation of colorectal neoplasia. <b>Main recommendations</b> <b>1</b> ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). <b>2</b> ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). <b>2b</b> ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). <b>3</b> ESGE recommends the routine use of 0.1 % methylene blue or 0.1 % – 0.5 % indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). <b>4</b> ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). <b>5</b> ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). <b>Conclusion</b> Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs.
A phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer.
Authors: EL Mayer, SJ Isakoff, K Hannagan, J Savoie, J Beckman, G Klement, R Gelman, EP Winer, HJ Burstein
Journal: Cancer Research (2009)

Abstract Abstract #906 Background: Vandetanib (V) is an oral tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptors 2 and 3 and epidermal growth factor receptor. Metronomic chemotherapy, continuous low-dose oral cyclophosphamide and methotrexate (CM), has activity in combination with anti-angiogenic treatments. We sought to define the safety and tolerability of all-oral combination therapy with V and CM in advanced breast cancer.&amp;#x2028; Patients and Methods: Eligible patients (pts) had stage IV breast cancer; measurable disease was not required and stable brain metastases were acceptable. Up to 4 prior chemotherapy regimens were allowable, as was prior bevacizumab. Pts with systemic anticoagulation or QTc abnormalities were excluded. Three sequential dose escalation cohorts of approximately 8 pts were enrolled. All pts received CM (C 50 mg PO qd, M 2.5 mg PO d1-2 q week), and V in 3 dose-escalation cohorts: 100 mg qd (Cohort 1), 200 mg qd (Cohort 2), and 300 mg qd (Cohort 3). Pts received V + CM until progression or unacceptable toxicity; dose adjustments were made for treatment related toxicity. The primary endpoint was safety and toxicity of the regimen; secondary endpoints included response rate, non-invasive vascular analysis of hypertension, and platelet proteomics.&amp;#x2028; Results: 24 pts (median age 49 years) entered the study. 83% had visceral disease, 92% had received prior chemotherapy for metastatic disease (median number of regimens, 2), and 38% had received prior bevacizumab. Median cycles of therapy completed was 2 (range 1-8); median number of weeks on study was 8 (range 2-33). Toxicities in Cohorts 1 and 2 were generally manageable, and most commonly consisted of diarrhea, nausea, fatigue, abnormal hepatic function, and hyperglycemia. Despite fewer cycles of drug exposure, increased toxicity was observed in Cohort 3, including 3 episodes of dose limiting toxicity (mucositis/rash, 1; abnormal hepatic function, 2). One-third of pts required V dose reduction, and 21% of pts came off study for toxicities including cerebrovascular event (1), pulmonary embolus (1), rash (1), abnormal hepatic function (1), and myocarditis (1). Moderate hypertension was observed in 42% of pts, with a single grade 3 event. Of the 20 response-evaluable pts, 2 (10%, 95% CI 1.2 – 31.7 %) demonstrated partial response, one lasting over 30 weeks, and 3 had stable disease &amp;gt; 24 wks (15%, 95% CI 3.2 – 37.9%). Results from correlative vascular hypertension analyses and platelet proteomics will be presented.&amp;#x2028; Conclusions: The all-oral regimen of V + CM was tolerable at a maximum dose of V 200 mg qd. Dose-limiting toxicity was seen in the V 300 mg cohort. Modest clinical activity in this heavily pretreated population was observed, and supports further investigation of this anti-angiogenic regimen in advanced breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 906.