tbuckley/cabot-search huggingface dataset:
Longitudinal Trajectories and Associated Baseline Predictors in Youths With Bipolar Spectrum Disorders
Authors: Boris Birmaher, Mary Kay Gill, David A. Axelson, Benjamin I. Goldstein, Tina R. Goldstein, Haifeng Yu, Fangzi Liao, Satish Iyengar, Rasim S. Diler, Michael Strober, Heather Hower, Shirley Yen, Jeffrey Hunt, John A. Merranko, Neal D. Ryan, Martin B. Keller
Journal: American Journal of Psychiatry (2014)

Objective The authors sought to identify and evaluate longitudinal mood trajectories and associated baseline predictors in youths with bipolar disorder. Method A total of 367 outpatient youths (mean age, 12.6 years) with bipolar disorder with at least 4 years of follow-up were included. After intake, participants were interviewed on average 10 times (SD=3.2) over a mean of 93 months (SD=8.3). Youths and parents were interviewed for psychopathology, functioning, treatment, and familial psychopathology and functioning. Results Latent class growth analysis showed four different longitudinal mood trajectories: “predominantly euthymic” (24.0%), “moderately euthymic” (34.6%), “ill with improving course” (19.1%), and “predominantly ill” (22.3%). Within each class, youths were euthymic on average 84.4%, 47.3%, 42.8%, and 11.5% of the follow-up time, respectively. Multivariate analyses showed that better course was associated with higher age at onset of mood symptoms, less lifetime family history of bipolar disorder and substance abuse, and less history at baseline of severe depression, manic symptoms, suicidality, subsyndromal mood episodes, and sexual abuse. Most of these factors were more noticeable in the “predominantly euthymic” class. The effects of age at onset were attenuated in youths with lower socioeconomic status, and the effects of depression severity were absent in those with the highest socioeconomic status. Conclusions A substantial proportion of youths with bipolar disorder, especially those with adolescent onset and the above-noted factors, appear to be euthymic over extended periods. Nonetheless, continued syndromal and subsyndromal mood symptoms in all four classes underscore the need to optimize treatment.
High-resolution aCGH and expression profiling identifies a novel genomic subtype of ER negative breast cancer
Authors: Suet F Chin, Andrew E Teschendorff, John C Marioni, Yanzhong Wang, Nuno L Barbosa-Morais, Natalie P Thorne, Jose L Costa, Sarah E Pinder, Mark A van de Wiel, Andrew R Green, Ian O Ellis, Peggy L Porter, Simon Tavaré, James D Brenton, Bauke Ylstra, Carlos Caldas
Journal: Genome biology (2007)

Abstract Background The characterization of copy number alteration patterns in breast cancer requires high-resolution genome-wide profiling of a large panel of tumor specimens. To date, most genome-wide array comparative genomic hybridization studies have used tumor panels of relatively large tumor size and high Nottingham Prognostic Index (NPI) that are not as representative of breast cancer demographics. Results We performed an oligo-array-based high-resolution analysis of copy number alterations in 171 primary breast tumors of relatively small size and low NPI, which was therefore more representative of breast cancer demographics. Hierarchical clustering over the common regions of alteration identified a novel subtype of high-grade estrogen receptor (ER)-negative breast cancer, characterized by a low genomic instability index. We were able to validate the existence of this genomic subtype in one external breast cancer cohort. Using matched array expression data we also identified the genomic regions showing the strongest coordinate expression changes ('hotspots'). We show that several of these hotspots are located in the phosphatome, kinome and chromatinome, and harbor members of the 122-breast cancer CAN-list. Furthermore, we identify frequently amplified hotspots on 8q22.3 ( EDD1 , WDSOF1 ), 8q24.11-13 ( THRAP6 , DCC1 , SQLE , SPG8 ) and 11q14.1 ( NDUFC2 , ALG8 , USP35 ) associated with significantly worse prognosis. Amplification of any of these regions identified 37 samples with significantly worse overall survival (hazard ratio (HR) = 2.3 (1.3-1.4) p = 0.003) and time to distant metastasis (HR = 2.6 (1.4-5.1) p = 0.004) independently of NPI. Conclusion We present strong evidence for the existence of a novel subtype of high-grade ER-negative tumors that is characterized by a low genomic instability index. We also provide a genome-wide list of common copy number alteration regions in breast cancer that show strong coordinate aberrant expression, and further identify novel frequently amplified regions that correlate with poor prognosis. Many of the genes associated with these regions represent likely novel oncogenes or tumor suppressors.
Molecular analysis of T cell receptor (Ti) variable region (V) gene expression. Evidence that a single Ti beta V gene family can be used in formation of V domains on phenotypically and functionally diverse T cell populations.
Authors: O Acuto, T J Campen, H D Royer, R E Hussey, C B Poole, E L Reinherz
Journal: The Journal of Experimental Medicine (1985)

