tbuckley/cabot-search huggingface dataset:
Somatic Mutations of <i>ERBB2</i> Kinase Domain in Gastric, Colorectal, and Breast Carcinomas
Authors: Jong Woo Lee, Young Hwa Soung, Si Hyung Seo, Su Young Kim, Cho Hyun Park, Young Pil Wang, Kyeongmee Park, Suk Woo Nam, Won Sang Park, Sang Ho Kim, Jung Young Lee, Nam Jin Yoo, Sug Hyung Lee
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Recent reports revealed that the kinase domain of the ERBB2 gene is somatically mutated in lung adenocarcinoma, suggesting the mutated ERBB2 gene as an oncogene in human cancers. However, because previous reports focused the mutational search of ERBB2 primarily on lung cancers, the data on ERBB2 mutations in other types of human cancers have been largely unknown. Experimental Design: Here, we did a mutational analysis of the ERBB2 kinase domain by PCR single-strand conformational polymorphism assay in gastric, colorectal, and breast carcinoma tissues. Results: We detected the ERBB2 kinase domain mutations in 9 of 180 gastric carcinomas (5.0%), in 3 of 104 colorectal carcinomas (2.9%), and in 4 of 94 breast carcinomas (4.3%). All of the detected ERBB2 mutations except for one in-frame deletion mutation were missense mutations. Of the 16 ERBB2 mutations detected, 4 affected Val777 in the exon 20 site, and 3 affected Leu755 in the exon 19 site. We simultaneously analyzed the somatic mutations of EGFR, K-RAS, PIK3CA, and BRAF genes in the 16 samples with ERBB2 mutations, and found that all of the 3 colorectal carcinoma samples with ERBB2 mutations harbored K-RAS mutations. Conclusion: This study showed that in addition to lung adenocarcinomas, ERBB2 kinase domain mutation occurs in other common human cancers such as gastric, breast, and colorectal cancers, and suggested that alterations of ERBB2-mediated signaling pathway by ERBB2 mutations alone or together with K-RAS mutations may contribute to the development of human cancers.
Intravenous Protein-Free Pyrogen
Authors: KURT N. VON KAULLA
Journal: Circulation (1958)

Administration of a variety of nonfibrinolytic, nonenzymatic substances induces fibrinolysis in man. The most potent materials of this type known at present are purified protein-free pyrogens. Their action after intravenous injection on the human fibrinolytic system, on some of its components, and on the clotting system of 67 individuals has been studied. The possible therapeutic implications are discussed of the marked fibrinolysis.
Modulation of apoprotein E secretion in response to receptor-mediated endocytosis in resident and inflammatory macrophages.
Authors: R Takemura, Z Werb
Journal: The Journal of Experimental Medicine (1984)

We have determined the effect of various endocytic ligands on the secretion of ApoE by macrophages. ApoE was a major secreted protein of resident macrophages, but BCG-activated macrophages secreted little ApoE and periodate-elicited macrophages secreted intermediate amounts of ApoE. Resident, periodate-elicited, and BCG-activated mouse peritoneal macrophages were incubated with AcLDL, EIgG, EIgMC, dextran sulfate, latex, or zymosan, and the resulting protein secretion patterns were analyzed by [35S]methionine labeling and SDS-polyacrylamide gel electrophoresis. AcLDL increased total [35S]methionine incorporation into secreted proteins. Although AcLDL increased the secretion of ApoE by resident macrophages less than or equal to fivefold in a dose-dependent manner, with maximal stimulation at 4.8 micrograms/ml, it decreased the secretion of ApoE by periodate-elicited macrophages to almost nothing and did not affect the low rate of secretion of ApoE by BCG-activated macrophages. However, EIgG, which increases cellular cholesterol content of macrophages as AcLDL does, did not increase ApoE secretion, and dextran sulfate, which is recognized by the same receptor as AcLDL, also did not increase ApoE secretion. The binding and uptake of EIgG, dextran sulfate, zymosan, latex, and EIgMC all decreased the secretion of ApoE. These endocytic ligands also altered the pattern of secreted and cellular proteins other than ApoE. The pattern of response was ligand-specific. However, increased secretion of polypeptides of Mr 62,000 and 68,000 was common to many stimuli. We conclude that receptor-mediated endocytosis modulates the secretion of ApoE and other proteins pleiotypically in resident, inflammatory, and activated macrophages.
Cell Type–Specific Regulation of Angiogenic Growth Factor Gene Expression and Induction of Angiogenesis in Nonischemic Tissue by a Constitutively Active Form of Hypoxia-Inducible Factor 1
Authors: Brian D. Kelly, Sean F. Hackett, Kiichi Hirota, Yuji Oshima, Zheqing Cai, Shannon Berg-Dixon, Ashley Rowan, Zhijiang Yan, Peter A. Campochiaro, Gregg L. Semenza
Journal: Circulation Research (2003)

