tbuckley/cabot-search huggingface dataset:
Characterisation of pleural inflammation occurring after primary spontaneous pneumothorax
Authors: A. De Smedt, E. Vanderlinden, C. Demanet, M. De Waele, A. Goossens, M. Noppen
Journal: European Respiratory Journal (2004)

The aim of this study was to examine the inflammatory reaction occurring in the pleural space of patients suffering from primary spontaneous pneumothorax (PSP) using pleural lavage, which was performed in patients with PSP and in healthy control subjects (essential hyperhidrosis patients undergoing thoracoscopy for sympathicolysis treatment). Cellular and solute composition of lavage fluid, peripheral blood and parietal pleural biopsies were analysed. PSP lavage fluid showed an increase in all differentiated leucocytes, but most strikingly eosinophils and neutrophils. In the blood of patients with PSP, the total number of leucocytes and the absolute number of eosinophils, neutrophils and monocytes were also significantly increased. The time in which air was present in the pleural space was positively correlated with the increase of eosinophils in lavage fluid, parietal pleura and blood. Eosinophilic cationic protein was elevated after PSP and strongly correlated with the absolute number of lavage eosinophils. Chemo and cytokine analysis in lavage fluid showed differences in concentrations of interleukin (IL)‐5, IL‐6, IL‐8, IL‐12p40, tumour necrosis factor‐α and RANTES, but not of eotaxin. Surprisingly, high levels of lipopolysaccharide binding protein were also measured. Primary spontaneous pnumothorax is associated with a substantial pleural inflammatory reaction. The authors hypothesise that mechanical stretch factors, lipopolysaccharide binding protein/lipopolysaccharide complexes or other environmental components trigger pleural inflammation after primary spontaneous pnumothorax.
Haplotypic Background of a Private Allele at High Frequency in the Americas
Authors: Kari B. Schroeder, Mattias Jakobsson, Michael H. Crawford, Theodore G. Schurr, Simina M. Boca, Donald F. Conrad, Raul Y. Tito, Ludmilla P. Osipova, Larissa A. Tarskaia, Sergey I. Zhadanov, Jeffrey D. Wall, Jonathan K. Pritchard, Ripan S. Malhi, David G. Smith, Noah A. Rosenberg
Journal: Molecular Biology and Evolution (2009)

Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across ∼500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the "American Modal Haplotype" (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all modern Native Americans and Western Beringians trace a large portion of their ancestry to a single founding population that may have been isolated from other Asian populations prior to expanding into the Americas.
Stretching before exercise: an evidence based approach
Authors: Ian Shrier
Journal: British Journal of Sports Medicine (2000)

Clinicians are under increasing pressure to base their treatment of patients on research findings—that is, to practice evidence based medicine.1 Although some authors argue that only research from human randomised clinical trials (RCTs) should be used to determine clinical management,2 an alternative is to consider the study design (RCT, cohort, basic science, etc) as one of many variables, and that no evidence should be discarded a priori. In other words, the careful interpretation of all evidence is, and has always been, the real art of medicine.3 This editorial explores these concepts using the sport medicine example of promoting stretching before exercise to prevent injury. In summary, a previous critical review of both clinical and basic science literature suggested that such stretching would not prevent injury.4 This conclusion was subsequently supported by a large RCT published five months later.5 Had the review relied only on previous RCT data, or even RCT and cohort data, the conclusions would likely have been the opposite, and incorrect.

