tbuckley/cabot-search huggingface dataset:
Identification of differentially expressed genes in pancreatic cancer using digital differential display
Authors: Deepak Kumar, Carolyn Cousin, Song Tian, Malika Danner, Prafulla C. Gokhale, Mark Raffeld, Peter G. Shields, Norman S. Kondo
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1716 

Pancreatic Cancer is the second most common gastrointestinal malignancy and the fifth leading cause of cancer deaths in the United States. New specific targets are urgently needed to develop effective biomarkers and therapies. Digital Differential Display (DDD) is an in-silico method that can compare the frequencies of Expressed Sequence Tags (ESTs) between normal and tumor expression libraries. Using DDD, we compared the expression profiles of five pooled pancreatic tumor libraries (total of 43,953 clustered ESTs) with eighteen libraries representing normal pancreas and other tissues (total of 181,216 clustered ESTs). DDD identifies ESTs differentially expressed with a statistical significance of P < 0.05 (Fisher’s exact test). We selected fifteen cDNAs over expressed in pancreatic tumor libraries as compared with libraries from normal tissues (P<0.007). PubMed and Genbank database search revealed that thirteen known genes were overexpressed in various cancers and two genes DDD1 and DDD2 were novel. The novel DDD1 cDNA sequence is 1679 bp long and contains an Open Reading Frame (ORF) of 1191 bp coding for a putative protein of 396 amino acids (∼44 kDa). The DDD1 ORF was subcloned into the mammalian expression vector pDEST53 using Gateway™ (Invitrogen) technology according to manufacturer’s instructions for the expression of N-terminal Green Fluorescent Protein (GFP)-tagged DDD1 fusion protein. Transfection in COS-1 cells detected a fusion protein of ∼71 kDa (44 kDa of DDD1 + 27 kDa of GFP) in GFP-DDD1 transfected cells as compared to 27kDa GFP only protein in vector transfectants. Live confocal green fluorescence microscopy studies of the transfected COS-1 cells suggest that DDD1 is a cytosolic protein. Our preliminary in situ hybridization experiments on cancer tissue microarray suggest that DDD1 is overexpressed in various cancers. The characterization of DDD1 may provide insight into the mechanism of pancreatic cancer and development of new biomarkers and therapeutic targets.
Limiting early mortality: Do's and don'ts in the management of patients with newly diagnosed multiple myeloma
Authors: Wilson I. Gonsalves, Kelly Godby, Shaji K. Kumar, Luciano J. Costa
Journal: American Journal of Hematology (2015)

In the era of novel biological agents, multiple myeloma (MM) is often approached as a chronic condition. While survival continues to improve, population-level data indicate that early mortality remains a substantial barrier to advances in MM outcomes. Here we provide "do's and don'ts" management recommendations that may minimize the risk of early mortality and ensure that patients have the opportunity to benefit from the long term impact of new effective MM agents. Such recommendations encompass the early introduction of novel agents even in the presence of comorbidities and advanced age and aggressive management of MM-related complications.
Psychotherapy of dysthymia
Authors: J C Markowitz
Journal: American Journal of Psychiatry (1994)

The author reviews empirical research on the psychotherapy of dysthymia. Dysthymia, a prevalent mood disorder, has been shown frequently to respond to antidepressant medication. The need for a treatment for dysthymic subjects unable or unwilling to take, or unresponsive to, medication still remains.Studies were located by computerized search and the author's knowledge of the literature. All reports of studies on psychotherapy outcome for dysthymic patients, except studies of late-life chronic major depression, were included.Psychotherapy research on dysthymia has been confined to small, usually uncontrolled studies with varying methods and limited follow-up. Cognitive approaches have been most frequently studied; the results have not been dramatic but do suggest that some dysthymic patients respond to brief cognitive therapies. Preliminary results of an ongoing study of interpersonal psychotherapy are promising.Given the public health importance of dysthymia and the availability of treatments, the time is ripe for clinical trials of antidysthymic psychotherapy. The author proposes the following guidelines for such trials: time-limited, manual-based psychotherapy, interpersonal focus, serial design, continuation and maintenance treatment, combined treatments, and follow-up assessments.
Case-control association analysis of candidate genes in asthma, rhinitis and COPD: A preliminary report
Authors: Cristina Bombieri, Anna Rita Lo Presti, Francesca Belpinati, Simone Accordini, Alessandro Baldan, Marcello Ferrari, Giovanni Malerba, Elisabetta Zanolin, Pier Franco Pignatti, Roberto de Marco
Journal: European Respiratory Journal (2012)