Understanding molecular mechanisms regulating angiogenesis may lead to novel therapies for ischemic disorders. Hypoxia-inducible factor 1 (HIF-1) activates vascular endothelial growth factor (VEGF) gene expression in hypoxic/ischemic tissue. In this study we demonstrate that exposure of primary cultures of cardiac and vascular cells to hypoxia or AdCA5, an adenovirus encoding a constitutively active form of HIF-1alpha, modulates the expression of genes encoding the angiogenic factors angiopoietin-1 (ANGPT1), ANGPT2, placental growth factor, and platelet-derived growth factor-B. Loss-of-function effects were also observed in HIF-1alpha-null embryonic stem cells. Depending on the cell type, expression of ANGPT1 and ANGPT2 was either activated or repressed in response to hypoxia or AdCA5. In all cases, there was complete concordance between the effects of hypoxia and AdCA5. Injection of AdCA5 into mouse eyes induced neovascularization in multiple capillary beds, including those not responsive to VEGF alone. Analysis of gene expression revealed increased expression of ANGPT1, ANGPT2, platelet-derived growth factor-B, placental growth factor, and VEGF mRNA in AdCA5-injected eyes. These results indicate that HIF-1 functions as a master regulator of angiogenesis by controlling the expression of multiple angiogenic growth factors and that adenovirus-mediated expression of a constitutively active form of HIF-1alpha is sufficient to induce angiogenesis in nonischemic tissue of an adult animal.
Do Patients With Schizophrenia Consciously Recollect Emotional Events Better Than Neutral Events?
Authors: Jean-Marie Danion, Mathilde Kazes, Caroline Huron, Nourdine Karchouni
Journal: American Journal of Psychiatry (2003)

The influence of the emotional valence of words on conscious awareness was assessed in patients with schizophrenia.The remember/know procedure was used to test 24 patients with schizophrenia and 24 normal comparison subjects.Patients' "remember" responses and conscious recollection were more frequent for emotional words than for neutral words. In contrast, the levels of "know" responses and familiarity were independent of emotional words.Patients with schizophrenia consciously recollected emotional words better than neutral words.
Neonatal screening of β‐thalassemias by thin layer isoelectric focusing
Authors: Gianfranco Cossu, Mario Manca, M. Gavina Pirastru, Renza Bullitta, Adriana Bianchi Bosisio, Elisabetta Gianazza, Pier Giorgio Righetti
Journal: American Journal of Hematology (1982)

Abstract As an alternative to the recently proposed screening for β‐thalassemias by isoelectric focusing (IEF) of denatured globin chains in urea‐detergent gels [6], IEF of intact hemoglobins, obtained from umbilical cord blood in neonatal units, is reported here. For maximum separation, IEF should be performed in nonlinear pH gradients, in gels containing 0.2 M β‐alanine and 0.2 M 6‐amino caproic acid, which flatten the pH gradient around pH 7, thus increasing the resolution between HbA and HbF ac . The method can unambiguously detect homozygous and heterozygous β‐thalassemic conditions. A bimodal distribution of HbA at birth has been found: In heterozygous patients, HbA values of 9.02% (range 6.8–9.98%) have been found while in normal newborns HbA levels of 20.34% (range 11.02–30.6%) have been demonstrated.
TOTAL SUPPORT OF THE CIRCULATION OF A PATIENT WITH POST-CARDIOTOMY STONE-HEART SYNDROME BY A PARTIAL ARTIFICIAL HEART (ALVAD) FOR 5 DAYS FOLLOWED BY HEART AND KIDNEY TRANSPLANTATION
Authors: J.C. Norman, D.A. Cooley, B.D. Kahan, A.S. Keats, E.K. Massin, R.T. Solis, W.E. Luper, M.I. Brook, T. Klima, O.H. Frazier, Jerriann Hacker, J.M. Duncan, C.C. Dacso, D.S. Winston, G.J. Reul
Journal: The Lancet (1978)
Her2 and Progesterone Receptor Status Are Not Predictive of Response to Fulvestrant Treatment
Authors: Rupert Bartsch, Catharina Wenzel, Gabriela Altorjai, Ursula Pluschnig, Robert M. Mader, Michael Gnant, Raimund Jakesz, Margaretha Rudas, Christoph C. Zielinski, Guenther G. Steger
Journal: Clinical Cancer Research (2007)

