tbuckley/cabot-search huggingface dataset:
Molecular Microscope Strategy to Improve Risk Stratification in Early Antibody-Mediated Kidney Allograft Rejection
Authors: Alexandre Loupy, Carmen Lefaucheur, Dewi Vernerey, Jessica Chang, Luis G. Hidalgo, Thibaut Beuscart, Jerome Verine, Olivier Aubert, Sébastien Dubleumortier, Jean-Paul Duong van Huyen, Xavier Jouven, Denis Glotz, Christophe Legendre, Philip F. Halloran
Journal: Journal of the American Society of Nephrology (2014)

Antibody-mediated rejection (ABMR) is the leading cause of kidney allograft loss. We investigated whether the addition of gene expression measurements to conventional methods could serve as a molecular microscope to identify kidneys with ABMR that are at high risk for failure. We studied 939 consecutive kidney recipients at Necker Hospital (2004-2010; principal cohort) and 321 kidney recipients at Saint Louis Hospital (2006-2010; validation cohort) and assessed patients with ABMR in the first 1 year post-transplant. In addition to conventional features, we assessed microarray-based gene expression in transplant biopsy specimens using relevant molecular measurements: the ABMR Molecular Score and endothelial donor-specific antibody-selective transcript set. The main outcomes were kidney transplant loss and progression to chronic transplant injury. We identified 74 patients with ABMR in the principal cohort and 54 patients with ABMR in the validation cohort. Conventional features independently associated with failure were donor age and humoral histologic score (g+ptc+v+cg+C4d). Adjusting for conventional features, ABMR Molecular Score (hazard ratio [HR], 2.22; 95% confidence interval [95% CI], 1.37 to 3.58; P=0.001) and endothelial donor-specific antibody-selective transcripts (HR, 3.02; 95% CI, 1.00 to 9.16; P<0.05) independently associated with an increased risk of graft loss. The results were replicated in the independent validation group. Adding a gene expression assessment to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 1.01; 95% CI, 0.57 to 1.46; P<0.001; integrated discrimination improvement, 0.16; P<0.001). Compared with conventional assessment, the addition of gene expression measurement in kidney transplants with ABMR improves stratification of patients at high risk for graft loss.
PPARα activation in portal hypertension
Authors: Hongqun Liu, Samuel S. Lee, Roberto J. Groszmann, Yasuko Iwakiri, Tamar H. Taddei
Journal: Hepatology (2012)

Abstract Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor activated by ligands that regulates genes related to vascular tone, oxidative stress, and fibrogenesis, pathways implicated in the development of cirrhosis and portal hypertension. This study aims at evaluating the effects of PPARα activation with fenofibrate on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl(4)-cirrhotic rats. Mean arterial pressure (MAP), portal pressure (PP), and portal blood flow (PBF) were measured in cirrhotic rats treated with oral fenofibrate (25mg/kg/day, n=10) or its vehicle (n=12) for 7 days. The liver was then perfused and dose-relaxation curves to acetylcholine (Ach) were performed. We also evaluated Sirius Red staining of liver sections, collagen-I mRNA expression, and smooth muscle actin (α-SMA) protein expression, cyclo-oxygenase-1 (COX-1) protein expression, and cGMP levels in liver homogenates, and TXB(2) production in perfusates. Nitric oxide (NO) bioavailability and eNOS activation were measured in hepatic endothelial cells (HEC) isolated from cirrhotic rat livers. CCl(4) cirrhotic rats treated with fenofibrate had a significantly lower PP (-29%) and higher MAP than those treated with vehicle. These effects were associated with a significant reduction in hepatic fibrosis and improved vasodilatory response to acetylcholine. Moreover, a reduction in COX-1 expression and TXB(2) production in rats receiving fenofibrate and a significant increase in NO bioavailability in HEC with fenofibrate were observed. PPARα activation markedly reduced PP and liver fibrosis and improved hepatic endothelial dysfunction in cirrhotic rats, suggesting it may represent a new therapeutic strategy for portal hypertension in cirrhosis.
Experience with experimental biological treatment and local gene therapy in Sjogren's syndrome: implications for exocrine pathogenesis and treatment
Authors: B M Lodde, B J Baum, P P Tak, G Illei
Journal: Annals of the Rheumatic Diseases (2006)

