tbuckley/cabot-search huggingface dataset:
Role of Cardiac Myocyte CXCR4 Expression in Development and Left Ventricular Remodeling After Acute Myocardial Infarction
Authors: Udit Agarwal, Wael Ghalayini, Feng Dong, Kristal Weber, Yong-Rui Zou, Sina Y. Rabbany, Shahin Rafii, Marc S. Penn
Journal: Circulation Research (2010)

Rationale: Stromal cell–derived factor (SDF)-1/CXCR4 axis has an instrumental role during cardiac development and has been shown to be a potential therapeutic target for optimizing ventricular remodeling after acute myocardial infarction (AMI) and in ischemic cardiomyopathy. Although a therapeutic target, the specific role of cardiac myocyte CXCR4 (CM-CXCR4) expression following cardiogenesis and survival of cardiac myocyte and left ventricular remodeling after AMI is unknown. Objective: We hypothesized that cardiac myocyte derived CXCR4 is critical for cardiac development, but it may have no role in adulthood secondary to the short transient expression of SDF-1 and the delayed expression of CM-CXCR4 following AMI. To address this issue, we developed congenital and conditional CM-CXCR4 −/− mouse models. Methods and Results: Two strains of CM-CXCR4 flox/flox mice were generated by crossing CXCR4 flox/flox mice with MCM-Cre +/− mouse and MLC2v-Cre +/− mouse on the C57BL/6J background, yielding CXCR4 flox/flox MCM-Cre +/− and CXCR4 flox/flox MLC2v-Cre +/− mice. Studies demonstrated recombination in both models congenitally in the MLC2v-Cre +/− mice and following tamoxifen administration in the MCM-Cre +/− mice. Surprisingly the CXCR4 flox/flox MLC2v-Cre +/− are viable, had normal cardiac function, and had no evidence of ventricular septal defect. CXCR4 flox/flox MCM +/− treated with tamoxifen 2 weeks before AMI demonstrated 90% decrease in cardiac CXCR4 expression 48 hours after AMI. Twenty-one days post AMI, echocardiography revealed no statistically significant difference in the wall thickness, left ventricular dimensions or ejection fraction (40.9±7.5 versus 34.4±2.6%) in CXCR4 flox/flox mice versus CM-CXCR4 −/− mice regardless of strategy of Cre expression. No differences in vascular density (2369±131 versus 2471±126 vessels/mm 2 ; CXCR4 flox/flox versus CM-CXCR4 −/− mouse), infarct size, collagen content, or noninfarct zone cardiac myocyte size were observed 21 days after AMI. Conclusions: We conclude that cardiac myocyte–derived CXCR4 is not essential for cardiac development and, potentially because of the mismatch in timings of peaks of SDF-1 and CXCR4, has no major role in ventricular remodeling after AMI.
Changes in Gene Expression Predicting Local Control in Cervical Cancer: Results from Radiation Therapy Oncology Group 0128
Authors: Joanne B. Weidhaas, Shu-Xia Li, Kathryn Winter, Janice Ryu, Anuja Jhingran, Bridgette Miller, Adam P. Dicker, David Gaffney
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To evaluate the potential of gene expression signatures to predict response to treatment in locally advanced cervical cancer treated with definitive chemotherapy and radiation. Experimental Design: Tissue biopsies were collected from patients participating in Radiation Therapy Oncology Group (RTOG) 0128, a phase II trial evaluating the benefit of celecoxib in addition to cisplatin chemotherapy and radiation for locally advanced cervical cancer. Gene expression profiling was done and signatures of pretreatment, mid-treatment (before the first implant), and “changed” gene expression patterns between pre- and mid-treatment samples were determined. The ability of the gene signatures to predict local control versus local failure was evaluated. Two-group t test was done to identify the initial gene set separating these end points. Supervised classification methods were used to enrich the gene sets. The results were further validated by leave-one-out and 2-fold cross-validation. Results: Twenty-two patients had suitable material from pretreatment samples for analysis, and 13 paired pre- and mid-treatment samples were obtained. The changed gene expression signatures between the pre- and mid-treatment biopsies predicted response to treatment, separating patients with local failures from those who achieved local control with a seven-gene signature. The in-sample prediction rate, leave-one-out prediction rate, and 2-fold prediction rate are 100% for this seven-gene signature. This signature was enriched for cell cycle genes. Conclusions: Changed gene expression signatures during therapy in cervical cancer can predict outcome as measured by local control. After further validation, such findings could be applied to direct additional therapy for cervical cancer patients treated with chemotherapy and radiation.
Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XI. Pseudogenetic restrictions of hybridoma suppressor factors
Authors: K Okuda, M Minami, DH Sherr, ME Dorf
Journal: The Journal of Experimental Medicine (1981)

