tbuckley/cabot-search huggingface dataset:
Glomerular filtration rate equations for liver-kidney transplantation in patients with cirrhosis: Validation of current recommendations
Authors: Claire Francoz, Mitra K. Nadim, Aurore Baron, Dominique Prié, Corinne Antoine, Jacques Belghiti, Dominique Valla, Richard Moreau, François Durand
Journal: Hepatology (2013)

Simultaneous liver and kidney transplantation (SLKT) remains the procedure of choice for patients with both endstage liver disease and kidney failure. Stringent guidelines are needed to avoid unnecessary kidney transplantation. A recent consensus meeting proposed criteria based on the Modified Diet in Renal Disease (MDRD)-6 equation to estimate glomerular filtration rate (GFR). The aims of this study were to compare GFR equations to true GFR in candidates for liver transplantation (LT) and to determine the impact of inaccuracies on the current guidelines for SLKT. Three hundred stable cirrhosis patients evaluated for LT were studied. All patients had iohexol clearance to measure GFR at evaluation under stable conditions. Measured GFR (mGFR) was compared to MDRD-4, MDRD-6, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. MDRD-6 was the most accurate equation to predict GFR. In the 290 patients with mGFR &gt;30 mL/min/1.73 m 2 , 15 patients (7%) had estimated GFR (eGFR) ≤40 mL/min/1.73 m 2 based on the MDRD-6 equation, defining “discordant” patients. Among them, two underwent SLKT and 13 underwent LT alone. None of those who survived more than 1 year after LT alone (n = 8) developed renal dysfunction thereafter. In multivariate analysis, discordant patients were older ( P = 0.03) and had lower sodium level ( P = 0.02). Conclusion : The MDRD-6 equation was superior to other equations at identifying cirrhosis patients with true GFR &lt;30 mL/min/1.73 m 2 . However, the MDRD-6 equation also tended to underestimate renal function in a subgroup of patients with true GFR &gt;30 mL/min/1.73 m 2 , with a potential risk of unnecessary kidney transplantation if applying current U.S. recommendations for SLKT. (HEPATOLOGY 2014;59:1514-1521)
Classical dendritic cells as a unique immune cell lineage
Authors: Boris Reizis
Journal: The Journal of Experimental Medicine (2012)

Despite the critical role of classical dendritic cells (cDCs) in the initiation of adaptive immune responses, the genetic and phenotypic definition of cDCs remains moot. Two new studies designate Zbtb46 as a novel transcription factor that is specifically expressed in all cDCs in both humans and mice. Although Zbtb46 appears dispensable for cDC development, its specific pattern of expression supports the notion that cDCs constitute a unique immune cell lineage. Furthermore, these two studies provide novel tools that will aid in the study of cDC progenitors, visualization of cDCs in vivo, and depletion of cDCs for functional analysis.
Randomized Comparison of Intensified Six-Drug Versus Standard Three-Drug Chemotherapy for High-Risk Nonmetastatic Rhabdomyosarcoma and Other Chemotherapy-Sensitive Childhood Soft Tissue Sarcomas: Long-Term Results From the International Society of Pediatric Oncology MMT95 Study
Authors: Odile Oberlin, Annie Rey, José Sanchez de Toledo, Hélène Martelli, Meriel E.M. Jenney, Marcelo Scopinaro, Christophe Bergeron, Johannes H.M. Merks, Nathalie Bouvet, Caroline Ellershaw, Anna Kelsey, David Spooner, Michael C.G. Stevens
Journal: Journal of Clinical Oncology (2012)

MMT95 was the fourth of a series of International Society of Pediatric Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft tissue sarcoma (STS). The principal objective was to explore survival advantage for an intensified chemotherapy strategy in a randomized trial.From July 1995 to June 2003, 457 previously untreated patients with incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma, and soft tissue primitive neuroectodermal tumor at all sites except paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over 27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m(2) (both arms), epirubicin 450 mg/m(2), etoposide 1,350 mg/m(2) (six-drug regimen). Poor responders after three courses of IVA were to be switched to the other arm. Delivery of radiotherapy was determined according to site and/or response to chemotherapy with or without surgery.Overall survival (OS) for all patients was 81% (95% CI, 77% to 84%) at 3 years. No significant difference in outcome in either OS or event-free survival was noted between the two arms (3-year OS: 82% [95% CI, 76% to 86%] for IVA and 80% [95% CI, 74% to 85%] for the six-drug arm). Toxicity was significantly greater (infection, myelosuppression, and mucositis) in the six-drug arm. Overall burden of local therapy was consistent with data from previous SIOP studies and showed no difference between the two chemotherapy regimens.Intensification of chemotherapy for nonmetastatic RMS and other chemotherapy-sensitive STS provides no survival advantage or reduction in the intensity of local therapy and adds toxicity.
Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma
Authors: A Baldi
Journal: Thorax (2004)

