tbuckley/cabot-search huggingface dataset:
MicroRNA Regulation in Extreme Environments: Differential Expression of MicroRNAs in the Intertidal Snail <i>Littorina Littorea</i> During Extended Periods of Freezing and Anoxia
Authors: Kyle K. Biggar, Samantha F. Kornfeld, Yulia Maistrovski, Kenneth B. Storey
Journal: Genomics Proteomics & Bioinformatics (2012)

Abstract Several recent studies of vertebrate adaptation to environmental stress have suggested roles for microRNAs (miRNAs) in regulating global suppression of protein synthesis and/or restructuring protein expression patterns. The present study is the first to characterize stress-responsive alterations in the expression of miRNAs during natural freezing or anoxia exposures in an invertebrate species, the intertidal gastropod Littorina littorea. These snails are exposed to anoxia and freezing conditions as their environment constantly fluctuates on both a tidal and seasonal basis. The expression of selected miRNAs that are known to influence the cell cycle, cellular signaling pathways, carbohydrate metabolism and apoptosis was evaluated using RT-PCR. Compared to controls, significant changes in expression were observed for miR-1a-1, miR-34a and miR-29b in hepatopancreas and for miR-1a-1, miR-34a, miR-133a, miR-125b, miR-29b and miR-2a in foot muscle after freezing exposure at −6 °C for 24 h (P &amp;lt; 0.05). In addition, in response to anoxia stress for 24 h, significant changes in expression were also observed for miR-1a-1, miR-210 and miR-29b in hepatopancreas and for miR-1a-1, miR-34a, miR-133a, miR-29b and miR-2a in foot muscle (P &amp;lt; 0.05). Moreover, protein expression of Dicer, an enzyme responsible for mature microRNA processing, was increased in foot muscle during freezing and anoxia and in hepatopancreas during freezing. Alterations in expression of these miRNAs in L. littorea tissues may contribute to organismal survival under freezing and anoxia.
Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis
Authors: J G Walker, M J Ahern, M Coleman, H Weedon, V Papangelis, D Beroukas, P J Roberts-Thomson, M D Smith
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objectives:</b> To characterise the phenotype of the putative dendritic cells strongly expressing Jak3 and STAT4, which have been previously identified in the synovial tissue of patients with active rheumatoid arthritis (RA). <b>Methods:</b> Synovial biopsy specimens were obtained at arthroscopy from 30 patients with active RA (42 synovial biopsies). Immunohistological analysis was performed using monoclonal antibodies to detect dendritic cell subsets, including activation markers and cytokines relevant to dendritic cell function. Co-localisation of cell surface markers and cytokines was assessed primarily using sequential sections, with results confirmed by dual immunohistochemistry and immunofluorescence with confocal microscopy. <b>Results:</b> The dendritic cells identified in RA synovial tissue that strongly express Jak3 also strongly express STAT4 and STAT 6 and are correlated with the presence of serum rheumatoid factor. These cells are not confined to a single dendritic cell subset, with cells having phenotypes consistent with both myeloid- and plasmacytoid-type dendritic cells. The activation status of these dendritic cells suggests that they are maturing or mature dendritic cells. These dendritic cells produce IL12 as well as interferon α and γ. <b>Conclusions:</b> The close correlation of these dendritic cells with the presence of serum rheumatoid factor, a prognostic factor for worse disease outcome, and the strong expression by these cells of components of the Jak/STAT transcription factor pathway suggest a potential therapeutic target for the treatment of RA.
F-18 FDG PET in Infectious Diseases in Children
Authors: Gisele Depas, Thierry Decortis, Nadine Francotte, Guy Bricteux, Roland Hustinx
Journal: Clinical Nuclear Medicine (2007)

