tbuckley/cabot-search huggingface dataset:
Abstract 4900: <i>MAGE-A11</i> expression in castration-recurrent prostate cancer: association with a global epigenetic defect
Authors: Smitha R. James, Lena D. Forti, James L. Mohler, Elizabeth M. Wilson, Adam R. Karpf
Journal: Cancer Research (2010)

Abstract Despite the initial clinical response to androgen deprivation therapy, most prostate cancer patients subsequently develop castration-recurrent disease. Elucidation of the mechanisms driving this process is expected to lead to improved strategies to prevent and treat advanced prostate cancer. Epigenetic alterations, including DNA hypomethylation, play a key role in human cancer development. DNA hypomethylation is thought to promote oncogenesis in part by driving oncogene expression, but its potential role in castration-recurrent prostate cancer is unknown. Melanoma Antigen A-11 (MAGE-A11) is a cancer germline (CG) antigen that stabilizes the androgen receptor (AR), facilitates AR association with co-activators, and promotes AR transcriptional activity; thus it appears to play an oncogenic role in castration-recurrent disease. We have recently reported that MAGE-A11 is over-expressed in prostate cancer cell lines, prostate cancer xenografts, and human prostate cancer tissues; in each setting MAGE-A11 overexpression is associated with DNA hypomethylation at the MAGE-A11 promoter CpG island (Karpf et al., Molecular Cancer Research 7; 523-535, 2009). Critically, MAGE-A11 expression and promoter hypomethylation correlate with castration-recurrent cancer growth, both in the CWR-22 xenograft model and in primary human prostate cancer tissues. In the current study we examined whether MAGE-A11 expression and hypomethylation in prostate cancer is an isolated molecular event, or alternatively whether it coincides with a global DNA hypomethylation defect. To test this, we analyzed the global DNA methylation status of prostate cancer cell lines, CWR-22 cancer xenografts, and primary prostate cancer, in which MAGE-A11 expression and methylation was also characterized. We assessed global DNA methylation by measuring total genomic 5-methyl-2′-deoxycytidine (5mdC), LINE-1 repetitive DNA element methylation, and the expression and methylation of several other CG antigen genes, including MAGE-A1, NY-ESO-1, XAGE-1, and BORIS/CTCFL. Taken together, our data provide evidence for a global DNA hypomethylation phenotype in castration-recurrent prostate cancers that express MAGE-A11. Ongoing studies are using HpaII tiny fragment enrichment by ligation-mediated PCR (HELP assay) to define the epigenome of castration-recurrent prostate cancer displaying MAGE-A11 expression. In summary, our data provide evidence that global DNA hypomethylation contributes to castration-recurrent prostate cancer, at least in part by promoting MAGE-A11 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4900.
Bone marrow disseminated tumor cells, loco-regional and adjuvant treatment are prognostic factors for loco-regional relapses in early breast cancers.
Authors: F Bidard, Y Kirova, A Vincent-Salomon, S Alran, Y De Rycke, B Sigal-Zafrani, X Sastre-Garau, L Mignot, A Fourquet, J Pierga
Journal: Cancer Research (2009)

Abstract Abstract #307 Purpose: To study in early breast cancer (BC) patients (pts) if bone marrow (BM) disseminated tumor cells (DTC) are associated with a specific loco-regional dissemination of cancer cells, according to the radiotherapy fields and to the pattern of loco-regional relapses.&amp;#x2028; Patient and methods: BM aspirates were prospectively screened for cytokeratin positive (CK+) cells at primary treatment in stage I-III BC pts. Local recurrence (LR) was defined as recurrence of the breast or chest wall; Regional recurrence (RR) was defined as lymph node recurrence after loco-regional treatment. Irradiation fields, BM DTC status, clinical and pathological variables of the pts were correlated with loco-regional relapse-free survival (LRRFS).&amp;#x2028; Results: BM DTC were detected in 94 out of 621 pts (15%) and were not associated with the axillary lymph node status and other prognostic factors. After a median follow-up of 56 months, 18 pts (2,9%) experienced loco-regional relapses: 15 LR occurred in the RT fields whereas 2 LR and 1 RR were out. 8 of the 18 relapsing pts (44%) were DTC positive (8 LR in the RT fields). BM DTC detection was the only prognostic factor for LRRFS (p=0.0005, OR=5.2 [2.0-13.1]) in multivariate analysis. In BM DTC positive patients, longer LRRFS were observed in those who were given adjuvant hormonal therapy (p=0.03) and RT on supra-clavicular (SCN) and internal mammary (IMN) nodes (p=0.055) (multivariate analysis).&amp;#x2028; Conclusions: BM DTC strongly influence loco-regional relapse in early BC patients. Our data support the hypothesis of a different lymphatic spread of BM DTC positive BC and of a possible re-seeding of BM DTC to the breast. Survival analyses suggest that BM DTC positive patients take advantage of adjuvant hormone therapy but also of adjuvant SCN and IMN irradiation. This observation could be one explanation of the influence of systemic treatment on locoregional relapse and of radiotherapy on distant metastatic dissemination. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 307.
A Case of Left-sided Appendicitis
Authors: J. W. L. Haddon
Journal: BMJ (1945)