A study was undertaken to analyse the potential prognostic value of the immunohistochemical expression of cyclooxygenase-2 (COX-2) and p27 in 29 malignant mesotheliomas already screened for the expression of p21 and p53.Immunohistochemistry was used to determine the expression of COX-2 and p27. The correlation with survival of these factors and of p21 and p53 expression was assessed by univariate and multivariate analyses.A positive statistically significant correlation was found between p27 and p21 expression (p<0.0001), but there was a negative correlation between COX-2 expression and both p27 (p = 0.001) and p21 (p<0.0001). No statistically significant correlation was recorded between p53 and all the other immunohistochemical parameters. Univariate analysis showed that overall survival was strongly influenced by p21, p27, and COX-2 expression, but multivariate Cox regression analysis showed that the only immunohistochemical parameter to influence overall survival of patients with mesothelioma was COX-2.These findings suggest that COX-2 expression may be a useful prognostic parameter for mesothelioma.
α1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells
Authors: Stephanie Thebault, Morad Roudbaraki, Vadim Sydorenko, Yaroslav Shuba, Loic Lemonnier, Christian Slomianny, Etienne Dewailly, Jean-Louis Bonnal, Brigitte Mauroy, Roman Skryma, Natalia Prevarskaya
Journal: Journal of Clinical Investigation (2003)

The prostate gland is a rich source of α1-adrenergic receptors (α1-ARs). α1-AR antagonists are commonly used in the treatment of benign prostatic hyperplasia symptoms, due to their action on smooth muscle cells. However, virtually nothing is known about the role of α1-ARs in epithelial cells. Here, by using two human prostate cancer epithelial (hPCE) cell models — primary cells from resection specimens (primary hPCE cells) and an LNCaP (lymph node carcinoma of the prostate) cell line — we identify an α1A subtype of adrenergic receptor (α1A-AR) and show its functional coupling to plasmalemmal cationic channels via direct diacylglycerol (DAG) gating. In both cell types, agonist-mediated stimulation of α1A-ARs and DAG analogues activated similar cationic membrane currents and Ca2+ influx. These currents were sensitive to the α1A-AR antagonists, prazosin and WB4101, and to transient receptor potential (TRP) channel blockers, 2–aminophenyl borate and SK&F 96365. Chronic activation of α1A-ARs enhanced LNCaP cell proliferation, which could be antagonized by α1A-AR and TRP inhibitors. Collectively, our results suggest that α1-ARs play a role in promoting hPCE cell proliferation via TRP channels.
The need to redefine non-cystic fibrosis bronchiectasis in childhood
Authors: K M Eastham
Journal: Thorax (2004)

<b>Background:</b> Non-cystic fibrosis (CF) bronchiectasis has previously been reported to be rare and progressive in children living in western societies. <b>Method:</b> A clinical and radiological review was undertaken of 93 children with non-CF bronchiectasis defined by high resolution computed tomographic (HRCT) scanning presenting to a tertiary paediatric respiratory centre since 1996. <b>Results:</b> Cases constituted 9.6% of all new referrals. Male to female ratio was 2:1. Median age at symptom onset was 1.1 years (range 0–16) and of HRCT diagnosis was 7.2 years (1.6–18.8). The most common referral diagnosis of asthma was refuted in 39 of 45 cases. Associations were previous pneumonic illness (30%), immunocompromise (21%), obliterative bronchiolitis (9%), congenital lung abnormality (5%), chronic aspiration (3%), eosinophilic oesophagitis (2%), familial syndrome (2%), primary ciliary dyskinesia (1%), and right middle lobe syndrome (1%). 8% had two associated diagnoses and 18% were idiopathic. There was agreement between the chest radiograph and HRCT scan for diagnosis and lobe affected in only five cases (5%). A repeat HRCT scan in 18 cases at a minimum interval of 18 months showed total resolution of the changes in six, improvement in one, progression in five, and was unchanged in six. <b>Conclusions:</b> Radiologically defined non-CF bronchiectasis in children is not uncommon. Diagnostic delay is a problem. The most common association is a previous pneumonia. Chest radiography is of little diagnostic value, but resolution is possible on HRCT scanning. Bronchiectasis is currently defined as a condition which is both permanent and progressive. This term is not necessarily appropriate for all paediatric patients for whom we suggest an alternative nomenclature.
Salmonella Virulence Effector SopE and Host GEF ARNO Cooperate to Recruit and Activate WAVE to Trigger Bacterial Invasion
Authors: Daniel Humphreys, Anthony Davidson, Peter J. Hume, Vassilis Koronakis
Journal: Cell Host & Microbe (2012)