Suppressor factor derived from three different murine T cell hybridomas were characterized . They specifically inhibited 4-hydroxy-3-nitrophenyl acetyl cutaneous sensitivity responses. The factors bind antigen and bear I-J and idiotypic determinants, but lack conventional immunoglobulin constant-region determinants. The factors function during the induction phase of the immune response, by inducing a second population of suppressor cells (Ts(e)). Suppressor factor can inhibit both cellular and plaque-forming cell responses in appropriate strains of mice. These hybridoma suppressor factors directly suppress strains of mice that are Igh-V homologous with the strain producing the factor. Thus, there is an apparent Igh-V restriction in the activity of these factors. However, this is a pseudogenetic restriction because these factors generate second order suppressor cells (Ts(e)) in Igh-incompatible mice, but in order to express the suppressive activity, the cells must be adoptively transferred into recipients that are Igh compatible with the strain producing the suppressor factor. Finally, it was shown that the factor-induced Ts(e) population is under an apparent dual genetic restriction. Thus, Igh and H-2 homology is required in order for the Ts(e) population to express its suppressive activity.
Outbreak of isoniazid resistant tuberculosis in north London
Authors: M C Ruddy
Journal: Thorax (2004)

A description is given of a major outbreak of isoniazid monoresistant tuberculosis (TB) chiefly in north London, including prisons. The earliest case was diagnosed in 1995 with most cases appearing after 1999.Confirmation of a local cluster of cases was confirmed by restriction fragment length polymorphism (RFLP IS6110) typing or "rapid epidemiological typing" (RAPET). Further cases were found by retrospective analysis of existing databases, prospective screening of new isolates, and targeted epidemiological case detection including questionnaire analysis.By the end of 2001, 70 confirmed cases in London had been linked with a further 13 clinical cases in contacts and nine epidemiologically linked cases outside London. The epidemic curve suggests that the peak of the outbreak has not yet been reached. Cases in the outbreak largely belong to a social group of young adults of mixed ethnic backgrounds including several individuals from professional/business backgrounds. Compared with other cases of TB reported to the enhanced surveillance scheme in London during 1999-2001, the cases are more likely to be of white (26/70 (37%) v 1308/7666 (17%)) or black Caribbean ethnicity (17/70 (24%) v 312/7666 (4%)), born in the UK (41/70 (59%) v 1335/7666 (17%)), and male (52/70 (74%) v 4195/7666 (55%)). Drug misuse and/or prison detention are factors common to many cases.The investigation of the outbreak revealed significant problems on an individual patient and population based level including difficulties with contact tracing, compliance, and the risk of developing multidrug resistance. This incident has demonstrated the value of molecular strain typing in investigating an extensive outbreak of TB. This is the first documented outbreak involving a UK prison.
Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer
Authors: B. Glimelius, R. Ristamäki, M. Kjaer, P. Pfeiffer, T. Skovsgaard, K.M. Tveit, T. Linné, J.E. Frödin, B. Boussard, D. Oulid-Aïssa, S. Pyrhönen
Journal: Annals of Oncology (2002)
Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression
Authors: Gary S. Sachs, Andrew A. Nierenberg, Joseph R. Calabrese, Lauren B. Marangell, Stephen R. Wisniewski, Laszlo Gyulai, Edward S. Friedman, Charles L. Bowden, Mark D. Fossey, Michael J. Ostacher, Terence A. Ketter, Jayendra Patel, Peter Hauser, Daniel Rapport, James M. Martinez, Michael H. Allen, David J. Miklowitz, Michael W. Otto, Ellen B. Dennehy, Michael E. Thase
Journal: New England Journal of Medicine (2007)