MEDBRII OURNAL 9Comments If the population of Middlesex be taken as 2,000,000 it can be calculated that there are approximately 1,200,000 persons in the 14-55 age group.Allowing that the age distribution of the females in the above survey is very skew, being -excessively overweighted at ages 14-24, it appears that there are probably some 3,000 undiagnosed cases of pulmonary tuberculosis in the county in need of treatment, and that half of these cases are without symptoms.
The effects of non-insulin-dependent diabetes mellitus on the kinetics of onset of insulin action in hepatic and extrahepatic tissues.
Authors: D Turk, A Alzaid, S Dinneen, K S Nair, R Rizza
Journal: Journal of Clinical Investigation (1995)

The mechanism(s) of insulin resistance in non-insulin-dependent diabetes mellitus remains ill defined. The current studies sought to determine whether non-insulin-dependent diabetes mellitus is associated with (a) a delay in the rate of onset of insulin action, (b) impaired hepatic and extrahepatic kinetic responses to insulin, and (c) an alteration in the contribution of gluconeogenesis to hepatic glucose release. To answer these questions, glucose disappearance, glucose release, and the rate of incorporation of 14CO2 into glucose were measured during 0.5 and 1.0 mU/kg-1 per min-1 insulin infusions while glucose was clamped at approximately 95 mg/dl in diabetic and nondiabetic subjects. The absolute rate of disappearance was lower (P < 0.05) and the rate of increase slower (P < 0.05) in diabetic than nondiabetic subjects during both insulin infusions. In contrast, the rate of suppression of glucose release in response to a change in insulin did not differ in the diabetic and nondiabetic subjects during either the low (slope 30-240 min:0.02 +/- 0.01 vs 0.02 +/- 0.01) or high (0.02 +/- 0.00 vs 0.02 +/- 0.00) insulin infusions. However, the hepatic response to insulin was not entirely normal in the diabetic subjects. Both glucose release and the proportion of systemic glucose being derived from 14CO2 (an index of gluconeogenesis) was inappropriately high for the prevailing insulin concentration in the diabetic subjects. Thus non-insulin-dependent diabetes mellitus slows the rate-limiting step in insulin action in muscle but not liver and alters the relative contribution of gluconeogenesis and glycogenolysis to hepatic glucose release.
Author's reply to Rogers
Authors: M. J. Brown
Journal: BMJ (2012)

Unfortunately, there are two answers to the question,1 2 depending on whether absolute or relative risk is plotted against blood pressure.

The first is the “raw data,” but the second is, in the Oxford view of risk, the more valid way of disentangling the influence of blood pressure from confounders such as age.3 The log-linear relation between …
Plasmacytoid dendritic cells and Th17 immune response contribution in gastrointestinal acute graft-versus-host disease
Authors: C. Bossard, F. Malard, J. Arbez, P. Chevallier, T. Guillaume, J. Delaunay, J.-F. Mosnier, Pierre Tiberghien, Philippe Saas, M. Mohty, B. Gaugler
Journal: Leukemia (2012)
Alpha-Fetoprotein Response After Locoregional Therapy for Hepatocellular Carcinoma
Authors: Saadettin Kilickap, Cagatay Arslan, Soner Senel, Hilmi Ataseven
Journal: Journal of Clinical Oncology (2010)