Salmonella virulence effectors elicit host cell membrane ruffling to facilitate pathogen invasion. The WAVE regulatory complex (WRC) governs the underlying membrane-localized actin polymerization, but how Salmonella manipulates WRC is unknown. We show that Rho GTPase activation by the Salmonella guanine nucleotide exchange factor (GEF) SopE efficiently triggered WRC recruitment but not its activation, which required host Arf GTPase activity. Invading Salmonella recruited and activated Arf1 to facilitate ruffling and uptake. Arf3 and Arf6 could also enhance invasion. RNAi screening of host Arf-family GEFs revealed a key role for ARNO in pathogen invasion and generation of pathogen-containing macropinosomes enriched in Arf1 and WRC. Salmonella recruited ARNO via Arf6 and the phosphoinositide phosphatase effector SopB-induced PIP3 generation. ARNO in turn triggered WRC recruitment and activation, which was dramatically enhanced when SopE and ARNO cooperated. Thus, we uncover a mechanism by which pathogen and host GEFs synergize to regulate WRC and trigger Salmonella invasion.
An overview on the development of a bio‐artificial pancreas as a treatment of insulin‐dependent diabetes mellitus
Authors: Ana Isabel Silva, António Norton de Matos, I. Gabrielle Brons, Marília Mateus
Journal: Medicinal Research Reviews (2005)

Abstract This paper presents the concept and most of the research undertaken all over the world for the development of a bio‐artificial pancreas (BAP) device over the last 30 years. The devices studied, meant to mimic the insulin secretion of the natural organ, were diverse and have been reviewed. Allogeneic or xenogeneic cells or cell clusters have been separated from the host's immune system by synthetic biocompatible semipermeable membranes to prevent the need, of the host, for immune‐suppressing regimens. The biocompatible polymer used as a barrier and its intrinsic characteristics, the cell immobilization or suspension media, the existence or not of co‐immobilized molecules or cells, the number of devices used and the implantation site, were addressed. © 2005 Wiley Periodicals, Inc. Med Res Rev
Role of sorbitol accumulation and myo-inositol depletion in paranodal swelling of large myelinated nerve fibers in the insulin-deficient spontaneously diabetic bio-breeding rat. Reversal by insulin replacement, an aldose reductase inhibitor, and myo-inositol.
Authors: D A Greene, S Chakrabarti, S A Lattimer, A A Sima
Journal: Journal of Clinical Investigation (1987)

Axo-glial dysjunction refers to the disruption of important junctional complexes that anchor terminal loops of myelin to the paranodal axolemma in diabetic human and animal peripheral nerve. Neither axo-glial dysjunction nor the preceeding acute localized paranodal swelling has been specifically attributed to discrete metabolic consequences of insulin deficiency or hyperglycemia. Two metabolic sequelae of hyperglycemia in diabetic nerve, sorbitol accumulation via aldose reductase, and (Na,K)-ATPase deficiency related to myo-inositol depletion, were explored as possible underlying causes of acute paranodal swelling in the spontaneously diabetic bio-breeding rat. 3 wk of insulin replacement, or therapy with an aldose reductase inhibitor or myo-inositol completely reversed paranodal swelling in sural nerve fibers after 3 wk of untreated insulin deficiency. These observations suggest that insulin deficiency and hyperglycemia cause reversible paranodal swelling, and ultimately poorly reversible axo-glial dysjunction, via the myo-inositol-related (Na,K)-ATPase defect rather than by the osmotic effects of sorbitol accumulation within nerve fibers.
Mutation spectrum of Drosophila CNVs revealed by breakpoint sequencing
Authors: Margarida Cardoso-Moreira, J Roman Arguello, Andrew G Clark
Journal: Genome biology (2012)

Abstract Background The detailed study of breakpoints associated with copy number variants (CNVs) can elucidate the mutational mechanisms that generate them and the comparison of breakpoints across species can highlight differences in genomic architecture that may lead to lineage-specific differences in patterns of CNVs. Here, we provide a detailed analysis of Drosophila CNV breakpoints and contrast it with similar analyses recently carried out for the human genome. Results By applying split-read methods to a total of 10x coverage of 454 shotgun sequence across nine lines of D. melanogaster and by re-examining a previously published dataset of CNVs detected using tiling arrays, we identified the precise breakpoints of more than 600 insertions, deletions, and duplications. Contrasting these CNVs with those found in humans showed that in both taxa CNV breakpoints fall into three classes: blunt breakpoints; simple breakpoints associated with microhomology; and breakpoints with additional nucleotides inserted/deleted and no microhomology. In both taxa CNV breakpoints are enriched with non-B DNA sequence structures, which may impair DNA replication and/or repair. However, in contrast to human genomes, non-allelic homologous-recombination (NAHR) plays a negligible role in CNV formation in Drosophila . In flies, non-homologous repair mechanisms are responsible for simple, recurrent, and complex CNVs, including insertions of de novo sequence as large as 60 bp. Conclusions Humans and Drosophila differ considerably in the importance of homology-based mechanisms for the formation of CNVs, likely as a consequence of the differences in the abundance and distribution of both segmental duplications and transposable elements between the two genomes.
Rituximab in Idiopathic Membranous Nephropathy
Authors: Piero Ruggenenti, Paolo Cravedi, Antonietta Chianca, Annalisa Perna, Barbara Ruggiero, Flavio Gaspari, Alessandro Rambaldi, Maddalena Marasà, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2012)

Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria <0.3 g/24 h and partial remission as persistent proteinuria <3 g/24 h, each also having >50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m(2) among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.
Hereditary Infections With Mammary Tumor Viruses in Mice
Authors: Bentvelzen, P., Daams, J. H.
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article Hereditary Infections With Mammary Tumor Viruses in Mice Get access P. Bentvelzen, P. Bentvelzen MTV Research Unit, Antoni van Leeuwenhoek-huis, The Netherlands Cancer Institute, Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar J. H. Daams J. H. Daams MTV Research Unit, Antoni van Leeuwenhoek-huis, The Netherlands Cancer Institute, Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 43, Issue 5, November 1969, Pages 1025–1035, https://doi.org/10.1093/jnci/43.5.1025 Published: 01 November 1969 Article history Received: 04 March 1969 Accepted: 21 June 1969 Published: 01 November 1969
Peroxynitrite-dependent activation of protein phosphatase type 2A mediates microvascular endothelial barrier dysfunction
Authors: F. Wu, J. X. Wilson
Journal: Cardiovascular Research (2008)

AimsWe investigated the mechanism by which proinflammatory stimulation induces microvascular endothelial barrier dysfunction. Since protein phosphatase type 2A (PP2A) can mediate paracellular leak and can be inactivated by tyrosine phosphorylation in its catalytic subunit (PP2Ac), we hypothesized that microvascular endothelial cells exposed to proinflammatory stimulation produce peroxynitrite that nitrates PP2Ac, and this nitration inhibits tyrosine phosphorylation of PP2Ac and thereby increases PP2A activity to mediate endothelial barrier dysfunction.
Interobserver variability in the application of the novel IASLC/ATS/ERS classification for pulmonary adenocarcinomas
Authors: Arne Warth, Albrecht Stenzinger, Ann-Christin von Brünneck, Benjamin Goeppert, Judith Cortis, Iver Petersen, Hans Hoffmann, Philipp A. Schnabel, Wilko Weichert
Journal: European Respiratory Journal (2012)

Recently, a novel classification for pulmonary adenocarcinomas (ADCs) was published, the cornerstone of which is the quantification of growth patterns. Data on reproducibility in the routine diagnostic setting are lacking. 100 constitutive cases of lung ADC resection specimens from our archives were classified independently by five pulmonary pathologists and two residents according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The most frequent predominant pattern in our cohort was solid (37%), followed by acinar (35%), lepidic (20%), papillary (5%) and micropapillary (3%). κ-values for the denomination of the predominant pattern revealed substantial agreement for pulmonary pathologists (κ=0.44-0.72) and fair agreement for residents (κ=0.38-0.47). Interobserver variability was significantly higher in cases with higher slide numbers (p=0.028) and was considerably reduced after training. Intraobserver variability was low (κ=0.79-0.87). Papillary and micropapillary patterns were the most complicated patterns to evaluate, while evaluation of lepidic and solid tumour growth was straightforward. Our data imply that the novel classification of pulmonary ADC is applicable with acceptable interobserver variability if performed by specifically trained pathologists. Additional efforts are needed to harmonise the application of this novel and clinically important classification scheme of pulmonary ADC.
Studies on intestinal absorption of amino acids and a dipeptide in a case of Hartnup disease
Authors: F. Navab, A. M. Asatoor
Journal: Gut (1970)

A severely affected case of Hartnup disease is reported, where the patient responded rapidly to nicotinamide. This supports the view that all the clinical features, except reduced stature from general nutritional defect, are secondary to tryptophan and nicotinamide deficiency rather than to an unknown toxic factor. Severe malabsorption of both tryptophan and phenylalanine was demonstrated. The dipeptide carnosine was absorbed normally whereas when the two constituent amino acids, beta-alanine and L-histidine, were ingested, absorption of the former was normal but that of the latter was grossly defective. The suggestion is advanced that in cases of Hartnup disease protein nutrition is maintained by intestinal uptake of amino acids as oligopeptides rather than as free amino acids. By contrast, both modes of absorption are probably important in normal subjects. Radiology of the small intestine is abnormal in Hartnup disease when a large amount of protein is admixed with the barium meal.