tbuckley/cabot-search huggingface dataset:
Quantitative immunohistochemical detection of gamma-H2AX in paraffin-embedded human tumor samples at National Clinical Target Validation Laboratory
Authors: S. X. Yang, D. Nguyen, S. M. Steinberg, J. Ji, R. Parchment, R. Kinders, S. Kummar, M. Gutierrez, A. Murgo, J. E. Tomaszewski, J. H. Doroshow
Journal: Journal of Clinical Oncology (2007)

10565 Background: DNA double-strand breaks (DSBs) caused by exposure to DNA damaging agents initiate phosphorylation of histone H2AX to form gamma-H2AX, which is considered a surrogate marker of DSBs. However, it is a challenge to quantitatively measure gamma-H2AX in clinical samples such as tumor biopsies. The aim of this study was to develop an immunohistochemical detection method for gamma-H2AX and to quantitatively evaluate the levels of gamma-H2AX in paraffin-embedded tumor samples. Methods: Human breast cancer MCF-7 cells were treated with the topoisomerase I inhibitor irinotecan at 1 μM or vehicle for 1 h, and fixed in 10% neutral buffered formalin and embedded in paraffin. Staining with gamma-H2AX antibody was performed on sections of treated MCF-7 cells, tumor specimens, and biopsies at baseline and after doxorubicin-containing chemotherapy from cancer patients. Numbers of foci and level of gamma-H2AX expression per tumor nucleus were determined by manual counting under a light microscope and an Automated Cellular Imaging System. Results: There was a rise in the mean numbers of nuclear foci and intensity of gamma-H2AX in MCF-7 cells treated with irinotecan versus vehicle (19.9 ± 2.7 vs. 9.95 ± 3.6; P &lt; 0.0001 and 61.2 ± 8.5 vs. 16.2 ± 13.6; P &lt; 0.0001 by Wilcoxon rank sum test). The level of gamma-H2AX foci in human tumor samples was 18.8 ± 13.1, 44.8 ± 14.5, 51.2 ± 20.8, or 69.7 ± 21.2 in carcinomas of the breast, colon, ovary, or prostate. In a patient with stable disease, levels of gamma-H2AX foci were 62.7 ± 26.9 at baseline and 67.2 ± 25.3 after doxorubicin-containing regimen chemotherapy. Conclusions: Our data suggest that the quantitative immunohistochemical detection of gamma-H2AX levels is facilitated by a digital imaging system, and is a reliable method to measure the effects of DNA damaging agents in cells and paraffin-embedded human tumor samples. Its application may help evaluate tumor response to various DNA damaging agents currently in the clinic and those presently undergoing clinical development. No significant financial relationships to disclose.
Genotype-corrected reference values for serum angiotensin-converting enzyme
Authors: H. Biller, G. Zissel, B. Ruprecht, M. Nauck, A. Busse Grawitz, J. Müller-Quernheim
Journal: European Respiratory Journal (2006)

The deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene has the greatest impact on serum ACE level in Caucasians of any factor yet discovered. The aim of the present study was to establish new ACE genotype-corrected normal ranges for serum ACE level in a population of central European origin. After a medical examination, 159 healthy Caucasians volunteered to donate blood for the study. ACE genotypes were assessed by PCR and serum ACE levels were determined using two different kinetic tests. The distribution of the D/I polymorphism of the ACE gene was in accordance with the Hardy–Weinberg equilibrium. Serum ACE levels and ACE genotypes correlated significantly, with the highest serum ACE levels in subjects with ACE genotype D/D, and the lowest serum ACE levels in subjects with genotype I/I (mean± sd, assay 1: D/D 59.3±15.1 U·L -1 , D/I 45.5±15.2 U·L -1 , I/I 34.8±13.7 U·L -1 ; assay 2: D/D 43.7±14.1 U·L -1 , D/I 33.7±12.1 U·L -1 , I/I 25.4±9.5 U·L -1 ). Although they gave different absolute values of serum ACE levels, the results of the two test kits correlated significantly. In conclusion, the present authors recommend the use of new, genotype-specific reference values for serum angiotensin-converting enzyme levels, especially to improve the sensitivity and specificity of tests for angiotensin-converting enzyme in the follow-up of sarcoidosis.
An ounce of prevention?: Table 1
Authors: L Engebretsen, R Bahr
Journal: British Journal of Sports Medicine (2005)

Justification is provided for the need to focus on research into sports injury prevention