Sjögren's syndrome is an autoimmune exocrinopathy, mainly affecting the lacrimal and salivary glands, and resulting in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). The aetiology and pathogenesis are largely unknown, and only palliative treatment is currently available. Data obtained from experimental animal and human studies using biological agents or gene therapeutics can offer insight into the disease process of Sjögren's syndrome. This article reviews the current literature on these approaches and assesses the lessons learnt about the pathogenesis of Sjögren's syndrome.
Accuracy and disagreement of computed tomography and magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma and dysplastic nodules: Role of biopsy
Authors: Thomas Sersté, Vincent Barrau, Violaine Ozenne, Marie-Pierre Vullierme, Pierre Bedossa, Olivier Farges, Dominique-Charles Valla, Valérie Vilgrain, Valérie Paradis, Françoise Degos
Journal: Hepatology (2011)

Liver macronodules, ranging from benign to low-grade or high-grade dysplastic nodules (LGDNs/HGDNs) and hepatocellular carcinoma (HCC), may develop during chronic liver diseases (CLDs). Current guidelines were recently updated and the noninvasive criteria for the diagnosis of small HCC are based on a single typical radiological pattern and nonconclusive coincidental findings with two techniques. This study aimed to assess the accuracy and disagreements of noninvasive multiphasic examinations for the diagnosis of HCC and dysplastic nodules (DNs) and the role of biopsy. Seventy-four consecutive patients with CLD with ultrasound-detected 1-2-cm nodules underwent, within 1 month, multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and biopsy of the nodule. Median age was 60 years; 33 patients (45%) had hepatitis C virus, 20 (27%) had hepatitis B virus, and 13 (18%) patients had no cirrhosis. Biopsy revealed 47 HCCs, 6 HGDNs, 1 LGDNs, 1 cholangiocarcinoma, and 1 epithelioid hemangioendothelioma. There were no tumors in the other 18 patients. All patients (31 of 31; 100%) who had conclusive coincidental findings (i.e., arterial enhancement and washout) on both examinations had HCC or HGDN (sensitivity, 57%; specificity, 100%). All patients (51 of 51; 100%) who had conclusive findings on at least one of the two examinations had HCC or HGDN (sensitivity, 96%; specificity, 100%). There was a disagreement regarding imaging findings between CT and MRI in 21 of 74 (28%) patients and no washout on both examinations in 23 of 74 patients (31%). In these 44 patients, liver biopsy provided an initial accurate diagnosis. Conclusion : The noninvasive diagnosis of HCC or HGDN can be obtained if arterial enhancement and washout are found in a single dynamic imaging examination. These findings are frequently discordant on both CT and MRI, supporting the place of biopsy for the diagnosis of small HCCs.
The Body of Evidence for Advanced Technology in Radiation Oncology
Authors: J. E. Bekelman, S. M. Hahn
Journal: JNCI Journal of the National Cancer Institute (2012)

Proton therapy has struck a nerve in the national dialogue about cancer comparative effectiveness research in the United States. Unlike photon-based radiotherapy, proton therapy delivers radiation within a finite range, depositing dose in a tumor target with essentially no residual radiation beyond the tumor. Proton therapy radiation dose distributions often appear superior to photon-based treatments like intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy, particularly in the reduction of low and intermediate radiation dose to normal tissues.
Pharmacokinetics, Metabolism, and Oral Bioavailability of the DNA Methyltransferase Inhibitor 5-Fluoro-2′-Deoxycytidine in Mice
Authors: Jan H. Beumer, Julie L. Eiseman, Robert A. Parise, Erin Joseph, Julianne L. Holleran, Joseph M. Covey, Merrill J. Egorin
Journal: Clinical Cancer Research (2006)

