tbuckley/cabot-search huggingface dataset:
Long-Term Changes in Adiposity and Glycemic Control Are Associated With Past Adenovirus Infection
Authors: Wan-Yu Lin, Olga Dubuisson, Rohina Rubicz, Nianjun Liu, David B. Allison, Joanne E. Curran, Anthony G. Comuzzie, John Blangero, Charles T. Leach, Harald Göring, Nikhil V. Dhurandhar
Journal: Diabetes Care (2012)

OBJECTIVE Ad36, a human adenovirus, increases adiposity but improves glycemic control in animal models. Similarly, natural Ad36 infection is cross-sectionally associated with greater adiposity and better glycemic control in humans. This study compared longitudinal observations in indices of adiposity (BMI and body fat percentage) and glycemic control (fasting glucose and insulin) in Ad36-infected versus uninfected adults. RESEARCH DESIGN AND METHODS Baseline sera from Hispanic men and women (n = 1,400) were screened post hoc for the presence of Ad36-specific antibodies. Indices of adiposity and glycemic control at baseline and at ∼10 years past the baseline were compared between seropositive and seronegative subjects, with adjustment for age and sex. In addition to age and sex, indices of glycemic control were adjusted for baseline BMI and were analyzed only for nondiabetic subjects. RESULTS Seropositive subjects (14.5%) had greater adiposity at baseline, compared with seronegative subjects. Longitudinally, seropositive subjects showed greater adiposity indices but lower fasting insulin levels. Subgroup analyses revealed that Ad36-seropositivity was associated with better baseline glycemic control and lower fasting insulin levels over time in the normal-weight group (BMI ≤25 kg/m2) and longitudinally, with greater adiposity in the overweight (BMI 25–30 kg/m2) and obese (BMI &amp;gt;30 kg/m2) men. Statistically, the differences between seropositive and seronegative individuals were modest in light of the multiple tests performed. CONCLUSIONS This study strengthens the plausibility that in humans, Ad36 increases adiposity and attenuates deterioration of glycemic control. Panoptically, the study raises the possibility that certain infections may modulate obesity or diabetes risk. A comprehensive understanding of these under-recognized factors is needed to effectively combat such metabolic disorders.
Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development
Authors: Gregory Golling, Adam Amsterdam, Zhaoxia Sun, Marcelo Antonelli, Ernesto Maldonado, Wenbiao Chen, Shawn Burgess, Maryann Haldi, Karen Artzt, Sarah Farrington, Shuh-Yow Lin, Robert M. Nissen, Nancy Hopkins
Journal: Nature Genetics (2002)
Selective coexpression of VEGF receptor 2 in EGFRvIII-positive glioblastoma cells prevents cellular senescence and contributes to their aggressive nature
Authors: Karra A. Jones, Andrew S. Gilder, Michael S. Lam, Na Du, Michael A. Banki, Aran Merati, Donald P. Pizzo, Scott R. VandenBerg, Steven L. Gonias
Journal: Neuro-Oncology (2015)

In glioblastoma (GBM), the gene for epidermal growth factor receptor (EGFR) is frequently amplified. EGFR mutations also are common, including a truncation mutation that yields a constitutively active variant called EGFR variant (v)III. EGFRvIII-positive GBM progresses rapidly; however, the reason for this is not clear because the activity of EGFRvIII is attenuated compared with EGF-ligated wild-type EGFR. We hypothesized that EGFRvIII-expressing GBM cells selectively express other oncogenic receptors that support tumor progression.Mining of The Cancer Genome Atlas prompted us to test whether GBM cells in culture, which express EGFRvIII, selectively express vascular endothelial growth factor receptor (VEGFR)2. We also studied human GBM propagated as xenografts. We then applied multiple approaches to test the effects of VEGFR2 on GBM cell growth, apoptosis, and cellular senescence.In human GBM, EGFR overexpression and EGFRvIII positivity were associated with increased VEGFR2 expression. In GBM cells in culture, EGFRvIII-initiated cell signaling increased expression of VEGFR2, which prevented cellular senescence and promoted cell cycle progression. The VEGFR-selective tyrosine kinase inhibitor cediranib decreased tumor DNA synthesis, increased staining for senescence-associated β-galactosidase, reduced retinoblastoma phosphorylation, and increased p27(Kip1), all markers of cellular senescence. Similar results were obtained when VEGFR2 was silenced.VEGFR2 expression by GBM cells supports cell cycle progression and prevents cellular senescence. Coexpression of VEGFR2 by GBM cells in which EGFR signaling is activated may contribute to the aggressive nature of these cells.
Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene.
Authors: Jeffrey F Waring, Roger G Ulrich, Nick Flint, David Morfitt, Arno Kalkuhl, Frank Staedtler, Michael Lawton, Johanna M Beekman, Laura Suter
Journal: Environmental Health Perspectives (2004)