The First World Congress on Sports Injury Prevention is taking place in Oslo, Norway 23–25 June 2005. At a time when there is an abundance of medical meetings, journals, and papers, some might argue that the last thing we need is a new congress focusing on yet another field of research. What would justify such an emphasis on a new and developing research field in medicine?1 Firstly, it must ask important questions not answered by others. Secondly, the new research field should have the potential to create truly new knowledge, lead to new ways of thinking, and lay the foundation for improved health for our patients. This is usually not possible without a multidisciplinary approach, involving a mixture of basic scientists and clinicians. Thirdly, research results from the new field should be publishable in respected journals, recognised and cited by peers, presentable at high quality meetings, and fundable on competitive grant review.1

Let us examine each of these issues to see if there is sufficient merit in research into sports injury prevention. Firstly, is injury prevention important? Epidemiological studies show that, of injuries seen by a doctor in Scandinavia, every sixth is sustained during sporting activity.2 Among children, every third hospital-treated injury is the result of sports participation.2 A research group within the English Football Association found that …
DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression
Authors: Shichun Zheng, E. Andres Houseman, Zachary Morrison, Margaret R. Wrensch, Joseph S. Patoka, Christian Ramos, Daphne A. Haas-Kogan, Sean McBride, Carmen J. Marsit, Brock C. Christensen, Heather H. Nelson, David Stokoe, Joseph L. Wiemels, Susan M. Chang, Michael D. Prados, Tarik Tihan, Scott R. Vandenberg, Karl T. Kelsey, Mitchel S. Berger, John K. Wiencke
Journal: Neuro-Oncology (2011)

We explored the associations of aberrant DNA methylation patterns in 12 candidate genes with adult glioma subtype, patient survival, and gene expression of enhancer of zeste human homolog 2 (EZH2) and insulin-like growth factor-binding protein 2 (IGFBP2). We analyzed 154 primary glioma tumors (37 astrocytoma II and III, 52 primary glioblastoma multiforme (GBM), 11 secondary GBM, 54 oligodendroglioma/oligoastrocytoma II and III) and 13 nonmalignant brain tissues for aberrant methylation with quantitative methylation-specific PCR (qMS-PCR) and for EZH2 and IGFBP2 expression with quantitative reverse transcription PCR (qRT-PCR). Global methylation was assessed by measuring long interspersed nuclear element-1 (LINE1) methylation. Unsupervised clustering analyses yielded 3 methylation patterns (classes). Class 1 (MGMT, PTEN, RASSF1A, TMS1, ZNF342, EMP3, SOCS1, RFX1) was highly methylated in 82% (75/91) of lower-grade astrocytic and oligodendroglial tumors, 73% (8/11) of secondary GBMs, and 12% (6/52) of primary GBMs. The primary GBMs in this class were early onset (median age 37 years). Class 2 (HOXA9 and SLIT2) was highly methylated in 37% (19/52) of primary GBMs. None of the 10 genes for class 3 that were differentially methylated in classes 1 and 2 were hypermethylated in 92% (12/13) of nonmalignant brain tissues and 52% (27/52) of primary GBMs. Class 1 tumors had elevated EZH2 expression but not elevated IGFBP2; class 2 tumors had both high IGFBP2 and high EZH2 expressions. The gene-specific hypermethylation class correlated with higher levels of global LINE1 methylation and longer patient survival times. These findings indicate a generalized hypermethylation phenotype in glioma linked to improved survival and low IGFBP2. DNA methylation markers are useful in characterizing distinct glioma subtypes and may hold promise for clinical applications.
GLI2-Mediated Melanoma Invasion and Metastasis
Authors: Vasileia-Ismini Alexaki, Delphine Javelaud, Leon C. L. Van Kempen, Khalid S. Mohammad, Sylviane Dennler, Flavie Luciani, Keith S. Hoek, Patricia Juàrez, James S. Goydos, Pierrick J. Fournier, Claire Sibon, Corine Bertolotto, Franck Verrecchia, Simon Saule, Veronique Delmas, Robert Ballotti, Lionel Larue, Philippe Saiag, Theresa A. Guise, Alain Mauviel
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundThe transforming growth factor-β (TGF-β) pathway, which has both tumor suppressor and pro-oncogenic activities, is often constitutively active in melanoma and is a marker of poor prognosis. Recently, we identified GLI2, a mediator of the hedgehog pathway, as a transcriptional target of TGF-β signaling.
"BEAU'S LINES" IN HAIR. Reduction of Hair Shaft Diameter Associated With Illness.
Authors: R. T. SIMS
Journal: British Journal of Dermatology (1967)