In vivo, 5-fluoro-2'-deoxycytidine (FdCyd) is rapidly and sequentially converted to 5-fluoro-2'-deoxyuridine, 5-fluorouracil, and 5-fluorouridine. The i.v. combination of FdCyd and 3,4,5,6-tetrahydrouridine (THU), a cytidine deaminase (CD) inhibitor that blocks the first metabolic step in FdCyd catabolism, is being investigated clinically for its ability to inhibit DNA methyltransferase. However, the full effects of THU on FdCyd metabolism and pharmacokinetics are unknown. We aimed to characterize the pharmacokinetics, metabolism, and bioavailability of FdCyd with and without THU in mice.We developed a sensitive high-performance liquid chromatography tandem mass spectrometry assay to quantitate FdCyd and metabolites in mouse plasma. Mice were dosed i.v. or p.o. with 25 mg/kg FdCyd with or without coadministration of 100 mg/kg THU p.o. or i.v.The oral bioavailability of FdCyd alone was approximately 4%. Coadministration with THU increased exposure to FdCyd and decreased exposure to its metabolites; i.v. and p.o. coadministration of THU increased exposure to p.o. FdCyd by 87- and 58-fold, respectively. FdCyd exposure after p.o. FdCyd with p.o. THU was as much as 54% that of i.v. FdCyd with i.v. THU.FdCyd is well absorbed but undergoes substantial first-pass catabolism by CD to potentially toxic metabolites that do not inhibit DNA methyltransferase. THU is sufficiently bioavailable to reduce the first-pass effect of CD on FdCyd. Oral coadministration of THU and FdCyd is a promising approach that warrants clinical testing because it may allow maintaining effective FdCyd concentrations on a chronic basis, which would be an advantage over other DNA methyltransferase inhibitors that are currently approved or in development.
Repair of the lower and middle parts of the face by composite tissue allotransplantation in a patient with massive plexiform neurofibroma: a 1-year follow-up study
Authors: Laurent Lantieri, Jean-Paul Meningaud, Philippe Grimbert, Frank Bellivier, Jean-Pascal Lefaucheur, Nicolas Ortonne, Marc-David Benjoar, Philippe Lang, Pierre Wolkenstein
Journal: The Lancet (2008)
Evidence of improving survival of patients with rectal cancer in France: a population based study
Authors: C Finn-Faivre, J Maurel, A M Benhamiche, C Herbert, E Mitry, G Launoy, J Faivre
Journal: Gut (1999)

Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known.To determine trends in management and prognosis of rectal cancer in two French regions.1978 patients with a rectal carcinoma diagnosed between 1978 and 1993.Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed.Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17. 7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978-1981 period to 57.0% for the 1985-1989 period).Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival.
Renal Artery Stenosis: A Common, Treatable Cause of Renal Failure?
Authors: Stephen C. Textor, Christopher S. Wilcox
Journal: Annual Review of Medicine (2001)

▪ Abstract Chronic azotemic renovascular disease is common in patients with atherosclerosis. Its prevalence appears to be increasing in the aging population. How often it is the primary cause of end-stage renal disease (ESRD) is not yet certain. Some studies suggest that 10%–40% of elderly hypertensive patients with newly documented ESRD and no demonstrable primary renal disease have significant renal artery stenosis (RAS). Atherosclerotic vascular occlusive disease of the renal arteries does progress, but current rates of progression and occlusion are lower than those reported a decade ago. Methods of identifying patients whose renal function is at true risk from vascular occlusive disease and determining who will benefit from intervention remain elusive. The presence of RAS in an azotemic patient can be assessed with noninvasive and risk-free radiologic techniques, including Duplex doppler velicometry and magnetic resonance angiography. Functional tests that predict the change in renal function after revascularization are not yet available. However, a renal length of greater than 7.5 cm in the absence of renal cysts and a short history of renal functional deterioration indicate a good prognosis. Patients with recent deterioration in renal function, those with bilateral renal artery stenosis or stenosis to a single functioning kidney, those with flash pulmonary edema, advanced chronic renal failure, or ESRD (who have much to gain), those with reversible azotemia during angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB) therapy, and those whose conditions cannot be managed medically should be considered for revascularization. Results from recent controlled clinical trials of the response to percutaneous transluminal renal artery angioplasty (PTRA) and stenting indicate that improvement in blood pressure control or renal function is not a predictable outcome of renal revascularization. In azotemic groups, 25%–30% of patients achieve important recovery of renal function. Thus, significant progress has been made recently in determining whether RAS is a frequent, treatable cause of renal failure. The decision to recommend revascularization remains a difficult balance between the risks and expense of the procedure and the undoubted benefits that accrue if renal function is successfully stabilized.
Chromium in Human Nutrition
Authors: E G Offenbacher, F X Pi-Sunyer
Journal: Annual Review of Nutrition (1988)