This study aims to determine the genetic involvement in the susceptibility to asthma, rhinitis and COPD, by candidate gene association analysis, in a large and accurately defined series of Italian subjects, even considering exposure to some environmental contexts and life-styles.  The study population included 1075 subjects (aged 20-66 years) from the general population, enrolled in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study between 2007 and 2010. Cases and controls were diagnosed during a clinical examination that included a detailed interview, pre/post bronchodilator spirometry, methacoline challenge, skin prick tests.  A panel of 384 Single Nucleotide Polymorphisms (Tag-SNP), representative of 63 candidate genes with a previous indication of possible association to the studied diseases, was genotyped by a customized GoldenGate Genotyping assay. Presently, genotyping of 725/1075 subjects are completed. A preliminary association study of candidate gene polymorphisms was conducted on these data, for the susceptibility to one or more of the studied phenotypes, by basic association test based on allele frequency comparison. Presence of association (unadjusted p
Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases
Authors: H Kobayashi, KT Montgomery, SK Bohlander, CN Adra, BL Lim, RS Kucherlapati, H Donis-Keller, MS Holt, MM Le Beau, JD Rowley
Journal: Blood (1994)
Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2
Authors: None Covello, None Smith, None Sillevis Smitt, None Paller, None Munro, None Jonkman, None Uitto, None H.I.Mclean
Journal: British Journal of Dermatology (1998)

Journal Article Keratin 17 mutations cause either steatocystoma multiplex or pachyonychia congenita type 2 Get access S.P. Covello, S.P. Covello Epithelial Genetics Group, Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107, U.S.A., Search for other works by this author on: Oxford Academic Google Scholar F.J.D. Smith, F.J.D. Smith Epithelial Genetics Group, Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107, U.S.A., Search for other works by this author on: Oxford Academic Google Scholar J.H. Sillevis Smitt, J.H. Sillevis Smitt Department of Dermatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands, Search for other works by this author on: Oxford Academic Google Scholar A.S. Paller, A.S. Paller Division of Dermatology, Children's Memorial Hospital, Chicago, IL 60614, U.S.A., Search for other works by this author on: Oxford Academic Google Scholar C.S. Munro, C.S. Munro Department of Dermatology, Southern General Hospital, Glasgow G51 4TF, U.K., Search for other works by this author on: Oxford Academic Google Scholar M.F. Jonkman, M.F. Jonkman Department of Dermatology, University Hospital, Hanzeplein 1, NL‐9700 Groningen, The Netherlands, Search for other works by this author on: Oxford Academic Google Scholar J. Uitto, J. Uitto Department of Dermatology and Cutaneous Biology, Jefferson Institute for Molecular Medicine, 233 South 10th Street, Philadelphia, PA 19107, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar W.H.I. Mclean W.H.I. Mclean Epithelial Genetics Group, Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107, U.S.A., Dr Irwin McLean E‐mail: w.mclean@hgmp.mrc.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 3, 1 September 1998, Pages 475–480, https://doi.org/10.1046/j.1365-2133.1998.02413.x Published: 01 September 1998
HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study
Authors: Wei-Li Xu, Nancy L. Pedersen, Lina Keller, Grégoria Kalpouzos, Hui-Xin Wang, Caroline Graff, Bengt Winblad, Lars Bäckman, Laura Fratiglioni
Journal: PLoS Medicine (2015)

Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19–2.32) and 1.66 (95% CI 1.06–2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40–7.18) and 4.81 (95% CI 1.88–8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63–8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45–9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04–2.99) and 1.64 (1.02–2.33) for the diabetes–AD and dementia–AD associations, respectively, and 4.06 (95% CI 1.06–7.58, p = 0.039) and 3.29 (95% CI 1.02–8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. Conclusions A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people.
Clinical and molecular complexity of breast cancer metastases
Authors: Siker Kimbung, Niklas Loman, Ingrid Hedenfalk
Journal: Seminars in Cancer Biology (2015)

Clinical oncology is advancing toward a more personalized treatment orientation, making the need to understand the biology of metastasis increasingly acute. Dissecting the complex molecular, genetic and clinical phenotypes underlying the processes involved in the development of metastatic disease, which remains the principal cause of cancer-related deaths, could lead to the identification of more effective prognostication and targeted approaches to prevent and treat metastases. The past decade has witnessed significant progress in the field of cancer metastasis research. Clinical and technological milestones have been reached which have tremendously enriched our understanding of the complex pathways undertaken by primary tumors to progress into lethal metastases and how some of these processes might be amenable to therapy. The aim of this review article is to highlight the recent advances toward unraveling the clinical and molecular complexity of breast cancer metastases. We focus on genes mediating breast cancer metastases and organ-specific tropism, and discuss gene signatures for prediction of metastatic disease. The challenges of translating this information into clinically applicable tools for improving the prognostication of the metastatic potential of a primary breast tumor, as well as for therapeutic interventions against latent and active metastatic disease are addressed.
Chicken Resistance to Dimethylnitrosamine Acute Effects on the Liver: A Comparative Study With Other Species&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: H M Godoy, M I Díaz Gómez, A Marzi, E C de Ferreyra, O M de Fenos, J A Castro
Journal: JNCI Journal of the National Cancer Institute (1982)