Journal Article “BEAU'S LINES” IN HAIR. Reduction of Hair Shaft Diameter Associated With Illness. Get access R. T. SIMS, M.A., B.Sc, M.B., B.S. R. T. SIMS, M.A., B.Sc, M.B., B.S. Lecturer in Anatomy, Cambridge University and Honorary Registrar, Addenbrooke's Hospital. Anatomy School, Downing St., Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 1, 1 January 1967, Pages 43–49, https://doi.org/10.1111/j.1365-2133.1967.tb11395.x Published: 01 January 1967
Increased BAL Levels of Surfactant Protein (SP)-D in a Transgenic Mouse Model of Allergic Bronchopulmonary Aspergillosis
Authors: S.L. Koehm, P.S. Hutcheson, S. Kierstein, C.J. Bellone, A. Haczku, R.G. Slavin
Journal: Journal of Allergy and Clinical Immunology (2006)
Irinotecan (CPT-11) High-Dose Escalation Using Intensive High-Dose Loperamide to Control Diarrhea
Authors: D. Abigerges, J.-P. Armand, G. G. Chabot, L. D. Costa, E. Fadel, C. Cote, P. Herait, D. Gandia
Journal: JNCI Journal of the National Cancer Institute (1994)

Background: Diarrhea is a serious side effect that may prevent the administration of high doses of the antitumor drug Irinotecan (CPT-11). Purpose: Intensive, high-dose loper-amide was used in an attempt to control or downstage CPT-11-in-duced diarrhea and thus permit the use of higher dose intensities of CPT-11. Methods: Twenty-three patients with various cancers were treated with doses of CPT-11 ranging from 400 to 600 mg/m 2 , administered as a 30-minute intravenous infusion every 3 weeks. Starting 8 hours or more after the administration of CPT-11, any episode of diarrhea was treated with 2 mg of loperamide taken every 2 hours. Patients stopped taking loperamide only after a 12-hour diarrhea-free period. If diarrhea was not controlled after 3 consecutive days of nonstop loperamide intake, or if the patient was dehydrated, loperamide was stopped and the patient was hospitalized for intravenous fluids. If blood or mucus were found in the stools at any time during diarrhea, loperamide was stopped and the patient was hospitalized. Results: Seventeen of 23 patients had diarrhea while on CPT-11 treatment. Eighty-two CPT-11 cycles were administered to these 17 patients, and diarrhea occurred in 49 of these cycles, at a median time-to-onset of 6 days after CPT-11 administration. The loperamide protocol was followed in 46 of the 49 episodes of diarrhea, with 21 capsules of loperamide the median number being taken (range, 5-72). Only one patient was hospitalized for failure to respond to loperamide, and no major toxicity was associated with loperamide use. Fourteen of the 17 patients who experienced diarrhea were rechallenged with CPT-11 three or more times, and seven patients six or more times. Conclusions: High-dose loperamide controlled diarrhea in patients receiving CPT-11 and allowed administration of higher doses of CPT-11. Implications: The effectiveness of CPT-11 might be increased by higher dose intensities, which can be made tolerable by control of diarrhea with loperamide. [J Natl Cancer Inst 86:446-449, 1994]
Incidence of rheumatic fever.
Authors: C B Perry
Journal: BMJ (1990)

the communities integrate.In the mean time it is clear that we should direct our attention towards ensuring that those women at increased risk of fetal malformations are offered preconceptual advice and, in the case of neural tube defects, perhaps periconceptual vitamin supplementation.'They should also be encouraged to book early for antenatal care so that the relevant screening tests are available to them should they wish.
Elevated PAI-1 is associated with poor clinical outcomes in pediatric patients with acute lung injury
Authors: Anil Sapru, Martha A. Q. Curley, Sandra Brady, Michael A. Matthay, Heidi Flori
Journal: Intensive Care Medicine (2009)