We read with great interest the report by Riaz et al, 1 in which they demonstrated that the response of serum alphafetoprotein (AFP) level after locoregional therapy in patients with hepatocellular carcinoma (HCC) was a useful surrogate marker to determinate tumor response and survival.In this study, AFP response was seen in 81 (64.8%) of 125 patients treated with chemoembolization and radioembolization.Also, the authors reported that AFP response was a prognostic factor for overall survival in univariate and multivariate analyses.It is still unclear whether serial AFP measurement or AFP/tumor volume for monitoring treatment response in patients with HCC should be used.Some studies have shown that serum AFP level might be used as a surrogate marker for response to systemic chemotherapy. 2,3A significant correlation between serum AFP levels and both size and number of HCC lesions has been reported. 4AFP/tumor volume may be a better prognostic indicator for patients with HCC than serum AFP value alone. 4Also, significant correlation between higher AFP levels and higher stages has been reported. 5ecause the results of a multivariate analysis give important messages to readers, the analysis should be carefully used.For accurately interpreted results of a study, the sample size should be sufficient to perform multivariate analysis.Some authors have recommended that a minimum of 20 patients per predictor should be used for an accurately interpreted multivariate analysis. 6Also, each parameter considered to be a prognostic factor must be evaluated before univariate or multivariate analysis is performed, because one factor may interact with the others.We think that the statistical assessment is the most important limitation of the study by Riaz et al. 1 The study included a total of 125 patients and six prognostic factors, such as stage, performance status, Child Pugh class, WHO response, European Association for the Study of the Liver response, and AFP response, which were evaluated for multivariate analysis.We think that the sample size of the study was quite small for multivariate analysis, and the interaction probability among prognostic factors analyzed in the study was quite high.We believe that this problematic issue may have affected the results presented in the report.
Coronary reperfusion enhances recovery of atrial natriuretic peptide secretion. Salvaging endocrine function in patients with acute right ventricular infarction.
Authors: S Yasuda, H Nonogi, S Miyazaki, Y Goto, K Haze
Journal: Circulation (1994)

The heart has been demonstrated not only to be a pumping organ but also an endocrine organ secreting atrial natriuretic peptide (ANP). We hypothesized that myocardial ischemia may affect ANP secretion and that reperfusion therapy for acute myocardial infarction can preserve endocrine function of the heart.Twenty patients with acute right ventricular infarction were examined who underwent reperfusion therapy on admission. These patients had proximal occlusion of the dominant right coronary artery involving the right atrial branches: 9 patients with successful reperfusion (SRP group) and the remaining 11 patients with unsuccessful reperfusion (URP group). Within 24 hours after the onset of infarction, a volume loading test was performed after reperfusion therapy with measurements for plasma ANP levels and hemodynamics. Before the volume loading test, the plasma ANP level and mean right atrial pressure were similar between these two groups. However, in the URP group, percent increase in ANP in response to volume loading was strikingly smaller (URP, 45 +/- 18% versus SRP, 133 +/- 25%; P < .01) despite similar percent increase in mean right atrial pressure (URP, 100 +/- 46% versus SRP, 86 +/- 23%). The peak ANP level occurred significantly later in the URP group (69 +/- 16 hours) than in the SRP group (28 +/- 9 hours, P < .001) after the onset of infarction.The response of ANP release to volume loading is attenuated in patients with right ventricular infarction without coronary reperfusion. However, successful reperfusion induces a rapid recovery of cardiac endocrine function as well as its mechanical function. A sufficiently elevated plasma ANP level may be a useful predictor of hemodynamic improvement in patients with right ventricular infarction.
Rupture of the Rectus Abdominis Muscle
Authors: A. G. Horsburgh
Journal: BMJ (1962)

difference cannot be considered proved in a retrospective study such as this, but clinical studies at present going forward (J. A. Tulloch, 1962, unpublished) should elucidate the problem.Summary Among 1,100 necropsy records, from August, 1959, to November, 1961, reviewed, 273 cases of renal disease were found.Chronic pyelonephritis was the most common disease encountered.An attempt has been made to divide this into a primary and a secondary group and to show the difference in clinical presentation and mode of death.The nephrotic syndrome in Africans is discussed, and especially its relation to chronic pyelonephritis.Other types of renal disease encountered, notably chronic glomerulonephritis and amyloid disease, are discussed briefly.
Dermatologic Conditions Misdiagnosed as Evidence of Child Abuse
Authors: Kenya H. Anders
Journal: JAMA (1989)

