tbuckley/cabot-search huggingface dataset:
Early Life Programming of Abdominal Adiposity in Adolescents: The HELENA Study
Authors: Idoia Labayen, Jonatan R. Ruiz, Germán Vicente-Rodríguez, Dominique Turck, Gerardo Rodríguez, Aline Meirhaeghe, Denes Molnár, Michael Sjöström, Manuel J. Castillo, Frederic Gottrand, Luis A. Moreno
Journal: Diabetes Care (2009)

OBJECTIVE To examine the relationship between birth weight and abdominal adiposity in adolescents. RESEARCH DESIGN AND METHODS A total of 284 adolescents (49.3% of whom were female) aged 14.9 ± 1.2 years were included in the study. Birth weight and gestational age were obtained from parental records. Abdominal adiposity (in three regions: R1, R2, and R3) and trunk and total body fat mass were measured by dual-energy X-ray absorptiometry. Regional fat mass indexes (FMIs) were thereafter calculated as fat mass divided by the square of height (Trunk FMI and abdominal FMI R1, R2, and R3). RESULTS Birth weight was negatively associated with abdominal FMI R1, R2, and R3 independently of total fat mass, gestational age, sex, breast-feeding duration, pubertal stage, physical activity, and socioeconomic status (all P &amp;lt; 0.01). CONCLUSIONS Our study shows an inverse association between birth weight and abdominal adiposity in adolescents independently of total fat mass and other potential confounders. These findings suggest that fetal nutrition, as reflected by birth weight, may have a programming effect on abdominal adiposity later in life.
Testis Cancer Survivors' Health Behaviors: Comparison With Age-Matched Relative and Demographically Matched Population Controls
Authors: Eileen H. Shinn, Richard J. Swartz, Bob B. Thornton, Philippe E. Spiess, Louis L. Pisters, Karen M. Basen-Engquist
Journal: Journal of Clinical Oncology (2010)

To determine the prevalence rate of health behaviors in testis cancer survivors and to determine whether the rate of health behaviors in survivors was significantly different than those of their age-matched relative controls and a population-based control group matched for age, sex, education, and income.
Myasthenia gravis-like syndrome induced by expression of interferon gamma in the neuromuscular junction.
Authors: D Gu, L Wogensen, N A Calcutt, C Xia, S Zhu, J P Merlie, H S Fox, J Lindstrom, H C Powell, N Sarvetnick
Journal: The Journal of Experimental Medicine (1995)

Abnormal humoral responses toward motor end plate constituents in muscle induce myasthenia gravis (MG). To study the etiology of this disease, and whether it could be induced by host defense molecules, we examined the consequences of interferon (IFN) gamma production within the neuromuscular junction of transgenic mice. The transgenic mice exhibited gradually increasing muscular weakness, flaccid paralysis, and functional disruption of the neuromuscular junction that was reversed after administration of an inhibitor of acetylcholinesterase, features which are strikingly similar to human MG. Furthermore, histological examination revealed infiltration of mononuclear cells and autoantibody deposition at motor end plates. Immunoprecipitation analysis indicated that a previously unidentified 87-kD target antigen was recognized by sera from transgenic mice and also by sera from the majority of human MG patients studied. These results suggest that expression of IFN-gamma at motor end plates provokes an autoimmune humoral response, similar to human MG, thus linking the expression of this factor with development of this disease.
Postischemic myocardial recovery and oxidative stress status of vitamin C deficient rat hearts
Authors: C Vergely
Journal: Cardiovascular Research (2001)

