tbuckley/cabot-search huggingface dataset:
Abnormal T cell differentiation persists in patients with rheumatoid arthritis in clinical remission and predicts relapse
Authors: C H Burgoyne, S L Field, A K Brown, E M Hensor, A English, S L Bingham, R Verburg, U Fearon, C A Lawson, P J Hamlin, L Straszynski, D Veale, P Conaghan, M A Hull, J M van Laar, A Tennant, P Emery, J D Isaacs, F Ponchel
Journal: Annals of the Rheumatic Diseases (2007)

An abnormal CD4+ T cell subset related to inflammation exposure (inflammation-related cells, IRC) has been identified in rheumatoid arthritis (RA). Patients with inflammatory and non-inflammatory diseases were used to examine the relationship between inflammation and this T cell subset in vivo.Blood was collected from healthy controls and patients with RA (active disease or in clinical remission), Crohn's disease and osteoarthritis. IRC and chemokine receptors were quantified by flow cytometry. Thymic activity and apoptotic factors were measured by real-time polymerase chain reaction. Circulating cytokines were measured by enzyme-linked immunosorbent assay. CXCR4 and SDF1 in synovial biopsies were measured using immunohistochemistry.IRC were identified in patients with RA (p<0.0001) and Crohn's disease (p = 0.005), but not in those with osteoarthritis. In RA in remission, IRC persisted (p<0.001). In remission, hyperproliferation of IRC was lost, chemokine receptor expression was significantly lowered (p<0.007), Bax expression dropped significantly (p<0.001) and was inversely correlated with IRC (rho = -0.755, p = 0.03). High IRC frequency in remission was associated with relapse within 18 months (OR = 6.4, p<0.001) and a regression model predicted 72% of relapse.These results suggest a model in which, despite the lack of systemic inflammation, IRC persist in remission, indicating that IRC are an acquired feature of RA. They have, however, lost their hyper-responsiveness, acquired a potential for survival, and no longer express chemokine receptors. IRC persistence in remission confirms their important role in chronic inflammation as circulating precursors of pathogenic cells. This was further demonstrated by much higher incidence of relapse in patients with high IRC frequency in remission.
αB-Crystallin: A Novel Regulator of Breast Cancer Metastasis to the Brain
Authors: Dmitry Malin, Elena Strekalova, Vladimir Petrovic, Allison M. Deal, Abraham Al Ahmad, Barbara Adamo, C. Ryan Miller, Andrey Ugolkov, Chad Livasy, Karen Fritchie, Erika Hamilton, Kimberly Blackwell, Joseph Geradts, Matt Ewend, Lisa Carey, Eric V. Shusta, Carey K. Anders, Vincent L. Cryns
Journal: Clinical Cancer Research (2013)

Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and are associated with a high incidence of brain metastases and poor clinical outcomes. The molecular chaperone αB-crystallin is predominantly expressed in triple-negative breast cancer (TNBC) and contributes to an aggressive tumor phenotype in preclinical models. We investigated the potential role of αB-crystallin in brain metastasis in TNBCs.αB-crystallin expression in primary breast carcinomas and brain metastases was analyzed by immunohistochemistry among patients with breast cancer with brain metastases. αB-crystallin was overexpressed or silenced in two different TNBC cell lines. The effects on cell adhesion to human brain microvascular endothelial cells (HBMEC) or extracellular matrix proteins, transendothelial migration, and transmigration across a HBMEC/astrocyte coculture blood-brain barrier (BBB) model were examined. In addition, the effects of overexpressing or silencing αB-crystallin on brain metastasis in vivo were investigated using orthotopic TNBC models.In a cohort of women with breast cancer brain metastasis, αB-crystallin expression in primary breast carcinomas was associated with poor overall survival and poor survival after brain metastasis, even among patients with TNBC. Stable overexpression of αB-crystallin in TNBC cells enhanced adhesion to HBMECs, transendothelial migration, and BBB transmigration in vitro, whereas silencing αB-crystallin inhibited these events. αB-crystallin promoted adhesion of TNBC cells to HBMECs, at least in part, through an α3β1 integrin-dependent mechanism. αB-crystallin overexpression promoted brain metastasis, whereas silencing αB-crystallin inhibited brain metastasis in orthotopic TNBC models.αB-crystallin is a novel regulator of brain metastasis in TNBC and represents a potential biomarker and drug target for this aggressive disease.
Merit Awards for General Practitioners
Authors: J. G. Ball, A. A. Walker, J. S. Price, E. M. Lurring, R. F. Lurring, A. M. Wadsworth, G. R. C. Campion, P. M. E. Dutton, G. J. Wilcox, J. M. Elliott, D. E. Sargent
Journal: BMJ (1966)
Postconditioning: Reperfusion of “reperfusion injury” after hibernation
Authors: D GARCIADORADO, H PIPER
Journal: Cardiovascular Research (2005)

