tbuckley/cabot-search huggingface dataset:
ED-17 * GENETIC MODULATION OF NEUROCOGNITIVE FUNCTION AND OUTCOMES IN GLIOMA PATIENTS
Authors: Y. Liu, R. Zhou, E. Sulman, M. Scheurer, N. Boehling, M. Gilbert, T. Armstrong, M. Bondy, J. Wefel
Journal: Neuro-Oncology (2014)

BACKGROUND: Genetic polymorphisms associated with neurocognitive function (NCF) in glioma patients have not been studied. Determining such markers may help identify patients at increased risk for treatment related neurotoxicity, suggesting possible targets for treatment, and facilitate development of new neuroprotective therapies to improve the patients' quality of life. METHODS: To identify the effect of genetic variants on NCF, we compared the genotype frequencies of 10,967 SNPs mapping to 580 genes from five pathways: Inflammation, DNA repair, Metabolism, Neurocognitive, and TERT, in 233 newly diagnosed glioma patients with neurocognitive evaluations before surgical resection. Five neuropsychological tests that measured memory (Hopkins Verbal Learning Test – Revised [HVLT-R]), processing speed (Trail Making Test A [TMTA]), and executive function (Controlled Oral Word Association [COWA], and Trail Making Test B (TMTB]) were examined. RESULTS: Nineteen SNPs were associated with TMTA, 12 SNPs with TMTB, two SNPs (MCPH1 rs6999296 and TANK rs270952) were associated with COWA, and one SNP (RAD51L1 rs9323505) was associated with HVLT-R Total Recall (FDR ≤ 0.05). For TMTA, the strongest signals were in IRS1 rs6725330 in the inflammation pathway (P = 2.59E-10; P adjusted = 1.21E-06), ERCC4 rs1573638 in DNA repair pathway (P = 3.46E-07; P adjusted = 0.00036), and ABCC1 rs8187858 in metabolism pathway (P = 6.63E-07; P adjusted = 0.0001). For TMTB, the strongest associations were in NOS1 rs11611788 in inflammation pathway (P = 1.85E-8; P adjusted = 8.63E-05), POLE rs5744761 in DNA repair pathway (P = 6.06E-07; P adjusted = 0.0013), and IL16 rs1912124 in inflammation pathway (P = 6.06E-07; P adjusted = 0.0014). Joint effect analysis found significant gene-dosage effects for TMTA (P trend = 9.46e -16) and TMTB (P trend =6.69e-15). CONCLUSION: Genetic polymorphisms in the Inflammation, DNA repair, Metabolism, Neurocognitive, and TERT pathways are associated with neurocognitive impairment in glioma patients and may affect clinical outcomes.
P822 MULTIPARAMETRIC MAGNETIC RESONANCE SHOWS THAT OBESITY IS STRONGLY ASSOCIATED WITH HEPATIC STEATOSIS IN ADULTS AND CHILDREN AND CAN DIFFERENTIATE PATIENTS WITH NASH FROM NAFLD
Authors: R. Banerjee, B. Rial, M. Pavlides, C. Osuchukwu, A.J. Lewandowski, J.D. Collier, J.E. Schneider, S. Neubauer, E. Barnes
Journal: Journal of Hepatology (2014)
Molecular Pathways of Monocyte Emigration into the Alveolar Air Space of Intact Mice
Authors: ULRICH MAUS, JULIA HUWE, LEANDER ERMERT, MONIKA ERMERT, WERNER SEEGER, JÜRGEN LOHMEYER
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The adhesive interactions involved in monocyte recruitment to the alveolar space in vivo are only poorly defined. To study these interactions, we used a recently developed mouse model that allowed the separation and quantification of freshly recruited monocytes, resident alveolar macrophages (rAM), neutrophils, and lymphocytes in the bronchoalveolar compartment by fluorescence activated cell sorting technology. In these mice, the combined intratracheal administration of the monocyte chemoattractant JE/monocyte chemotactic protein (MCP)-1 and low dose Escherichia coli lipopolysaccharide (LPS) induces a self-limiting pulmonary inflammatory response, characterized by well-controlled sequelae of both neutrophil and monocyte emigration into the alveolar space. In contrast, challenge with JE/MCP-1 provokes the emigration only of monocytes in the absence of lung inflammation. Using an array of function-blocking monoclonal antibodies (mAb) (anti-CD11a, -CD11b, -CD18, -CD49d, -CD54, and -CD106), we characterized the adhesive interactions underlying the transendothelial and transepithelial leukocyte traffic in intact animals. Alveolar monocyte recruitment elicited by JE/MCP-1 alone was strictly dependent on CD11b/CD18, CD54, and CD49d, and partly dependent on CD11a, but not dependent on CD106. In response to JE/MCP-1 plus E. coli LPS, we observed additional engagement of CD11a and CD106 for enhanced alveolar monocyte transmigration. Comigrating neutrophils were found to primarily utilize CD11b, CD18, and CD54, but not CD49d, CD106, or, surprisingly, CD11a. This contrasted with the effect of CD11a on alveolar challenge with macrophage inflammatory protein (MIP)-1 α instead of JE/MCP-1. In conclusion, we found that in an intact mouse model allowing detailed phenotyping of leukocyte traffic into the alveolar space, the molecular pathways involved in JE/MCP-1–driven monocyte efflux differed under noninflammatory and inflammatory (presence of LPS) conditions. Moreover, the profile of adhesive interactions underlying the monocyte efflux differed from that characterizing neutrophil trafficking.
Congenital symptomatic dermographism as the first symptom of mastocytosis
Authors: V. Grimm, M. Mempel, J. Ring, D. Abeck
Journal: British Journal of Dermatology (2000)

