tbuckley/cabot-search huggingface dataset:
Search for a Gene Expression Signature of Breast Cancer Local Recurrence in Young Women
Authors: Nicolas Servant, Marc A. Bollet, Hans Halfwerk, Kevin Bleakley, Bas Kreike, Laurent Jacob, Daoud Sie, Ron M. Kerkhoven, Philippe Hupé, Rim Hadhri, Alain Fourquet, Harry Bartelink, Emmanuel Barillot, Brigitte Sigal-Zafrani, Marc J. van de Vijver
Journal: Clinical Cancer Research (2012)

A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment.
Selective suppression of the major idiotypic component of an antihapten response by soluble T cell-derived factors with idiotypic or anti-idiotypic receptors.
Authors: Y Hirai, A Nisonoff
Journal: The Journal of Experimental Medicine (1980)

Evidence is presented for the selective suppression of the major idiotypic component of the humoral response to the phenylarsonate hapten by soluble factors derived from T cells (TsF). The existence of TsF with anti-idiotypic receptors was also demonstrated. It was found that TsF with idiotypic and anti-idiotypic receptors coexist in cultures of spleen cells prepared from idiotypically suppressed, hyperimmunized mice. By gel filtration the molecular weight of each factor was found to be 50,000-100,000. Each is sensitive to trypsin and is bound to a column containing anti-H-2a antibodies. Evidence is discussed which suggests the possibility of mutual stimulation of suppressor T cells with idiotypic and anti-idiotypic receptors.
Carcinogenicity and Hepatotoxicity of Cycasin and Its Aglycone Methylazoxymethanol Acetate in Nonhuman Primates&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S M Sieber, P Correa, D W Dalgard, K R McIntire, R H Adamson
Journal: JNCI Journal of the National Cancer Institute (1980)

The carcinogenic potential of cycasin and methylazoxymethanol (MAM) acetate was investigated in nonhuman primates. Old-world monkeys (rhesus, cynomolgus, and African green monkeys) received cycasin and/or MAM acetate by oral or ip routes up to 11 years. Eighteen monkeys survived longer than 2 months after initiation of treatment with cycasin (50-75 mg/kg) or MAM acetate (1.5-3.0 mg/kg) given orally 5 days/week; 9 of the animals were necropsied. Histopathologic examination of a liver tumor from 1 of these monkeys revealed well-differentiated hepatocellular carcinoma. A second monkey had multiple tumors, including hepatocellular carcinoma, intrahepatic bile duct adenocarcinoma, renal carcinoma and adenomas, and adenomatous polyps of the colon. Although liver tumors were not observed in the other monkeys, all but 1 monkey had hepatic lesions such as toxic hepatitis and cirrhosis. These monkeys had received cycasin and/or MAM acetate for an average of 57 months (range, 2-133 mo). A group of 10 monkeys received MAM acetate by weekly ip injections (3-10 mg/kg). Six of these animals developed tumors after receiving an average of 6.14 g (range, 3.58-9.66 g) of MAM acetate for an average of 75 months (range, 50-89 mo). Four of the monkeys developed hepatocellular carcinomas, and 2 had multiple primary tumors including hepatocellular carcinomas, renal carcinomas, squamous cell carcinomas of the esophagus, and adenocarcinomas of the small intestine. Our results showed that long-term administration of cycasin and/or MAM acetate by oral and ip routes was hepatotoxic and carcinogenic in old-world monkeys.
Association of IL2RA and IL2RB with rheumatoid arthritis: a replication study in a Dutch population
Authors: F A S Kurreeman, N A Daha, M Chang, J J Catanese, A B Begovich, T W J Huizinga, R E M Toes
Journal: Annals of the Rheumatic Diseases (2009)