The newly developed concept of postconditioning as a way of reducing reperfusion injury has been receiving much attention in the literature, both in basic science and clinical circles. Cardiovascular Research will be hosting a Spotlight Issue entitled “ Cardiac Protection by Pre- and Postconditioning ” in May of this year. This editorial is thought to serve as an introduction to the upcoming issue.

One of the major advances of all times in cardiovascular therapy has been the development and generalization of reperfusion treatment in patients with acute coronary occlusion and evolving myocardial infarction. The experimental basis for that therapy was provided in the early 1980s by the group of Jennings and Reimer at Duke University with the demonstration that early reperfusion can salvage ischemic myocardium that otherwise would die, and that the effectiveness of reperfusion depends on the severity and duration of prior ischemia [1]. Despite its overall beneficial effect, experimental myocardial reperfusion was associated with prominent arrhythmias, enzyme release, and other adverse phenomena that were grouped under the imprecise term “reperfusion injury”. Reperfusion injury attracted the attention of many basic scientists, but the success of large clinical trials demonstrating the beneficial effect of reperfusion in patients pushed research on reperfusion injury into the background [2]. A second origin of the concept of reperfusion injury came from the work of Hearse et al. in London who showed in the mid-1970s that reperfusion of an isolated ischemic heart could provoke myocardial contracture and massive myocytolysis [3]. Since they attributed this phenomenon to tissue reoxygenation and the potentially detrimental role of oxygen, they termed this phenomenon the “oxygen paradox” [3,4]. In …
Intrinsic functional deficits associated with increased risk of ankle injuries: a systematic review with meta-analysis
Authors: Jeremy Witchalls, Peter Blanch, Gordon Waddington, Roger Adams
Journal: British Journal of Sports Medicine (2011)

Background A history of ankle injury is known to be associated with an increased risk of future injuries. Prevention of a first-time injury to an ankle will also prevent subsequent re-injury; yet these participants are often overlooked in reports of preventive testing. Determining the functional deficits which promote injury risk in all ankles, through studies inclusive of previously injured and never injured ankles, will enable training to be directed at improving known deficits in all sports participants. Objective To review studies investigating the measurement of intrinsic functions in healthy ankles and assess their predictive value for injury. Method Systematic review and meta-analysis of journal articles from selected electronic databases. Using all papers that included sufficient data for extraction in any paradigm, the authors pooled results for measures of strength, postural control, proprioception, muscle reaction time in response to perturbation, range of movement and ligament stability. Results Thirteen papers were found with adequate data reporting to allow calculation of pooled standardised mean difference (SMD) or pooled RR. The following are all associated with an increased risk of ankle injury: higher postural sway (SMD=0.693, 95% CI=0.151 to 1.235, p=0.012), being in the lower postural stability group (RR=2.06, 95% CI=1.364 to 3.111, p=0.001), lower inversion proprioception (0.573, 0.244 to 0.902, &lt;0.001), higher concentric plantar flexion strength at faster speeds (0.372, 0.092 to 0.652, 0.009) and lower eccentric eversion strength at slower speeds (0.337, 0.117 to 0.557, 0.003). Conclusion There is a set of intrinsic functional and structural ankle deficits associated with significantly increased risk of ankle injury. These findings will enable clinicians and sports trainers to measure and train specific deficits in sports people for the prevention of ankle injury.
Hepatitis C viral RNA in serum of patients with chronic non-A, non-B hepatitis: Detection by the polymerase chain reaction using multiple primer sets
Authors: Karen Cristiano, Adrian M. Di Bisceglie, Jay H. Hoofnagle, Stephen M. Feinstone
Journal: Hepatology (1991)