Several studies using microarrays have shown that changes in gene expression provide information about the mechanism of toxicity induced by xenobiotic agents. Nevertheless, the issue of whether gene expression profiles are reproducible across different laboratories remains to be determined. To address this question, several members of the Hepatotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute evaluated the liver gene expression profiles of rats treated with methapyrilene (MP). Animals were treated at one facility, and RNA was distributed to five different sites for gene expression analysis. A preliminary evaluation of the number of modulated genes uncovered striking differences between the five different sites. However, additional data analysis demonstrated that these differences had an effect on the absolute gene expression results but not on the outcome of the study. For all users, unsupervised algorithms showed that gene expression allows the distinction of the high dose of MP from controls and low dose. In addition, the use of a supervised analysis method (support vector machines) made it possible to correctly classify samples. In conclusion, the results show that, despite some variability, robust gene expression changes were consistent between sites. In addition, key expression changes related to the mechanism of MP-induced hepatotoxicity were identified. These results provide critical information regarding the consistency of microarray results across different laboratories and shed light on the strengths and limitations of expression profiling in drug safety analysis.
Long term effect of alpha interferon in children with chronic hepatitis B
Authors: F Bortolotti
Journal: Gut (2000)

The purpose of this study was to better define the long term prognosis of infection and disease in children with chronic hepatitis B treated with interferon (IFN) alpha.A total of 107 children with chronic hepatitis B who received IFN alpha for three or six months in two clinical trials were followed for a mean period of 69 (17) months. Response to treatment was defined as loss of hepatitis B e antigen (HBeAg) within 12 months after stopping treatment. A control group of 59 patients was also followed for a shorter mean time (46 (19) months).Sixteen (15%) treated children responded during therapy and 18 (17%) during post-treatment follow up; 31 (29%) non-responders lost HBeAg during subsequent years. High pretreatment levels of transaminases and a greater histological activity index were predictors of response. Kaplan-Meier estimates of cumulative HBeAg clearance rates at five years were similar between treated patients (60%) and controls (65%). After HBeAg clearance, all cases lost hepatitis B virus DNA and 94% had normal transaminase levels. Loss of hepatitis B surface antigen (HBsAg) occurred in four (25%) patients who responded during treatment but in none of the other treated or untreated patients.After five years' observation, the proportion of treated children with sustained HBeAg clearance comprised an equal number of responders and non-responders and did not differ from that observed in untreated controls, suggesting that IFN simply accelerated a spontaneous event. However, IFN significantly improved the rate of HBsAg loss in cases with more prominent disease activity who were early responders, and may be particularly useful in this type of patient.
Mechanisms of viral pathogenesis in rheumatic disease
Authors: A. PERL
Journal: Annals of the Rheumatic Diseases (1999)