Was there ever any evidence to suggest that stretching before exercise prevents injury? In 1983 Ekstrand et al 6 found that a …
Determination of Infused Epinephrine and Norepinephrine in Plasma Using Isolated Guinea Pig Heart Technique
Authors: Walter M. Booker, Tracy Walton, Rafael Linares, Andre F. De Schaepdryver
Journal: Circulation Research (1962)

Experiments have been described which show the very high sensitivity of the isolated perfused guinea pig heart preparation in the estimation of plasma levels of catecholamines after intravenous infusion in dogs. It was observed that crude plasma samples show the same pattern of positive inotropic response as extracts of these samples. By means of the isolated guinea pig heart method, the presence of circulating catecholamines could still be detected 30 minutes after the end of infusion. The observation that dichloroisoproterenol may block the positive inotropic effect of epinephrine, while only slightly reducing the positive inotropic effect of norepinephrine, may be used to differentiate between these two catecholamines.
Synergistic Tumor Suppression by Coexpression of FHIT and p53 Coincides with FHIT-Mediated MDM2 Inactivation and p53 Stabilization in Human Non-Small Cell Lung Cancer Cells
Authors: Masahiko Nishizaki, Ji-ichiro Sasaki, Bingliang Fang, Edward. N. Atkinson, John D. Minna, Jack A. Roth, Lin Ji
Journal: Cancer Research (2004)

Abstract Aberrations of the tumor suppressor genes FHIT and p53 are frequently associated with a wide range of human cancers, including lung cancer. We studied the combined effects of FHIT and p53 proteins on tumor cell proliferation and apoptosis in human non-small cell lung carcinoma (NSCLC) cells in vitro and on tumor growth in animal models by adenoviral vector-mediated cotransfer of wild-type FHIT and p53 genes. We found that the coexpression of FHIT and p53 synergistically inhibited tumor cell proliferation in NSCLC cells in vitro and suppressed the growth of human tumor xenografts in nude mice. Furthermore, we found that this synergistic inhibition of tumor cell growth corresponded with the FHIT-mediated inactivation of MDM2, which thereby blocked the association of MDM2 with p53, thus stabilizing the p53 protein. Our results therefore reveal a novel molecular mechanism consisting of FHIT-mediated tumor suppression and the interaction of FHIT with other cellular components in the pathways regulating p53 activity. These findings show that combination treatment with synergistic tumor-suppressing gene therapy such as Ad-FHIT and Ad-p53 may be an effective therapeutic strategy for NSCLC and other cancers.
Chronic lymphocytic leukemia: A monoclonal disease
Authors: Dilip L. Solanki, Paul R. McCurdy, Richard P. Macdermott
Journal: American Journal of Hematology (1982)

Abstract A black woman with chronic lymphocytic leukemia (CLL) was found to have monoclonal B lymphocytes with one type of surface immunoglobulin and one variant of G6PD (glucose‐6‐phosphate dehydrogenase) (G6PD A). Erythrocytes and T cells contained both G6PD A and G6PD B and hence were of polyclonal origin. The CLL cells in this patient likely arose from a developmental stage later than the step of differentiation into T and B lymphocytes. Furthermore, her erythrocytes did not arise from a stem cell affected by the CLL process.
Higher Expression of the Androgen-Regulated Gene <i>PSA/HK3</i> mRNA in Prostate Cancer Tissues Predicts Biochemical Recurrence-Free Survival
Authors: Joseph R. Sterbis, Chunling Gao, Bungo Furusato, Yongmei Chen, Syed Shaheduzzaman, Lakshmi Ravindranath, David J. Osborn, Inger L. Rosner, Albert Dobi, David G. McLeod, Isabell A. Sesterhenn, Shiv Srivastava, Jennifer Cullen, Gyorgy Petrovics
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Alterations of the androgen receptor (AR)-mediated signaling through numerous mechanisms are increasingly recognized in prostate cancer (CaP) progression. We hypothesized that the assessment of well-defined AR transcriptional targets (e.g., PSA/HK3 mRNA) in CaP tissues will provide in vivo readout of AR dysfunctions. Moreover, quantitative expression features of PSA/HK3 mRNA in prostate tumor cells may serve as a prognostic indicator of disease progression. Experimental Design: Paired benign and malignant epithelial cells (242 specimens) were obtained from laser capture microdissection of frozen OCT-embedded tissue sections prepared from radical prostatectomy specimens of 121 patients. Quantitative expression of PSA/HK3 mRNA in the matched malignant and benign cells was analyzed by real-time reverse transcription-PCR. Results: CaP cells express significantly lower PSA/HK3 mRNA levels than matched benign cells (P = 0.0133). Moreover, low PSA/HK3 mRNA expression in malignant cells was associated with increased risk of biochemical recurrence (P = 0.0217), as well as with time to recurrence (P = 0.0371), in patients with intermediate preoperative serum prostate-specific antigen levels (2-10 ng/mL). The expression of androgen-dependent genes in clinical samples correlates with each other in patients with higher expression of PSA/HK3 mRNA but not in patients with lower expression of PSA/HK3 mRNA reflecting AR pathway dysfunction. Conclusions: Our study has unraveled a novel prognostic utility of quantitative measurements of PSA/HK3 mRNA reflecting AR transcriptional activity in CaP cells, which is independent of serum prostate-specific antigen. It also has potential in stratifying subsets of patients exhibiting progressive disease associated with dampened AR transcriptional functions who may be targeted by tailored therapeutic strategies.
Benefits and Harms of Prostate-Specific Antigen Screening for Prostate Cancer: An Evidence Update for the U.S. Preventive Services Task Force
Authors: Kenneth Lin, Robert Lipsitz, Therese Miller, Supriya Janakiraman
Journal: Annals of Internal Medicine (2008)

