tbuckley/cabot-search huggingface dataset:
Hormonal and Metabolic Factors Associated With Variations in Insulin Sensitivity in Human Pregnancy
Authors: H. David McIntyre, Allan M. Chang, Leonie K. Callaway, David M. Cowley, Alan R. Dyer, Tatjana Radaelli, Kristen A. Farrell, Larraine Huston-Presley, Saeid B. Amini, John P. Kirwan, Patrick M. Catalano
Journal: Diabetes Care (2009)

OBJECTIVE The objective of this study was to determine maternal hormonal and metabolic factors associated with insulin sensitivity in human pregnancy. RESEARCH DESIGN AND METHODS This was a prospective observational cross-sectional study of 180 normal pregnant women, using samples collected at the time of a blinded oral glucose tolerance test (OGTT) between 24 and 32 weeks' gestation as an ancillary to the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The study was conducted at two public university teaching hospitals, Cleveland, Ohio, and Brisbane, Australia. Fasting maternal serum cholesterol, triglycerides, free fatty acids, insulin, leptin, tumor necrosis factor-α, placental growth hormone (PGH), insulin-like growth factors (IGFs) 1 and 2, and insulin-like growth factor binding proteins (IGFBPs) 1 and 3 were assayed. Correlation and multiple regression analyses were used to determine factors associated with maternal insulin sensitivity (IS) estimated using both OGTT-derived (ISOGTT) and fasting (using the homeostasis model assessment [HOMA]; ISHOMA) insulin and glucose concentrations. RESULTS Insulin sensitivity correlated (r = x and y for ISOGTT and ISHOMA, respectively) with fasting maternal serum leptin (−0.44 and −0.52), IGFBP1 (0.42 and 0.39), and triglycerides (−0.31 and −0.27). These factors were significantly associated with insulin sensitivity in multiple regression analyses (adjusted R2 0.44 for ISOGTT and ISHOMA). These variables explained more than 40% of the variance in estimates of insulin sensitivity. CONCLUSIONS Maternal hormonal and metabolic factors related to the placenta, adipose tissue, and the growth hormone axis are associated with the variation in insulin sensitivity seen during normal human pregnancy.
Anti-Aβ antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice
Authors: Robert P. Brendza, Brian J. Bacskai, John R. Cirrito, Kelly A. Simmons, Jesse M. Skoch, William E. Klunk, Chester A. Mathis, Kelly R. Bales, Steven M. Paul, Bradley T. Hyman, David M. Holtzman
Journal: Journal of Clinical Investigation (2005)

Neuritic plaques are a defining feature of Alzheimer disease (AD) pathology. These structures are composed of extracellular accumulations of amyloid-β peptide (Aβ) and other plaque-associated proteins, surrounded by large, swollen axons and dendrites (dystrophic neurites) and activated glia. Dystrophic neurites are thought to disrupt neuronal function, but whether this damage is static, dynamic, or reversible is unknown. To address this, we monitored neuritic plaques in the brains of living PDAPP;Thy-1:YFP transgenic mice, a model that develops AD-like pathology and also stably expresses yellow fluorescent protein (YFP) in a subset of neurons in the brain. Using multiphoton microscopy, we observed and monitored amyloid through cranial windows in PDAPP;Thy-1:YFP double-transgenic mice using the in vivo amyloid-imaging fluorophore methoxy-X04, and individual YFP-labeled dystrophic neurites by their inherent fluorescence. In vivo studies using this system suggest that amyloid-associated dystrophic neurites are relatively stable structures in PDAPP;Thy-1:YFP transgenic mice over several days. However, a significant reduction in the number and size of dystrophic neurites was seen 3 days after Aβ deposits were cleared by anti-Aβ antibody treatment. This analysis suggests that ongoing axonal and dendritic damage is secondary to Aβ and is, in part, rapidly reversible.
Incidence of Childhood Cancer in Finland
Authors: Lyly Teppo, Tuula Salonen, Timo Hakulinen
Journal: JNCI Journal of the National Cancer Institute (1975)