Mechanisms of viral pathogenesis in rheumatic diseaseConsiderable evidence indicates that viruses may be important environmental factors in the pathogenesis of autoimmune rheumatic diseases.A concordance rate of 25% for the most common illnesses, such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in monozygotic twins shows that genetic factors influence susceptibility to autoimmune diseases. 1Alternatively, a 70% discordance rate emphasises the importance of environmental factors.Forensic studies of archeological sites revealed the presence of RA-like erosive bony changes in pre-Columbian New World populations dating back 6500 years and the absence of RA in the Old World before the 18th century. 2 This geographical distribution suggests that RA may have spread from the Americas through environmental factors, possibly by a virus, another microorganism, or an antigen.Viruses can elicit acute or subacute and, less often, chronic forms of arthritis.These viral arthritis syndromes can be diagnosed by recognition of well defined clinical signs and detection of viral antibodies and nucleic acids.Viral elements may also play a part in the pathogenesis of idiopathic autoimmune rheumatic diseases.This editorial will assess mechanisms of viral pathogenesis in rheumatic disease by focusing on known viruses capable of causing inflammatory arthritis syndromes and comparing virally induced immunological aberrations with those noted in rheumatic disease patients. Well defined virus induced rheumatic diseasesViral infections often lead to inflammatory syndromes where arthralgias or arthritis may represent a major manifestation.Most cases of viral arthritis, such as rubella or parvovirus B19 arthropathies are short-term and self limited as a result of an eYcient elimination of the organism by the immune system.Chronic arthropathies have been associated with persistent or latent viral infections, virus induced autoimmunity, polyclonal B cell activation, and immunodeficiency resulting in opportunistic infections, largely because of an inability of the immune system to eliminate the pathogen.This latter group of viruses include human immunodeficiency virus 1 (HIV-1), human T-cell lymphotropic virus type I (HTLV-I), and hepatitis C virus (HCV). VIRUS INDUCED TRANSIENT ARTHRITIS SYNDROMES Parvovirus B19Parvovirus B19 is one of the most frequent causes of viral arthritis. 3Joint manifestations are temporally associated with production of anti-B19 IgM antibodies.While involvement of B19 has been repeatedly raised in classic RA, large surveys failed to demonstrate an association between erosive RA and parvovirus B19. 3 Rubella virusRubella is known to cause mild and self limited arthralgias and acute arthritis. 4Chronic arthropathy was reported in 1-4% of postpartum female recipients of the RA27/3 vaccine strain. 5Other studies found no increase of chronic arthritis in women receiving the RA27/3 rubella vaccine. 6oreover, no rubella virus can be recovered from periph-on August 22, 2023 by guest.
The Unfinished Legacy of Liver Transplantation: Emphasis on Immunology
Authors: Thomas E. Starzl, Fadi G. Lakkis
Journal: Hepatology (2006)

Liver transplantation radically changed the philosophy of hepatology practice, enriched multiple areas of basic science, and had pervasive ripple effects in law, public policy, ethics, and theology. Why organ engraftment was feasible remained enigmatic, however, until the discovery in 1992 of donor leukocyte microchimerism in long-surviving liver, and other kinds of organ recipients. Following this discovery, the leukocyte chimerism-associated mechanisms were elucidated that directly linked organ and bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. We describe here how the initially controversial paradigm shift mandated revisions of cherished dogmas. With the fresh insight, the reasons for numerous inexplicable phenomena of transplantation either became obvious or have become susceptible to discriminate experimental testing. The therapeutic implications of the "new immunology" in hepatology and in other medical disciplines, have only begun to be explored. Apart from immunology, physiologic investigations of liver transplantation have resulted in the discovery of growth factors (beginning with insulin) that are involved in the regulation of liver size, ultrastructure, function, and the capacity for regeneration. Such studies have partially explained functional and hormonal relationships of different abdominal organs, and ultimately they led to the cure or palliation by liver transplantation of more than 2 dozen hepatic-based inborn errors of metabolism. Liver transplantation should not be viewed as a purely technologic achievement, but rather as a searchlight whose beams have penetrated the murky mist of the past, and continue to potentially illuminate the future.
A Dietary Anthocyanidin Delphinidin Induces Apoptosis of Human Prostate Cancer PC3 Cells <i>In vitro</i> and <i>In vivo</i>: Involvement of Nuclear Factor-κB Signaling
Authors: Bilal Bin Hafeez, Imtiaz Ahmad Siddiqui, Mohammad Asim, Arshi Malik, Farrukh Afaq, Vaqar Mustafa Adhami, Mohammad Saleem, Maria Din, Hasan Mukhtar
Journal: Cancer Research (2008)