Deposition of fibrin in the alveolar space is a hallmark of acute lung injury (ALI). Plasminogen activator inhibitor-1 (PAI-1) is an antifibrinolytic agent that is activated during inflammation. Increased plasma and pulmonary edema fluid levels of PAI-1 are associated with increased mortality in adults with ALI. This relationship has not been examined in children. The objective of this study was to test whether increased plasma PAI-1 levels are associated with worse clinical outcomes in pediatric patients with ALI.We measured plasma PAI-1 levels on the first day of ALI among 94 pediatric patients enrolled in two separate prospective, multicenter investigations and followed them for clinical outcomes. All patients met American European Consensus Conference criteria for ALI.A total of 94 patients were included. The median age was 3.2 years (range 16 days-18 years), the PaO(2)/F(i)O(2) was 141 +/- 72 (mean +/- SD), and overall mortality was 14/94 (15%). PAI-1 levels were significantly higher in nonsurvivors compared to survivors (P < 0.01). The adjusted odds of mortality doubled for every log increase in the level of plasma PAI-1 after adjustment for age and severity of illness.Higher PAI-1 levels are associated with increased mortality and fewer ventilator-free days among pediatric patients with ALI. These findings suggest that impaired fibrinolysis may play a role in the pathogenesis of ALI in pediatric patients and suggest that PAI-1 may serve as a useful biomarker of prognosis in patients with ALI.
Airway Distension Promotes Leukocyte Recruitment in Rat Tracheal Circulation
Authors: Lina H. K. Lim, Elizabeth M. Wagner
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Mechanical distortion of blood vessels is known to activate endothelial cells. Whether airway distension likewise activates the vascular endothelium within the airway wall is unknown. Using intravital microscopy in the rat trachea, we investigated if airway distention with the application of positive end-expiratory pressure (PEEP) caused leukocyte recruitment to the airway. Tracheal postcapillary venules were visualized and leukocyte kinetics monitored in anesthetized, mechanically ventilated rats (80 breaths/minute, 6 ml/kg VT, 1 cm H(2)O PEEP). Leukocyte rolling velocity (Vwbc) and the number of adherent cells were not altered with normal ventilation over the course of 2 hours. Ventilation with sustained PEEP (8 cm H(2)O for 1 hour reduced Vwbc and increased adhesion, reaching a maximum at 1 hour of PEEP. Intermittent (2x and 5x) 8 cm H(2)O PEEP also induced a similar reduction in Vwbc, accompanied by an increase in adhesion. However, leukocyte recruitment after airway distension is localized to the airways because increased PEEP did not induce leukocyte recruitment in the mesenteric microcirculation or when PEEP was applied to the lung distal to the site of measurement. Pretreatment with endothelin receptor and selectin inhibitors blocked the effects of distension on leukocyte recruitment, suggesting their involvement in the proinflammatory response.
P126 The prevalence of self reported respiratory symptoms and diagnoses amongst patients attending a drug dependance clinic: Abstract P126 Table 1.
Authors: A Tridimas, T Archer, Z Rehman, S Oelbaum, H Burhan
Journal: Thorax (2013)

<h3>Introduction</h3> In England it is estimated that between the ages of 15–64, 2.2% use cocaine, 6.8% use cannabis and 0.8% use opiates on a regular basis<sup>1</sup>. Illicit drug use such as crack cocaine smoking, heroin smoking and intravenous heroin also contribute to a range of respiratory conditions. A significant proportion of drug users also smoke tobacco. For a wide range of social, psychological and economic reasons, respiratory conditions within this population may often go undiagnosed for many years. Often their disease can progress to become severe before any medical input is sought. Aim: To ascertain a detailed tobacco and non-tobacco smoking history and the prevalence of respiratory symptoms, prior diagnostic investigations and diagnoses amongst clients in the criminal justice system attending an inner city drug treatment clinic run by Addaction. <h3>Methods</h3> Questionnaires were administered by Addaction staff and junior doctors from the respiratory department as part of a service evaluation. In order to ascertain whether their symptoms were likely to represent underlying COPD, a validated questionnaire was used<sup>5</sup>. The definitive diagnostic test for COPD is spirometryhowever in this particular group of people this is difficult to obtain due to frequently chaotic lifestyles. <h3>Results</h3> A total of 62 clients completed questionnaires. 44 (71%) smoked cigarettes, 39 (63%) tobacco (mean pack years (SD) combined cigarettes/tobacco 23.5 (25)), 40 (65%) marijuana, 54 (87%) crack and 57 (92%) heroin. 26 clients (42%) injected heroin. Only 17 (24%) reported having had spirometry. Clients were divided into tertiles (9heavy9, 9moderate9 and 9mild9 exposure to smoked tobacco and drugs) according to total smoking history (combined pack years, joints/day years, rocks/day years and bags/day years respectively for tobacco, marijuana, crack and heroin). There were no statistically significant differences between groups - See Table 1. <h3>Conclusions</h3> The majority of the clients reported at least one symptom suggestive of airways disease. A larger study incorporating spirometry based at drug clinics may haelp to diagnose, and thereby facilitate effective treatment, of underlying COPD in this population. Early diagnosis and treatment could reduce illness within this population, prevent admissions and lead to significant savings in NHS spending. <h3>References</h3> United Nations Office on Drugs and Crime, World Drugs report 2012 Pulmonary effects of illicit drug use, <i>Clin Chest Med</i>. 2004 Mar;25(1):203–16, Wolff AJ <i>et al</i>. 5. Scoring System and Clinical Application of COPD Diagnostic Questionnaires, <i>CHEST</i>. June 2006;129(6):1531–1539. doi:10.1378/chest.129.6.1531, Price DB <i>et al</i>.
Conservation of Breast Cancer Molecular Subtypes and Transcriptional Patterns of Tumor Progression Across Distinct Ethnic Populations
Authors: Kun Yu, Chee How Lee, Puay Hoon Tan, Patrick Tan
Journal: Clinical Cancer Research (2004)