Between 1953 and 1970, 2,605 malignant tumors in children under 15 years of age were reported to the Finnish Cancer Registry, a population-based registry that covers the whole country (population, 4.6 million). The mean annual age-adjusted incidence rates per million were 128 in males and 108 in females. The most common neoplasms were leukemia (age-adjusted incidence rates, 43.7 in males; 34.7 in females), brain tumors (26.4 in males, 22.8 in females), renal tumors (10.0 in males, 9.1 in females), lymphomas (10.8 in males, 5.3 in females), and bone tumors (5.3 in males, 5.1 in females). This distribution is roughly the same as that observed in many other white populations. However, the incidence rates of leukemia, lymphomas, neuroblastomas, and soft-tissue tumors were somewhat lower than the figures reported in the Third National Cancer Survey of the United States.
A multicenter comparison of the effects of simvastatin and fenofibrate therapy in severe primary hypercholesterolemia, with particular emphasis on lipoproteins defined by their apolipoprotein composition
Authors: J.-M. Bard, H.-J. Parra, R. Camare, G. Luc, O. Ziegler, C. Dachet, E. Bruckert, P. Douste-Blazy, P. Drouin, B. Jacotot, J.-L. De Gennes, U. Keller, J.-C. Fruchart
Journal: Metabolism (1992)
Crizotinib for <i>ALK</i>-Rearranged Non–Small Cell Lung Cancer: A New Targeted Therapy for a New Target
Authors: Leena Gandhi, Pasi A. Jänne
Journal: Clinical Cancer Research (2012)

Abstract Crizotinib (PF02341066, Xalkori; Pfizer) was recently approved by the U.S. Food and Drug Administration for treatment of ALK-positive non–small cell lung cancer (NSCLC) as defined by a jointly approved diagnostic test using a break-apart fluorescence in situ hybridization assay. The approval was based on dramatic response rates in ALK-positive NSCLC patients of 54% to 61% in phase I and II trials. To date, the overall disease control rates in these trials are close to 90%. Progression-free survival approaches 10 months. This review focuses on the ALK-inhibitory activity of crizotinib in preclinical and clinical trials that led to approval, as well as the diagnostic methods to classify patients with ALK-positive NSCLC. Although these patients represent a small subset of all patients with NSCLC, the rapid time course from identification of this unique target to an approved targeted therapy with striking benefit serves as a paradigm for the development of targeted therapeutics in an era of personalized medicine. Clin Cancer Res; 18(14); 3737–42. ©2012 AACR.
Collagen Type I Induces Disruption of E-Cadherin–Mediated Cell-Cell Contacts and Promotes Proliferation of Pancreatic Carcinoma Cells
Authors: Alexander Koenig, Claudia Mueller, Cornelia Hasel, Guido Adler, Andre Menke
Journal: Cancer Research (2006)

Abstract Pancreatic cancer is characterized by its invasiveness, early metastasis, and the production of large amounts of extracellular matrix (ECM). We analyzed the influence of type I collagen and fibronectin on the regulation of cellular adhesion in pancreatic cancer cell lines to characterize the role of ECM proteins in the development of pancreatic cancer. We show that collagen type I is able to initiate a disruption of the E-cadherin adhesion complex in pancreatic carcinoma cells. This is due to the increased tyrosine phosphorylation of the complex protein β-catenin, which correlates with collagen type I–dependent activation of the focal adhesion kinase and its association with the E-cadherin complex. The activation and recruitment of focal adhesion kinase to the E-cadherin complex depends on the interaction of type I collagen with β1-containing integrins and an integrin-mediated activation of the cellular kinase Src. The disassembly of the E-cadherin adhesion complex correlates with the nuclear translocation of β-catenin, which leads to an increasing expression of the β-catenin-Lef/Tcf target genes, cyclin D1 and c-myc. In addition to that, cells grown on collagen type I show enhanced cell proliferation. We show that components of the ECM, produced by the tumor, contribute to invasiveness and metastasis by reducing E-cadherin–mediated cell-cell adhesion and enhance proliferation in pancreatic tumor cells. (Cancer Res 2006; 66(9): 4662-71)
Cardiovascular benefits of omega-3 fatty acids
Authors: C VONSCHACKY, W HARRIS
Journal: Cardiovascular Research (2006)

Cardiac societies recommend the intake of 1 g/day of the two omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for cardiovascular disease prevention, treatment after a myocardial infarction, prevention of sudden death, and secondary prevention of cardiovascular disease. These recommendations are based on a body of scientific evidence that encompasses literally thousands of publications. Of four large scale intervention studies three also support the recommendations of these cardiac societies. One methodologically questionable study with a negative result led a Cochrane meta-analysis to a null conclusion. This null conclusion, however, has not swayed the recommendations of the cardiac societies mentioned, and has been refuted with good reason by scientific societies.
High-Resolution Array CGH and Gene Expression Profiling of Alveolar Soft Part Sarcoma
Authors: Shamini Selvarajah, Saumyadipta Pyne, Eleanor Chen, Ramakrishna Sompallae, Azra H. Ligon, Gunnlaugur P. Nielsen, Glenn Dranoff, Edward Stack, Massimo Loda, Richard Flavin
Journal: Clinical Cancer Research (2014)

