tbuckley/cabot-search huggingface dataset:
Down-Regulation of Hedgehog-Interacting Protein through Genetic and Epigenetic Alterations in Human Hepatocellular Carcinoma
Authors: Motohisa Tada, Fumihiko Kanai, Yasuo Tanaka, Keisuke Tateishi, Miki Ohta, Yoshinari Asaoka, Motoko Seto, Ryosuke Muroyama, Kenichi Fukai, Fumio Imazeki, Takao Kawabe, Osamu Yokosuka, Masao Omata
Journal: Clinical Cancer Research (2008)

Hedgehog (Hh) signaling is activated in several cancers. However, the mechanisms of Hh signaling activation in hepatocellular carcinoma (HCC) have not been fully elucidated. We analyzed the involvement of Hh-interacting protein (HHIP) gene, a negative regulator of Hh signaling, in HCC.Glioma-associated oncogene homologue (Gli) reporter assay, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, and quantitative real-time reverse transcription-PCR for the target genes of the Hh signals were performed in HHIP stably expressing hepatoma cells. Quantitative real-time PCR for HHIP was performed in hepatoma cells and 36 HCC tissues. The methylation status of hepatoma cells and HCC tissues was also analyzed by sodium bisulfite sequencing, demethylation assay, and quantitative real-time methylation-specific PCR. Loss of heterozygosity (LOH) analysis was also performed in HCC tissues.HHIP overexpression induced significant reductions of Gli reporter activity, cell viability, and transcription of the target genes of the Hh signals. HHIP was hypermethylated and transcriptionally down-regulated in a subset of hepatoma cells. Treatment with a demethylating agent led to the HHIP DNA demethylation and restoration of HHIP transcription. HHIP transcription was also down-regulated in the majority of HCC tissues, and more than half of HCC tissues exhibited HHIP hypermethylation. The HHIP transcription level in HHIP-methylated HCC tissues was significantly lower than in HHIP-unmethylated HCC tissues. More than 30% of HCC tissues showed LOH at the HHIP locus.The down-regulation of HHIP transcription is due to DNA hypermethylation and/or LOH, and Hh signal activation through the inactivation of HHIP may be implicated in the pathogenesis of human HCC.
Increased nitric oxide excretion in patients with severe acute pancreatitis: evidence of an endotoxin mediated inflammatory response?
Authors: S H Rahman
Journal: Gut (2003)

Nitric oxide represents a potential key mediator of the local and systemic manifestations of acute pancreatitis (AP) in experimental models but its role in human disease is uncertain. We therefore sought to assess if systemic nitric oxide (NO) production is elevated in severe AP and determine whether this is a reflection of biochemical severity or endotoxin exposure.Patients were recruited within 72 hours of pain onset. NO derived nitrite excretion determined from a 24 hour sterile urine collection was correlated with intestinal macromolecular permeability (polyethylene glycol excretion ratio), markers of systemic endotoxin exposure (IgG:IgM endotoxin core antibody (EndoCAb) ratio), disease severity, and the magnitude of systemic inflammation (peak C reactive protein (CRP) and Acute Physiology and Chronic Health Evaluation score II (APACHE-II)).In patients with a severe attack (n=20), nitrite excretion was increased significantly compared with patients with a mild attack (n=45, 20.6 micro g v 15.65 micro g; p<0.00) and the latter with healthy controls (n=20, p=0.004). Nitrite excretion correlated strongly with both intestinal permeability (r=0.7, p=0.006) and EndoCAb ratio (r=0.7, p<0.01) but not with CRP or APACHE-II scores (p>0.1).Total urinary nitrite excretion is increased in patients with severe AP, and may not be simply a reflection of systemic inflammation, but potentially a consequence of endotoxin mediated upregulation of inducible NO synthase activity.
COPD exacerbations {middle dot} 4: Prevention
Authors: S Scott
Journal: Thorax (2006)