Dimethylnitrosamine (DMN)-induced liver damage, as measured by the increase in plasma isocitrate dehydrogenase as well as by histologic assessment of necrosis, was marked after DMN ip administration (70 mg/kg) in males of all noninbred species tested (BALB/c mouse, Sprague-Dawley rat, Syrian golden hamster, general purpose guinea pig) but not in the noninbred White Leghorn chicken. At 1 and 3 hours after DMN injection, liver DMN levels were not lower in the chicken as compared to levels in the other species. Furthermore, in all species except the chicken, significant decreases were found at 3 hours as compared to 1 hour after DMN administration. DMN metabolism to CO2 and to formaldehyde, as well as covalent binding of DMN-reactive metabolites to either proteins or nucleic acid, was measured with the use of liver slices, microsomes, and/or 9,000 X g supernatants. Results indicated that chicken liver had a very low capacity for metabolism and activation (29-3,166 times lower than comparable data in mice or hamsters).
Fibrosing mediastinitis and tuberculosis: A Brazilian case report
Authors: Beatriz Leão, Livia Bissoli, Guilherme Eler de Almeida, Marcia Seiscento, Lisete Teixeira, Roberta Sales
Journal: European Respiratory Journal (2014)

Introduction  Fibrosing mediastinitis (FM) is a rare, often progressive condition that consists on a proliferation of fibrous tissue within the mediastinum. Etiology is usually unknown, but in endemic areas granulomatous infections have been implicated.  Objectives  We describe a rare case of a patient with pleural tuberculosis (TB) and FM.  Methods  Medical consultation, exams and analysis of the medical files.  Discussion  A 42 year old male with pleural TB histologically confirmed, receiving standard treatment, referred syncope episodes, with no prodromes, associated with orthopnea, dyspnea (mMRC 2) and cervical swelling. HRCT showed a mediastinal infiltrative mass obliterating the superior vena cava9s lumen, some mediastinal and hilar lymphadenomegalies and right pleural effusion. Mediastinoscopic guided biopsy showed no granulomas or atypical cells, revealing many areas of fibrohyalinosis with calcificating necrosis in conjunctive and lymphoid tissues, and cultures were negative for fungi and mycobacteria. The cava compression was confirmed by angiotomography and doppler ultrasonography of cervical vessels, also diagnosing right internal jugular acute vein thrombosis.  Despite anticoagulation and the TB treatment completion, with full resolution of the other findings, there was no regression of the mediastinal mass or vascular compression.  Conclusion  Clinical, radiological and histological findings leaded to the diagnosis of superior vena cava syndrome and FM, here presented in its diffuse pattern, which happens in 18% of the cases.  FM could be a sequel of successfully treated tuberculosis. It often has an unpredictable course; periods of both spontaneous remission and exacerbation of symptoms have been reported.
Human Leukemia Antigen. I. Production and Characterization of Antisera&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: R Billing, P I Terasaki
Journal: JNCI Journal of the National Cancer Institute (1974)

Rabbits were immunized with papain digests of cell membranes from the cultured Iymphoblastoid RAJI cell line and fresh human lymphoma tissue. Without any prior absorptions, the antisera showed specificity for leukemia cells. The undiluted antisera were not cytotoxic to normal lymphocytes, normal granulocytes, and Iymphocytes from leukemia patients in remission. However, the antisera were cytotoxic to all types of myeloid and Iymphocytic leukemia cells. The RAJI antiserum was active to a titer of 1 ∶ 16 and the lymphoma antiserum to a titer of 1 ∶ 128. The antisera did not appear to be acting solely against blast cell antigens because normal phytohemagglutinin blasts and bone marrow cells were not killed. Lymphoblastoid cell lines were killed but at a much lower titer (1 ∶ 2 and 1 ∶ 8). The antibody activity could be removed by absorption with RAJI cells and leukemia cells but not by normal granulocytes. Twentyfold more normal Iymphocytes than RAJI cells could also absorb the leukemia antibody. Experiments suggested that human lymphocytes could nonspecifically absorb rabbit antibodies. The potential clinical use of the leukemia antisera was discussed.
Unusual Presentations of Malignancy
Authors: Anna R. Thorner, Anne C. Travis, Jonathan L. Hecht, David S. Conrow, David C. Fisher
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.13.3291 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11432899 Unusual Presentations of Malignancy Case 3. Mantle-Cell Lymphoma of Soft Tissue Anna R. ThornerxAnna R. ThornerSearch for articles by this author , Anne C. TravisxAnne C. TravisSearch for articles by this author , Jonathan L. HechtxJonathan L. HechtSearch for articles by this author , David S. ConrowxDavid S. ConrowSearch for articles by this author , David C. FisherxDavid C. FisherSearch for articles by this author Show More Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2001.19.13.3291 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Issues With the Diagnosis and Classification of Hyperglycemia in Early Pregnancy
Authors: H. David McIntyre, David A. Sacks, Linda A. Barbour, Denice S. Feig, Patrick M. Catalano, Peter Damm, Aidan McElduff
Journal: Diabetes Care (2015)