The recently introduced antibody test for hepatitis C virus infection has already proved to be valuable in many situations such as screening blood donors and diagnosing chronically infected patients, but this antibody assay has certain limitations. Hepatitis C virus itself is usually present in clinical specimens at very low titers; therefore a useful assay for the virus must have very high sensitivity. We have developed a simple, highly sensitive assay for hepatitis C virus RNA based on the polymerase chain reaction. In this test RNA extracted from hepatitis C virus—infected serum or plasma is used as the template for double polymerase chain reaction with nested primers. Sensitivity studies demonstrate that this assay is able to detect hepatitis C virus at or beyond the sensitivity level of chimpanzee infectivity. Preliminary studies in chronic non-A, non-B hepatitis showed that 16 of 36 patients positive for antibody to hepatitis C virus and 2 of 4 patients negative for antibody to hepatitis C virus were positive in the polymerase chain reaction test. By retesting the polymerase chain reaction—negative patients with several sets of polymerase chain reaction primers, we found hepatitis C virus RNA in 35 of the 40 patients including all 4 seronegative patients. Normal human plasma and plasma from patients with hepatitis B infection did not react in this test. This assay has proved to be valuable for determining the presence of hepatitis C virus RNA in various samples. Furthermore, it offers the possibility of diagnosis of hepatitis C virus infection in patients who do not react in the presently available antibody tests. (HEPATOLOGY 1991;14:51-55.)
Regulation of cation content and cell volume in hemoglobin erythrocytes from patients with homozygous hemoglobin C disease.
Authors: C Brugnara, A S Kopin, H F Bunn, D C Tosteson
Journal: Journal of Clinical Investigation (1985)