Abstract A review of the evidence that the prevention of COPD works and, if so, the effectiveness of this strategy COPD, chronic obstructive pulmonary diseaseFEV1, forced expiratory volume in 1 secondNAC, N-acetylcysteinechronic obstructive pulmonary diseaseexacerbationsprevention
Deletion of 3(p14p23) in Secondary Erythroleukemia Arising in Long-Term Survivors of Small Cell Lung Cancer
Authors: J. Whang-Peng, E. C. Lee, J. D. Minna, M. D. Abeloff, E. C. Bradley, R. C. Young, Dan. L Longo
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Deletion of 3(p14p23) in Secondary Erythroleukemia Arising in Long-Term Survivors of Small Cell Lung Cancer Get access Jacqueline Whang-Peng, Jacqueline Whang-Peng * 2Medicine Branch, Clinical Oncology Program (J. Whang-Peng, E.C. Lee, R C. Young, D. L. Longo), and NCI-Navy Medical Oncology Branch (J. D. Minna), Division of Cancer Treatment, National Cancer InstituteBethesda, MD. *Correspondence to: Dr. Jacqueline Whang-Peng, Bldg. 10, Rm. 12N226, National Institutes of Health, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Elaine C. Lee, Elaine C. Lee 2Medicine Branch, Clinical Oncology Program (J. Whang-Peng, E.C. Lee, R C. Young, D. L. Longo), and NCI-Navy Medical Oncology Branch (J. D. Minna), Division of Cancer Treatment, National Cancer InstituteBethesda, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar John D. Minna, John D. Minna 2Medicine Branch, Clinical Oncology Program (J. Whang-Peng, E.C. Lee, R C. Young, D. L. Longo), and NCI-Navy Medical Oncology Branch (J. D. Minna), Division of Cancer Treatment, National Cancer InstituteBethesda, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin D. Abeloff, Martin D. Abeloff 3Johns Hopkins Oncology Center, The Johns Hopkins University School of MedicineBaltimore, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward C. Bradley, Edward C. Bradley 4Cetus CorporationEmeryville, CA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert C. Young, Robert C. Young 2Medicine Branch, Clinical Oncology Program (J. Whang-Peng, E.C. Lee, R C. Young, D. L. Longo), and NCI-Navy Medical Oncology Branch (J. D. Minna), Division of Cancer Treatment, National Cancer InstituteBethesda, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan. L Longo Dan. L Longo 2Medicine Branch, Clinical Oncology Program (J. Whang-Peng, E.C. Lee, R C. Young, D. L. Longo), and NCI-Navy Medical Oncology Branch (J. D. Minna), Division of Cancer Treatment, National Cancer InstituteBethesda, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 15, 5 October 1988, Pages 1253–1255, https://doi.org/10.1093/jnci/80.15.1253 Published: 05 October 1988 Article history Received: 25 May 1988 Revision received: 25 July 1988 Accepted: 25 July 1988 Published: 05 October 1988
Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets
Authors: Mimi Kjaersgaard, Rukhsana Aslam, Michael Kim, Edwin R. Speck, John Freedman, Donald I. H. Stewart, Erik J. Wiersma, John W. Semple
Journal: Blood (2007)
Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease
Authors: Robert Clarke, John F. Peden, Jemma C. Hopewell, Theodosios Kyriakou, Anuj Goel, Simon C. Heath, Sarah Parish, Simona Barlera, Maria Grazia Franzosi, Stephan Rust, Derrick Bennett, Angela Silveira, Anders Malarstig, Fiona R. Green, Mark Lathrop, Bruna Gigante, Karin Leander, Ulf de Faire, Udo Seedorf, Anders Hamsten, Rory Collins, Hugh Watkins, Martin Farrall
Journal: New England Journal of Medicine (2009)

An increased level of Lp(a) lipoprotein has been identified as a risk factor for coronary artery disease that is highly heritable. The genetic determinants of the Lp(a) lipoprotein level and their relevance for the risk of coronary disease are incompletely understood.We used a novel gene chip containing 48,742 single-nucleotide polymorphisms (SNPs) in 2100 candidate genes to test for associations in 3145 case subjects with coronary disease and 3352 control subjects. Replication was tested in three independent populations involving 4846 additional case subjects with coronary disease and 4594 control subjects.Three chromosomal regions (6q26-27, 9p21, and 1p13) were strongly associated with the risk of coronary disease. The LPA locus on 6q26-27 encoding Lp(a) lipoprotein had the strongest association. We identified a common variant (rs10455872) at the LPA locus with an odds ratio for coronary disease of 1.70 (95% confidence interval [CI], 1.49 to 1.95) and another independent variant (rs3798220) with an odds ratio of 1.92 (95% CI, 1.48 to 2.49). Both variants were strongly associated with an increased level of Lp(a) lipoprotein, a reduced copy number in LPA (which determines the number of kringle IV-type 2 repeats), and a small Lp(a) lipoprotein size. Replication studies confirmed the effects of both variants on the Lp(a) lipoprotein level and the risk of coronary disease. A meta-analysis showed that with a genotype score involving both LPA SNPs, the odds ratios for coronary disease were 1.51 (95% CI, 1.38 to 1.66) for one variant and 2.57 (95% CI, 1.80 to 3.67) for two or more variants. After adjustment for the Lp(a) lipoprotein level, the association between the LPA genotype score and the risk of coronary disease was abolished.We identified two LPA variants that were strongly associated with both an increased level of Lp(a) lipoprotein and an increased risk of coronary disease. Our findings provide support for a causal role of Lp(a) lipoprotein in coronary disease.
Variations of basal cell carcinomas according to gender, age, location and histopathological subtype
Authors: Y. Scrivener, E. Grosshans, B. Cribier
Journal: British Journal of Dermatology (2002)