Delphinidin, a major anthocyanidin present in many pigmented fruits and vegetables, possesses antioxidant, anti-inflammatory, and antiangiogenic properties. In this study, we provide evidence that it could be developed as a novel agent against human prostate cancer (PCa). We observed that delphinidin treatment to human PCa LNCaP, C4-2, 22Rnu1, and PC3 cells resulted in a dose-dependent inhibition of cell growth without having any substantial effect on normal human prostate epithelial cells. We selected PC3 cells as a test model system because of their highly aggressive proliferative nature. Delphinidin treatment of cells resulted in a dose-dependent induction of apoptosis and arrest of cells in G(2)-M phase. This induction of apoptosis seems to be mediated via activation of caspases because N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluromethylketone significantly reduced apoptosis induced by delphinidin. We also observed that delphinidin treatment of cells resulted in a dose-dependent decrease in (a) phosphorylation of IkappaB kinase gamma (NEMO), (b) phosphorylation of nuclear factor-kappaB (NF-kappaB) inhibitory protein IkappaBalpha, (c) phosphorylation of NF-kappaB/p65 at Ser(536) and NF-kappaB/p50 at Ser(529), (d) NF-kappaB/p65 nuclear translocation, and (e) NF-kappaB DNA binding activity. Delphinidin administration (2 mg, i.p. thrice weekly) to athymic nude mice implanted with PC3 cells resulted in a significant inhibition of tumor growth. Analysis of tumors from delphinidin-treated mice showed significant decrease in the expression of NF-kappaB/p65, Bcl2, Ki67, and PCNA. Taken together, our data suggest that delphinidin could be developed as an agent against human PCa.
Dynamic recruitment and maximal force of respiratory muscles in healthy subjects undergone strenuous exercise
Authors: Renata Pletsch, Andre Albuquerque, Pedro Caruso, Leticia Cardenas, Pauliane Vieira Santana, Renan Maloni, Andre Apanavicius, Jeferson George Ferreira, Joao Marcos Salge, Carlos Roberto Ribeiro De Carvalho
Journal: European Respiratory Journal (2013)

Background :The force of respiratory muscles and their respective recruitment during exercise progression is still not fully described even in healthy subjects. Understanding these physiologic responses is essential for comparisons with respiratory patients. Aim :To measure the strength achieved in strenuous exercise and describe the recruitment of ins and expiratory muscles during exercise progression. Method :14 healthy subjects were monitored with surface electromyography of the respiratory acessories muscles as well as esophageal and gastric catheter for transdiaphragmatic pressure (Pdi). The maximal force was obtained by isometric maneuvers for ins and expiratory accessory muscles, while maximal Pdi was measured by Sniff test. Subjects underwent cycle exercise increasing the effort up to exhaustion and the maximum load was termed as mild, moderate and strenuous efforts based on the respective tertile. Results :All ins and expiratory muscles at strenuous exercise have not achieved their maximal force. The dynamic recruitment during exercise was progressive and mild intensity was already enough to recruit all muscles, including accessories.

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Conclusion :In healthy subjects, the diaphragm and the accessory muscles are already recruited even in mild intensity. Strenuous exercise was not able to exhaust the maximal force of respiratory muscles, with a higher reserve for diaphragm in contrast to the accessories.

 [1]: pending:yes
Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting in X-linked agammaglobulinemia (XLA).
Authors: Q Zhu, M Zhang, D J Rawlings, M Vihinen, T Hagemann, D C Saffran, S P Kwan, L Nilsson, C I Smith, O N Witte, S H Chen, H D Ochs
Journal: The Journal of Experimental Medicine (1994)