Rheumatoid arthritis (RA) is an autoimmune disease with a worldwide prevalence of approximately 1%. The aetiology of RA is largely unknown, but it is thought that both genetic and environmental factors play a role in the pathogenesis of the disease. Genome-wide association studies (GWAS) and candidate gene approaches have led to the association of a number of genetic susceptibility loci.1 2 3 4 5 6 7 The Wellcome Trust case-control consortium (WTCCC), the first GWAS in RA, identified a number of loci reaching genome-wide significance including the HLA region and the PTPN22 gene.5 To identify new genetic risk factors, Thomson et al investigated whether tier 2 single nucleotide polymorphisms (SNPs) (p = 1×10−5−1×10−7) in the WTCCC-GWAS showed an association with RA in an independent validation study …
Frequency of telomerase-specific CD8+ T lymphocytes in patients with cancer
Authors: Gilberto Filaci, Marco Fravega, Maurizio Setti, Paolo Traverso, Enrico Millo, Daniela Fenoglio, Simone Negrini, Francesca Ferrera, Andrea Romagnoli, Monica Basso, Paola Contini, Marta Rizzi, Massimo Ghio, Umberto Benatti, Gianluca Damonte, Jean Louis Ravetti, Giorgio Carmignani, Maurizio Zanetti, Francesco Indiveri
Journal: Blood (2005)
Parity, Breastfeeding, and the Subsequent Risk of Maternal Type 2 Diabetes
Authors: Bette Liu, Louisa Jorm, Emily Banks
Journal: Diabetes Care (2010)

OBJECTIVE To examine the effect of childbearing and maternal breastfeeding on a woman's subsequent risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS Using information on parity, breastfeeding, and diabetes collected from 52,731 women recruited into a cohort study, we estimated the risk of type 2 diabetes using multivariate logistic regression. RESULTS A total of 3,160 (6.0%) women were classified as having type 2 diabetes. Overall, nulliparous and parous women had a similar risk of diabetes. Among parous women, there was a 14% (95% CI 10–18%, P &amp;lt; 0.001) reduced likelihood of diabetes per year of breastfeeding. Compared to nulliparous women, parous women who did not breastfeed had a greater risk of diabetes (odds ratio 1.48, 95% CI 1.26–1.73, P &amp;lt; 0.001), whereas for women breastfeeding, the risk was not significantly increased. CONCLUSIONS Compared with nulliparous women, childbearing women who do not breastfeed have about a 50% increased risk of type 2 diabetes in later life. Breastfeeding substantially reduces this excess risk.
Ursodeoxycholic acid in chronic liver disease.
Authors: J S de Caestecker, R P Jazrawi, M L Petroni, T C Northfield
Journal: Gut (1991)

The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome.
Radiopharmaceuticals for Palliation of Bone Pain in Patients with Castration-resistant Prostate Cancer Metastatic to Bone: A Systematic Review
Authors: Joyce M. van Dodewaard-de Jong, Daniela E. Oprea-Lager, Lotty Hooft, John M.H. de Klerk, Haiko J. Bloemendal, Henk M.W. Verheul, Otto S. Hoekstra, Alfons J.M. van den Eertwegh
Journal: European Urology (2015)
Population Diversity and Adaptive Evolution in Keratinization Genes: Impact of Environment in Shaping Skin Phenotypes
Authors: Pramod Gautam, Amit Chaurasia, Aniket Bhattacharya, Ritika Grover, Mitali Mukerji, Vivek T. Natarajan
Journal: Molecular Biology and Evolution (2014)