Sir, A 14‐month‐old caucasian boy had suffered from symptomatic dermographism since birth. Light scratching of the skin immediately induced the development of persistent weals with flare reactions. From the third month the weals were accompanied by marked pruritus, such that he tried to scratch himself, inducing additional itchy weals. Insect stings induced the development of yellow vesicles. At the age of 9 months the boy developed persistent, brownish pigmented lesions on his neck and had recurrent diarrhoea and vomiting. The family history revealed two episodes of generalized urticaria in his elder brother. Examination revealed linear dermographic weals and flares at sites where he had scratched himself (Fig. 1). Four brownish‐white nodules were present at the nuchal and shoulder region which, when firmly stroked, developed a weal and flare reaction (positive Darier’s sign). Biopsy of one of these nodules showed a solid collection of mast cells on Giemsa staining, consistent with the clinical finding of mastocytomas.
Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors
Authors: Frederick Samaha
Journal: Annals of Internal Medicine (2007)

Letters2 January 2007Effects of a Mediterranean-Style Diet on Cardiovascular Risk FactorsFrederick Samaha, MDFrederick Samaha, MDFrom University of Pennsylvania, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-146-1-200701020-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: The recently published study by the PREDIMED (Prevención con Dieta Mediterránea) investigators (1) concluded that “[c]ompared with a low-fat diet, Mediterranean diets supplemented with olive oil or nuts have beneficial effects on cardiovascular risk factors.” The investigators deserve credit for successfully performing the large multicenter study, for including persons who were at high cardiovascular risk (for example, having diabetes), and for achieving a high completion rate. However, 2 points merit clarification to avoid bias in the paper toward a Mediterranean diet. First, is it really fair to compare Mediterranean diets with a “low-fat” diet when the intervention ...Reference1. Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Ruiz-Gutierrez V, Covas MI, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006;145:1-11. [PMID: 16818923] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Pennsylvania, Philadelphia, Pennsylvania.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffects of a Mediterranean-Style Diet on Cardiovascular Risk Factors Ramon Estruch , Miguel Ángel Martínez-González , Dolores Corella , Jordi Salas-Salvadó , Valentina Ruiz-Gutiérrez , María Isabel Covas , Miguel Fiol , Enrique Gómez-Gracia , Mari Carmen López-Sabater , Ernest Vinyoles , Fernando Arós , Manuel Conde , Carlos Lahoz , José Lapetra , Guillermo Sáez , Emilio Ros , and Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors Miguel Ángel Martínez-González , Emilio Ros , and Ramón Estruch Metrics Cited BySelf-Reported and Objectively Measured Activity Related to Biomarkers Using NHANES 2 January 2007Volume 146, Issue 1Page: 73KeywordsConflicts of interestDietInsulin resistanceLipidsMedical risk factorsOils ePublished: 2 January 2007 Issue Published: 2 January 2007 CopyrightCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Nausea, vomiting, and deaths from ectopic pregnancy
Authors: G. Masukume
Journal: BMJ (2011)