Background: Prostate cancer is the most common nonskin cancer in men in the United States, and prostate cancer screening has increased in recent years. In 2002, the U.S. Preventive Services Task Force concluded that evidence was insufficient to recommend for or against screening for prostate cancer with prostate-specific antigen (PSA) testing. Purpose: To examine new evidence on benefits and harms of screening asymptomatic men for prostate cancer with PSA. Data Sources: English-language articles identified in PubMed and the Cochrane Library (search dates, January 2002 to July 2007), reference lists of retrieved articles, and expert suggestions. Study Selection: Randomized, controlled trials and meta-analyses of PSA screening and cross-sectional and cohort studies of screening harms and of the natural history of screening-detected cancer were selected to answer the following questions: Does screening for prostate cancer with PSA, as a single-threshold test or as a function of multiple tests over time, decrease morbidity or mortality? What are the magnitude and nature of harms associated with prostate cancer screening, other than overtreatment? What is the natural history of PSA-detected, nonpalpable, localized prostate cancer? Data Extraction: Studies were reviewed, abstracted, and rated for quality by using predefined U.S. Preventive Services Task Force criteria. Data Synthesis: No good-quality randomized, controlled trials of screening for prostate cancer have been completed. In 1 cross-sectional and 2 prospective cohort studies of fair to good quality, false-positive PSA screening results caused psychological adverse effects for up to 1 year after the test. The natural history of PSA-detected prostate cancer is poorly understood. Limitations: Few eligible studies were identified. Long-term adverse effects of false-positive PSA screening test results are unknown. Conclusion: Prostate-specific antigen screening is associated with psychological harms, and its potential benefits remain uncertain.
Circulating Tumor Cell Analysis in Metastatic Triple-Negative Breast Cancers
Authors: Mark Jesus M. Magbanua, Lisa A. Carey, Amy DeLuca, Jimmy Hwang, Janet H. Scott, Mothaffar F. Rimawi, Erica L. Mayer, P. Kelly Marcom, Minetta C. Liu, Francisco J. Esteva, John W. Park, Hope S. Rugo
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Recent developments in rare-cell technology have led to improved blood-based assays that allow for the reliable detection, enumeration, and more recently, genomic profiling of circulating tumor cells (CTC). We evaluated two different approaches for enumeration of CTCs in a prospective therapeutic study of patients with metastatic triple-negative breast cancer (TNBC). Experimental Design: The CellSearch system, a commercially available and U.S. Food and Drug Administration (FDA)–cleared assay for CTC enumeration, and IE/FC, an alternative method using EPCAM-based immunomagnetic enrichment and flow cytometry that maintains cell viability, were used to enumerate CTCs in the blood of patients with metastatic TNBC. CTC numbers were assessed at baseline and 7 to 14 days after initiation of therapy with cetuximab ± carboplatin in a phase II multicenter clinical trial (TBCRC 001). Results: CTC numbers from two methods were significantly correlated at baseline (r = 0.62) and at 7 to 14 days (r = 0.53). Baseline CTCs showed no association with time-to-progression (TTP), whereas CTCs at 7 to 14 days were significantly correlated with TTP (CellSearch P = 0.02; IE/FC P = 0.03). CTCs at both time points were significantly associated with overall survival (OS) [CellSearch: baseline (P = 0.0001) and 7 to 14 days (P &amp;lt; 0.0001); IE/FC: baseline (P = 0.0009) and 7 to 14 days (P = 0.0086)]. Conclusions: Our findings demonstrate that CTC enumeration by two different assays was highly concordant. In addition, results of both assays were significantly correlated with TTP and OS in patients with TNBC. The IE/FC method is also easily adapted to isolation of pure populations of CTCs for genomic profiling. Clin Cancer Res; 21(5); 1098–105. ©2014 AACR.
Compartmentalization of the Inflammatory Response to Inhaled Grain Dust
Authors: SUSANNE BECKER, WILLIAM A. CLAPP, JACQUELINE QUAY, KATHY L. FREES, HILLEL S. KOREN, DAVID A. SCHWARTZ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Interleukin (IL)-1 β , IL-6, IL-8, tumor necrosis factor (TNF)- α , and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower respiratory tract of workers exposed by inhalation to aqueous extracts of corn dust extract. Alveolar macrophages (AM) have long been considered the cell type responsible for producing these cytokines, and only recently has it been realized that airway epithelial cells may also be involved in cytokine production. In order to determine whether airway epithelia are involved in the inflammatory response to inhaled corn dust extract and to compare the magnitude of response of bronchial epithelial cells (BE) and bronchoalveolar lavage (BAL) cells, we used the reverse transcriptase/polymerase chain reaction (RT/PCR) technique in a semiquantitative manner to evaluate the concentration of IL-1 β , IL-6, IL-8, TNF- α , and sIL-1RA. Alveolar cells were obtained by BAL, and BE were obtained by endobronchial brush biopsy from 15 grain handlers 6 h after experimental inhalation of saline or an aqueous corn dust extract. After inhalation of saline, BE expressed low but detectable levels of IL-6, IL-8, and IL-1 β ( > 1 complementary DNA [cDNA] molecule/cell). After inhalation of corn dust extract, the expression of messenger RNA (mRNA) for IL-1 β and IL-8 in the BE were significantly increased, whereas no change was seen in IL-6, sIL-1RA, and TNF- α mRNA expression. Comparing cytokine mRNA levels in BE and BAL cells from the same subjects after inhalation of corn dust extract, BE and BAL cells expressed equivalent amounts of IL-8 mRNA; IL-1 β was 11-fold higher in BAL cells; and TNF- α and sIL-1RA were expressed exclusively by BAL cells. Immunostaining for the cytokines in BAL cells showed cytokine protein expression in AMs but not in polymorphonuclear cells (PMNs). On the other hand, sIL-1RA was strongly expressed in both AMs and PMNs. Analysis of cytokine protein levels in endobronchial lavage (EBL) fluid demonstrated that only IL-8 was released in detectable amounts into the airway lumen, whereas all the other cytokines of interest were exclusively found in the BAL fluid. Thus, within 6 h after inhalation exposure to corn dust extract, BE appear to contribute to airway inflammation by producing IL-8. AMs are responsible for most of the IL-1 β and IL-6 production in the alveolar region, whereas AMs and PMNs both produce sIL-1RA. Our findings suggest that the inflammatory response to inhaled grain dust is compartmentalized, involving specific mediators of inflammation released by macrophages, neutrophils, and airway epithelial cells.
Randomized trial of intrapatient dose escalation of single agent carboplatin as first-line treatment for advanced ovarian cancer: An SGCTG study (SCOTROC 4)
Authors: S. B. Kaye, P. Vasey, G. Rustin, S. Pledge, C. Williams, H. Gabra, G. Skailes, A. Lamont, L. Lewsley, J. Paul
Journal: Journal of Clinical Oncology (2009)

