tbuckley/cabot-search huggingface dataset:
Dilated cardiomyopathy and impaired cardiac hypertrophic response to angiotensin II in mice lacking FGF-2
Authors: Corinne Pellieux, Alessandro Foletti, Giovanni Peduto, Jean-François Aubert, Jürg Nussberger, Friedrich Beermann, Hans-R. Brunner, Thierry Pedrazzini
Journal: Journal of Clinical Investigation (2001)

FGF-2 has been implicated in the cardiac response to hypertrophic stimuli. Angiotensin II (Ang II) contributes to maintain elevated blood pressure in hypertensive individuals and exerts direct trophic effects on cardiac cells. However, the role of FGF-2 in Ang II–induced cardiac hypertrophy has not been established. Therefore, mice deficient in FGF-2 expression were studied using a model of Ang II–dependent hypertension and cardiac hypertrophy. Echocardiographic measurements show the presence of dilated cardiomyopathy in normotensive mice lacking FGF-2. Moreover, hypertensive mice without FGF-2 developed no compensatory cardiac hypertrophy. In wild-type mice, hypertrophy was associated with a stimulation of the c-Jun N-terminal kinase, the extracellular signal regulated kinase, and the p38 kinase pathways. In contrast, mitogen-activated protein kinase (MAPK) activation was markedly attenuated in FGF-2–deficient mice. In vitro, FGF-2 of fibroblast origin was demonstrated to be essential in the paracrine stimulation of MAPK activation in cardiomyocytes. Indeed, fibroblasts lacking FGF-2 expression have a defective capacity for releasing growth factors to induce hypertrophic responses in cardiomyocytes. Therefore, these results identify the cardiac fibroblast population as a primary integrator of hypertrophic stimuli in the heart, and suggest that FGF-2 is a crucial mediator of cardiac hypertrophy via autocrine/paracrine actions on cardiac cells.
Fixed-drug eruption presenting as an acute paronychia
Authors: R. BARAN, C. PERRIN
Journal: British Journal of Dermatology (1991)

Journal Article Fixed‐drug eruption presenting as an acute paronychia Get access R. BARAN, R. BARAN Department of Dermatology, Cannes General Hospital, Cannes, France Dr Robert Baran, 42 rue des Serbes, 06400 Cannes, France. Search for other works by this author on: Oxford Academic Google Scholar C. PERRIN C. PERRIN Department of Pathology, Hôpital Pasteur, Nice. France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 6, 1 December 1991, Pages 592–595, https://doi.org/10.1111/j.1365-2133.1991.tb14802.x Published: 01 December 1991
Injury situations in Freestyle Ski Cross (SX): a video analysis of 33 cases
Authors: Stefan Randjelovic, Stig Heir, Lars Nordsletten, Tone Bere, Roald Bahr
Journal: British Journal of Sports Medicine (2013)