Objective: To investigate the role of vitamin C tissue content as a protective agent during myocardial ischemia–reperfusion injury, we have evaluated the postischemic functional recovery and free radical release of osteogenic disorder Shionogi (ODS) inherently scorbutic rat hearts and compared them to healthy Wistar rat hearts. Methods: Isolated perfused hearts of ODS or Wistar rats underwent 30 min of a global total normothermic ischemia followed by 30 min of reperfusion. The lipid-soluble spin trap α-phenyl N-tert-butylnitrone (3 mM) was perfused upstream of the coronary bed. Functional parameters were recorded and samples of coronary effluents were analysed using electron spin resonance spectroscopy to characterise and quantify the amount of radical species released. Results: From the onset of reperfusion, a large and long-lasting release of alkyl/alkoxyl radicals was detected, with a peak value of 29.0±3.2 nM obtained after 13 min, which was associated with a persistent contractile dysfunction. However, ODS rat hearts showed a higher myocardial recovery with lower left ventricular end diastolic pressure (44.34±1.74 vs. 55.03±1.57 mmHg for Wistar), higher recovery of rate pressure product (12.3±1.4 vs. 1.9±1.7×103 mmHgbeats/min for Wistar) and shorter duration of contractile abnormalities during reperfusion (3.7±1.0 vs. 20.8±5.3 min for Wistar). Moreover, free radical release was identical in ODS rat hearts as compared to control Wistar rats. Ascorbic acid tissue content was significantly altered in ODS rats (31.9±3.3 vs. 591.0±54.9 mmol/g of tissue for Wistar) but superoxide dismutases, glutathion peroxidases and inducible heat shock protein 70 genes were up-regulated. Conclusions: This study shows that ascorbic-acid-deficient ODS rat hearts are more resistant to an ischemic insult than control Wistar rats, probably through the development of alternative protective defences, like the induction of heat shock proteins. These paradoxical results raise the question of the relative importance of each endogenous antioxidant in the cardiac resistance to ischemia–reperfusion injury.
A Novel Tumor Necrosis Factor–mediated Mechanism of Direct Epithelial Sodium Channel Activation
Authors: István Czikora, Abdel Alli, Hui-Fang Bao, David Kaftan, Supriya Sridhar, Hans-Jürgen Apell, Boris Gorshkov, Richard White, Astrid Zimmermann, Albrecht Wendel, Meike Pauly-Evers, Jürg Hamacher, Irène Garcia-Gabay, Bernhard Fischer, Alexander Verin, Zsolt Bagi, Jean Francois Pittet, Waheed Shabbir, Rosa Lemmens-Gruber, Trinad Chakraborty, Ahmed Lazrak, Michael A. Matthay, Douglas C. Eaton, Rudolf Lucas
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Alveolar liquid clearance is regulated by Na(+) uptake through the apically expressed epithelial sodium channel (ENaC) and basolaterally localized Na(+)-K(+)-ATPase in type II alveolar epithelial cells. Dysfunction of these Na(+) transporters during pulmonary inflammation can contribute to pulmonary edema.In this study, we sought to determine the precise mechanism by which the TIP peptide, mimicking the lectin-like domain of tumor necrosis factor (TNF), stimulates Na(+) uptake in a homologous cell system in the presence or absence of the bacterial toxin pneumolysin (PLY).We used a combined biochemical, electrophysiological, and molecular biological in vitro approach and assessed the physiological relevance of the lectin-like domain of TNF in alveolar liquid clearance in vivo by generating triple-mutant TNF knock-in mice that express a mutant TNF with deficient Na(+) uptake stimulatory activity.TIP peptide directly activates ENaC, but not the Na(+)-K(+)-ATPase, upon binding to the carboxy-terminal domain of the α subunit of the channel. In the presence of PLY, a mediator of pneumococcal-induced pulmonary edema, this binding stabilizes the ENaC-PIP2-MARCKS complex, which is necessary for the open probability conformation of the channel and preserves ENaC-α protein expression, by means of blunting the protein kinase C-α pathway. Triple-mutant TNF knock-in mice are more prone than wild-type mice to develop edema with low-dose intratracheal PLY, correlating with reduced pulmonary ENaC-α subunit expression.These results demonstrate a novel TNF-mediated mechanism of direct ENaC activation and indicate a physiological role for the lectin-like domain of TNF in the resolution of alveolar edema during inflammation.
The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases
Authors: F. A. S. Kurreeman, G. N. Goulielmos, B. Z. Alizadeh, B. Rueda, J. Houwing-Duistermaat, E. Sanchez, M. Bevova, T. R. Radstake, M. C. Vonk, E. Galanakis, N. Ortego, W. Verduyn, M. I. Zervou, B. O. Roep, B. Dema, L. Espino, E. Urcelay, D. T. Boumpas, L. H. van den Berg, C. Wijmenga, B. P. C. Koeleman, T. W. J. Huizinga, R. E. M. Toes, J. Martin
Journal: Annals of the Rheumatic Diseases (2009)