Alveolar soft part sarcoma (ASPS) is a soft tissue sarcoma with poor prognosis, and little molecular evidence exists for its origin, initiation, and progression. The aim of this study was to elucidate candidate molecular pathways involved in tumor pathogenesis.We employed high-throughput array comparative genomic hybridization (aCGH) and cDNA-Mediated Annealing, Selection, Ligation, and Extension Assay to profile the genomic and expression signatures of primary and metastatic ASPS from 17 tumors derived from 11 patients. We used an integrative bioinformatics approach to elucidate the molecular pathways associated with ASPS progression. FISH was performed to validate the presence of the t(X;17)(p11.2;q25) ASPL-TFE3 fusion and, hence, confirm the aCGH observations.FISH analysis identified the ASPL-TFE3 fusion in all cases. aCGH revealed a higher number of numerical aberrations in metastatic tumors relative to primaries, but failed to identify consistent alterations in either group. Gene expression analysis highlighted 1,063 genes that were differentially expressed between the two groups. Gene set enrichment analysis identified 16 enriched gene sets (P < 0.1) associated with differentially expressed genes. Notable among these were several stem cell gene expression signatures and pathways related to differentiation. In particular, the paired box transcription factor PAX6 was upregulated in the primary tumors, along with several genes whose mouse orthologs have previously been implicated in Pax6 DNA binding during neural stem cell differentiation.In addition to suggesting a tentative neural line of differentiation for ASPS, these results implicate transcriptional deregulation from fusion genes in the pathogenesis of ASPS.
Properdin: Emerging Roles of a Pattern-Recognition Molecule
Authors: Claudia Kemper, John P. Atkinson, Dennis E. Hourcade
Journal: Annual Review of Immunology (2009)

Complement is an innate immune system that is a first line of defense against pathogens and facilitates elimination of apoptotic and injured cells. During complement activation, the complement convertases are assembled on target surfaces and initiate their proteolytic activities, a process that marks targets for phagocytosis and/or lysis. The complement alternative activation pathway has been implicated in a number of autoimmune conditions including arthritis and age-related macular degeneration. Properdin, a plasma component that is also released by activated neutrophils, is critical in the stabilization of alternative pathway convertases. Recently, it has been shown that properdin is also a pattern-recognition molecule that binds to certain microbial surfaces, apoptotic cells, and necrotic cells. Once bound to a surface, properdin can direct convertase formation and target uptake. New studies are now focusing on a role for properdin in inflammatory and autoimmune diseases. This review examines the new properdin findings and their implications.
Allergologic exploration of germins and germin‐like proteins, a new class of plant allergens
Authors: E. Jensen‐Jarolim, B. Schmid, F. Bernier, A. Berna, T. Kinaciyan, M. Focke, C. Ebner, O. Scheiner, G. Boltz‐Nitulescu
Journal: Allergy (2002)

Germins and the related germin-like proteins (GLPs) are glycoproteins expressed in many plants in response to biotic and abiotic stress. To test the potential impact of germins and GLPs, recombinant germin from Triticum aestivum (tGermin) and GLPs from Arabidopsis thaliana (tGLP), both produced in transformed tobacco plants, were used.Sera from 82 patients with type I allergy to birch, grass or mugwort pollen and/or wheat were tested in immunoblot for IgE binding to tGermin and tGLP, and the IgE reactivity after chemical and enzymatic deglycosylation was analysed. The biological activity of tGermin and tGLP was determined in a histamine release assay and in skin prick testing (SPT).In an immunoblotting assay, 24 out of 82 tested sera (29.26%) from allergic patients showed IgE-binding to tGermin, and 18 of these sera (21.95%) displayed also IgE-binding to tGLP. The deglycosylation experiments indicated that glycan moieties contribute significantly to the IgE-binding of tGermin and tGLP. Both tGermins and tGLP induced specifically histamine release in an in vitro assay as well as in SPT.Our in vitro and in vivo findings demonstrate that germin and GLPs are capable to bind IgE most likely via carbohydrate determinants, and represent allergenic molecules.
New guidelines on the management of asthma
Authors: P J. Rees
Journal: BMJ (2003)