Background Although injury risk in Freestyle Ski Cross (SX) is high, little is known about the situations leading up to time-loss injuries. Objective To describe the situations leading up to time-loss injuries in elite Freestyle SX. Study design Descriptive video analysis. Methods Thirty-three video recordings of SX injuries reported through the International Ski Federation Injury Surveillance System for four World Cup seasons (2006/2007 through 2010) were obtained. Five experts in the fields of sport medicine and SX analysed each case to describe in detail the situation leading up to the injury (skiing situation and skier behaviour). Results Injuries occurred in four different skiing situations: jumping (n=16), turning (n=8), jumping and turning (n=7) and rollers (n=2). All injured skiers lost control before time of injury (n=33), due to skier–opponent contact (n=13), technical errors (n=8) or inappropriate strategy (n=8), which led to a fall (n=29). Contact occurred in 21 of 33 cases, usually unintentional at landing or take-off, caused by the opponent (n=11) or injured skier (n=8). The technical error cases (n=8) were dominated by bad jumping technique (n=6) and too much inside lean in turning situations (n=2), while inappropriate course line and bad timing at take off (n=7) dominated the inappropriate strategy cases (n=8). Conclusions We identified four main injury situations in elite SX, dominated by jumping situations. The primary cause of injury was unintentional skier–opponent contact in jumping, bank turning and roller situations. Another common cause of injury was personal errors (inappropriate technique and strategy) at take-off and in turning situations.
Classification Based on the Combination of Molecular and Pathologic Predictors is Superior to Molecular Classification on Prognosis in Colorectal Carcinoma
Authors: Fangying Xu, Fenjuan Wang, Meijuan Di, Qiong Huang, Min Wang, Hu Hu, Yisen Jin, Jiankang Dong, Maode Lai
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Classification based on a combination of molecular and pathologic predictors had never been done using hierarchical cluster analysis. For this purpose, we identified prognostic classification based on molecular predictors, pathologic and molecular predictors, and compared their respective prognostic efficacy together with that of tumor-node-metastasis (TNM) stage. Moreover, we investigated the prognostic significance of molecular classification in different TNM stage. Experimental Design: Six pathologic predictors (p) and 13 immunohistochemical predictors (m) were investigated in 221 colorectal carcinomas. Unsupervised hierarchical clustering analysis was done to group the data. Survival analysis was done by Kaplan-Meier method and log-rank test, and by multivariate COX proportional hazard model. Results: Six pathologic predictors and four molecular predictors were of significant prognostic value (P ≤ 0.05). One molecular predictor showed a trend toward significance (P = 0.085). Hierarchical clustering analysis was done based on different combinations (5p, 13m, 5m, 5p13m, and 5p5m), and distinct groups were produced except 5p (the TNM stage was excluded). Groups identified by 5m (P = 0.053) and 5p5m (P = 0.000) showed significant differences in prognosis. Groups identified by 5p5m and TNM stage were confirmed as the independent prognostic factors in a multivariate COX proportional hazard model. Moreover, groups identified by 5m could predict different prognoses in patients with stage II disease. Conclusions: Classification based on pathologic and immunohistochemical predictors is superior to that based only on molecular predictors on prognosis. Classification based on 5m could identify additional different prognoses in patients with stage II disease.
Incorporation of intermediary products of 5-FU anabolism into colorectal cancer.
Authors: G R Giles, L Woodhouse, P J Finan, E M Chisholm
Journal: Gut (1986)

In 18 patients intermediary anabolic metabolites of 5-FU were measured in normal colonic mucosa and colorectal cancer tissue of intravenous bolus injection or continuous infusion. Higher total concentrations of 5-FU products were found in the cancers when compared with normal colonic tissue. There appeared to be no evidence, however, that some patients had a selectively increased ability to incorporate 5-FU into their tumours. Overall higher concentrations of tumour incorporation of 5-FU were found after bolus injection rather than the infusion method, although this difference is statistically not significant.
Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis
Authors: M Hasegawa
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Fractalkine expressed on endothelial cells mediates activation and adhesion of leucocytes expressing its receptor, CX<sub>3</sub>CR1. Soluble fractalkine exhibits chemotactic activity for leucocytes expressing CX<sub>3</sub>CR1. <b>Objective:</b> To determine the role of fractalkine and its receptor in systemic sclerosis (SSc) by assessing their expression levels in patients with this disease. <b>Methods:</b> The expression of fractalkine and CX<sub>3</sub>CR1 in the skin and lung tissues was immunohistochemically examined. Circulating soluble fractalkine levels were examined by enzyme linked immunosorbent assay (ELISA). Blood samples from patients with SSc were stained for CX<sub>3</sub>CR1 with flow cytometric analysis. <b>Results:</b> CX<sub>3</sub>CR1 levels on peripheral monocytes/macrophages and T cells were found to be raised in patients with diffuse cutaneous SSc. The numbers of cells expressing CX<sub>3</sub>CR1, including monocytes/macrophages, were increased in the lesional skin and lung tissues from patients with diffuse cutaneous SSc. Fractalkine was strongly expressed on endothelial cells in the affected skin and lung tissues. Soluble fractalkine levels were significantly raised in sera and were associated with raised erythrocyte sedimentation rates, digital ischaemia, and severity of pulmonary fibrosis. <b>Conclusions:</b> Up regulated expression of fractalkine and CX<sub>3</sub>CR1 cooperatively augments the recruitment of mononuclear cells expressing CX<sub>3</sub>CR1 into the affected tissue of SSc, leading to inflammation and vascular injury.
Adjunctive Olanzapine for SSRI-Resistant Combat-Related PTSD: A Double-Blind, Placebo-Controlled Study
Authors: Murray B. Stein, Neal A. Kline, Jeffrey L. Matloff
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Posttraumatic stress disorder (PTSD), particularly in combat veterans with chronic illness, is often refractory to standard pharmacological interventions. There is a need to test adjunctive treatments to boost response. METHOD: Subjects were 19 patients with PTSD who were minimally responsive to 12 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) at maximum tolerated dose. Outcomes were compared among subjects whose treatment was augmented with 8 weeks of double-blind olanzapine or placebo administration. RESULTS: Olanzapine augmentation was associated with statistically significantly greater reduction than placebo in specific measures of posttraumatic stress, depressive, and sleep disorder symptoms. Clinician-rated global response rates did not, however, significantly differ between groups. CONCLUSIONS: This is most likely the first double-blind, placebo-controlled study of an adjunct to SSRIs for PTSD. Despite the small group size, the findings suggest a role for olanzapine or other atypical antipsychotics in treating SSRI-resistant PTSD. Sleep symptoms may especially benefit.
Lung versus heart-lung transplantation for cystic fibrosis: is the debate still open?
Authors: P. Thomas
Journal: European Respiratory Journal (2005)