Erythrocytes from patients with homozygous hemoglobin C disease (CC cells) contain less K, Na, and water than do erythrocytes from normal subjects that contain only hemoglobin A (AA cells). In this paper, we provide evidence that the reduced K content and volume of CC cells are due to the activity in these but not in AA cells of a K transport system that is: (a) insensitive to ouabain and bumetanide, and (b) stimulated by increased cell volume, and dependent on internal pH (pHi). When the cation and water content of CC cells was increased (by making the membrane temporarily permeable to cations with nystatin) and the cells were then incubated in an isotonic medium containing 140 mM NaCl and 4 mM KCl, they lost K and shrunk back toward the original volume. This regulatory K and volume decrease was not inhibited by ouabain or bumetanide. When CC cells were incubated in a hypotonic medium, with ouabain and bumetanide, they also lost K and shrunk toward the original volume. This behavior was not observed in control AA cells. The ouabain- and bumetanide-resistant K efflux from CC cells was volume and pH dependent: K efflux from CC cells rose from 5-6 to 20-25 mmol/liter of cells X h, when cell volume was increased by increasing cell solute content (nystatin method) or by exposure to hypotonic media. In CC cells, the dependence of K efflux on pHo had a bell shape, with a maximal flux (20-25 mmol/liter of cells X h) at pHo 6.8-7.0. In contrast, the K efflux from control cells was minimal at pH 7.4 (1.2 mmol/liter of cells X h) and was slightly stimulated by both acid and alkaline pH. In order to study the effect of pHi and pHo on K efflux, CC cells were incubated with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (150 microM) and acetazolamide (1 mM) at different pHi (6.7, 7.3, and 7.8), and resuspended in media with different pHo (6.75, 7.4, and 8): K efflux was stimulated by reducing pHi but was independent of pHo. The ouabain- and bumetanide-resistant K efflux from CC cells was not inhibited by some inhibitors of the Ca2+-activated K permeability. It seems likely that the genetically determined change in the primary structure of hemoglobin C directly or indirectly causes this modification in K transport. One possible mechanism could involve an electrostatic interaction between C hemoglobin and components of the erythrocyte membrane.
Treatment of Nosocomial Pneumonia and Tracheobronchitis Caused by Multidrug-Resistant <i>Pseudomonas aeruginosa</i> with Aerosolized Colistin
Authors: DAVIDSON H. HAMER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Gram-negative bacilli including multidrug-resistant (MDR) Pseudomonas aeruginosa are responsible for a significant proportion of episodes of nosocomial pneumonia. Since the development of new antibiotics with activity against gram-negative organisms has not kept pace with the increase in prevalence of MDR pathogens, there has been renewed interest in antimicrobial agents that had previously been used but had been abandoned because of toxic side effects. This report describes three patients with nosocomial pneumonia or tracheobronchitis due to multiresistant strains of P. aeruginosa for whom aerosolized colistin proved beneficial as supplemental therapy. Aerosolized colistin merits further consideration as a therapeutic intervention for patients with pulmonary infections due to MDR P. aeruginosa.
Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies
Authors: H Vally
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose sulfited wine challenge protocol was employed to establish if wine sensitive asthmatics as a group have an increased sensitivity to sulfites. <h3>METHODS</h3> In study 1, 24 asthmatic patients with a strong history of wine induced asthma were screened. Subjects showing positive responses to single blind high sulfite (300 ppm) wine challenge were rechallenged on separate days in a double blind, placebo controlled fashion with wines of varying sulfite levels to characterise their responses to these drinks. In study 2, wine sensitive asthmatic patients (n=12) and control asthmatics (n=6) were challenged cumulatively with wine containing increasing concentrations of sulfite in order to characterise further their sensitivity to sulfites in wine. <h3>RESULTS</h3> Four of the 24 self-reporting wine sensitive asthmatic patients were found to respond to sulfite additives in wine when challenged in a single dose fashion (study 1). In the double blind dose-response study all four had a significant fall in forced expiratory volume in one second (FEV<sub>1</sub>) (&gt;15% from baseline) following exposure to wine containing 300 ppm sulfite, but did not respond to wines containing 20, 75 or 150 ppm sulfite. Responses were maximal at 5 minutes (mean (SD) maximal decline in FEV<sub>1</sub> 28.7 (13)%) and took 15–60 minutes to return to baseline levels. In the cumulative dose-response study (study 2) no significant difference was observed in any of the lung function parameters measured (FEV<sub>1</sub>, peak expiratory flow (PEF), mid phase forced expiratory flow (FEF<sub>25–75</sub>)) between wine sensitive and normal asthmatic subjects. <h3>CONCLUSIONS</h3> Only a small number of wine sensitive asthmatic patients responded to a single dose challenge with sulfited wine under laboratory conditions. This may suggest that the role of sulfites and/or wine in triggering asthmatic responses has been overestimated. Alternatively, cofactors or other components in wine may play an important role in wine induced asthma. Cumulative sulfite dose challenges did not detect an increased sensitivity to sulfite in wine sensitive asthmatics and an alternative approach to identifying sulfite/wine sensitive asthma may be required.
Breast Implants and Cancer
Authors: L. A. Brinton, S. L. Brown
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Although silicone breast implants have been linked to various short-term complications, less is known about their long-range effects. Most attention has focused on connective tissue disorders, but the range of immunologic disturbances observed in women with implants suggests that consideration also be given to other chronic diseases, including cancer. The greatest attention has focused on breast cancer, given clinical reports suggesting an association and observations that mammographic visualization is deterred by implants. Findings from epidemiologic studies, however, actually suggest that breast cancer risk might be reduced among women with implants, although the biologic mechanism remains undefined. In addition, most studies do not suggest that women with breast implants have more advanced breast cancer at diagnosis or a worse prognosis than those without implants. The majority of studies have focused on women who received implants for cosmetic reasons, with little previous investigation of women who received implants for breast reconstruction following cancer surgery. In terms of other cancers, animal as well as clinical data suggest potential risks of sarcomas and hematologic cancers, including multiple myeloma. The risk of these cancers has not yet been adequately addressed by epidemiologic studies, although several ongoing studies should provide insights. It will be important for studies to consider effects of other lifestyle factors as well as to analyze relationships according to duration of implantation, a demonstrated determinant of implant deterioration. In addition, consideration should be given to type of implant, including implants with polyurethane foam covers, which can leak toluene diamine, a demonstrated carcinogen in animals.
Alcohol Consumption and Breast Cancer Recurrence and Survival Among Women With Early-Stage Breast Cancer: The Life After Cancer Epidemiology Study
Authors: Marilyn L. Kwan, Lawrence H. Kushi, Erin Weltzien, Emily K. Tam, Adrienne Castillo, Carol Sweeney, Bette J. Caan
Journal: Journal of Clinical Oncology (2010)