Previous guidelines for the management of asthma produced by the British Thoracic Society and others have been disseminated widely and have been influential on the approach to asthma management in the United Kingdom and internationally. The latest full version was produced in 1993,1 with a review and position statement in 1995.2 The coordinating committee at that time predicted that the next revision would be a rewrite in 1997-8, so a new version is overdue. When we reviewed the 1993 guidelines we pointed out a lack of clarity on the evidence base and the need for expert opinion where evidence is lacking.3 Both of these areas are addressed in the new guidelines4 through the methods and format familiar from the Scottish Intercollegiate Guidelines Network (http://www.sign.ac.uk/). The new British guidelines have been produced jointly by the British Thoracic Society and Scottish Intercollegiate Guidelines Network, in collaboration with various other bodies.

The levels of evidence and grades of recommendations are given a clear hierarchy, but the method of the Scottish Intercollegiate Guidelines Network also identifies “recommended best practice based on the clinical experience …
Double-Blind Comparison of Addition of a Second Mood Stabilizer Versus an Antidepressant to an Initial Mood Stabilizer for Treatment of Patients With Bipolar Depression
Authors: L. Trevor Young, Russell T. Joffe, Janine C. Robb, Glenda M. MacQueen, Michael Marriott, Irene Patelis-Siotis
Journal: American Journal of Psychiatry (2000)

This study's purpose was to clarify the appropriate treatment of bipolar depression by comparing the addition of an antidepressant versus a second mood stabilizer for inpatients being treated with lithium carbonate or divalproex sodium.Twenty-seven patients were randomly assigned to groups that received double-blind treatment with paroxetine or a second mood stabilizer (lithium carbonate or divalproex sodium) for 6 weeks.Both groups showed significant improvement in depressive symptoms during the 6-week trial. There were significantly more noncompleters in the group being treated with the two mood stabilizers than in the group being treated with a mood stabilizer and paroxetine.Both treatments appeared to be effective; however, the addition of an antidepressant may have greater clinical utility in the treatment of bipolar depression.
On the role of the transmembrane anchor sequence of influenza hemagglutinin in target cell recognition by class I MHC-restricted, hemagglutinin-specific cytolytic T lymphocytes.
Authors: T J Braciale, V L Braciale, M Winkler, I Stroynowski, L Hood, J Sambrook, M J Gething
Journal: The Journal of Experimental Medicine (1987)

We have examined the requirement for the transmembrane hydrophobic anchor sequence of the influenza hemagglutinin (HA) in the formation of the antigenic moiety on the surface of target cells recognized by class I MHC-restricted murine CTL. For this analysis we have used a line of CV-1 monkey epithelial cells that express the transfected murine H-2Kd gene product as target cells and have used recombinant SV40-based late replacement vectors to achieve expression of genes encoding wild-type and mutant forms of HA. We have found that the majority of Kd-restricted HA-specific CTL clones recognize target cells that express a secreted HA molecule that lacks the transmembrane and cytoplasmic domains of the parent glycoprotein. Several Kd-restricted CTL clones that recognize subtype-specific and crossreactive epitopes on HA fail to recognize the anchor-negative, secreted HA or chimeric HA molecules containing the transmembrane and cytoplasmic domains of unrelated glycoproteins. These CTL clones appear to be directed to antigenic epitopes located within the transmembrane domain of HA, as defined by their capacity to recognize target cells sensitized with a synthetic 23-amino-acid peptide corresponding to sequences within this domain. The implications of these results for class I MHC-restricted CTL recognition are discussed.
Waning immunity to plasma-derived hepatitis B vaccine and the need for boosters 15 years after neonatal vaccination
Authors: Chun–Yi Lu, Bor–Luen Chiang, Wei–Kuang Chi, Mei–Hwei Chang, Yen–Hsuan Ni, Hsu–Mei Hsu, Shiing–Jer Twu, Ih–Jen Su, Li–Min Huang, Chin–Yun Lee
Journal: Hepatology (2004)