The aim is to report our observations regarding the role of F-18 FDG PET in children's infectious processes.A presentation is made of 3 neonatal infections unresponsive to treatment, 2 invasive infections in immunocompromised children, and 1 discitis in an immunocompetent child. PET or PET/CT was performed to address a specific question pertaining to the management of the diseases. Results were correlated with the clinical outcome. The impact on patient management is discussed.In 1 neonate, PET localized the infection in a bone which allowed surgical curettage. In another one, it localized the infection in recently renewed exogenous material and led to subsequent removal. It was negative in the third one, whose evolution was rapidly favorable. In the immunocompromised children, treatment of invasive infection was adapted according to the metabolic inflammatory activity of the disease. In a limping child with slight abnormalities on bone scintigraphy but major misleading involvement on MRI, PET/CT demonstrated hypermetabolism limited to a disc, thus avoiding further invasive procedures.Although not meant as a first choice examination, F-18 FDG PET should be considered in difficult cases of neonatal infection or in challenging diagnoses like discitis in the young child. It provides more accurate staging and treatment monitoring of the inflammatory process in invasive infections of immunocompromised children.
Clara Cell Specific Protein (CC16) Expression after Acute Lung Inflammation Induced by Intratracheal Lipopolysaccharide Administration
Authors: KARIM ARSALANE, FABRICE BROECKAERT, BERNARD KNOOPS, MURIELLE WIEDIG, GERARD TOUBEAU, ALFRED BERNARD
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Clara cell secretory protein (CC16, CC10, or CCSP), the major secretory protein of the Clara cell, presents several biologic properties, suggesting that it may play a protective role against intrapulmonary inflammatory processes. The aim of the present study was to investigate the changes of CC16 concentrations in the lung, bronchoalveolar lavage fluid (BALF), and serum of rats with acute lung injury induced by lipopolysaccharide (LPS). These changes were compared with Clara cell density, CC16 mRNA level in the lung and classic indices of inflammation in BALF. Injected at doses of 10, 100, or 200 μ g/100 g body weight, LPS induced an acute lung inflammation as estimated by an increased influx of cells and albumin in the BALF. This inflammatory response was associated with a marked reduction of CC16 concentrations in BALF and lung homogenate as well as of the CC16 mRNA levels in the lung. At the highest dose of LPS, the CC16-positive cell density in the bronchiolar epithelium was also decreased. In serum, by contrast, the concentration of CC16 was elevated as a consequence of increased airway permeability. Pretreating rats intraperitoneally with dexamethasone (2 mg/kg) significantly lowered the leukocyte influx and attenuated the albumin increase in BALF. Dexamethasone, however, failed to prevent the increased airway permeability to CC16, suggesting that during inflammation different mechanisms regulate the leakage of proteins across the alveolocapillary barrier depending on the direction of passage and/or the size of the protein. Our results show a marked decrease of the secretion and synthesis of CC16 during LPS-induced acute lung inflammation.
Stage 2 Genome-Wide Association Study of Candidate Low Penetrance Genes Implicated in Breast Cancer Risk.
Authors: G. Ross, N. Johnson, O. Fletcher, N. Orr, F. Hosking, A. Ashworth, I. dos Silva Santos, M. Lathrop, R. Houlston, J. Peto
Journal: Cancer Research (2009)

Abstract The risk of breast cancer in the first-degree female relatives of breast cancer cases is approximately double the risk in the general population. BRCA1 and BRCA2 account for less than 20% of this excess risk; the majority is probably due to the multiplicative effects of large numbers of low penetrance risk alleles. Genome-wide association studies (GWAS) have successfully identified 13 low-penetrance breast cancer risk alleles (Easton et al 2007, Hunter et al 2007, Stacey et al 2007, Zheng et al 2009, Ahmed et al 2009, Thomas et al 2009) but power calculations suggest that many more are still to be discovered.We have recently conducted a genome wide association study of 1,500 bilateral breast cancer cases, 200 cases with at least two affected first degree relatives and 1,450 controls from the 1958 birth cohort (WTCCC, 2007) using the Illumina HumanHap 370 chip. Based on these data and publicly available data from the Cancer Genetic Markers of Susceptibility (CGEMS) study we have selected 1,200 of the most significant SNPs to genotype in a stage 2 study comprising 5,500 breast cancer cases and 4,500 controls. All 13 of the known loci were replicated in this 2-stage analysis.Additional candidates at novel genomic loci are being genotyped in a replication study of 6,000 cases and 6,000 controls. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6136.
AIDS and medical confidentiality.
Authors: R Gillon
Journal: BMJ (1987)