In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) panel published consensus-based recommendations on the diagnosis and classification of hyperglycemia in pregnancy (1). Within that document, the recommendations regarding early pregnancy testing were designed to facilitate early detection and treatment of hyperglycemia (HbA1c ≥6.5% [48 mmol/mol], fasting venous plasma glucose ≥7.0 mmol/L, random plasma glucose ≥11.1 mmol/L with confirmation) that, outside pregnancy, would be classified as diabetes. The term “overt diabetes” was suggested to describe these women. Subsequently, the World Health Organization (WHO) adopted the IADPSG criteria with some modifications and promoted the use of the term “diabetes in pregnancy” (2) for this group.

Cognizant that milder degrees of hyperglycemia would also be detected by early pregnancy testing, the IADPSG also recommended that fasting …
Microbes and obesity—interrelationship between infection, adipose tissue and the immune system
Authors: V. Hegde, N.V. Dhurandhar
Journal: Clinical Microbiology and Infection (2013)

The world is currently experiencing an obesity epidemic as declared by the World Health Organization. The traditional view is that behaviour leading to overeating and under-activity is the major contributing factor for this worldwide epidemic. However, several microbes are linked to obesity in animals and humans. On the one hand, various microbes, including animal and human viruses, bacteria, parasites and scrapie agents, increase adiposity in several animal models. Some of these microbes show an association with human obesity, but conclusive evidence for a causative role of microbes in human obesity is lacking. On the other hand, obese individuals show an altered response to infections. Obesity is often associated with impaired immune function, which may lead to increased susceptibility to infection with a number of different pathogens. Hence, certain microbes appear to induce obesity, whereas, obesity itself may exacerbate certain other infections. Linking the two phenomenon is the immunological property of adipocytes and their progenitors. For instance, proliferating pre-adipocytes share embryonic origin with immune cells and exhibit phagocytic activity. Taken together it appears that there is a close interrelationship between adipose tissue, inflammatory response, immune system and infections. Hence, it is conceivable that in response to certain infections, adipose tissue expands similar to the expansion of cells of the immune system. The impaired immune function of adipose tissue in obesity may exacerbate infections. Considering the global obesity epidemic, it is necessary to further investigate both phenomena.
Functional annotation of high-quality SNP biomarkers of gastric cancer susceptibility: the Yin Yang of<i>PSCA</i>rs2294008
Authors: Hyuna Sung, Howard H Yang, Nan Hu, Hua Su, Philip R Taylor, Paula L Hyland
Journal: Gut (2015)

Dear Editor,

We read the recent article by Mocellin et al 1 with great interest. Their comprehensive meta-analysis nominated 11 germline variants at nine loci with high level of cumulative evidence for genetic susceptibility to gastric cancer (GC). Evidence for five of the nine loci ( PKLR at 1q22, CASP8 at 2q33.1, MUC1 at 1q22, TGFBR2 at 3p241 and GSTP1 at 11q13.2) came from hypothesis-driven studies based on biological relevance, while the remaining loci were identified through genome-wide association studies (GWAS). However, all loci await functional annotation in the relevant normal tissue to further our understanding of the mechanisms underlying the associations. To explore their functional relevance, we annotated each variant (and its high LD SNPs) using publicly available bioinformatics data in conjunction with our own GWAS and mRNA expression data (figure 1).



Figure 1 
Differential effects of rs2294008T on the expression of PSCA in tumour vs normal gastric tissues presumably via interaction with YY1. (A) Expression quantitative trait loci (eQTL) analysis between rs2294008 (risk allele=T) genotypes and PSCA mRNA expression in normal gastric tissues. In the Shanxi study, mRNA levels were assessed using the Affymetrix\_U133A probe 205319\_at in 89 paired cancer/adjacent normal gastric tissue samples, and correlation coefficients (rho) were estimated using non-parametric Spearman rank correlation tests. From Genotype-Tissue Expression (GTEx), p values were obtained using linear regression between log and quantile normalised RNA-sequencing expression values (of the coding transcript ENS0301258 l; …