INTRODUCTION   543 EVIDENCE THAT CHROMIUM (Cr) IS ESSENTIAL   544 Early Studies  544 Documentation of Human Cr Deficiency  545 Role of Cr in Lipid Metabolism ......   547 Supplementation Trials  548 Cr Deficiency as a Factor in Other Conditions   55l MEASUREMENT OF Cr IN THE BODy. . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . ..... . . . . . . . . . . . . . 55l Cr in Blood   .   552 Cr in Urine   . ... . ..... .. .. . .... .   552 Cr in Hair  553 Current and Future Capabilities  554 Cr METABOLISM AND FUNCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 554 Absorption of Dietary Cr  555 Cr Transport  555 Identification of Metabolically Active Molecules   556 Other Metabolic Functions  557 IS Cr MARGINAL OR INADEQUATE IN THE DIETS OF SOME PEOPLE? ... ..... 557
Improving Quality of Care in Diabetes Through a Comprehensive Pharmacist-Based Disease Management Program
Authors: Sandra Leal, Jon J. Glover, Richard N. Herrier, Anthony Felix
Journal: Diabetes Care (2004)

In the U.S., a large percentage of patients with diabetes receive less than optimal care (1). The use of pharmacists, nurse practitioners, and multidisciplinary teams in a variety of settings have led to improvements in disease control in patients with diabetes and other chronic diseases (2–14). This report describes the utility of a pharmacist-run disease management program in improving the care of predominately indigent, Spanish-speaking patients with diabetes and common comorbid conditions.

The study was conducted at El Rio Health Center, which is a federally qualified health center located in Tucson, Arizona. The patient population is comprised mostly of indigent, Spanish-speaking, and sometimes transient patients with primarily type 2 diabetes. The program was implemented in August 2001, using a residency-trained, bilingual PharmD as the provider for patients referred to the pharmacist-based diabetes service by staff physicians. The pharmacist served as the primary care provider for the patients’ diabetes and comorbid conditions, hypertension, and hyperlipidemia. Using medical staff–approved collaborative practice agreements, the pharmacist provided appropriate diagnostic, educational, and therapeutic management services, including prescribing medication and ordering laboratory tests. The collaborative practice agreements were based on national …
Efficacy of anti-IL-1 treatment in Majeed syndrome
Authors: Troels Herlin, Bente Fiirgaard, Mette Bjerre, Gitte Kerndrup, Henrik Hasle, Xinyu Bing, Polly J Ferguson
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objective</h3> Majeed syndrome is an autosomal recessive disorder characterised by the triad of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anaemia and a neutrophilic dermatosis that is caused by mutations in <i>LPIN2</i>. Long-term outcome is poor. This is the first report detailing the treatment of Majeed syndrome with biological agents and demonstrates clinical improvement with IL-1blockade. <h3>Methods</h3> We describe the clinical presentation, genetic analysis, cytokine profiles and response to biological therapy in two brothers with Majeed syndrome. <h3>Results</h3> Both boys were homozygous for a novel 2-base pair deletion in <i>LPIN2</i> (c.1312_1313delCT; p.Leu438fs+16X), confirming the diagnosis. Their bone disease and anaemia were refractory to treatment with corticosteroids. Both siblings had elevated proinflammatory cytokines in their serum, including tumour necrosis factor α (TNF-α), however a trial of the TNF inhibitor etanercept resulted in no improvement. IL-1 inhibition with either a recombinant IL-1 receptor antagonist (anakinra) or an anti-IL-1β antibody (canakinumab) resulted in dramatic clinical and laboratory improvement. <h3>Conclusions</h3> The differential response to treatment with TNF-α or IL-1 blocking agents sheds light into disease pathogenesis; it supports the hypothesis that Majeed syndrome is an IL-1β dependent autoinflammatory disorder, and further underscores the importance of IL-1 in sterile bone inflammation.
Maternal and Paternal Risk Factors for Cryptorchidism and Hypospadias: A Case–Control Study in Newborn Boys
Authors: Frank H. Pierik, Alex Burdorf, James A. Deddens, Rikard E. Juttmann, Rob F.A. Weber
Journal: Environmental Health Perspectives (2004)