5537 Background: In the absence of toxicity, carboplatin (the most widely used drug in ovarian cancer) is generally given at the same (flat) dose with each treatment cycle. However, retrospective data suggest a correlation between extent of myelosuppression and outcome, as has been observed in other diseases. Our hypothesis was therefore that intrapatient dose escalation, according to nadir blood counts, could lead to an improved outcome compared to conventional flat dosing. Methods: Patients with previously untreated stage IC to IV ovarian cancer were randomized to receive 6 cycles of carboplatin AUC 6 q3 w either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2–6 based on nadir FBC (Arm B). The primary outcome measure was progression-free survival (PFS), and a target accrual of 1300 pts was envisaged, aimed at detecting a 20% increase in PFS with 80% power (5% 2-sided level of statistical significance). Results: From March 2004 to November 2008, 937 pts were recruited from 70 centres. Dose escalation occurred in 82% pts on Arm B. The median AUCs actually received were 6.0 (Arm A) and 6.84 (Arm B). As expected, more myelosuppression was seen in Arm B (p &lt; 0.001 for all parameters). More grade 3/4 non-haematological toxicity was also seen in Arm B (31%, vs 22% in Arm A, p &lt; 0.001) but there was no significant difference in global quality of life. To date, 477 PFS events have been observed out of a planned total of 950. The median PFS was 13.9m in Arm A, and 13.5m in Arm B, and the observed hazard ratio (Arm B/Arm A) is 1.04, with 95% C.I. of 0.87 to 1.24. This excludes the clinically relevant benefit of 0.83 used to design the study. A futility analysis also indicated that the probability of a statistically significant result in favour of Arm B at the planned study end was 0.12 at best. Conclusions: Following the Data Monitoring Committee recommendation, the trial has therefore been closed to recruitment, with no evidence of benefit for intra-patient dose escalation of carboplatin. A separate analysis of tissue samples, aimed at elucidating mechanisms of (single agent) carboplatin resistance is ongoing. No significant financial relationships to disclose.
Alloresistance to engraftment of allogeneic donor bone marrow is mediated by an Lyt-2+ T cell in mixed allogeneic reconstitution (C57BL/10Sn + B10.D2/nSn----C57BL/10Sn).
Authors: S T Ildstad, J A Bluestone, D H Sachs
Journal: The Journal of Experimental Medicine (1986)