Several studies have demonstrated the role of climatic factors in shaping skin phenotypes, particularly pigmentation. Keratinization is another well-designed feature of human skin, which is involved in modulating transepidermal water loss (TEWL). Although this physiological process is closely linked to climate, presently it is not clear whether genetic diversity is observed in keratinization and whether this process also responds to the environmental pressure. To address this, we adopted a multipronged approach, which involved analysis of 1) copy number variations in diverse Indian and HapMap populations from varied geographical regions; 2) genetic association with geoclimatic parameters in 61 populations of dbCLINE database in a set of 549 genes from four processes namely keratinization, pigmentation, epidermal differentiation, and housekeeping functions; 3) sequence divergence in 4,316 orthologous promoters and corresponding exonic regions of human and chimpanzee with macaque as outgroup, and 4) protein sequence divergence (Ka/Ks) across nine vertebrate classes, which differ in their extent of TEWL. Our analyses demonstrate that keratinization and epidermal differentiation genes are under accelerated evolution in the human lineage, relative to pigmentation and housekeeping genes. We show that this entire pathway may have been driven by environmental selection pressure through concordant functional polymorphisms across several genes involved in skin keratinization. Remarkably, this underappreciated function of skin may be a crucial determinant of adaptation to diverse environmental pressures across world populations.
Novel pH-sensitive multifunctional envelope-type nanodevice for siRNA-based treatments for chronic HBV infection
Authors: Naoki Yamamoto, Yusuke Sato, Tsubasa Munakata, Masakazu Kakuni, Chise Tateno, Takahiro Sanada, Yuichi Hirata, Shuko Murakami, Yasuhito Tanaka, Kazuaki Chayama, Hiroto Hatakeyama, Mamoru Hyodo, Hideyoshi Harashima, Michinori Kohara
Journal: Journal of Hepatology (2015)

Antiviral agents including entecavir (ETV) suppress the replication of the hepatitis B virus (HBV) genome in human hepatocytes, but they do not reduce the abundance of viral proteins. The present study focused on effectively reducing viral protein levels.We designed siRNAs (HBV-siRNA) that target consensus sequences in HBV genomes. To prevent the emergence of escaped mutant virus, we mixed three HBV-siRNAs (HBV-siRNAmix); the mixture was encapsulated in a novel pH-sensitive multifunctional envelope-type nanodevice (MEND), a hepatocyte-specific drug delivery system. Coagulation factor 7 siRNA was used to assess delivery and knockdown efficiencies of MEND/siRNA treatments in mice. The potency of MEND/HBV-siRNAmix was evaluated in primary human hepatocytes and in chimeric mice with humanized liver persistently infected with HBV.Effective knockdown of targets, efficient delivery of siRNA, and liver-specific delivery were each observed with MEND. MEND/HBV-siRNA caused efficient reduction of HBsAg and HBeAg in vitro and in vivo. However, ETV treatment did not efficiently reduce HBsAg or HBeAg when compared with a single MEND/HBV-siRNAmix treatment. Furthermore, the suppressive effects of a single dose of MEND/HBV-siRNAmix persisted for 14days in vitro and in vivo.We demonstrated that MEND/HBV-siRNA controlled HBV more efficiently than did ETV. Furthermore, the effect of a single dose of MEND/HBV-siRNA persisted for a long time. These results indicated that MEND/HBV-siRNA may be a promising novel HBV treatment that is more effective than reverse transcriptase inhibitors.
The risk of thromboembolic events in kidney transplant patients
Authors: Jacobien C. Verhave, Vicky Tagalakis, Samy Suissa, François Madore, Marie-Josée Hébert, Héloïse Cardinal
Journal: Kidney International (2014)

Little is known about the risk of venous thrombosis following kidney transplant. To determine this we estimated the risk of thromboembolic events (TEs) in a cohort of consecutive patients who underwent kidney transplantation at a single tertiary care center over an 11-year period and calculated standardized incidence ratios (SIRs) for a first TE in kidney transplant recipients compared with the general population. We then performed a nested case-control study and compared patients with and without TEs to identify risk factors for thrombosis. Among 913 kidney transplant recipients (KTRs), 68 patients developed these events. The SIR for TEs in KTRs compared with the general population was 7.9 over the duration of follow-up. The risk was particularly higher in the first post-transplant year (SIR 26.1) but remained elevated afterward (SIR 5.2). Hospitalization, use of sirolimus, low hemoglobin level, and use of renin-angiotensin system inhibitors were independently associated with these events. When cases of TEs that occurred during hospitalization were excluded, the risk of these events remained elevated. The risk of TEs in KTRs was eightfold higher than in the general population but not fully explained by the increased risk associated with hospitalization. Our results underscore the important risk of thrombosis in patients who received a kidney transplant, making vigilance mandatory especially during hospitalization.
GRP and Pavlov's dogs
Authors: M FELDMAN
Journal: Gut (2001)