In summary, I have argued that the arguments offered or hinted at in favour of doctors' breaking medical confidentiality by passing on information about their patients' HIV state to others, including other doctors, when this is against the patient's considered wishes are generally unconvincing. Although in highly exceptional cases there may be justifications for overriding confidentiality, the requirement of medical confidentiality is a very strong, though not absolute, obligation. Patients, their contacts, doctors and their staff, and the common good are most likely to be best served if that tradition continues to be honoured.One of the dilemmas facing British consultants in sexually transmitted diseases who are treating AIDS patients is whether to disclose the diagnosis to patients' general practitioners. Arguments have been advanced for specialists' breaching confidentiality and notifying general practitioners against patients' wishes in the interest of normal medical practice, the patients' best interests, the interests of health personnel and other patients, and the interests of society in general. Gillon examines each argument and concludes that none is sufficient to justify violating physician patient confidentiality in most cases. He argues that the goal of slowing the spread of AIDS is most likely to be achieved by gaining and keeping the "trust and cooperation of those at greatest risk" for the disease, and that protecting the confidentiality of the AIDS diagnosis is in everyone's best interest.A problem arises when people are found to be positive for HIV in a clinic for sexually transmitted diseases and refuse permission for the information to be passed on, despite advice about why it would be preferable for their general practitioner to be informed. The main justifications stated or implied in favor of breaking confidentiality in such circumstances are: 1) that it is normal medical practice; 2) that it is in the interests of the patient by leading to better medical care; 3) that it is in the interests of the general practitioner and associated staff by reducing their risks of accidentally acquiring HIV infection; 4) that it may be in the interests of other patients who might risk becoming infected by the patient; and 5) that it is in the interests of society in general by helping to reduce the spread of the AIDS epidemic. The arguments offered in favor of doctors' breaking medical confidentiality by passing on information about their patients' HIV state to others, including other doctors, when this is against the patient's considered wishes are generally unconvincing. Although in highly exceptional cases there may be justifications for overriding confidentiality, the requirement of medical confidentiality is a very strong, though not absolute, obligation, Patients, their contacts, doctors and their staff, and the common good are most likely to be best served if that tradition continues to be honored.
Age-Dependent Effect of Abciximab in Patients With Acute Coronary Syndromes Treated With Percutaneous Coronary Interventions
Authors: Gjin Ndrepepa, Adnan Kastrati, Julinda Mehilli, Franz-Josef Neumann, Jurriën ten Berg, Olga Bruskina, Franz Dotzer, Melchior Seyfarth, Jürgen Pache, Josef Dirschinger, Kurt Ulm, Peter B. Berger, Albert Schömig
Journal: Circulation (2006)

No studies have specifically performed an age-based analysis of the efficacy of abciximab in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention (PCI). The aim of the study was to assess whether there are age-dependent differences in the clinical benefit of abciximab in patients with acute coronary syndrome treated with PCI.We performed this retrospective analysis of 2022 patients with acute coronary syndrome enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) study and randomized to receive abciximab or placebo during a PCI procedure. The incidence of major adverse cardiac events (MACE) during the 30 days after PCI was the primary end point of the study. On the basis of the cutoff age value provided by logistic regression in connection with bootstrap resampling, patients were divided into those younger (n=1220) and older (n=802) than 70 years. Among younger patients, the incidence of MACE was 7.7% in the abciximab group versus 13.3% in the placebo group (relative risk 0.57, 95% confidence interval 0.40 to 0.80, P=0.001). In contrast, no difference was observed among older patients: The incidence of MACE was 10.9% in the abciximab group versus 9.9% in the placebo group (relative risk 1.10, 95% confidence interval 0.72 to 1.69, P=0.65). After adjustment for other variables, including cardiac troponin, there was a significant interaction between age and abciximab (P=0.04) with respect to MACE reduction, with abciximab being more effective in younger patients.In patients with non-ST-elevation acute coronary syndromes undergoing PCI, the efficacy of abciximab appears to be age-dependent, with greater benefit among younger patients.
Religion, Mental Health, and Personality: A Review of Empirical Studies
Authors: VICTOR D. SANUA
Journal: American Journal of Psychiatry (1969)