In the mixed allogeneic reconstitution (B10 + B10.D2----B10) model, alloresistance to engraftment of allogeneic donor results if the syngeneic component of the mixed bone marrow inoculum is not depleted of Lyt-2+ cells before transplantation. Resultant experimental animals repopulate as fully syngeneic, reject B10.D2 skin allografts, and are reactive to B10.D2 lymphoid cells in vitro, as assessed by mixed lymphocyte culture proliferative and cellular cytotoxicity assays. In contrast, depletion of Lyt-2-reactive cells from the syngeneic component of the mixed bone marrow inoculum results in mixed lymphopoietic chimerism and specific in vivo transplantation tolerance to B10.D2 allogeneic donor skin grafts and in vitro unreactivity to B10.D2 lymphoid elements. Full reactivity to third party is evident both in vitro and in vivo in these animals. This model may be helpful in further study of the syngeneic host-type cell phenotypes responsible for alloresistance to bone marrow engraftment.
Joint working in health and social care remains patchy despite years of effort
Authors: A. O'Dowd
Journal: BMJ (2011)

Professionals in health and social care are still not working together closely enough to provide care for people despite years of efforts to improve joint working, says the public spending watchdog.

Smooth integrated care is not being achieved across England concludes the report Joining up health and social care published by the Audit Commission on 1 December.

Significant money could be saved if every area were efficient, and primary care trusts could have saved £132m (€154m, $207m) in a year by handling emergency admissions better, said the authors.

The report, the second in a series of …