<h3>Objective</h3> This study aimed to investigate the association between age and the risk of 30-day unplanned readmission among adult patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). <h3>Methods</h3> This retrospective analysis included patients from the Nationwide Readmissions Database with AMI who underwent PCI during 2013–2014. We used multivariable logistic regression model to calculate adjusted odds ratios (AORs) for risk of readmission. To examine potential non-linear association, we performed logistic regression with restricted cubic splines (RCS). <h3>Results</h3> Of the 492 550 patients with AMI aged above 18 years undergoing PCI during the index hospitalisation, 48 630 (9.87%) were readmitted within 30 days. Although the crude readmission rate of younger patients (aged 18–54 years) was the lowest (7.27%), younger patients had higher risk of readmission compared with patients aged 55–64 years for all-causes (AOR 1.06 (1.01 to 1.11), p=0.0129) and specific causes, such as AMI and chest pain (both cardiac and non-specific) after adjusted for covariates. Patients aged 65–74 years were at lower risk of all-cause readmission. Older patients (age ≥75 years) had higher risk of readmission for heart failure (AOR 1.50 (1.29 to 1.74)) and infection (AOR 1.44 (1.16 to 1.79)), but lower risk for chest pain. RCS analyses showed a U-shaped relationship between age and readmission risk. <h3>Conclusions</h3> Our results suggest higher risk of readmission in younger patients for all-cause unplanned readmission after adjusted for covariates. The trends of readmission risk along with age were different for specific causes. Age-targeted initiatives are warranted to reduce preventable readmissions in patients with AMI undergoing PCI.
Beware the fortune tellers peddling genetic tests
Authors: R. Moynihan
Journal: BMJ (2011)

We need urgently to evaluate and regulate the next wave of overmedicalisation



An enduring memory of my niece’s third birthday party is the fortune telling session that took place under the dining room table. A creative parent had donned a headscarf and extravagant earrings, and soon a line of toddlers were waiting to hear about the magic of their future. Given the state of the science a decade later it’s highly possible that this fortune telling was just as reliable as the high tech horoscopes arising from the marketing of genetic tests for common diseases.

When the US Government Accountability Office recently ran a covert operation on genetic tests for 15 common conditions, including Alzheimer’s disease, breast cancer, and restless legs syndrome, it uncovered the most extraordinary mess.1 It found that identical DNA samples produced wildly contradictory results. One donor was told by four different firms that he was at below average risk, average risk, and above average risk of having high blood pressure and prostate cancer.

Its report concluded that genetic tests marketed directly to the public were “misleading and of little or no practical use.” Yet hundreds of thousands …
Yersinia enterocolitica Pharyngitis
Authors: CAROL O. TACKET
Journal: Annals of Internal Medicine (1983)

During the investigation of a large multistate outbreak of milk-borne yersiniosis, 14 patients who presented with pharyngitis had Yersinia enterocolitica isolated from the throat. Their illness was characterized by sore throat and fever without enteritis; 3 needed hospitalization. All patients tested had leukocytosis and an elevated convalescent-phase serum titer against the outbreak strain. In contrast to patients with enteritis, who were children, all patients with pharyngitis were adults. Thus, Y. enterocolitica may be responsible for some sporadic cases of pharyngitis in which the throat culture is negative for other pathogens.
Temporal diffeomorphic free-form deformation: Application to motion and strain estimation from 3D echocardiography
Authors: Mathieu De Craene, Gemma Piella, Oscar Camara, Nicolas Duchateau, Etelvino Silva, Adelina Doltra, Jan D’hooge, Josep Brugada, Marta Sitges, Alejandro F. Frangi
Journal: Medical Image Analysis (2011)
Amyloidosis in Still's Disease
Authors: J. A. James, F. G. Bolton
Journal: Annals of the Rheumatic Diseases (1951)