Most published series of basal cell carcinomas (BCCs) do not take into account the histopathological subtype. Recent studies suggest that the nodular and superficial types could be induced by different causal factors.To analyse the three major subtypes of BCC with regard to sex, age and anatomical distribution.We retrospectively included all cases of BCC diagnosed at a single centre of dermatopathology during 1967-96. The diagnosis and subtype (nodular, superficial, morphoeiform) were confirmed by two dermatopathologists. Gender, age at excision, number of tumours and location were recorded, and analysed by histopathological subtype.We recorded 13 457 cases in 10 245 patients (M/F ratio 0.92) of mean age 65 years. Of the BCCs, 78.7% were nodular, 15.1% superficial and 6.2% morphoeiform. Nodular tumours occurred at a mean age of 66.3 years, whereas superficial tumours were excised earlier (63.0 years) and more frequently in women (M/F ratio 0.96). Patients with morphoeiform BCC had a mean age of 65.8 years and were predominantly women (M/F ratio 0.73). Both nodular and morphoeiform types predominated on the head (89.6% and 94.8%), whereas the trunk was the most common location for the superficial type (45.9%). Superficial carcinomas were predominantly located on the head in women (44.8% vs. 34.7% in men), whereas they predominated on the trunk in men (49.9% vs. 42% in women). Tumours of the trunk were excised earlier than those of the face, whatever their histological subtype, in both men and women.This is the largest series of BCCs in the literature, and shows striking differences in anatomical distribution, sex and mean age according to histological type. The results suggest that the tumours of the trunk, and not only those of the superficial type, could represent a particular subtype of BCC. The analysis also suggests that the hypothesis of chronic vs. intermittent sun exposure cannot be simply extrapolated to BCC. Other causal factors, such as a genetic predisposition, could be involved in the development of carcinomas located on the trunk.
Morphea-like reaction to D-penicillamine therapy.
Authors: R M Bernstein, M A Hall, B E Gostelow
Journal: Annals of the Rheumatic Diseases (1981)

We report the case of a 48-year-old woman who developed morphea-like plaques after 1 year of treatment with D-penicillamine at 250 mg daily for a seronegative erosive arthritis of rheumatoid type. The rash began as several red itchy patches on the trunk; these became thickened and shiny over about 3 months. The histological appearance was of increased dermal fibrosis with an inflammatory infiltrate round dermal capillaries. However, epidermal changes were not typical of morphea. New lesions ceased to appear within a few months of stopping penicillamine, and by 1 year all the plaques were pale and symptomless.
PSYCHOSES AMONG WOMEN GOVERNMENT WORKERS IN WARTIME
Authors: HAROLD STEVENS
Journal: American Journal of Psychiatry (1945)

Statistical data on 89 non-resident white women, civil service employees have been presented with the inference that these psychotic workers present a universal problem in industrial medicine that may be expected to become more acute with rising proportion of women workers. It is felt that external influences hasten the onset—more than half the cases being hospitalized in less than six months after employment. With the decline in the quality of prospective employees, closer scrutiny of previous occupational records is indicated and particular emphasis is placed on the history of previous mental disease as a prognostic index
Air Pollution and Children — An Unhealthy Mix
Authors: W. James Gauderman
Journal: New England Journal of Medicine (2006)