Reviewing a number of recent studies pertinent to the common belief that religion is a basis of sound mental health, general well-being, and humanitarianism, this author finds no empirical support for the theory. He concludes that contemporary religious education does not seem to ensure healthier attitudes and discusses the possibilities for remedying this failure.
Orthopedic Surgery
Authors: Joseph S. Barr
Journal: New England Journal of Medicine (1948)

ALTHOUGH it is not the purpose of this paper to consider in detail the general factors that as a rule affect equally the growth of both limbs, a few words about normal growth may not be amiss.Nature produces regularly in the human being, as in many other animals, paired, symmetrical, mirror-imaged extremities of essentially identical length. These normal growth processes are complex and dynamic, beginning with the union of an ovum and a sperm, which carry in their chromosomes the hereditary factors (genes) that determine whether the person will have the muscular legs of an athlete, the shapely limbs . . .
Epigenetic Mechanisms of Promigratory Chemokine CXCL14 Regulation in Human Prostate Cancer Cells
Authors: Eun Young Song, Michael R. Shurin, Irina L. Tourkova, Dmitriy W. Gutkin, Galina V. Shurin
Journal: Cancer Research (2010)

Chemokines play the key role in initiating immune responses by regulating the attraction and homing of immune cells to the lymphoid and nonlymphoid tissues. CXCL14 is a chemokine that in tumors may act as chemoattractant for monocytes and dendritic cells (DC), which may modulate antitumor immune responses in certain cancers. In this study, we investigated the mechanisms of loss of CXCL14 in prostate cancer cells. Cell treatment with the demethylating agent 5-aza-2-deoxycytidine resulted in the recovery of CXCL14 mRNA and protein expression. Hypermethylated CpG island sequences encompassing the CXCL14 gene promoter were identified. The restoration of CXCL14 by 5-aza-2-deoxycytidine treatment had functional impact, based on the DC chemoattractant activity of conditioned medium from drug-treated cells. Conversely, CXCL14 removal from conditioned media by affinity chromatography abolished its chemotactic properties, confirming that functionally active CXCL14 was generated in prostate cancer cells by relieving its transcriptional silencing with 5-aza-2-deoxycytidine. Our findings offer the first direct evidence for epigenetic regulation of chemokine expression in tumor cells.
Re: Remien et al.: Mathematical modeling of liver injury and dysfunction after acetaminophen overdose
Authors: Drren G. Craig, Kenneth J. Simpson
Journal: Hepatology (2012)