Abstract Purpose: It has been hypothesized that response to endocrine therapy for breast cancer depends on Her2 and progesterone receptor status, grading, and tumor proliferation rate. In this study, we evaluated factors that are potentially predictive of response and time to progression in patients treated with fulvestrant. Experimental Design: One hundred fifty-five patients were included and followed prospectively. Patients received fulvestrant at standard dose by i.m. injection. Response was evaluated every 3 months using International Union Against Cancer criteria. Time to progression and overall survival were estimated with the Kaplan-Meier product limit method. A multivariate analysis was done to evaluate factors potentially influencing response and time to progression. Results: We observed a partial response in 19 patients (12.3%), stable disease ≥6 months in 56 patients (36.1%), stable disease &amp;gt;3 months but &amp;lt;6 months in 7 patients (4.5%), and progressive disease in 73 patients (47.1%). Median time to progression was 5 months, and median overall survival was 27 months. Probability of achieving clinical benefit was significantly associated with a low proliferation rate (P = 0.015), nonvisceral metastatic sites (P = 0.023), and first-line therapy (P = 0.023). First-line therapy was also associated with prolonged time to progression (P = 0.003). Conclusions: Response rate and time to progression are shown to be independent of Her2 status, grading, and progesterone receptor status. This is probably caused by the unique mechanism of action associated with fulvestrant: Due to receptor down-regulation, it blocks nuclear, cytoplasmatic, and membrane-bound estrogen receptor. Therefore, it seems to inhibit the cross-talk between growth factor receptor signaling and estrogen receptor in a more effective manner.
Quaternary Structure Constraints on Evolutionary Sequence Divergence
Authors: M. S. Fornasari, G. Parisi, J. Echave
Journal: Molecular Biology and Evolution (2006)

The structurally constrained protein evolution (SCPE) model simulates protein divergence considering protein structure explicitly. The model is based on the observation that protein structure is more conserved during evolution than the sequences encoding for that structure. In the previous work, the SCPE model considered only the tertiary structure. Here we show that the performance of the model is enhanced when the oligomeric structure is taken into account. Our results agree with recent evolutionary studies of oligomeric proteins, which show that conservation of the quaternary structure imposes additional constraints on sequence divergence. The incorporation of protein–protein interactions into protein evolution models may be important in the study of quaternary protein structures and complex protein assemblies.
Continuing Controversies in the Management of Thyroid Nodules
Authors: M. Regina Castro, Hossein Gharib
Journal: Annals of Internal Medicine (2005)

Although thyroid nodules are common, few are malignant and require surgical treatment. A systematic approach to their evaluation is important to avoid unnecessary surgery. Fine-needle aspiration biopsy has resulted in substantial improvements in diagnostic accuracy, cost reductions, and higher malignancy yield at time of surgery. The preferred approach when repeated fine-needle aspiration biopsy fails to yield an adequate specimen remains a challenge. Management of patients with nodules "suspicious for follicular neoplasm" is difficult, since only 15% to 20% of such lesions have been shown to be malignant. Immunohistochemical markers, such as galectin-3 and human bone marrow endothelial cell (HBME-1), have shown promise in preliminary studies. Routine calcitonin measurement in patients with thyroid nodules has been advocated for early detection of medullary thyroid cancer. However, the low frequency of this cancer, coupled with the high cost associated with case detection, has resulted in a lack of general acceptance of this recommendation.
Analysis of factors influencing inclusion of 102 patients with stage III/IV Hodgkin's lymphoma in a randomized trial for first-line chemotherapy
Authors: I. Biasoli, P. Franchi-Rezgui, D. Sibon, J. Brière, E. de Kerviler, C. Thieblemont, V. Levy, C. Gisselbrecht, P. Brice
Journal: Annals of Oncology (2008)
OrthoMaM v8: A Database of Orthologous Exons and Coding Sequences for Comparative Genomics in Mammals
Authors: E. J. P. Douzery, C. Scornavacca, J. Romiguier, K. Belkhir, N. Galtier, F. Delsuc, V. Ranwez
Journal: Molecular Biology and Evolution (2014)