Little is known on environmental risk factors for cryptorchidism and hypospadias, which are among the most frequent congenital abnormalities. The aim of our study was to identify risk factors for cryptorchidism and hypospadias, with a focus on potential endocrine disruptors in parental diet and occupation. In a case-control study nested within a cohort of 8,698 male births, we compared 78 cryptorchidism cases and 56 hypospadias cases with 313 controls. The participation rate was 85% for cases and 68% for controls. Through interviews, information was collected on pregnancy aspects and personal characteristics, lifestyle, occupation, and dietary phytoestrogen intake of both parents. Occupational exposure to potential endocrine disruptors was classified based on self-reported exposure and ratings of occupational hygienists based on job descriptions. Our findings indicate that paternal pesticide exposure was associated with cryptorchidism [odds ratio (OR) = 3.8; 95% confidence interval (95% CI), 1.1-13.4]. Smoking of the father was associated with hypospadias (OR = 3.8; 95% CI, 1.8-8.2). Maternal occupational, dietary, and lifestyle exposures were not associated with either abnormality. Both abnormalities were associated with suboptimal maternal health, a lower maternal education, and a Turkish origin of the parents. Being small for gestational age was a risk factor for hypospadias, and preterm birth was a risk factor for cryptorchidism. Because paternal pesticide exposure was significantly associated with cryptorchidism and paternal smoking was associated with hypospadias in male offspring, paternal exposure should be included in further studies on cryptorchidism and hypospadias risk factors.
Interferon-α plus ribavirin in chronic hepatitis C resistant to previous interferon-α course: results of a randomized multicenter trial
Authors: Pietro Andreone, Annagiulia Gramenzi, Carmela Cursaro, Giorgio Sbolli, Sirio Fiorino, Loriana Di Giammarino, Rita Miniero, Antonia D'Errico, Giovanni Gasbarrini, Mauro Bernardi
Journal: Journal of Hepatology (1999)
The Low-Density Lipoprotein Receptor–Related Protein Regulates Cancer Cell Survival and Metastasis Development
Authors: Valérie Montel, Alban Gaultier, Robin D. Lester, W. Marie Campana, Steven L. Gonias
Journal: Cancer Research (2007)

Abstract Low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional receptor involved in receptor-mediated endocytosis and cell signaling. In this study, we show that LRP-1 is abundantly expressed in severe combined immunodeficient (SCID) mouse xenografts by various human cancer cell lines that express very low or undetectable levels of LRP-1 when cultured in 21% O2 in vitro (standard cell culture conditions). To test whether LRP-1 expression in vivo may be explained by hypoxia in the xenografts, CL16 cells, which are derived from the MDA-MB-435 cell line, were cultured in 1.0% O2. A substantial increase in LRP-1 expression was observed. To test the activity of LRP-1 in cancer progression in vivo, LRP-1 expression was silenced in CL16 cells with short hairpin RNA. These cells formed tumors in SCID mice, in which LRP-1 expression remained silenced. Although LRP-1 gene silencing did not inhibit CL16 cell dissemination from the primary tumors to the lungs, the pulmonary metastases failed to enlarge, suggesting compromised survival or growth at the implantation site. In cell culture experiments, significantly increased cell death was observed when LRP-1–silenced CL16 cells were exposed to CoCl2, which models changes that occur in hypoxia. Furthermore, LRP-1–silenced cells expressed decreased levels of vascular endothelial growth factor in response to 1.0% O2. These results suggest mechanisms by which LRP-1 may facilitate the development and growth of cancer metastases in vivo. [Cancer Res 2007;67(20):9817–24]
Delayed Blanch and Opacity Pulse in Atopic Dermatitis
Authors: Colin Ramsay
Journal: British Journal of Dermatology (1969)

Journal Article Delayed Blanch and Opacity Pulse in Atopic Dermatitis Get access Colin Ramsay Colin Ramsay University of Wisconsin Medical Center Madison, Wisconsin, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 8, 1 August 1969, Pages 631–632, https://doi.org/10.1111/j.1365-2133.1969.tb16049.x Published: 01 August 1969