Still (1897) first described the form of chronic polyarthritis of childhood now associated with his name, and six years later Whitman (1903) described two such cases complicated by amyloidosis, but since then few cases with peost-mortemn findings have been reported.Portis (1938) gave the findings in two fatal cases of Still's disease with amyloidosis, and was able to find five further cases among twelve post-mortem accounts in the literature.Trasoff and others (1944), in a review of the literature, collected 31 cases of amyloidosis in rheumatoid arthritis (nine below 16 years of age), all but five of which are known to have died.They also described a case of a patient suffering from Still's disease with amyloidosis who recovered, and they quote a similar case from Kennedy (1935).Further cases of this combination of diseases are recorded from the Massachusetts General Hospital (1945), by Coss and Boots (1946), and by Pickard (1947).Dahlin (1949) has recently given an account of the pathology of amyloidosis.Amyloid disease complicating rheumatoid arthritis and Still's disease is of secondary type (Reimann and others, 1935) affecting mainly the kidneys, liver and spleen.The case presented below is one of Still's disease of severe nature, with gross pericarditis and complicated by amyloidosis.Our thanks are due to Prof. C.
Abstract IA21: Of niche construction and loss of homeostasis: New insights into the cancer diaspora
Authors: Kenneth J. Pienta
Journal: Cancer Research (2015)

Abstract Merging the social science concept of diaspora with ecological and population sciences concepts can inform the cancer field to understand the biology of tumorigenesis and metastasis and inspire new ideas for therapy. Together, cancer cells and host cells, interacting within their habitat, create an ecosystem. This ecosystem, in turn, exists within a larger environment (the host patient as biosphere). Cancer cells escape their confinement of their original habitat in the primary tumor, likely forced out by ecological changes in their home niche. A diaspora is the scattering of people away from an established homeland. To date, “diaspora” has been a uniquely human term utilized by social scientists, however, the application of the diaspora concept to metastasis may yield new biological insights as well as therapeutic paradigms. The diaspora paradigm takes into account and models several variables: the quality of the primary tumor microenvironment, the fitness of individual cancer cell migrants as well as migrant populations, the rate of bidirectional migration of cancer and host cells between cancer sites, and the quality of the target microenvironments to establish metastatic sites. Once seeded to a new site, diaspora populations do not assimilate into the new environment, they try “recapitulate” their homeland. Niche construction is the process in which an organism alters its own (and consequently, other species) environment, usually in a manner that increases its chances of survival. This creates a feedback relationship between natural selection and niche-construction: when organisms affect their environment, that change can then cause a shift in what traits are being naturally selected for. The effect of niche construction is especially pronounced in situations where environmental alterations persist for several generations, introducing the evolutionary role of ecological inheritance. Ecological scientific principles can be applied to the cancer diaspora to develop new therapeutic strategies (ecotherapy). It is easier to drain the swamp that the cancer cells created than swat a million cancer cell mosquitos. Alternatively, ecological traps, habitats that lead to the extinction of a species, could be developed to attract cancer cells to a place where they can be better exposed to treatments or to cells of the immune system for improved antigen presentation. Targeting the microenvironment in addition to the cancer cells themselves should improve therapeutic outcomes. Citation Format: Kenneth J. Pienta. Of niche construction and loss of homeostasis: New insights into the cancer diaspora. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr IA21. doi:10.1158/1538-7445.CHTME14-IA21
Tyrosine phosphorylation and association with phospholipase C gamma-1 of the GAP-associated 62-kD protein after CD2 stimulation of Jurkat T cell.
Authors: P Hubert, P Debré, L Boumsell, G Bismuth
Journal: The Journal of Experimental Medicine (1993)

Numerous substrates are tyrosine phosphorylated upon CD2 stimulation of human Jurkat T cells using a mitogenic pair of CD2 monoclonal antibodies, including the phospholipase C (PLC)gamma-1-p35/36 complex. Most of these substrates are identically tyrosine phosphorylated after CD3 ligation, suggesting that both stimuli share the same biochemical pathway. We show, however, in this report that a 63-kD protein is specifically phosphorylated on tyrosine residues after ligation of the CD2 molecule. The tyrosine phosphorylation of p63 can be induced independently of other substrates when using a single CD2 mAb recognizing the D66 epitope of the molecule. Importantly, this CD2-induced tyrosine phosphorylation of p63 can also occur in the absence of the CD3 zeta chain membrane expression, and is also distinct from the protein tyrosine kinases p56lck and p59fyn. We demonstrate, moreover, that p63 is physically linked with PLC gamma-1 and p35/36 upon CD2 stimulation. Finally, we also show that a 62-kD protein coimmunoprecipitating with the p21ras GTPase activating protein (GAP) is heavily tyrosine phosphorylated only after CD2 stimulation. This ultimately suggests that p63 may represent in fact the 62-kD protein that associates with GAP after tyrosine phosphorylation. Taken together, these results demonstrate the occurrence in Jurkat cells of a tyrosine kinase pathway specifically coupled to the CD2 molecule. They also suggest a function of the p62-GAP-associated protein as a link between PLC gamma-1 and p21ras activation pathways after CD2 activation.
As if exposure to toxins were not enough: the social and cultural system as a secondary stressor.
Authors: J S Kroll-Smith, S R Couch
Journal: Environmental Health Perspectives (1991)