<h3>To the Editor.—</h3> We appreciate the continuing efforts of professionals such as Mss Herman-Giddens and Berson<sup>1</sup>in the nationwide effort to identify and intervene in child abuse cases. Their article on three cases of child molestation under the guise of genital care of children is a sobering reminder of the intricacies of the problem. The photograph and clinical description of the genital lesions in case 3 of the article, however, are striking because of their resemblance to the dermatologic condition lichen sclerosus et atrophicus. This condition is characterized frequently in females by ivory papules coalescing to plaques in a "keyhole" distribution around the vagina and rectum. It can be associated with severe pruritus, irritation, and even bleeding and may require various forms of topical therapy for control of symptoms. The etiology is unknown, but lichen sclerosus et atrophicus occurs more frequently in females, often involving only the genitalia. It
PUNCTATE KERATOSIS OF THE PALMS OF THE HANDS AND SOLES OF THE EEET; TWO CASES OCCURRING IN COUSINS-GERMAN.
Authors: JAMES GALLOWAY, H. G. ADAMSON
Journal: British Journal of Dermatology (1918)

Journal Article PUNCTATE KERATOSIS OF THE PALMS OF THE HANDS AND SOLES OF THE EEET; TWO CASES OCCURRING IN COUSINS‐GERMAN. Get access JAMES GALLOWAY, K.B.E., M.D. Sir, JAMES GALLOWAY, K.B.E., M.D. Sir Search for other works by this author on: Oxford Academic Google Scholar H. G. ADAMSON H. G. ADAMSON Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 30, Issue 3, 1 July 1918, Pages 123–129, https://doi.org/10.1111/j.1365-2133.1918.tb13140.x Published: 01 July 1918
An outsider's view of the NHS reforms
Authors: K Bloor, A Maynard
Journal: BMJ (1994)

STUDY OBJECTIVE--The aim of the study was to analyse the extent to which mortality can be predicted from data on self assessed chronic illness. DESIGN--The study used data obtained from ongoing surveys of living conditions conducted by Statistics Sweden using annual interviews of cohorts of about 8000 people. SETTING--The study was a population based survey of the whole of Sweden. PARTICIPANTS--The analysis involved a group of 25,586 respondents (males 12,812, females 12,774), aged 25-74 years, interviewed in 1977 and 1979-81. MEASUREMENTS AND RESULTS--Mortality and occupational health selection were analysed in different occupational categories. The association between mortality and self reported morbidity was assessed. Level of physical strain at work was associated with mortality in men. Occupational health selection could be detected for men but not for women when mortality from all causes was investigated. Self assessment of health predicted mortality. CONCLUSIONS--Subjective assessments of health through surveys are valuable as predictors of mortality for both men and women.
Accelerated Partial Breast Irradiation in Early-Stage Breast Cancer
Authors: Mary Ella Sanders, Troy Scroggins, Federico L. Ampil, Benjamin D. Li
Journal: Journal of Clinical Oncology (2007)

Whole-breast irradiation, as part of breast-conservation therapy (BCT), has well-established results, good cosmesis, and low toxicity. Results from the BCT trials suggest that the risk for ipsilateral breast cancer recurrence resides within close proximity to the original tumor site. This leads investigators to consider the role of an accelerated and more tumor bed-focused course of radiotherapy. Accelerated partial-breast irradiation (APBI) involves treating a limited volume of breast tissue, with dose of irradiation per fraction increased and the treatment time course decreased. Four currently available methods of APBI are interstitial brachytherapy, intracavitary brachytherapy, intraoperative radiotherapy, and three-dimensional conformal external-beam radiotherapy. Patient selection is critical. This review article presents some preliminary clinical observations and limitations that suggest a potential role for APBI as a more user-friendly mode for delivering radiotherapy after lumpectomy for early breast cancer.
Clowning in hospitals is no joke
Authors: C. Simonds
Journal: BMJ (1999)