The TRAF1-C5 locus has recently been identified as a genetic risk factor for rheumatoid arthritis (RA). Since genetic risk factors tend to overlap with several autoimmune diseases, a study was undertaken to investigate whether this region is associated with type 1 diabetes (TID), celiac disease (CD), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE).The most consistently associated SNP, rs10818488, was genotyped in a total of 735 patients with T1D, 1049 with CD, 367 with SSc, 746 with SLE and 3494 ethnically- and geographically-matched healthy individuals. The replication sample set consisted of 99 patients with T1D, 272 with SLE and 482 healthy individuals from Crete.A significant association was detected between the rs10818488 A allele and T1D (OR 1.14, p=0.027) and SLE (OR 1.16, p=0.016), which was replicated in 99 patients with T1D, 272 with SLE and 482 controls from Crete (OR 1.64, p=0.002; OR 1.43, p=0.002, respectively). Joint analysis of all patients with T1D (N=961) and all patients with SLE (N=1018) compared with 3976 healthy individuals yielded an allelic common OR of 1.19 (p=0.002) and 1.22 (p=2.6 x 10(-4)), respectively. However, combining our dataset with the T1D sample set from the WTCCC resulted in a non-significant association (OR 1.06, p=0.087). In contrast, previously unpublished results from the SLEGEN study showed a significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02 x 10(-6)) in a total of 1577 patients with SLE and 4215 healthy individuals.A significant association was found for the TRAF1-C5 locus in SLE, implying that this region lies in a pathway relevant to multiple autoimmune diseases.
A prospective study of the incidence of complications associated with dermatological surgery
Authors: J.M. Amici, A.M. Rogues, A. Lasheras, J.P. Gachie, P. Guillot, C. Beylot, L. Thomas, A. Taieb
Journal: British Journal of Dermatology (2005)

Background Dermatological surgery is a relatively new and expanding subspecialty within dermatology. Little information is available about complications in this kind of surgery in the European setting. Objectives The aim of this study was to assess the incidence of anaesthetic, haemorrhagic and infectious complications in dermatological surgery and to highlight the factors associated with these complications. Methods Data were collected prospectively over a 3‐month period for all surgical procedures performed by a network of dermatologists (n = 84 dermatologists) in France, including the excision of all benign or malignant tumours but excluding sebaceous cysts and pyodermas. Information was collected regarding dermatologists, patients, procedures and complications. Results A total of 3788 surgical procedures were available for review; 236 complications, mostly minor, occurred in a total of 213 surgical procedures (6%), bleeding being the most common (3%). Vaso‐vagal syncope was the main anaesthetic complication (51 of 54). Infectious complications occurred in 79 patients (2%). Superficial suppuration accounted for 92% of surgical site infections. Only one patient had a systemic infection. Complications requiring additional antibiotic treatment or repeat surgery accounted for only 22 cases of 3788 (1%). No statistically significant correlation was found with the characteristics of the dermatologists, especially with respect to their training or amount of surgical experience. Similarly, no link could be established between complications and surgical conditions. Multivariate analysis showed that anaesthetic or haemorrhagic complications were independent factors for infectious complications. Sex, administration of an anticoagulant or immunosuppressant, type of procedure performed and duration exceeding 24 min were independent factors for haemorrhagic complications. Conclusions This study shows a low rate of complications associated with dermatological surgery performed by dermatologists under local anaesthesia on an outpatient basis.
Preliminary Results From a Phase II Trial of Conformal Radiation Therapy and Evaluation of Radiation-Related CNS Effects for Pediatric Patients With Localized Ependymoma
Authors: Thomas E. Merchant, Raymond K. Mulhern, Matthew J. Krasin, Larry E. Kun, Tani Williams, Chenghong Li, Xiaoping Xiong, Raja B. Khan, Robert H. Lustig, Frederick A. Boop, Robert A. Sanford
Journal: Journal of Clinical Oncology (2004)

Purpose We conducted a phase II trial of conformal radiation therapy (CRT) for localized childhood ependymoma to determine whether the irradiated volume could be reduced to decrease CNS-related side effects without diminishing the rate of disease control. Patients and Methods Between July 1997 and January 2003, 88 pediatric patients (median age, 2.85 ± 4.5 years) received CRT in which doses (59.4 Gy to 73 patients or 54.0 Gy after gross-total resection to 15 patients younger than 18 months) were administered to the gross tumor volume and a margin of 10 mm. Patients were categorized according to extent of resection (underwent gross total resection, n = 74; near-total resection, n = 6; subtotal resection, n = 8), prior chemotherapy (n = 16), tumor grade (anaplastic, n = 35), and tumor location (infratentorial, n = 68). An age-appropriate neurocognitive battery was administered before and serially after CRT. Results The median length of follow-up was 38.2 months (± 16.4 months); the 3-year progression-free survival estimate was 74.7% ± 5.7%. Local failure occurred in eight patients, distant failure in eight patients, and both in four patients. The cumulative incidence of local failure as a component of failure at 3 years was 14.8% ± 4.0%. Mean scores on all neurocognitive outcomes were stable and within normal limits, with more than half the cohort tested at or beyond 24 months. Conclusion Limited-volume irradiation achieves high rates of disease control in pediatric patients with ependymoma and results in stable neurocognitive outcomes.
Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice.
Authors: Shixia Huang, Yi Li, Yidong Chen, Katrina Podsypanina, Mario Chamorro, Adam B Olshen, Kartiki V Desai, Anne Tann, David Petersen, Jeffrey E Green, Harold E Varmus
Journal: Genome biology (2005)