We read with interest the recent analysis by Remien et al.1 of the prognostic accuracy of the Model for Acetaminophen-induced Liver Damage (MALD). By combining serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and international normalized ratio INR, the authors demonstrate a negative predictive value (NPV) of 100% for predicting death when applied to a mixed cohort of 53 acetaminophen overdoses. This complex model has several limitations to its use at present, including the difficulty in calculating the formula at the patients' bedside, and in the use of serum AST, which may not always be routinely available in some centers. However, the study does highlight the importance of accurate triage when considering the potential need for liver transplantation following acetaminophen overdose. We similarly demonstrated an extremely high NPV following acetaminophen overdose by utilizing the Sequential Organ Failure Assessment (SOFA) score, where a SOFA score <7 by 96 hours following single timepoint overdose had a NPV of 98.2%.2 The SOFA score is similarly helpful at ruling out death following multiple timepoint (staggered) acetaminophen overdose, with a SOFA score <6 at tertiary care admission carrying an NPV of 100.0% (Craig DG, unpubl. data). SOFA is a simple scoring system that can be rapidly recalculated at the bedside throughout admission, and, because it is an ordinal rather than a dichotomous variable, a rising SOFA score could function as a gatekeeper to identify deteriorating patients at an early stage and expedite transfer to liver centers. Although the MALD score appears promising as a triage marker, we would urge caution before adopting it as a primary transplant listing criterion. In keeping with several other prognostic studies, the authors compared the prognostic accuracy of their model with the King's College Criteria (KCC) at a single timepoint (hospital admission) rather than dynamically throughout admission, as originally intended, which is likely to invalidate comparisons with the KCC.3 Furthermore, MALD does not explicitly include hepatic encephalopathy, thereby raising the possibility of undertaking liver transplantation inappropriately in patients with high MALD scores from other (nonacetaminophen) etiologies. As ever, there remains a balance between ensuring patients at risk of death are not missed through the inappropriate use of highly specific listing criteria, such as the KCC, as triage markers, while minimizing unnecessary transplantation of patients who might spontaneously survive. Further evaluation of the MALD and SOFA scores as triage markers in prospective studies between several large centers would be welcome. Drren G. Craig M.R.C.P.*, Kenneth J. Simpson MD, Ph.D.*, * Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.
Permission for Aliens to Practise
Authors: J. M. Done
Journal: BMJ (1945)

Basophils have been shown to accumulate in allergic airways and other extravascular sites. Mechanisms responsible for the selective recruitment of basophils from the blood into tissue sites remain poorly characterized. In this study, we characterized human basophil rolling and adhesion on HUVECs under physiological shear flow conditions. Interestingly, treatment of endothelial cells with the basophil-specific cytokine IL-3 (0.01–10 ng/ml) promoted basophil and eosinophil, but not neutrophil, rolling and exclusively promoted basophil adhesion. Preincubation of HUVECs with an IL-3R-blocking Ab (CD123) before the addition of IL-3 inhibited basophil rolling and adhesion, implicating IL-3R activation on endothelial cells. Incubation of basophils with neuraminidase completely abolished both rolling and adhesion, indicating the involvement of sialylated structures in the process. Abs to the β<sub>1</sub> integrins, CD49d and CD49e, as well as to P-selectin and P-selectin glycoprotein ligand 1, inhibited basophil rolling and adhesion. Furthermore, blocking chemokine receptors expressed by basophils, such as CCR2, CCR3, and CCR7, demonstrated that CCR7 was involved in the observed recruitment of basophils. These data provide novel insights into how IL-3, acting directly on endothelium, can cause basophils to preferentially interact with blood vessels under physiological flow conditions and be selectively recruited to sites of inflammation.
THE PRESENT STATUS OF HEXYL-RESORCINOL AS AN INTERNAL URINARY DISINFECTANT
Authors: VEADER LEONARD
Journal: JAMA (1925)

Chiefly as the result of the comprehensive researches of Dr. Edwin Davis,<sup>1</sup>in Dr. Hugh Young's urologic clinic at the Johns Hopkins Hospital, the chemical and biologic properties essential to an effective internal urinary antiseptic were known and clearly stated long before any substance possessing these properties had been described. According to Davis, the ideal internal urinary antiseptic should be: (1) chemically stable; (2) nontoxic; (3) nonirritating to the urinary tract; (4) antiseptic in high dilution in urine of any reaction, and (5) eliminated in high percentage by the kidney. Having examined the possibilities in more than 400 compounds, many of which had been especially synthesized for the purpose of internal urinary antisepsis by Dr. E. C. White of Baltimore, Davis<sup>2</sup>felt justified, only four years ago, in stating that "there is no sound experimental or clinical proof of the fitness of any known drug for use as