See article on page 23 

The cephalic phase of gastric acid secretion has been a topic of great interest to physiologists and physicians since its description by Pavlov 100 years ago.1 In classic “sham” feeding studies performed on dogs equipped with an oesophageal stoma and a gastric fistula, Pavlov demonstrated that food was a prompt and powerful stimulant of gastric secretion. This stimulation occurred despite the fact that the ingested food entered the dog's mouth and pharynx and exited through the stoma, never actually reaching the stomach. Pavlov went on to demonstrate that severing the vagus nerves just above the diaphragm abolished the gastric acid secretory response to sham feeding in dogs. His experiments demonstrated that sham feeding elicited a potent gastric acid secretory response via the vagus nerves.

Although experiments involving surgically created fistulas could not be conducted in humans, in the 1970s Knutson and Olbe developed a “modified” sham feeding technique to study the cephalic phase of gastric acid secretion in patients with duodenal ulcer disease.2-4 Patients chewed and expectorated appetising food without swallowing it, and a tube inserted into the stomach collected gastric fluid for acid analysis. Using modified sham feeding …
Update on deep brain stimulation in Parkinson’s disease
Authors: Daniel Martinez-Ramirez, Wei Hu, Alberto R. Bona, Michael S. Okun, Aparna Wagle Shukla
Journal: Translational Neurodegeneration (2015)

Deep brain stimulation (DBS) is considered a safe and well tolerated surgical procedure to alleviate Parkinson's disease (PD) and other movement disorders symptoms along with some psychiatric conditions. Over the last few decades DBS has been shown to provide remarkable therapeutic effect on carefully selected patients. Although its precise mechanism of action is still unknown, DBS improves motor functions and therefore quality of life. To date, two main targets have emerged in PD patients: the globus pallidus pars interna and the subthalamic nucleus. Two other targets, the ventralis intermedius and zona incerta have also been selectively used, especially in tremor-dominant PD patients. The main indications for PD DBS have traditionally been motor fluctuations, debilitating medication induced dyskinesias, unpredictable "off time" state, and medication refractory tremor. Medication refractory tremor and intolerable dyskinesia are potential palliative indications. Besides aforementioned targets, the brainstem pedunculopontine nucleus (PPN) is under investigation for the treatment of ON-state freezing of gait and postural instability. In this article, we will review the most recent literature on DBS therapy for PD, including cutting-edge advances and data supporting the role of DBS in advanced neural-network modulation.
Embryonic stem cells--sources and destinations
Authors: D. C. Lopez
Journal: Journal of the Royal Society of Medicine (2005)

Embryonic stem cells-sources and destinationsVats et al. (August 2005 JRSM 1 ) are correct in stating that embryonic stem cells (SCs) represent a unique opportunity to study cellular differentiation processes, and that progress in the related arena of tissue engineering depends on generation of suitable cells and their ability to perform specific biological functions.But, as the authors discussed, social and ethical discord has complicated the availability of human embryonic SCs.In the mouse, they have been produced from single blastomeres obtained from nondestructive biopsy of embryos destined for transfer, or from the isolation of karyotypically normal blastomeres from disaggregated ('dead') embryos regarded unsuitable for transfer. 2As neither of these laboratory techniques harms a viable source embryo, application of such methods to human embryos might satisfy some of the objections currently lodged against this research.Indeed, the successful translation of this work to humans could potentiate further advancements in tissue engineering, where preliminary experiments have shown promise for correction of severe organ pathology.
Overexpression of Dimethylarginine Dimethylaminohydrolase Protects Against Cerebral Vascular Effects of Hyperhomocysteinemia
Authors: Roman N. Rodionov, Hayan Dayoub, Cynthia M. Lynch, Katina M. Wilson, Jeff W. Stevens, Daryl J. Murry, Masumi Kimoto, Erland Arning, Teodoro Bottiglieri, John P. Cooke, Gary L. Baumbach, Frank M. Faraci, Steven R. Lentz
Journal: Circulation Research (2009)