Abstract Background In human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ , invasive cancer, and metastasis. The changes in gene expression associated with this stepwise progression are unclear. Mice transgenic for mouse mammary tumor virus (MMTV)- Wnt-1 exhibit discrete steps of mammary tumorigenesis, including hyperplasia, invasive ductal carcinoma, and distant metastasis. These mice might therefore be useful models for discovering changes in gene expression during cancer development. Results We used cDNA microarrays to determine the expression profiles of five normal mammary glands, seven hyperplastic mammary glands and 23 mammary tumors from MMTV- Wnt-1 transgenic mice, and 12 mammary tumors from MMTV- Neu transgenic mice. Adipose tissues were used to control for fat cells in the vicinity of the mammary glands. In these analyses, we found that the progression of normal virgin mammary glands to hyperplastic tissues and to mammary tumors is accompanied by differences in the expression of several hundred genes at each step. Some of these differences appear to be unique to the effects of Wnt signaling; others seem to be common to tumors induced by both Neu and Wnt-1 oncogenes. Conclusion We described gene-expression patterns associated with breast-cancer development in mice, and identified genes that may be significant targets for oncogenic events. The expression data developed provide a resource for illuminating the molecular mechanisms involved in breast cancer development, especially through the identification of genes that are critical in cancer initiation and progression.
Temperature-Related Reaction Norms of Gene Expression: Regulatory Architecture and Functional Implications
Authors: Jun Chen, Viola Nolte, Christian Schlötterer
Journal: Molecular Biology and Evolution (2015)

The environment has profound effects on the expression of many traits and reaction norms describe the expression dynamics of a trait across a broad range of environmental conditions. Here, we analyze gene expression in Drosophila melanogaster across four different developmental temperatures (13-29 °C). Gene expression is highly plastic with 83.3% of the genes being differentially expressed. We distinguished three components of plasticity: 1) Dynamics of gene expression intensity (sum of change), 2) direction of change, and 3) curvature of the reaction norm (linear vs. quadratic). Studying their regulatory architecture we found that all three plasticity components were most strongly affected by the number of different transcription factors (TFs) binding to the target gene. More TFs were found in genes with less expression changes across temperatures. Although the effect of microRNAs was weaker, we consistently noted a trend in the opposite direction. The most plastic genes were regulated by fewer TFs and more microRNAs than less plastic genes. Different patterns of plasticity were also reflected by their functional characterization based on gene ontology. Our results suggest that reaction norms provide an important key to understand the functional requirements of natural populations exposed to variable environmental conditions.
Therapeutic Potential of Poly(ADP-ribose) Polymerase Inhibitor AG014699 in Human Cancers With Mutated or Methylated BRCA1 or BRCA2
Authors: Yvette Drew, Evan A. Mulligan, Wan-Tse Vong, Huw D. Thomas, Samra Kahn, Suzanne Kyle, Asima Mukhopadhyay, Gerrit Los, Zdenek Hostomsky, Elizabeth R. Plummer, Richard J. Edmondson, Nicola J. Curtin
Journal: JNCI Journal of the National Cancer Institute (2010)