Episodes of depression are the most frequent cause of disability among patients with bipolar disorder. The effectiveness and safety of standard antidepressant agents for depressive episodes associated with bipolar disorder (bipolar depression) have not been well studied. Our study was designed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania.
Serum metabolomic profile as a means to distinguish stage of colorectal cancer
Authors: Farshad Farshidfar, Aalim M Weljie, Karen Kopciuk, W Don Buie, Anthony MacLean, Elijah Dixon, Francis R Sutherland, Andrea Molckovsky, Hans J Vogel, Oliver F Bathe
Journal: Genome Medicine (2012)

Presently, colorectal cancer (CRC) is staged preoperatively by radiographic tests, and postoperatively by pathological evaluation of available surgical specimens. However, present staging methods do not accurately identify occult metastases. This has a direct effect on clinical management. Early identification of metastases isolated to the liver may enable surgical resection, whereas more disseminated disease may be best treated with palliative chemotherapy.Sera from 103 patients with colorectal adenocarcinoma treated at the same tertiary cancer center were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). Metabolic profiling was done using both supervised pattern recognition and orthogonal partial least squares-discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. The metabolomic profiles generated from each platform were compared between the following groups: locoregional CRC (N = 42); liver-only metastases (N = 45); and extrahepatic metastases (N = 25).The serum metabolomic profile associated with locoregional CRC was distinct from that associated with liver-only metastases, based on 1H NMR spectroscopy (P = 5.10 × 10-7) and GC-MS (P = 1.79 × 10-7). Similarly, the serum metabolomic profile differed significantly between patients with liver-only metastases and with extrahepatic metastases. The change in metabolomic profile was most markedly demonstrated on GC-MS (P = 4.75 × 10-5).In CRC, the serum metabolomic profile changes markedly with metastasis, and site of disease also appears to affect the pattern of circulating metabolites. This novel observation may have clinical utility in enhancing staging accuracy and selecting patients for surgical or medical management. Additional studies are required to determine the sensitivity of this approach to detect subtle or occult metastatic disease.
Planned Parenthood v Casey
Authors: H. Paul Lasky
Journal: JAMA (1993)

<h3>To the Editor.</h3> —In her article entitled "<i>Planned Parenthood v Casey</i>: The Impact of the New Undue Burden Standard on Reproductive Health Care," Ms Benshoof<sup>1</sup>takes a number of positions that I must take issue with. She opposes the parental consent restriction with a number of arguments, some of which may have merit. Nevertheless, as a physician, I would never provide treatment to a minor in nonemergent situations unless I had parental consent. Why should abortion, an invasive procedure, be exempt from this requirement? Furthermore, minors who are seeking an abortion are having unprotected intercourse and are therefore at risk of contracting sexually transmitted diseases such as acquired immunodeficiency syndrome. This makes parental involvement all the more important. I would doubt that an abortion clinic would be motivated to instruct its customers on how to avoid being its clients. I would therefore suggest that the potential benefits of parental
The Effect of Sustained-Release Morphine on Breathlessness and Quality of Life in Severe Chronic Obstructive Pulmonary Disease
Authors: PHILLIPPA J. POOLE, ANDREW G. VEALE, PETER N. BLACK
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Morphine has been proposed as a treatment for breathlessness in patients with severe chronic obstructive pulmonary disease (COPD), but there is uncertainty as to whether or not it is effective. Orally administered sustained-release morphine was compared with placebo in a randomized, double-blind, crossover trial with two 6-wk treatment periods separated by a 2-wk washout period. The primary end point was quality of life measured using the Chronic Respiratory Disease Questionnaire (CRQ). Secondary end points included 6-min walk (6MW), distance, and breathlessness scores. Sixteen subjects with a mean age 70.7 yr, FEV1 of 0.6 L, and VC of 1.90 L were studied. There was no change in the total CRQ score with either treatment, but the score on the Mastery subscale was significantly worse with morphine (p = 0.02). The 6MW distance increased by 21 m from the beginning to the end of the placebo treatment period, but it decreased by 35 m with morphine (p = 0.04). There were no differences between treatments in breathlessness scored on daily diary cards or on the Dyspnea subscale of the CRQ. Almost all the subjects experienced adverse effects related to morphine. Sustained-release morphine was not a useful treatment for breathlessness in these patients with severe COPD.
Bronchoscopic lung volume reduction for emphysema: where next?
Authors: Pallav L. Shah, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2012)