Comparative genomic studies extensively rely on alignments of orthologous sequences. Yet, selecting, gathering, and aligning orthologous exons and protein-coding sequences (CDS) that are relevant for a given evolutionary analysis can be a difficult and time-consuming task. In this context, we developed OrthoMaM, a database of ORTHOlogous MAmmalian Markers describing the evolutionary dynamics of orthologous genes in mammalian genomes using a phylogenetic framework. Since its first release in 2007, OrthoMaM has regularly evolved, not only to include newly available genomes but also to incorporate up-to-date software in its analytic pipeline. This eighth release integrates the 40 complete mammalian genomes available in Ensembl v73 and provides alignments, phylogenies, evolutionary descriptor information, and functional annotations for 13,404 single-copy orthologous CDS and 6,953 long exons. The graphical interface allows to easily explore OrthoMaM to identify markers with specific characteristics (e.g., taxa availability, alignment size, %G+C, evolutionary rate, chromosome location). It hence provides an efficient solution to sample preprocessed markers adapted to user-specific needs. OrthoMaM has proven to be a valuable resource for researchers interested in mammalian phylogenomics, evolutionary genomics, and has served as a source of benchmark empirical data sets in several methodological studies. OrthoMaM is available for browsing, query and complete or filtered downloads at http://www.orthomam.univ-montp2.fr/.
Changes in size, subclass, and metabolic properties of serum immunoglobulin A in liver diseases and in other diseases with high serum immunoglobulin A.
Authors: D L Delacroix, K B Elkom, A P Geubel, H F Hodgson, C Dive, J P Vaerman
Journal: Journal of Clinical Investigation (1983)

We have studied the relative contributions of monomeric (m-) and polymeric IgA (p-IgA) and of IgA1 and IgA2 to total serum IgA in healthy adults and patients with liver disease (LD) or with other diseases and high serum IgA. Serum concentration of total secretory component (SC) was also determined. In addition, fractional catabolic rates (FCR) and synthetic rates for both m- and p-IgA were measured in nine controls and nine cirrhotics. Our results support four main conclusions: (a) In healthy adults, intravascular p-IgA contributes to only 4-22% (mean 12%) of serum IgA, because its FCR and synthetic rate are approximately two times higher and four times smaller, respectively, than those of intravascular m-IgA. (b) in LD, biliary obstruction does not result in a significant increase in serum p-IgA unlike in rats and rabbits, indicating that in humans the SC-dependent biliary transport of p-IgA plays a much less significant role in selective removal of p-IgA from plasma than in rats and rabbits. (c) In contrast to biliary obstruction, parenchymal LD results in a significant and preferential increase in serum p-IgA, which in cirrhotics correlates with a selective reduction of the p-IgA-FCR. This supports a role for the human liver in selective removal of p-IgA from plasma, but another mechanism than the SC-dependent biliary transport should be considered. (d) Total SC, p-IgA, and IgA2 in serum are unlinked parameters, not necessarily reflecting mucosal events. A marked increase in serum SC occurs almost selectively in LD. Although a shift to IgA2 is suggested in Crohn's disease and alcoholic cirrhosis, a shift to IgA1 frequently associated to a shift to p-IgA occurs in chronic active LD, primary Sicca, and connective tissue diseases.
Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study
Authors: Jean-Michel Molina, Bonaventura Clotet, Jan van Lunzen, Adriano Lazzarin, Matthias Cavassini, Keith Henry, Valeriv Kulagin, Naomi Givens, Carlos Fernando de Oliveira, Clare Brennan
Journal: The Lancet HIV (2015)
Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.
Authors: L Guillou, J M Coindre, F Bonichon, B B Nguyen, P Terrier, F Collin, M O Vilain, A M Mandard, V Le Doussal, A Leroux, J Jacquemier, H Duplay, X Sastre-Garau, J Costa
Journal: Journal of Clinical Oncology (1997)