We examine the rules governing Ti beta variable (V) gene segment usage in the formation of T cell antigen-MHC receptors in diverse regulatory and effector T lymphoid subpopulations. To this end, a single Ti beta V gene family and its products were analyzed. A monoclonal antibody, termed anti-Ti3A, which was shown to be reactive with an epitope encoded by members of the REX cell line Ti beta V gene family, and which was expressed on 2% of human T lymphocytes was used in selection of clones from unprimed peripheral T lymphocytes. Both T4+, as well as T8+ T cell clones with inducer, suppressor, and/or cytotoxic function were defined. Southern analysis, isoelectric focusing and two-dimensional peptide mapping indicated that individual members of the REX V gene family were linked to different Ti beta diversity and/or joining and constant region segments. Moreover, the Ti alpha chains of such clones were distinct. These results imply that Ti beta V gene usage is not restricted to any functionally or phenotypically defined T cell subsets, and there is presumably little, if any, restriction on the mechanisms that generate combinational, junctional or chain association-mediated diversity.
Echocardiography and pulmonary embolism severity index have independent prognostic roles in pulmonary embolism
Authors: Olivier Sanchez, Ludovic Trinquart, Benjamin Planquette, Francis Couturaud, Franck Verschuren, Vincent Caille, Nicolas Meneveau, Gérard Pacouret, Pierre-Marie Roy, Marc Righini, Arnaud Perrier, Laurent Bertoletti, Florence Parent, Christine Lorut, Guy Meyer
Journal: European Respiratory Journal (2012)

We analysed a cohort of patients with normotensive pulmonary embolism (PE) in order to assess whether combining echocardiography and biomarkers with the pulmonary embolism severity index (PESI) improves the risk stratification in comparison to the PESI alone. The PESI was calculated in normotensive patients with PE who also underwent echocardiography and assays of cardiac troponin I and brain natriuretic peptide. 30-day adverse outcome was defined as death, recurrent PE or shock. 529 patients were included, 25 (4.7%, 95% CI 3.2–6.9%) had at least one outcome event. The proportion of patients with adverse events increased from 2.1% in PESI class I–II to 8.4% in PESI class III–IV, and to 14.3% in PESI class V (p&lt;0.001). In PESI class I–II, the rate of outcome events was significantly higher in patients with abnormal values of biomarkers or right ventricular dilatation. In multivariate analysis, the PESI (class III–IV versus I–II, OR 3.1, 95% CI 1.2–8.3; class V versus I–II, OR 5.5, 95% CI 1.5–25.5 and echocardiography (right ventricular/left ventricular ratio, OR (for an increase of 0.1) 1.3, 95% CI 1.1–1.5) were independent predictors of an adverse outcome. In patients with normotensive PE, biomarkers and echocardiography provided additional prognostic information to the PESI.
Maintenance of cAMP in Non-Heart-Beating Donor Lungs Reduces Ischemia–Reperfusion Injury
Authors: STEVEN C. HOFFMANN, MARK S. BLEIWEIS, DAVID R. JONES, HYO CHAE PAIK, PAOLA CIRIACO, THOMAS M. EGAN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Studies suggest that pulmonary vascular ischemia–reperfusion injury (IRI) can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, assessed by capillary filtration coeficient (Kfc), in lungs retrieved from non-heart-beating donors (NHBDs) and reperfused with the addition of the β2-adrenergic receptor agonist isoproterenol (iso), and rolipram (roli), a phosphodiesterase (type IV) inhibitor. Using an in situ isolated perfused lung model, lungs were retrieved from NHBD rats at varying intervals after death and either ventilated with O2 or not ventilated. The lungs were reperfused with Earle's solution with or without a combination of iso (10 μ M) and roli (2 μ M). Kfc, lung viability, and pulmonary hemodynamics were measured. Lung tissue levels of adenine nucleotides and cAMP were measured by HPLC. Combined iso and roli (iso/roli) reperfusion decreased Kfc significantly (p < 0.05) compared with non-iso/roli-reperfused groups after 2 h of postmortem ischemia. Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso/roli-reperfused (r = 0.89) and iso/roli-reperfused (r = 0.97) lungs. cAMP levels correlated with Kfc (r = 0.93) in iso/roli-reperfused lungs. Pharmacologic augmentation of tissue TAN and cAMP levels might ameliorate the increased capillary permeability observed in lungs retrieved from NHBDs.
Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence
Authors: Masahiro Marshall Nakagawa, Keyur Thummar, Jonathan Mandelbaum, Laura Pasqualucci, Chozha Vendan Rathinam
Journal: The Journal of Experimental Medicine (2015)