Mutations in BRCA1 and BRCA2 (BRCA1/2), components of the homologous recombination DNA repair (HRR) pathway, are associated with hereditary breast and ovarian cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors are selectively cytotoxic to animal cells with defective HRR, but results in human cancer cells have been contradictory. We undertook, to our knowledge, the first comprehensive in vitro and in vivo investigations of the antitumor activity of the PARP inhibitor AG014699 in human cancer cells carrying mutated or epigenetically silenced BRCA1/2. We used nine human cell lines, four with nonmutated BRCA1/2 (MCF7, MDA-MB-231, and HCC1937-BRCA1 [breast cancer] and OSEC-2 [ovarian surface epithelial]), two with mutated BRCA1 (MDA-MB-436 and HCC1937 [breast cancer]), one with mutated BRCA2 (CAPAN-1 [pancreatic cancer]), one that was heterozygous for BRCA2 (OSEC-1 [ovarian surface epithelial]), and one with epigenetically silenced BRCA1 (UACC3199 [breast cancer]), and two Chinese hamster ovary cell lines, parental AA8 and XRCC3 mutated IRS 1SF. We assessed cytotoxicity, DNA damage, and HRR function. Antitumor activity of AG014699 was determined by growth of xenograft tumors (five mice per treatment group). Long-term safety of AG014699 was assessed. AG014699 (≤10 μM) was cytotoxic to cells with mutated BRCA1/2 or XRCC3 and to UACC3199 cells with epigenetically silenced BRCA1 but not to cells without BRCA1/2 or XRCC3 mutations or that were heterozygous for BRCA2 mutation. AG014699 induced DNA double-strand breaks in all nine cell lines studied. HRR was observed only in cells with functional BRCA1/2 proteins. Growth of xenograft tumors with BRCA1/2 mutations or with epigenetically silenced BRCA1 was reduced by AG014699 treatment, and combination treatment with AG014699 plus carboplatin was more effective than either drug alone. AG014699 was not toxic in mice with nonmutated or heterozygous BRCA2. Human cancer cells or xenograft tumors with mutated or epigenetically silenced BRCA1/2 were sensitive to AG014699 monotherapy, indicating a potential role for PARP inhibitors in sporadic human cancers.
Development and External Validation of an Extended 10-Core Biopsy Nomogram
Authors: Felix K.-H. Chun, Alberto Briganti, Markus Graefen, Francesco Montorsi, Christopher Porter, Vincenzo Scattoni, Andrea Gallina, Jochen Walz, Alexander Haese, Thomas Steuber, Andreas Erbersdobler, Thorsten Schlomm, Sascha A. Ahyai, Eike Currlin, Luc Valiquette, Hans Heinzer, Patrizio Rigatti, Hartwig Huland, Pierre I. Karakiewicz
Journal: European Urology (2006)
Positive Inotropy Mediated by Diacylglycerol in Rat Ventricular Myocytes
Authors: YeQing Pi, R. Sreekumar, XuPei Huang, Jeffery W. Walker
Journal: Circulation Research (1997)

Abstract Many neurohormones stimulate phospholipid hydrolysis and elevate diacylglycerol in the mammalian heart, but the physiological consequences of these intracellular events are unclear. Regulation of myocardial contraction by diacylglycerol was investigated in the present study by releasing the diacylglycerol analogue dioctanoylglycerol (diC 8 ) within adult rat ventricular myocytes by using a light-sensitive caged compound. This approach permitted us to avoid exposure of myocytes to extracellular diC 8 and yet to control the amount of diC 8 released into the cells. Photorelease of diC 8 produced a slowly developing (half-time, 1.9±0.1 minute; n=26) but robust (406±42%) enhancement of twitch amplitude in electrically paced myocytes (0.5 Hz, 1 mmol/L Ca 2+ Ringer’s solution [pH 7.4], 22°C). This positive inotropic effect was dose dependent, stereospecific for the S-enantiomer of diC 8 , synergistically enhanced by arachidonic acid, and blocked by the protein kinase C inhibitor chelerythrine. The data provide evidence that diacylglycerol can induce a strong positive inotropic effect in mammalian ventricular muscle, possibly by activating protein kinase C. By contrast, perfusion of diC 8 extracellularly onto myocytes caused a 42±2% decline in twitch amplitude, in accordance with previous reports. To account for this dependence on how diC 8 is applied, we postulate that diC 8 has distinct physiological actions at intracellular and extracellular sites. The peptide neurohormone endothelin-1, which elevates diacylglycerol in cardiac tissues, produced a positive inotropic effect that was similar to the response to photoreleased diC 8 . The diacylglycerol/protein kinase C pathway has now become a good candidate for mediator of at least a component of the positive inotropy associated with agents that stimulate phospholipid turnover in adult mammalian myocardium.
Secreted Semaphorins from Degenerating Larval ORN Axons Direct Adult Projection Neuron Dendrite Targeting
Authors: Lora B. Sweeney, Ya-Hui Chou, Zhuhao Wu, William Joo, Takaki Komiyama, Christopher J. Potter, Alex L. Kolodkin, K. Christopher Garcia, Liqun Luo
Journal: Neuron (2011)