Although medical management has considerably improved, cystic fibrosis (CF) remains a major cause of mortality from suppurative lung disease, in children and young adults. Lung transplantation is currently the only available efficient treatment of the life-limiting aspects of the condition to achieve improved quality of life and long-term survival in these patients, who stand to benefit more from transplantation than any other diagnostic group 1. In this issue of the European Respiratory Journal , Ganesh et al . 2 present the results of the UK Cardiothoracic Transplant Audit, with similar outcomes achieved by heart–lung transplantation (HLT) and bilateral lung transplantation (BLT) in CF recipients, thereby reopening a debate that was considered closed for a while. Indeed, very few HLTs are still performed for this indication, and the main reason for this is the trend for fewer HLT procedures being performed worldwide, which is reflected again in the international figures from last year's results of the Registry of the International Society of Heart and Lung Transplantation 3. Since ∼50% of CF patients die on the waiting list due to a scarcity in the supply of donor thoracic organs, current efforts involve any attempt to expand the lung donor pool: specifically, liberalisation …
International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT)
Authors: Ayalew Tefferi, Giovanni Barosi, Ruben A. Mesa, Francisco Cervantes, H. Joachim Deeg, John T. Reilly, Srdan Verstovsek, Brigitte Dupriez, Richard T. Silver, Olatoyosi Odenike, Jorge E Cortes, Martha Wadleigh, Lawrence A. Solberg, John K. Camoriano, Heinz Gisslinger, Pierre Noel, Juergen Thiele, James W. Vardiman, Ronald Hoffman, Nicholas C.P. Cross, D. Gary Gilliland, Hagop Kantarjian
Journal: Blood (2006)
Fibrotic extracellular matrix activates a profibrotic positive feedback loop
Authors: Matthew W. Parker, Daniel Rossi, Mark Peterson, Karen Smith, Kristina Sikström, Eric S. White, John E. Connett, Craig A. Henke, Ola Larsson, Peter B. Bitterman
Journal: Journal of Clinical Investigation (2014)

Pathological remodeling of the extracellular matrix (ECM) by fibroblasts leads to organ failure. Development of idiopathic pulmonary fibrosis (IPF) is characterized by a progressive fibrotic scarring in the lung that ultimately leads to asphyxiation; however, the cascade of events that promote IPF are not well defined. Here, we examined how the interplay between the ECM and fibroblasts affects both the transcriptome and translatome by culturing primary fibroblasts generated from IPF patient lung tissue or nonfibrotic lung tissue on decellularized lung ECM from either IPF or control patients. Surprisingly, the origin of the ECM had a greater impact on gene expression than did cell origin, and differences in translational control were more prominent than alterations in transcriptional regulation. Strikingly, genes that were translationally activated by IPF-derived ECM were enriched for those encoding ECM proteins detected in IPF tissue. We determined that genes encoding IPF-associated ECM proteins are targets for miR-29, which was downregulated in fibroblasts grown on IPF-derived ECM, and baseline expression of ECM targets could be restored by overexpression of miR-29. Our data support a model in which fibroblasts are activated to pathologically remodel the ECM in IPF via a positive feedback loop between fibroblasts and aberrant ECM. Interrupting this loop may be a strategy for IPF treatment.
Physiologic and Pharmacologic Effects of Glucocorticoids on Ion Transport across Rabbit Ileal Mucosa In Vitro
Authors: Joseph H. Sellin, Michael Field
Journal: Journal of Clinical Investigation (1981)