Residents in urban areas may be worried about the air they breathe. In recent reports, air pollution has been linked to increased mortality, an increased risk of asthma, and decreased development of lung function in childhood. In this issue of the Journal, Kulkarni et al.1 investigate this last finding. The authors show that carbon particles, similar to those in ambient air, are present in the airway macrophages of children and that an increased level of carbon in the macrophages correlates with decreased lung function.Why should we care about lung function in children? The lungs develop steadily throughout childhood, with . . .
Epistatic interaction between FCRL3 and NF B1 genes in Spanish patients with rheumatoid arthritis
Authors: A Martinez, E Sanchez, A Valdivia, G Orozco, M A Lopez-Nevot, D Pascual-Salcedo, A Balsa, B Fernandez-Gutierrez, E G de la Concha, A Garcia-Sanchez, B P C Koeleman, E Urcelay, J Martin
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc receptor-like 3 (<i>FCRL3</i>) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21–23. <b>Objectives:</b> To evaluate the association between rheumatoid arthritis and <i>FCLR3</i> polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the <i>FCRL3</i> polymorphisms and the transcription factor nuclear factor κB (NFκB), a functional polymorphism located in the <i>NFκB1</i> gene was included. <b>Methods:</b> 734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the <i>FCRL3</i> gene were studied by TaqMan technology. The −94ins/delATTG <i>NFκB1</i> promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 3×2 contingency tables and χ<sup>2</sup> values. <b>Results:</b> No overall differences were found in any of the <i>FCRL3</i> polymorphisms and in the <i>NFκB1</i> promoter polymorphism when patients were compared with controls. However, when stratified according to <i>NFκB1</i> genotypes, a susceptibility effect of <i>FCRL3</i> polymorphisms was observed in patients who were heterozygotes for <i>NFκB1</i> (p<sub>c</sub> = 0.003). <b>Conclusions:</b> The <i>FCRL3</i> polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between <i>NFκB1</i> and <i>FCRL3</i> in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations.
NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation
Authors: Jung-Hyun Kim, Rajesh K. Thimmulappa, Vineet Kumar, Wanchang Cui, Sarvesh Kumar, Ponvijay Kombairaju, Hao Zhang, Joseph Margolick, William Matsui, Thomas Macvittie, Sanjay V. Malhotra, Shyam Biswal
Journal: Journal of Clinical Investigation (2014)

A nuclear disaster may result in exposure to potentially lethal doses of ionizing radiation (IR). Hematopoietic acute radiation syndrome (H-ARS) is characterized by severe myelosuppression, which increases the risk of infection, bleeding, and mortality. Here, we determined that activation of nuclear factor erythroid-2–related factor 2 (NRF2) signaling enhances hematopoietic stem progenitor cell (HSPC) function and mitigates IR-induced myelosuppression and mortality. Augmenting NRF2 signaling in mice, either by genetic deletion of the NRF2 inhibitor Keap1 or by pharmacological NRF2 activation with 2-trifluoromethyl-2′-methoxychalone (TMC), enhanced hematopoietic reconstitution following bone marrow transplantation (BMT). Strikingly, even 24 hours after lethal IR exposure, oral administration of TMC mitigated myelosuppression and mortality in mice. Furthermore, TMC administration to irradiated transgenic Notch reporter mice revealed activation of Notch signaling in HSPCs and enhanced HSPC expansion by increasing Jagged1 expression in BM stromal cells. Administration of a Notch inhibitor ablated the effects of TMC on hematopoietic reconstitution. Taken together, we identified a mechanism by which NRF2-mediated Notch signaling improves HSPC function and myelosuppression following IR exposure. Our data indicate that targeting this pathway may provide a countermeasure against the damaging effects of IR exposure.
Fasting and Insulin Glargine in Individuals With Type 1 Diabetes
Authors: Gregory T. Mucha, Stacia Merkel, William Thomas, John P. Bantle
Journal: Diabetes Care (2004)

The Diabetes Control and Complications Trial demonstrated that intensive treatment of type 1 diabetes protected against the microvascular complications of diabetes (1). The results were obtained in a selected group of type 1 diabetic volunteers who received attentive clinical care and substantial diabetes education. Careful attention was paid to lifestyle issues, but optimal control of diabetes was still often difficult to accomplish (1,2). An important treatment barrier for many patients with type 1 diabetes was the need to eat, sleep, and take medication according to a consistent schedule. Insulin infusion pumps help provide flexibility in dealing with these issues (3,4). However, treatment with insulin pumps is expensive (4,5), and some people with type 1 diabetes are not good candidates for pump therapy (3,4). Other treatment methods that allow flexibility with lifestyle issues might improve both treatment outcomes and quality of life. Insulin glargine, a basal insulin, might be useful in this regard. To evaluate this possibility, we tested the hypothesis that glargine insulin would maintain euglycemia in type 1 diabetic subjects during an 18-h fast, such as would occur when a person with type 1 diabetes sleeps late or misses meals.