A balance between quiescence and proliferation is critical for proper maintenance of the hematopoietic stem cell (HSC) pool. Although a lot is known about hematopoiesis, molecular mechanisms that control HSC quiescence remain largely unknown. The ubiquitin-editing enzyme A20 functions as a central regulator of inflammation and adaptive immunity. Here, we show that a deficiency of A20 in the hematopoietic system causes anemia, lymphopenia, and postnatal lethality. Lack of A20 in HSCs results in diminished pool size, impaired radioprotection, defective repopulation, and loss of quiescence. A20-deficient HSCs display increased IFN-γ signaling, caused by augmented NF-κB activation. Strikingly, deletion of both IFN-γ and A20 in hematopoietic cells results in partial rescue of the HSC phenotype. We anticipate that our experiments will facilitate the understanding of mechanisms through which A20-mediated inflammatory signals control HSC quiescence and functions.
The role of proteins of the transforming growth factor-β superfamily in the intraovarian regulation of follicular development
Authors: J.L. Juengel, K.P. McNatty
Journal: Human Reproduction Update (2005)

Ovarian follicular development occurs in a hierarchical manner with each follicle having a unique biochemical composition at any moment in time. It has long been understood that a precise coordination between the growth and maturation of the oocyte and adjacent follicular cells (i.e. somatic cells) is essential in order to produce an oocyte that is fully competent to undergo fertilization and embryo development. In addition to the critical endocrine signalling pathways between the hypothalamus, pituitary and ovary, it is now evident that the oocyte itself is important in influencing the microenvironment of the developing follicle by regulating, via paracrine and autocrine mechanisms, its own maturation as well as somatic cell proliferation, differentiation and ovulation rate. Several of the key oocyte-derived regulating factors are members of the transforming growth factor-beta (TGF-beta) superfamily and to date the best understood are growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and BMP6. Significant species differences appear to exist in the relative importance of these growth factors and much remains to be elucidated about their roles in the human ovary. More information on the roles of these factors during ovarian follicular development is likely to advance new therapeutic applications for management of fertility as well as our understanding of how better to assess oocyte quality.
Increases in circulating and lymphoid tissue interleukin-10 in autoimmune lymphoproliferative syndrome are associated with disease expression
Authors: Uri Lopatin, Xu Yao, Richard K. Williams, Jack J. H. Bleesing, Janet K. Dale, David Wong, Julie Teruya-Feldstein, Scott Fritz, Matthew R. Morrow, Ivan Fuss, Michael C. Sneller, Mark Raffeld, Thomas A. Fleisher, Jennifer M. Puck, Warren Strober, Elaine S. Jaffe, Stephen E. Straus
Journal: Blood (2001)
Thrombolysis with human extrinsic (tissue-type) plasminogen activator in dogs with femoral vein thrombosis.
Authors: C Korninger, O Matsuo, R Suy, J M Stassen, D Collen
Journal: Journal of Clinical Investigation (1982)