Physiologic and pharmacologic effects of glucocorticoids on ileal ion transport were examined in vitro. Tissues were obtained from the three following groups of rabbits: (a) normal; (b) glucocorticoid deficient, which were treated with aminoglutethimide (AG), 100 mg twice daily for 3 d, with a resulting marked reduction in urinary cortisol excretion but no decrease in urinary aldosterone; and (c) methylprednisolone-treated (MP), 40 mg daily for 2 d. Transileal NaCl fluxes were measured with radioisotopes under short-circuit conditions, and the net HCO3 flux was assumed equal to that portion of the short-circuit current (Isc) not accounted for by Na and Cl. In NaCl Ringer's solution containing 25 mM HCO3 (pH 7.4), normals absorbed both Na and Cl and secreted HCO3; the Isc was greater in both AG and MP groups than in normals; in the AG group, no Na was absorbed, and Cl as well as HCO3 was secreted; in the MP group, more Na was absorbed and more HCO3 secreted than in normals. Addition of glucose to the luminal side caused similar increments in Isc in all three groups, suggesting similar rates of Na-coupled glucose absorption. Secretory response was assessed with a maximal secretory simulus (8-Br-cAMP) and also a submaximal, cGMP-related secretory stimulus (Escherichia coli heat-stable enterotoxin). After addition of 8-Br-cAMP, the rates of net Cl secretion were similar in all three groups, suggesting no effect of glucocorticoids on maximal secretory capacity. Because the AG group was already secreting Cl, however, the cAMP-induced change in net Cl flux was least in this group. After addition of heat-stable enterotoxin, there were similar changes in net Cl flux in all three groups. To examine specifically Cl-independent, electrogenic Na transport, we used a 10 mM HCO3, Cl-free SO4-Ringer (ph 7.2) in which net Na absorption was previously shown to be equal to the Isc. Under these conditions, Isc was greatest in the MP group and least in the AG group. In vitro addition of hydrocortisone, 50 μg/ml, to AG tissues had no effect on Cl fluxes or Isc over a 3.5-h period. No differences among groups were observed with respect to morphology, electrical resistance, or cGMP concentration. We conclude that (a) the effect of glucocorticoid deficiency is similar to that of a submaximal secretory stimulus in that Na absorption is inhibited and some Cl secretion develops; (b) electrogenic Na absorption is depressed in glucocorticoid deficiency and enhanced in glucocorticoid excess; (c) glucocorticoid excess increases HCO3 secretion; and (d) glucocorticoid status does not affect maximal secretory capacity.
Differential impact of Ink4a and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmi1-deficient mice
Authors: Hideyuki Oguro, Atsushi Iwama, Yohei Morita, Takehiko Kamijo, Maarten van Lohuizen, Hiromitsu Nakauchi
Journal: The Journal of Experimental Medicine (2006)

The polycomb group (PcG) protein Bmi1 plays an essential role in the self-renewal of hematopoietic and neural stem cells. Derepression of the Ink4a/Arf gene locus has been largely attributed to Bmi1-deficient phenotypes in the nervous system. However, its role in hematopoietic stem cell (HSC) self-renewal remained undetermined. In this study, we show that derepressed p16Ink4a and p19Arf in Bmi1-deficient mice were tightly associated with a loss of self-renewing HSCs. The deletion of both Ink4a and Arf genes substantially restored the self-renewal capacity of Bmi1−/− HSCs. Thus, Bmi1 regulates HSCs by acting as a critical failsafe against the p16Ink4a- and p19Arf-dependent premature loss of HSCs. We further identified a novel role for Bmi1 in the organization of a functional bone marrow (BM) microenvironment. The BM microenvironment in Bmi1−/− mice appeared severely defective in supporting hematopoiesis. The deletion of both Ink4a and Arf genes did not considerably restore the impaired BM microenvironment, leading to a sustained postnatal HSC depletion in Bmi1−/−Ink4a-Arf−/− mice. Our findings unveil a differential role of derepressed Ink4a and Arf on HSCs and their BM microenvironment in Bmi1-deficient mice. Collectively, Bmi1 regulates self-renewing HSCs in both cell-autonomous and nonautonomous manners.
Gtf2I Mutations are Frequent in Thymic Epithelial Tumors
Authors: I. Petrini, P.S. Meltzer, I. Kim, M. Lucchi, K. Park, G. Fontanini, J. Gao, P.A. Zucali, F. Calabrese, A. Favaretto, F. Rea, Y. Wang, G. Giaccone
Journal: Annals of Oncology (2014)
Cytokine <i>BAFF</i> Gene Variation Is Associated with Survival of Patients with T-cell Lymphomas
Authors: Kan Zhai, Xiaobo Tian, Chen Wu, Ning Lu, Jiang Chang, Liming Huang, Tongwen Zhang, Yuling Zhou, Yan Qiao, Dianke Yu, Wen Tan, Jieping Chen, Dongxin Lin
Journal: Clinical Cancer Research (2012)