Fifteen subjects with type 1 diabetes …
A Blinded, Randomized, Placebo-Controlled Trial of Percutaneous Laser Myocardial Revascularization to Improve Angina Symptoms in Patients With Severe Coronary Disease
Authors: Martin B. Leon, Ran Kornowski, William E. Downey, Giora Weisz, Donald S. Baim, Robert O. Bonow, Robert C. Hendel, David J. Cohen, Ernest Gervino, Roger Laham, Nicholas J. Lembo, Jeffrey W. Moses, Richard E. Kuntz
Journal: Journal of the American College of Cardiology (2005)
Improving Bayesian Population Dynamics Inference: A Coalescent-Based Model for Multiple Loci
Authors: M. S. Gill, P. Lemey, N. R. Faria, A. Rambaut, B. Shapiro, M. A. Suchard
Journal: Molecular Biology and Evolution (2012)

Effective population size is fundamental in population genetics and characterizes genetic diversity. To infer past population dynamics from molecular sequence data, coalescent-based models have been developed for Bayesian nonparametric estimation of effective population size over time. Among the most successful is a Gaussian Markov random field (GMRF) model for a single gene locus. Here, we present a generalization of the GMRF model that allows for the analysis of multilocus sequence data. Using simulated data, we demonstrate the improved performance of our method to recover true population trajectories and the time to the most recent common ancestor (TMRCA). We analyze a multilocus alignment of HIV-1 CRF02_AG gene sequences sampled from Cameroon. Our results are consistent with HIV prevalence data and uncover some aspects of the population history that go undetected in Bayesian parametric estimation. Finally, we recover an older and more reconcilable TMRCA for a classic ancient DNA data set.
TFPIα and TFPIβ are expressed at the surface of breast cancer cells and inhibit TF-FVIIa activity
Authors: Benedicte Stavik, Mari Tinholt, Marit Sletten, Grethe Skretting, Per Morten Sandset, Nina Iversen
Journal: Journal of Hematology & Oncology (2013)

Abstract Background Tissue factor (TF) pathway inhibitor-1 (TFPI) is expressed in several malignant tissues- and cell lines and we recently reported that it possesses anti-tumor effects in breast cancer cells, indicating a biological role of TFPI in cancer. The two main splice variants of TFPI; TFPIα and TFPIβ, are both able to inhibit TF-factor VIIa (FVIIa) activity in normal cells, but only TFPIα circulates in plasma. The functional importance of TFPIβ is therefore largely unknown, especially in cancer cells. We aimed to characterize the expression and function of TFPIα, TFPIβ, and TF in a panel of tumor derived breast cancer cell lines in comparison to normal endothelial cells. Methods TFPIα, TFPIβ, and TF mRNA and protein measurements were conducted using qRT-PCR and ELISA, respectively. Cell-associated TFPI was detected after phosphatidylinositol-phospholipase C (PI-PLC) and heparin treatment by flow cytometry, immunofluorescence, and Western blotting. The potential anticoagulant activity of cell surface TFPI was determined in a factor Xa activity assay. Results The expression of both isoforms of TFPI varied considerably among the breast cancer cell lines tested, from no expression in Sum149 cells to levels above or in the same range as normal endothelial cells in Sum102 and MDA-MB-231 cells. PI-PLC treatment released both TFPIα and TFPIβ from the breast cancer cell membrane and increased TF activity on the cell surface, showing TF-FVIIa inhibitory activity of the glycosylphosphatidylinositol- (GPI-) anchored TFPI. Heparin treatment released TFPIα without decreasing the cell surface levels, thus indicating the presence of intracellular storage pools of TFPIα in the breast cancer cells. Conclusion GPI-attached TFPI located at the surface of breast cancer cells inhibited TF activity and could possibly reduce TF signaling and breast cancer cell growth locally, indicating a therapeutic potential of the TFPIβ isoform.