PURPOSE Several histologic grading systems have been validated in soft tissue sarcomas (STS), but no system is currently accepted worldwide. The National Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems were examined comparatively in the same population of patients with STS to determine which system is the best prognosticator with regard to metastasis development and tumor mortality. PATIENTS AND METHODS Four hundred ten adult patients with nonmetastatic STS were examined. Histologic grade was established according to the NCI and FNCLCC systems in each case. The prognostic value of both systems was examined using univariate and multivariate (Cox's model) analyses, and special attention was devoted to tumors with discordant grades. RESULTS In univariate analysis, both the NCI and FNCLCC systems were of prognostic value to predict metastasis development and tumor mortality. In multivariate analysis, high-grade tumors, irrespective of the system used, size &gt; or = 10 cm, and deep location were found to be independent prognostic factors for the advent of metastases. Tumor grade had a higher predictive value than size or depth, and higher prognostic weight was assigned to the FNCLCC grading system in Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation with overall and metastasis-free survival within subpopulations with discordant grades were observed in favor of the FNCLCC system. CONCLUSION The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.
A9: Exploring Systemic Lupus Erythematosus from the Molecular Level and Dissecting the Disease Mechanism by Molecular Imaging
Authors: Shaofan Hu, Shi Ke, Wei Wang, Henry Ran, Meipu Chen, Fujun Zhang, Xiuchun Qiu, Ming Jiang, Chaoxia Zou, Rufeng Zhang, Li Cao, Rui Fu, Chaoying Chen
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

One and a half million Americans suffer from systemic lupus erythematosus (SLE), with increased death rate in the 15–44 year age group. SLE has a wide range of symptoms and affects multiple organs and tissues. SLE affects each person differently over time. Treatment options are limited with potential serious side effects. There is no cure currently due to the lack of understanding of the mechanism of disease at molecular levels. However, recent developments in the field of molecular imaging provide a tool for noninvasive, target-specific and longitudinal study of multiple disease components at the same time as well as understanding the dynamic change of the disease. We hypothesize genetic differences play a role in development and severity of the disease. In addition, multiple different disease molecules in different organs at one time point make SLE difficult to treat by standard regiments.



Methods:

We tested our hypothesis in animal models with two different genetic backgrounds and three target-specific molecular imaging agents. Two groups of mice carrying normal or mutant Fas gene with SLE were utilized in the study. Optical imaging agents that specifically target to pro-inflammatory cytokine (IL-11), cytokine from T-cells (CXCR4), or disease stroma (matrix metalloproteinase, MMP) were injected through the tail vein. Mice were imaged immediately after injection and for as long as 48 hours afterward. SAS software was used to analyze data by one-way-ANOVA or the general linear model. Data comparison was presented in notched box-and whisker plots. The significant level was set at 0.05 with two-tailed test.



Results:

Mice with a normal Fas gene have statistical higher signal intensities for all agents in the joint regions than the Fas mutant mice (P = 0.0139). Target-specific agents have different organ distributions in Fas mutant mice. The MMP signals are in the kidney (Fig. 1A) and IL-11 signals are in the lung (Fig. 1B). Both agents have statistical low signal intensities in the same organs in the control mice with normal Fas gene (P<0.0002). The animal with normal Fas gene has high IL-11 signal intensity in the knee (Fig. 1C). On contrary, CXCR4 has significantly low signal intensity in the Fas mutant mice. Fas mutant mice also have enlarged spleen and kidney by either size or weight than control mice (P<0.0001). 



Conclusion:

We found that different genetic backgrounds predispose to different disease manifestations. Each organ has different disease components even with same the genetic background at the same disease stage The method we developed here can be used as a tool to better understand genetic and disease components and improve the treatment plan for individual patient needs.
Primary Sjogren's syndrome: new clinical and therapeutic concepts
Authors: M Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2004)

Sicca features are the central clinical manifestations of Sjögren's syndrome (SS), but recent studies have confirmed that primary SS has a systemic expression, including extraglandular manifestations. Patients with a predominantly extraepithelial expression should be managed differently from patients with predominantly periepithelial or sicca limited disease. In coming years treatment will be based on muscarinic agonists for sicca features and immunosuppressive/biological agents for extraglandular features.
“Fair” outcomes without morality in cleaner wrasse mutualism
Authors: Redouan Bshary, Nichola Raihani
Journal: Behavioral and Brain Sciences (2013)

Baumard et al. propose a functional explanation for the evolution of a sense of fairness in humans: Fairness preferences are advantageous in an environment where individuals are in strong competition to be chosen for social interactions. Such conditions also exist in nonhuman animals. Therefore, it remains unclear why fairness (equated with morality) appears to be properly present only in humans.
Efficacy of narrowband ultraviolet B versus excimer radiation in repigmenting vitiligo after minigrafting on the distal arms
Authors: Vaneeta M. Sheth, Sharif D. Currimbhoy, Hattie Jill Feetham, Michael S. Graves, Joanna Chan, Linda S. Hynan, Amit G. Pandya
Journal: Journal of the American Academy of Dermatology (2012)