Breast cancers can display distinct clinical characteristics in different ethnic populations. Previous studies involving European and United States patients have shown that breast tumors can be divided by their gene expression profiles into distinct "molecular subtypes." In this report, we surveyed a series of invasive and preinvasive breast tumors from Asian-Chinese patients to investigate whether similar subtypes could also be observed in this ethnic group.An analysis of expression profiles generated from 11 nonmalignant breast tissues, 17 ductal carcinomas in situ (DCIS) and 98 invasive carcinomas identified three broad molecular subtypes of breast [estrogen receptor (ER)+, ERBB2+ and ER-] in the Asian-Chinese population. These subtypes were highly similar to the "Luminal," "ERBB2+," and "Basal" molecular subtypes defined in previous studies, and the subtype-specific expression signatures were also observed in preinvasive DCIS tumors. By comparing the expression profiles of nonmalignant DCIS and invasive breast cancers for two subtypes (ER+ and ERBB2+), we identified several genes that were regulated in both a common and subtype-specific manner during the normal/DCIS and DCIS/invasive carcinoma transitions. Several of these genes were validated by comparison with another recently published similar, but not identical, study.Our results suggest that molecularly similar subtypes of breast cancer are indeed broadly conserved between Asian and Caucasian patients, and that these subtypes are already present at the preinvasive stage of carcinogenesis. To our knowledge, this study is among the first to directly compare the expression profiles of breast tumors across two different ethnic populations.
Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels
Authors: Alpana P. Shukla, Radu G. Iliescu, Catherine E. Thomas, Louis J. Aronne
Journal: Diabetes Care (2015)

Postprandial hyperglycemia is an important therapeutic target for optimizing glycemic control and for mitigating the proatherogenic vascular environment characteristic of type 2 diabetes. Existing evidence indicates that the quantity and type of carbohydrate consumed influence blood glucose levels and that the total amount of carbohydrate consumed is the primary predictor of glycemic response (1). Previous studies have shown that premeal ingestion of whey protein, as well as altering the macronutrient composition of a meal, reduces postmeal glucose levels (2–4). There are limited data, however, regarding the effect of food order on postprandial glycemia in patients with type 2 diabetes (5). In this pilot study, we sought to examine the effect of food order, using a typical Western meal, incorporating vegetables, protein, and carbohydrate, on postprandial glucose and insulin excursions in overweight/obese adults with type 2 diabetes.

A total of 11 subjects (6 female, 5 male) with metformin-treated type 2 diabetes were studied …
Tracheal stenosis. Prevention and treatment
Authors: Igor Motus, Nadezhda Giss
Journal: European Respiratory Journal (2013)

OBJECTIVE. The aim of the study was to elucidate the sources of tracheal stenosis and find proper ways of its prevention and treatment.  METHODS. We reviewed the data of 848 patients subjected to long-time artificial lung ventilation via tracheostomy in Ekaterinburg from 2006 to 2011 years and found 54 (664%) patients with cicatrical tracheal stenosis (I group). In order to reveal early posttracheostomy alterations threatening with stenosis development we examined 149 patients (II group). The alterations concerned were found in 28 cases. The treatment for preventing the stenosis in its initial stage namely endoscopic sanation, granulematous tissue debridement, cryotherapy was undertaken in all 28 patients. Circular resections were performed in 23 cases (9 with and 14 without existing tracheostomy).  RESULTS. In I group urgent repeated tracheostomies became necessary in 7 patients. Bougienage and T-tube placement were necessary only in patients of I group and were performed in 41 and 6 cases respectively. Circular resection of the trachea was performed in 19 patients. Restenosis after resection developed in 2 cases and erosion hemorrhage in 2 patients. Of the 28 patients in II group 19 were cured and 11 are still under treatment. Circular resections of the trachea became necessary only in 4 cases in II group and were uneventful. There were no urgent repeated tracheostomies in this group.  CONCLUSIONS. Permanent observation of patients after prolonged tracheostomy is necessary to detect early signs of stenosis formation. Endoscopic treatment undertaken in proper time results in reducing the rate of stenosis, avoids urgent situations and improves the surgical conditions in tracheal resection.