Neonatal immunization with hepatitis B (HB) vaccine is highly effective; however, more needs to be learned about the duration of protection and indications for boosters. We measured antibody to HB core antigen (anti–HBc), HB surface antigen (HBsAg), and pre– and postbooster titers of HBsAg antibody (anti–HBs) 15 years after primary neonatal immunization with plasma–derived HB vaccines in 2 cohorts of 15–year–old children. Group A consisted of 78 children who were born to HB e antigen-positive HBsAg carrier mothers and had developed protective levels of anti–HBs antibodies (≥10 mIU/mL) following HB immunization. Group B consisted of 113 apparently healthy children whose anti–HBs titers after vaccination were unknown. Anti–HBs was undetectable (antibody titer &lt;10 mIU/mL) in 29.9% in group A and 62.4% in group B ( P &lt; .001). Anti–HBc was detected in 33.3 % in group A and 4.4 % in group B ( P &lt; .001). After a single booster dose of HB vaccine, 2.7% in group A and 3.3% in group B remained anti–HBs-negative. A blunted serological response was noted in approximately 20% in both groups. One HBsAg carrier was detected in group A (1.3%) and 4 in group B (3.5%). Fifteen years after neonatal immunization with plasma–derived HB vaccine, a large proportion of children exhibited waning immunity. This poses the risk of breakthrough infection. A single booster augmented the serological response to the vaccine in most but not all subjects. In conclusion , our findings suggest that one or more booster immunizations are needed in seronegative subjects by at least 15 years following neonatal immunization with plasma–derived HB vaccine. (Hepatology 2004;40:1415-1420.)
Aspirin-Sulfinpyrazone in Prophylaxis of Deep Venous Thrombosis in Total Hip Replacement
Authors: Richard D. Sautter
Journal: JAMA (1983)

In postoperative hip arthroplasty patients, treatment with aspirin and sulfinpyrazone resulted in a statistically significant reduction of venographically diagnosed thrombi in the proximal veins of the leg. This reduction was most apparent in thrombi that involved the iliac vein. When compared with their placebo-treated counterparts, female patients who received the active treatment experienced a statistically significant 75% reduction of thrombosis, compared with a 32% reduction for men that was not statistically significant. There were no serious adverse effects. Factors were identified that may influence the result of drug prophylaxis trials in deep-vein thrombosis. (<i>JAMA</i>1983;250:2649-2654)
Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load
Authors: Kai Neben, Anna Jauch, Thomas Hielscher, Jens Hillengass, Nicola Lehners, Anja Seckinger, Martin Granzow, Marc S. Raab, Anthony D. Ho, Hartmut Goldschmidt, Dirk Hose
Journal: Journal of Clinical Oncology (2013)

Purpose The aim of this study was to analyze chromosomal aberrations in terms of frequency and impact on time to progression in patients with smoldering multiple myeloma (SMM) on the background of clinical prognostic factors. Patients and Methods The chromosomal abnormalities 1q21, 5p15/5q35, 9q34, 13q14.3, 15q22, 17p13, t(11;14)(q13;q32), and t(4;14)(p16.3;q32) were assessed in CD138-purified myeloma cells by interphase fluorescent in situ hybridization (iFISH) alongside clinical parameters in a consecutive series of 248 patients with SMM. Results The high-risk aberrations in active myeloma (ie, del(17p13), t(4;14), and +1q21) present in 6.1%, 8.9%, and 29.8% of patients significantly confer adverse prognosis in SMM with hazard ratios (HRs) of 2.90 (95% CI, 1.56 to 5.40), 2.28 (95% CI, 1.33 to 3.91), and 1.66 (95% CI, 1.08 to 2.54), respectively. Contrary to the conditions in active myeloma, hyperdiploidy, present in 43.3% of patients, is an adverse prognostic factor (HR, 1.67; 95% CI, 1.10 to 2.54). Percentage of malignant bone marrow plasma cells assessed by iFISH and combination of M-protein and plasma cell infiltration as surrogates of tumor load significantly confer adverse prognosis with HRs of 4.37 (95% CI, 2.79 to 6.85) and 4.27 (95% CI, 2.77 to 6.56), respectively. In multivariate analysis, high-risk aberrations, hyperdiploidy, and surrogates of tumor load are independently prognostic. Conclusion The high-risk chromosomal aberrations del(17p13), t(4;14), and +1q21 are adverse prognostic factors in SMM just as they are in active myeloma, independent of tumor mass. Hyperdiploidy is the first example for an adverse prognostic factor in SMM of opposite predictiveness in active myeloma. Risk association of chromosomal aberrations is not only a priori treatment dependent (predictive) but is also an intrinsic property of myeloma cells (prognostic).