Extrinsic (tissue-type) plasminogen activator (plasminogen activator) was isolated either as a single-chain or as a two-chain molecule from the culture medium of a human melanoma cell line. The thrombolytic activity of both molecular forms of activator was investigated in beagle dogs with an experimental femoral vein thrombosis and compared with that of urokinase. The 125I-fibrinogen-labeled thrombus was formed in an isolated 4-cm segment of the vein, aged for 30 min, and the thrombolytic substances were infused over a 4-h period. The degree of thrombolysis was measured 2 h later as the difference between the injected and recovered 125I. In six control animals with a saline infusion the extent of thrombolysis was 16.3 +/- 3.8% (mean +/- SEM), in five dogs receiving 100,000 IU urokinase, 17.4 +/- 3.7% (P less than 0.4) and in four dogs with 1,000,000 IU urokinase 40.6 +/- 4.8% (P less than 0.001). Infusion of 100.000 IU single-chain plasminogen activator in five dogs resulted in 3.5 +/- 7.8% lysis (P less than 0.05) and of 100,000 IU two-chain plasminogen activator in five dogs in 60.1 +/- 10.8% (P less than 0.001). Infusion of 300,000 IU one-chain plasminogen activator yielded 57.5% lysis and of the same amount of two-chain plasminogen activator 72.9%. Significant activation of plasminogen, consumption of alpha 2-antiplasmin, and fibrinogen breakdown in plasma was only observed in animals receiving the high doses of urokinase but not in the saline, plasminogen activator, or the low-dose urokinase groups. It is thus concluded that in this thrombosis model human extrinsic plasminogen activator has a higher specific thrombolytic effect that urokinase. Plasminogen activator also appears to induce thrombolysis without systemic fibrinolytic activation and fibrinogen breakdown.
Mice lacking ghrelin receptors resist the development of diet-induced obesity
Authors: Jeffrey M. Zigman, Yoshihide Nakano, Roberto Coppari, Nina Balthasar, Jacob N. Marcus, Charlotte E. Lee, Juli E. Jones, Amy E. Deysher, Amanda R. Waxman, Ryan D. White, Todd D. Williams, Jennifer L. Lachey, Randy J. Seeley, Bradford B. Lowell, Joel K. Elmquist
Journal: Journal of Clinical Investigation (2005)

Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHSR; ghrelin receptor). Since its discovery, accumulating evidence has suggested that ghrelin may play a role in signaling and reversing states of energy insufficiency. For example, ghrelin levels rise following food deprivation, and ghrelin administration stimulates feeding and increases body weight and adiposity. However, recent loss-of-function studies have raised questions regarding the physiological significance of ghrelin in regulating these processes. Here, we present results of a study using a novel GHSR-null mouse model, in which ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons. We show that when fed a high-fat diet, both female and male GHSR-null mice eat less food, store less of their consumed calories, preferentially utilize fat as an energy substrate, and accumulate less body weight and adiposity than control mice. Similar effects on body weight and adiposity were also observed in female, but not male, GHSR-null mice fed standard chow. GHSR deletion also affected locomotor activity and levels of glycemia. These findings support the hypothesis that ghrelin-responsive pathways are an important component of coordinated body weight control. Moreover, our data suggest that ghrelin signaling is required for development of the full phenotype of diet-induced obesity.
ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer
Authors: Gershon Y. Locker, Stanley Hamilton, Jules Harris, John M. Jessup, Nancy Kemeny, John S. Macdonald, Mark R. Somerfield, Daniel F. Hayes, Robert C. Bast
Journal: Journal of Clinical Oncology (2006)