Cytokine BAFF is a potent molecule for the activation and survival of B cells, and it also plays an important role in T-cell function. Genetic polymorphism (rs9514828C>T) in BAFF has been associated with elevated BAFF transcription. We sought to determine whether rs9514828 is associated with T-cell lymphoma (TCL) survival.BAFF rs9514828 genotypes and survival of TCL were analyzed in the discovery group including 150 patients, and the results were replicated in an independent validation group of 120 patients. Kaplan-Meier analysis was conducted to compare survival among different genotypes. Cox proportional hazard models were used to identify independent significant variables. Luciferase reporter gene assays were conducted to examine the function of rs9514828 variant.We found that BAFF rs9514828 polymorphism was significantly associated with TCL survival. In pooled analysis of two independent groups, the favorable rs9514828 TC and TT genotypes had significantly better five-year survival rates compared with the CC genotype (47% and 53% vs. 22%, P = 2.27 × 10(-5) for log-rank test). Multivariate Cox regression analysis showed that rs9514828 was an independent prognostic factor, with HRs for patient death being 0.48 [95% confidence interval (CI), 0.32-0.71] for the CT and 0.47 (95% CI, 0.23-0.93) for the TT genotypes. Reporter gene assays indicated that the rs9514828T allele had significantly higher promoter activity than the rs9514828C counterpart.These findings suggest that functional polymorphism in BAFF might be a genetic determinant for the survival of patients with TCL.
Transformation of MCF-10A cells by random mutagenesis with frameshift mutagen ICR191: A model for identifying candidate breast-tumor suppressors
Authors: Helena Zientek-Targosz, Dimiter Kunnev, Lesleyann Hawthorn, Mikhail Venkov, Sei-Ichi Matsui, Richard T Cheney, Yuri Ionov
Journal: Molecular Cancer (2008)

Abstract Background Widely accepted somatic mutation theory of carcinogenesis states that mutations in oncogenes and tumor suppressor genes in genomes of somatic cells is the cause of neoplastic transformation. Identifying frequent mutations in cancer cells suggests the involvement of mutant genes in carcinogenesis. Results To develop an in vitro model for the analysis of genetic alterations associated with breast carcinogenesis, we used random mutagenesis and selection of human non-tumorigenic immortalized breast epithelial cells MCF-10A in tissue-culture conditions that mimic tumor environment. Random mutations were generated in MCF-10A cells by cultivating them in a tissue-culture medium containing the frameshift-inducing agent ICR191. The first selective condition we used to transform MCF1-10A cells was cultivation in a medium containing mutagen at a concentration that allowed cell replication despite p53 protein accumulation induced by mutagen treatment. The second step of selection was either cell cultivation in a medium with reduced growth-factor supply or in a medium that mimics a hypoxia condition or growing in soft agar. Using mutagenesis and selection, we have generated several independently derived cultures with various degrees of transformation. Gene Identification by Nonsense-mediated mRNA decay Inhibition (GINI) analysis has identified the ICR191-induced frameshift mutations in the TP53, smoothelin, Ras association (RalGDS/AF-6) domain family 6 (RASSF6) and other genes in the transformed MCF-10A cells. The TP53 gene mutations resulting in the loss of protein expression had been found in all independently transformed MCF-10A cultures, which form large progressively growing tumors with sustained angiogenesis in nude mice. Conclusion Identifying genes containing bi-allelic ICR191-induced frameshift mutations in the transformed MCF-10A cells generated by random mutagenesis and selection indicates putative breast-tumor suppressors. This can provide a model for studying the role of mutant genes in breast carcinogenesis.