Recently, patients with mutations in <i>DOCK8</i> have been reported to have a combined immunodeficiency characterized by cutaneous viral infections and allergies. NK cells represent a first-line defense against viral infections, suggesting that DOCK8 might participate in NK cell function. In this study, we demonstrate that DOCK8-suppressed human NK cells showed defects in natural cytotoxicity as well as specific activating receptor-mediated NK cytotoxicity. Additionally, compared with control NK cells, NK cells depleted of DOCK8 showed defective conjugate formation, along with decreased polarization of LFA-1, F-actin, and cytolytic granules toward the cytotoxic synapse. Using a proteomic approach, we found that DOCK8 exists in a macromolecular complex with the Wiskott-Aldrich syndrome protein, an actin nucleation-promoting factor activated by CDC42, as well as talin, which is required for integrin-mediated adhesion. Taken together, our results demonstrate an important role for DOCK8 in NK cell effector function and provide important new mechanistic insight into how DOCK8 regulates F-actin and integrin-mediated adhesion in immune cells.
Meeting Meaningful Use Criteria and Managing Patient Populations
Authors: Catherine M. DesRoches, Anne-Marie Audet, Michael Painter, Karen Donelan
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: Meaningful use, as defined by the Centers for Medicare & Medicaid Services, will require the aggregation of patient data to enable population assessment. Little is known about the proportion of physicians who are able to meet meaningful use criteria or their use of electronic health records (EHRs) to manage patient populations. Objective: To evaluate physicians' reports of EHR adoption and ease of use and their ability to use EHRs for patient panel management. Design: National mailed survey of practicing physicians (response rate of 60%). Setting: Late 2011 and early 2012. Participants: 1820 primary care physicians and specialists in office-based practices. Measurements: Proportion of physicians who have a basic EHR and meet meaningful use criteria and ease of use of computerized systems designed for patient population management tasks. Results: A total of 43.5% of physicians reported having a basic EHR, and 9.8% met meaningful use criteria. Computerized systems for managing patient populations were not widespread; fewer than one half of respondents reported the presence of computerized systems for any of the patient population management tasks included in the survey. Physicians with such functionalities reported that these systems varied in ease of use. Physicians with an EHR that met meaningful use criteria were significantly more likely than those not meeting the standard to rate panel management tasks as easy. Limitation: Ease-of-use measures are subjective. Conclusion: Few physicians could meet meaningful use criteria in early 2012 and using computerized systems for the panel management tasks was difficult. Results support the growing evidence that using the basic data input capabilities of an EHR does not translate into the greater opportunity that these technologies promise. Primary Funding Source: Commonwealth Fund and Robert Wood Johnson Foundation.
Early afterdepolarizations: mechanism of induction and block. A role for L-type Ca2+ current.
Authors: C T January, J M Riddle
Journal: Circulation Research (1989)

Early afterdepolarizations (EADs) are a type of triggered activity found in heart muscle. We used voltage-clamped sheep cardiac Purkinje fibers to examine the mechanism underlying EADs induced near action potential plateau voltages with the Ca2+ current agonist Bay K 8644 and the effect of several interventions known to suppress or enhance these EADs. Bay K 8644 produced an inward shift of the steady-state current-voltage relation near plateau voltages. Tetrodotoxin, lidocaine, verapamil, nitrendipine, and raising [K]o abolish EADs and shift the steady-state current-voltage relations outwardly. Using a two-pulse voltage-clamp protocol, an inward current transient was present at voltages where EADs were induced. The voltage-dependence of availability of the inward current transient and of EAD induction were similar. The time-dependence of recovery from inactivation of the inward current transient and of EAD amplitude were nearly identical. Without recovery of the inward current transient, EADs could not be elicited. The inward current transient was enhanced with Bay K 8644 and blocked by nitrendipine, but was not abolished by tetrodotoxin or replacement of [Na]o with an impermeant cation. These results support a hypothesis that the induction of EADs near action potential plateau voltages requires 1) a conditioning phase controlled by the sum of membrane currents present near the action potential plateau and characterized by lengthening and flattening of the plateau within a voltage range where, 2) recovery from inactivation and reactivation of L-type Ca2+ channels to carry the depolarizing charge can occur. Our results suggest an essential role for the L-type Ca2+ "window" current and provide a framework for understanding the role of several membrane currents in the induction and block of EADs.