Emphysema is an irreversible disease and although patients derive significant benefit from inhaled therapies [1] and pulmonary rehabilitation [2], many remain significantly disabled. The National Emphysema Treatment Trial of lung volume reduction clearly showed that in appropriately selected patients it is possible to improve lung function, exercise capacity, quality of life and survival [3, 4]. A search for new approaches to produce lung volume reduction, either avoiding the morbidity and mortality potentially associated with surgery or aimed at patients who do not meet the criteria for lung volume reduction surgery (LVRS), has been underway. Over the last decade, since the first report of bronchoscopic lung volume reduction in patients with emphysema [5], there has been a significant expansion in research and investment into this area [6–13]. Approaches have included the placement of endobronchial valves and RePneu™ endobronchial coils (PneumRX, Mountain View, CA, USA) [11], as well as biological agents to induce scarring [9] and airway bypass approaches, either endobronchially [13] or transpleurally [12].

Endobronchial valves are intended to prevent air reaching the target area of the lung, leading to resorption of air and reduction of gas trapping. The valve mechanism also allows air to leave and prevents the acute local hyperinflation reported with simple airway-blocking devices [14]. A limitation to this approach is the presence of interlobar collateral ventilation. Where this occurs, occlusion of all segmental bronchi will not isolate a lobe, because air can still enter through pathological channels from adjacent damaged lung.

Following initial case series [5, 7, 15], data from the US arm of the first randomised controlled trial of endobronchial valves, the Endobronchial Valve for Emphysema Palliation Trial (VENT), …
Positional sleep apnea amongst adults in United Arab Emirates
Authors: Sharina Aldhaheri, Mohammed Al-Houqani
Journal: European Respiratory Journal (2014)

Introduction:  Body position during sleep affects the frequency of apnea and hypopnea in individuals with obstructive sleep apnea (OSA).   Objectives:  To measure the frequency of supine-related positional OSA amongst adult diagnosed with OSA and determine the clinical characteristics and polysomnographic finding for positional OSA.   Methods:  This is a retrospective cross sectional study reviewing 278 records of patients age ≥ 18 years who had completed overnight sleep study for OSA assessment. Respiratory events were scored according to the AASM criteria. We defined positional OSA as overall apnea hypopnea index (AHI) ≥5, and AHI at least 50% lower in lateral positions than the AHI in the supine position with ≥ 20 min of sleep in non-supine position. Forty three records out of 278 were excluded as AHI   Results : Overall, 53% of patients had positional OSA. Patients with positional OSA were younger (p=0.005), lower BMI (p   Conclusions : A half of the OSA patients in our cohort had positional OSA. Positional OSA is more predominant amongst younger male adult, with lower BMI, nick and waist circumferences.   Keywords:  Obstructive Sleep apnea, positional, supine.
MEMP1972A, an anti-M1 prime monoclonal antibody, reduces serum IgE in healthy and allergic rhinitis subjects
Authors: Heleen Scheerens, Wendy Putnam, Yanan Zheng, Yehong Wang, Sofia Mosesova, Romeo Maciuca, Charlene Liao, Lawren Wu, John Matthews, Jeffrey Harris
Journal: European Respiratory Journal (2012)