The gene responsible for X-linked agammaglobulinemia (XLA) has been recently identified to code for a cytoplasmic tyrosine kinase (Bruton's agammaglobulinemia tyrosine kinase, BTK), required for normal B cell development. BTK, like many other cytoplasmic tyrosine kinases, contains Src homology domains (SH2 and SH3), and catalytic kinase domain. SH3 domains are important for the targeting of signaling molecules to specific subcellular locations. We have identified a family with XLA whose affected members have a point mutation (g--&amp;gt;a) at the 5' splice site of intron 8, resulting in the skipping of coding exon 8 and loss of 21 amino acids forming the COOH-terminal portion of the BTK SH3 domain. The study of three generations within this kinship, using restriction fragment length polymorphism and DNA analysis, allowed identification of the mutant X chromosome responsible for XLA and the carrier status in this family. BTK mRNA was present in normal amounts in Epstein-Barr virus-induced B lymphoblastoid cell lines established from affected family members. Although the SH3 deletion did not alter BTK protein stability and kinase activity of the truncated BTK protein was normal, the affected patients nevertheless have a severe B cell defect characteristic for XLA. The mutant protein was modeled using the normal BTK SH3 domain. The deletion results in loss of two COOH-terminal beta strands containing several residues critical for the formation of the putative SH3 ligand-binding pocket. We predict that, as a result, one or more crucial SH3 binding proteins fail to interact with BTK, interrupting the cytoplasmic signal transduction process required for B cell differentiation.
The management of metastatic pancreatic cancer: expert discussion and recommendations from the 14th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2012
Authors: C. Verslype, E. Van Cutsem, M. Dicato, N. Arber, J.D. Berlin, M.W. Büchler, A. Cervantes, F. Ciardiello, M. Ducreux, J.Y. Douillard, A. Grothey, D. Haller, K. Haustermans, V. Heinemann, M. Hidalgo, R. Labianca, J. Li, J.L. Marshall, B. Nordlinger, E.M. O'Reilly, A. Roth, P. Rougier, D. Ryan, W. Schmiegel, T. Seufferlein, H.J. Schmoll, A. Sobrero, J. Tabernero, M. Tempero, J.L. Van Laethem, M. Ychou, J. Zalcberg
Journal: Annals of Oncology (2013)
Psoriasis: improvement during and worsening after pregnancy
Authors: S.F. Dunna, A.Y. Finlay
Journal: British Journal of Dermatology (1989)

Journal Article Psoriasis: improvement during and worsening after pregnancy Get access S.F. Dunna, S.F. Dunna Department of Medicine (Dermatology), University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.Y. Finlay A.Y. Finlay Department of Medicine (Dermatology), University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 120, Issue 4, 1 April 1989, Page 584, https://doi.org/10.1111/j.1365-2133.1989.tb01338.x Published: 01 April 1989
Treatment of Philadelphia-Positive Chronic Myeloid Leukemia with Imatinib: Importance of a Stable Molecular Response
Authors: Francesca Palandri, Ilaria Iacobucci, Simona Soverini, Fausto Castagnetti, Angela Poerio, Nicoletta Testoni, Giuliana Alimena, Massimo Breccia, Giovanna Rege-Cambrin, Mario Tiribelli, Riccardo Varaldo, Elisabetta Abruzzese, Bruno Martino, Luigiana Luciano, Fabrizio Pane, Giuseppe Saglio, Giovanni Martinelli, Michele Baccarani, Gianantonio Rosti
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The achievement of a major molecular response (MMolR) at 12 months is a surrogate marker of progression-free survival in chronic myeloid leukemia patients treated with imatinib. Experimental Design: We evaluated the prognostic value of the long-term evolution of the molecular response based on a retrospective analysis of 130 late chronic phase chronic myeloid leukemia patients who achieved a complete cytogenetic response (CCgR) with 400 mg/d imatinib and have now a median follow-up of 72 months (range, 48-77). Results: In 71 (55%) patients, molecular response was consistently major (stable MMolR); in 19 (15%) patients, molecular response was occasionally less than major (unstable MMolR); in 40 (30%) patients, MMolR was never achieved (never MMolR) during all the course of CCgR. Patients with stable MMolR had a longer CCgR duration and a significantly better progression-free survival compared with patients with absent or unstable MMolR. The achievement of a MMolR, if maintained continuously, conferred a marked long-term stability to the CCgR: patients with a stable MMolR have a significantly lower risk of losing the CCgR than patients with unstable and never MMolR (4% versus 21%, P = 0.03, and 4% versus 33%, P &amp;lt; 0.0001, respectively). Finally, if a MMolR is not maintained consistently, the risk of losing the CCgR is higher but not significantly than if it is never achieved (33% versus 21%, P = 0.5). Conclusions: These data confirm that achieving a MMolR is prognostically important but point out that the prognostic value of achieving a MMolR is greater if the response is confirmed and stable.