To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of gastrointestinal cancers.For the 2006 update, an update committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of Medline and the Cochrane Collaboration Library were performed. The Update Committee's literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies.For colorectal cancer, it is recommended that carcinoembryonic antigen (CEA) be ordered preoperatively, if it would assist in staging and surgical planning. Postoperative CEA levels should be performed every 3 months for stage II and III disease for at least 3 years if the patient is a potential candidate for surgery or chemotherapy of metastatic disease. CEA is the marker of choice for monitoring the response of metastatic disease to systemic therapy. Data are insufficient to recommend the routine use of p53, ras, thymidine synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, microsatellite instability, 18q loss of heterozygosity, or deleted in colon cancer (DCC) protein in the management of patients with colorectal cancer. For pancreatic cancer, CA 19-9 can be measured every 1 to 3 months for patients with locally advanced or metastatic disease receiving active therapy. Elevations in serial CA 19-9 determinations suggest progressive disease but confirmation with other studies should be sought. New markers and new evidence to support the use of the currently reviewed markers will be evaluated in future updates of these guidelines.
Paradoxical Effects of Positioning in Patients with ARDS and Preexisting Pulmonary Vasculitis or Similar Disorders
Authors: Jean-Luc Diehl, Brice Lortat-Jacob, Noelle Lachaussée, Nadia Aissaoui, Marion Venot, Emmanuel Guérot, Jean-Yves Fagon
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Inhibition of the Interaction of AGE–RAGE Prevents Hyperglycemia-Induced Fibrosis of the Peritoneal Membrane
Authors: An S. De Vriese, Allan Flyvbjerg, Siska Mortier, Ronald G. Tilton, Norbert H. Lameire
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The peritoneal membrane of long-term peritoneal dialysis patients is characterized by a loss of ultrafiltration capacity, associated morphologically with submesothelial fibrosis and neoangiogenesis. Exposure to high glucose concentrations in peritoneal dialysate and the resultant advanced glycation end-products (AGE) accumulation have been implicated in the development of these changes, but their exact pathophysiological role is unknown. We examined the effect of the interaction of AGE with one of their receptors (i.e., RAGE) on the function and structure of the peritoneum exposed to high ambient glucose concentrations. Streptozotocin-induced diabetic rats and control rats were treated during 6 wk with either neutralizing monoclonal anti-RAGE antibodies or control antibodies. The expression of RAGE was strongly enhanced in the peritoneal membrane of the diabetic animals. The diabetic peritonea were characterized by an elevated transport of small solutes, lower ultrafiltration rates, a higher vascular density, and an upregulation of endothelial nitric oxide synthase expression. These parameters were unaffected by treatment with anti-RAGE antibodies. In contrast, anti-RAGE but not control antibodies prevented upregulation of TGF-β, development of submesothelial fibrosis, and fibronectin accumulation in the peritoneum of diabetic animals. In conclusion, binding of AGE to RAGE increases the expression of TGF-β and contributes to the development of submesothelial fibrosis. Neoangiogenesis and the resultant loss of ultrafiltration capacity are mediated by different pathogenetic pathways. E-mail: [email protected]
Modification of Ovarian Cancer Risk by <i>BRCA1/2</i>-Interacting Genes in a Multicenter Cohort of <i>BRCA1/2</i> Mutation Carriers
Authors: Timothy R. Rebbeck, Nandita Mitra, Susan M. Domchek, Fei Wan, Shannon Chuai, Tara M. Friebel, Saarene Panossian, Amanda Spurdle, Georgia Chenevix-Trench, Christian F. Singer, Georg Pfeiler, Susan L. Neuhausen, Henry T. Lynch, Judy E. Garber, Jeffrey N. Weitzel, Claudine Isaacs, Fergus Couch, Steven A. Narod, Wendy S. Rubinstein, Gail E. Tomlinson, Patricia A. Ganz, Olufunmilayo I. Olopade, Nadine Tung, Joanne L. Blum, Roger Greenberg, Katherine L. Nathanson, Mary B. Daly
Journal: Cancer Research (2009)

Inherited BRCA1/2 mutations confer elevated ovarian cancer risk. Knowledge of factors that can improve ovarian cancer risk assessment in BRCA1/2 mutation carriers is important because no effective early detection for ovarian cancers exists. A cohort of 1,575 BRCA1 and 856 BRCA2 mutation carriers was used to evaluate haplotypes at ATM, BARD1, BRIP1, CTIP, MRE11, NBS1, RAD50, RAD51, and TOPBP1 in ovarian cancer risk. In BRCA1 carriers, no associations were observed with ATM, BARD1, CTIP, RAD50, RAD51, or TOPBP1. At BRIP1, an association was observed for one haplotype with a multiple testing corrected P (P(corr)) = 0.012, although no individual haplotype was significant. At MRE11, statistically significant associations were observed for one haplotype (P(corr) = 0.007). At NBS1, we observed a P(corr) = 0.024 for haplotypes. In BRCA2 carriers, no associations were observed with CTIP, NBS1, RAD50, or TOPBP1. Rare haplotypes at ATM (P(corr) = 0.044) and BARD1 (P(corr) = 0.012) were associated with ovarian cancer risk. At BRIP1, two common haplotypes were significantly associated with ovarian cancer risk (P(corr) = 0.011). At MRE11, we observed a significant haplotype association (P(corr) = 0.012), and at RAD51, one common haplotype was significantly associated with ovarian cancer risk (P(corr) = 0.026). Variants in genes that interact biologically withBRCA1 and/or BRCA2 may be associated with modified ovarian cancer risk in women who carry BRCA1/2 mutations.