Background : MEMP1972A, a humanized monoclonal antibody specific for the M1 prime epitope of membrane IgE, depletes M1 prime-expressing IgE-switched B cells, IgE memory B cells and IgE plasmablasts .  MEMP1972A is in development for the treatment for allergic asthma.   Aim:  To evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of MEMP1972A in healthy and allergic rhinitis (AR) subjects.   Methods : Two Phase I, randomized, controlled trials investigated the safety, tolerability, PK and PD of MEMP1972A in (1) healthy adults (n=31 MEMP1972A, n=14 placebo [PB]) and (2) AR subjects (n=24 MEMP1972A, n=12 PB [NCT01160861]). In healthy adults, MEMP1972A was given as single escalating doses of 0.003–5 mg/kg intravenous (IV) or 3 mg/kg subcutaneous (SC). In AR subjects, monthly doses were given for 3 months at 1.5 and 5 mg/kg IV and 3 mg/kg SC.   Results : MEMP1972A was well tolerated, and the exposure of serum MEMP1972A was dose proportional. Following IV administration, the mean terminal half-life of MEMP1972A was 20–21 days and mean clearance was 2.2–2.7 mL/day/kg. MEMP1972A administration led to a dose dependent reduction in serum IgE in both studies. In healthy adults, a single dose of MEMP1972A at 3 and 5 mg/kg IV significantly reduced serum IgE by ∼25% relative to baseline at Day 85, with no significant reductions observed in the PB, lower IV or 3 mg/kg SC cohorts. Monthly doses of MEMP1972A at 5 mg/kg IV or 3 mg/kg SC in AR subjects reduced serum IgE by ∼25% relative to baseline at Day 85. Serum IgE reductions were sustained for 6 months.   Conclusion : MEMP1972A was well tolerated and reduced serum IgE in adults with or without allergic disease.
Monitoring of biological markers indicative of doping: the athlete biological passport
Authors: Martial Saugy, Carsten Lundby, Neil Robinson
Journal: British Journal of Sports Medicine (2014)

The athlete biological passport (ABP) was recently implemented in anti-doping work and is based on the individual and longitudinal monitoring of haematological or urine markers. These may be influenced by illicit procedures performed by some athletes with the intent to improve exercise performance. Hence the ABP is a valuable tool in the fight against doping. Actually, the passport has been defined as an individual and longitudinal observation of markers. These markers need to belong to the biological cascade influenced by the application of forbidden hormones or more generally, affected by biological manipulations which can improve the performance of the athlete. So far, the haematological and steroid profile modules of the ABP have been implemented in major sport organisations, and a further module is under development. The individual and longitudinal monitoring of some blood and urine markers are of interest, because the intraindividual variability is lower than the corresponding interindividual variability. Among the key prerequisites for the implementation of the ABP is its prospect to resist to the legal and scientific challenges. The ABP should be implemented in the most transparent way and with the necessary independence between planning, interpretation and result management of the passport. To ensure this, the Athlete Passport Management Unit (APMU) was developed and the WADA implemented different technical documents associated to the passport. This was carried out to ensure the correct implementation of a profile which can also stand the challenge of any scientific or legal criticism. This goal can be reached only by following strictly important steps in the chain of production of the results and in the management of the interpretation of the passport. Various technical documents have been then associated to the guidelines which correspond to the requirements for passport operation. The ABP has been completed very recently by the steroid profile module. As for the haematological module, individual and longitudinal monitoring have been applied and the interpretation cascade is also managed by a specific APMU in a similar way as applied in the haematological module. Thus, after exclusion of any possible pathology, specific variation from the individual norms will be then considered as a potential misuse of hormones or other modulators to enhance performance.
Fecal DNA Biomarkers for the Detection of Colorectal Neoplasia: Attractive, but Is It Feasible?
Authors: Dean E. Brenner, Gad Rennert
Journal: JNCI Journal of the National Cancer Institute (2005)

Because of the high mortality associated with advanced disease, accessibility to direct visual examination, extensive research, and recognition of the genetic mechanisms associated with its carcinogenesis, the colon and rectum have emerged as an important model for the introduction of innovative and effective cancer screening and early detection tools for large populations.
The polymorphisms in the VHL and HIF1A genes are associated with the prognosis but not the development of renal cell carcinoma
Authors: C. Qin, Q. Cao, X. Ju, M. Wang, X. Meng, J. Zhu, F. Yan, P. Li, Q. Ding, J. Chen, M. Gu, W. Zhang, C. Yin, Z. Zhang
Journal: Annals of Oncology (2011)