To examine the association of alcohol consumption after breast cancer diagnosis with recurrence and mortality among early-stage breast cancer survivors.Patients included 1,897 LACE study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years postdiagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry. Alcohol consumption (ie, wine, beer, and liquor) was assessed at cohort entry using a food frequency questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% CI with adjustment for known prognostic factors.Two hundred ninety-three breast cancer recurrences and 273 overall deaths were ascertained after an average follow-up of 7.4 years. Nine hundred fifty-eight women (51%) were considered drinkers (> 0.5 g/d of alcohol), and the majority drank wine (89%). Drinking ≥ 6 g/d of alcohol compared with no drinking was associated with an increased risk of breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83) and death due to breast cancer (HR, 1.51; 95% CI, 1.00 to 2.29). The increased risk of recurrence appeared to be greater among postmenopausal (HR, 1.51; 95% CI, 1.05 to 2.19) and overweight and obese women (HR, 1.60; 95% CI, 1.08 to 2.38). Alcohol intake was not associated with all-cause death and possibly associated with decreased risk of non-breast cancer death.Consuming three to four alcoholic drinks or more per week after a breast cancer diagnosis may increase risk of breast cancer recurrence, particularly among postmenopausal and overweight/obese women, yet the cardioprotective effects of alcohol on non-breast cancer death were suggested.
"Contrasting Patterns of Selection at Pinus pinaster Ait. Drought Stress Candidate Genes as Revealed by Genetic Differentiation Analyses"
Authors: E. Eveno, C. Collada, M. A. Guevara, V. Leger, A. Soto, L. Diaz, P. Leger, S. C. Gonzalez-Martinez, M. T. Cervera, C. Plomion, P. H. Garnier-Gere
Journal: Molecular Biology and Evolution (2007)

The importance of natural selection for shaping adaptive trait differentiation among natural populations of allogamous tree species has long been recognized. Determining the molecular basis of local adaptation remains largely unresolved, and the respective roles of selection and demography in shaping population structure are actively debated. Using a multilocus scan that aims to detect outliers from simulated neutral expectations, we analyzed patterns of nucleotide diversity and genetic differentiation at 11 polymorphic candidate genes for drought stress tolerance in phenotypically contrasted Pinus pinaster Ait. populations across its geographical range. We compared 3 coalescent-based methods: 2 frequentist-like, including 1 approach specifically developed for biallelic single nucleotide polymorphisms (SNPs) here and 1 Bayesian. Five genes showed outlier patterns that were robust across methods at the haplotype level for 2 of them. Two genes presented higher FST values than expected (PR-AGP4 and erd3), suggesting that they could have been affected by the action of diversifying selection among populations. In contrast, 3 genes presented lower FST values than expected (dhn-1, dhn2, and lp3-1), which could represent signatures of homogenizing selection among populations. A smaller proportion of outliers were detected at the SNP level suggesting the potential functional significance of particular combinations of sites in drought-response candidate genes. The Bayesian method appeared robust to low sample sizes, flexible to assumptions regarding migration rates, and powerful for detecting selection at the haplotype level, but the frequentist-like method adapted to SNPs was more efficient for the identification of outlier SNPs showing low differentiation. Population-specific effects estimated in the Bayesian method also revealed populations with lower immigration rates, which could have led to favorable situations for local adaptation. Outlier patterns are discussed in relation to the different genes' putative involvement in drought tolerance responses, from published results in transcriptomics and association mapping in P. pinaster and other related species. These genes clearly constitute relevant candidates for future association studies in P. pinaster.