A growing body of evidence indicates that toxic contamination, both indoor and outdoor, negatively affects sociocultural systems and that this in turn affects the social and psychological responses to the contamination. Using secondary case studies and primary survey, interview and observation data from three toxic contamination situations, this paper conceptualizes and summarizes the findings to date. We argue that using a sociocultural perspective helps us to understand much of the seemingly inexplicable behavior that accompanies cases of toxic contamination. Using examples from primary and secondary case studies, four areas in which the sociocultural system affected by toxic contamination can influence the outcome of the response are described: a) engineering options may be frustrated by sociocultural systems; b) communications may be frustrated by sociocultural systems; c) cultural images and social structural patterns of space usage can affect response; and d) sociocultural systems can affect medical outcomes. Given the nature of sociocultural systems and human behavior, measuring the relationship between contamination, social response, and individual behavior is difficult. An example of one approach using the concept of alienation is discussed, wherein linkages have been found between toxic contamination, alienation, and psychological coping difficulties. Implications for professionals responding to toxic contamination cases are also discussed. We conclude that a sociocultural perspective provides a necessary complement to medical and engineering perspectives if we are to fully understand human reactions to toxic contamination and move toward alleviating human health problems associated with these risks.
Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.
Authors: N Itoh, T Hanafusa, A Miyazaki, J Miyagawa, K Yamagata, K Yamamoto, M Waguri, A Imagawa, S Tamura, M Inada
Journal: Journal of Clinical Investigation (1993)

We examined pancreas biopsy specimens from 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients to elucidate the mechanism underlying beta cell destruction. Pancreas islets were seen in all patients and insulitis in eight patients. Infiltrating mononuclear cells consisted of CD4+T, CD8+T, B lymphocytes, and macrophages. Among them, CD8+T lymphocytes were predominant and macrophages followed. The expression of MHC class I antigens was increased in islet and endothelial cells in nine patients. MHC class II expression was increased in endothelial cells of the same patients. The expression of intercellular adhesion molecule-1 was increased in endothelial cells in two of the nine patients with MHC hyperexpression; in one of them, lymphocyte function-associated antigen-3 expression was also increased. Out of the eight patients with insulitis, seven showed MHC class I hyper-expression, whereas 2 of the 10 patients without insulitis showed the phenomenon (P < 0.05). The relation between insulitis and the hyperexpression of adhesion molecules was not evident. In conclusion, we revealed the close relation between CD8+T lymphocyte-predominant insulitis and MHC class I hyperexpression in islet cells. This suggests that infiltrating CD8+T lymphocytes recognize islet autoantigens in association with increased MHC class I molecules and act as major effector cells in autoimmune response against islet cells in IDDM pancreases. The role of adhesion molecules in the pathogenesis of IDDM still remains to be elucidated.
Targeting Cell Division Cycle 7 Kinase: A New Approach for Cancer Therapy
Authors: Alessia Montagnoli, Jürgen Moll, Francesco Colotta
Journal: Clinical Cancer Research (2010)

The cell division cycle 7 (Cdc7) is a serine-threonine kinase, originally discovered in budding yeast, required to initiate DNA replication. Human Cdc7 phosphorylates the minichromosome maintenance protein 2 (Mcm2), a component of the DNA replicative helicase needed for genome duplication. Inhibition of Cdc7 in cancer cells impairs progression through S phase, inducing a p53-independent apoptotic cell death, whereas in normal cells, it does not affect cell viability. Small molecule compounds able to interfere with Cdc7 activity have been identified and shown to be effective in controlling tumor growth in animal models. Two Cdc7 inhibitors are currently in phase I clinical development. Inhibition of Cdc7 kinase activity in cancer cells restricts DNA replication and induces apoptotic cell death by an unprecedented molecular mechanism of action.