Hyperhomocysteinemia is a cardiovascular risk factor that is associated with elevation of the nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA).Using mice transgenic for overexpression of the ADMA-hydrolyzing enzyme dimethylarginine dimethylaminohydrolase-1 (DDAH1), we tested the hypothesis that overexpression of DDAH1 protects from adverse structural and functional changes in cerebral arterioles in hyperhomocysteinemia.Hyperhomocysteinemia was induced in DDAH1 transgenic (DDAH1 Tg) mice and wild-type littermates using a high methionine/low folate (HM/LF) diet. Plasma total homocysteine was elevated approximately 3-fold in both wild-type and DDAH1 Tg mice fed the HM/LF diet compared with the control diet (P<0.001). Plasma ADMA was approximately 40% lower in DDAH1 Tg mice compared with wild-type mice (P<0.001) irrespective of diet. Compared with the control diet, the HM/LF diet diminished endothelium-dependent dilation to 10 micromol/L acetylcholine in cerebral arterioles of both wild-type (12 + or - 2 versus 29 + or - 3%; P<0.001) and DDAH1 Tg (14 + or - 3 versus 28 + or - 2%; P<0.001) mice. Responses to 10 micromol/L papaverine, a direct smooth muscle dilator, were impaired with the HM/LF diet in wild-type mice (30 + or - 3 versus 45 + or - 5%; P<0.05) but not DDAH1 Tg mice (45 + or - 7 versus 48 + or - 6%). DDAH1 Tg mice also were protected from hypertrophy of cerebral arterioles (P<0.05) but not from accelerated carotid artery thrombosis induced by the HM/LF diet.Overexpression of DDAH1 protects from hyperhomocysteinemia-induced alterations in cerebral arteriolar structure and vascular muscle function.
Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors
Authors: Akihiro Hirashiki, Yoshiji Yamada, Yosuke Murase, Yoriyasu Suzuki, Hiroki Kataoka, Yasutsugu Morimoto, Toru Tajika, Toyoaki Murohara, Mitsuhiro Yokota
Journal: Journal of the American College of Cardiology (2003)
Angiotensin degradation products mediate endothelium-dependent dilation of rabbit brain arterioles.
Authors: R L Haberl, P J Decker, K M Einhäupl
Journal: Circulation Research (1991)

This study demonstrates that the hexapeptide angiotensin II-(3-8) and L-arginine, generated through enzymatic degradation of angiotensin, mediate endothelium-dependent dilation in rabbit brain arterioles. Topical application of angiotensin II (10(-5) M) on the brain surface of anesthetized rabbits caused 21.6 +/- 4.5% (mean +/- SEM) cerebral arteriolar dilation. The cyclooxygenase inhibitor indomethacin did not change this dilation. The natural degradation product of angiotensin II in the brain, angiotensin III, also induced vasodilation at concentrations of 10(-7) to 10(-5) M. The dilation to angiotensin II and angiotensin III was eliminated in the presence of 10(-5) M methylene blue, a known inhibitor of endothelium-dependent vasodilation. Amastatin, an aminopeptidase inhibitor and blocker of enzymatic angiotensin degradation, also inhibited the response to angiotensin II and angiotensin III. The angiotensin fragment angiotensin II-(3-8), which lacks the amino-terminal L-arginine residue of angiotensin III, did not elicit an arteriolar response. When angiotensin II-(3-8) was topically applied subsequent to L-arginine, a 21.2 +/- 2.9% vasodilation was observed. L-Arginine itself induced only moderate vasodilation with a maximum of 4.0 +/- 0.9% at 10(-5) M L-arginine. The dilating response to angiotensin II-(3-8) after L-arginine was inhibited by methylene blue. It was not affected by amastatin. It is concluded that degradation products of angiotensin, rather than angiotensin II itself, induce endothelium-dependent dilation in rabbit brain arterioles without involvement of cyclooxygenase products.(ABSTRACT TRUNCATED AT 250 WORDS)