tbuckley/cabot-search huggingface dataset:
Comparison between two different assays for measurements of allergen‐specific IgE and skin prick test in the diagnosis of insect venom allergy
Authors: P. Eiken, H. Mosbech, L. Jacobsen, P. Larsen, B. Scharling, U. G. Svendsen, U. Søes‐Petersen
Journal: Allergy (1992)

Forty‐one patients stung by wasp and 29 by bee were evaluated by comparing the correlation between skin prick test (SPT), Phadebas radioallergosorbent test (P‐RAST) and Magic Lite SQ Specific IgE assay (LIA). All patients had had a systemic reaction to insect sting. In the patients stung by bee we found agreement between SPT and P‐RAST, and SPT and LIA. Similarly, there were no significant differences in sensitivity between P‐RAST and LIA (p&gt;0.05). In patients stung by wasp, SPT was found to be more sensitive than P‐RAST. There were no differences between SPT and LIA or between P‐RAST and LIA.
Estrogen Treatment of Postmenopausal Women
Authors: E. Stanton Shoemaker
Journal: JAMA (1977)

Estrogen treatment of postmenopausal women is effective in relieving the symptoms of vasomotor instability and urogenital atrophy; estrogen treatment is effective in preventing accelerated bone loss and osteoporosis in young women following castration, but in postmenopausal women aging is a more important determinant of accelerated bone loss than is decreased estrogen secretion. Low-dose estrogen treatment of postmenopausal women neither prevents nor increases the risk of arteriosclerotic cardiovascular disease or cerebral vascular disease. It cannot be definitively established that estrogen treatment of postmenopausal women causes an increased incidence of breast tumors, but it is clear that such treatment does not prevent these tumors. It is established that estrogen treatment of postmenopausal women increases the risk ratio of endometrial carcinoma. (<i>JAMA</i>238:1524-1530, 1977)
Reading Frame Correction by Targeted Genome Editing Restores Dystrophin Expression in Cells From Duchenne Muscular Dystrophy Patients
Authors: David G Ousterout, Pablo Perez-Pinera, Pratiksha I Thakore, Ami M Kabadi, Matthew T Brown, Xiaoxia Qin, Olivier Fedrigo, Vincent Mouly, Jacques P Tremblay, Charles A Gersbach
Journal: Molecular Therapy (2013)

Genome editing with engineered nucleases has recently emerged as an approach to correct genetic mutations by enhancing homologous recombination with a DNA repair template. However, many genetic diseases, such as Duchenne muscular dystrophy (DMD), can be treated simply by correcting a disrupted reading frame. We show that genome editing with transcription activator-like effector nucleases (TALENs), without a repair template, can efficiently correct the reading frame and restore the expression of a functional dystrophin protein that is mutated in DMD. TALENs were engineered to mediate highly efficient gene editing at exon 51 of the dystrophin gene. This led to restoration of dystrophin protein expression in cells from Duchenne patients, including skeletal myoblasts and dermal fibroblasts that were reprogrammed to the myogenic lineage by MyoD. Finally, exome sequencing of cells with targeted modifications of the dystrophin locus showed no TALEN-mediated off-target changes to the protein-coding regions of the genome, as predicted by in silico target site analysis. This strategy integrates the rapid and robust assembly of active TALENs with an efficient gene-editing method for the correction of genetic diseases caused by mutations in non-essential coding regions that cause frameshifts or premature stop codons.
Human complement factor H deficiency associated with hemolytic uremic syndrome.
Authors: N Rougier, M D Kazatchkine, J P Rougier, V Fremeaux-Bacchi, J Blouin, G Deschenes, B Soto, V Baudouin, B Pautard, W Proesmans, E Weiss, L Weiss
Journal: Journal of the American Society of Nephrology (1998)

This study reports on six cases of deficiency in the human complement regulatory protein Factor H (FH) in the context of an acute renal disease. Five of the cases were observed in children presenting with idiopathic hemolytic uremic syndrome (HUS). Two of the children exhibited a homozygous deficiency characterized by the absence of the 150-kD form of Factor H and the presence, upon immunoblotting, of the 42-kD Factor H-like protein 1 (FHL-1) and other FH-related protein (FHR) bands. Southern blot and PCR analysis of DNA of one patient with homozygous deficiency ruled out the presence of a large deletion of the FH gene as the underlying defect for the deficiency. The other four children presented with heterozygous deficiency and exhibited a normal immunoblotting pattern of proteins of the FH family. Factor H deficiency is the only complement deficiency associated with HUS. These observations suggest a role for FH and/or FH receptors in the pathogenesis of idiopathic HUS.
Cognitive architectures combine formal and heuristic approaches
Authors: Cleotilde Gonzalez, Christian Lebiere
Journal: Behavioral and Brain Sciences (2013)

Abstract Quantum probability (QP) theory provides an alternative account of empirical phenomena in decision making that classical probability (CP) theory cannot explain. Cognitive architectures combine probabilistic mechanisms with symbolic knowledge-based representations (e.g., heuristics) to address effects that motivate QP. They provide simple and natural explanations of these phenomena based on general cognitive processes such as memory retrieval, similarity-based partial matching, and associative learning.
Genetic variation in transmembrane 6 superfamily member 2 and the risk of nonalcoholic fatty liver disease and histological disease severity
Authors: Silvia Sookoian, Gustavo O. Castaño, Romina Scian, Pablo Mallardi, Tomas Fernández Gianotti, Adriana L. Burgueño, Julio San Martino, Carlos J. Pirola
Journal: Hepatology (2014)

We explored the role of transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 C/T nonsynonymous (p.Glu167Lys) variant in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and disease severity. A total of 361 individuals (135 control subjects and 226 patients with histologically proven NAFLD) were included in a sample with 97% power for the additive genetic model. A discrete trait analysis of NAFLD showed that rs58542926 was associated with a modest risk of fatty liver (P = 0.038; odds ratio [OR]: 1.37; 95% confidence interval [CI]: 1.02-1.84); nevertheless, conditioning on patatin-like phospholipase domain-containing 3 (PNPLA3)-rs738409 abolished this effect. We did not observe an interaction between rs738409 and rs58542926 variants on the risk of NAFLD. We observed a significant association of rs58542926 and disease severity (P = 0.027), but not lobular inflammation or fibrosis; rs58542926 was not associated with levels of liver enzymes. An allelic test showed that the T (Lys167) allele was significantly associated with disease progression (P = 0.021; OR, 1.66; 95% CI: 1.08-2.55). A significant association was found with the histological degree of liver steatosis (β, 0.15; standard error: 0.06; P = 0.0299) that was independent of rs738409. Homozygous carriers of the C (Glu167) allele showed increased risk for cardiovascular disease. TM6SF2 protein expression was decreased markedly in liver of NAFLD patients, compared to controls. In addition, TM6SF2 immunoreactivity was reduced in subjects carrying at least one copy of the T allele, consistent with a difference in liver allele-specific transcript abundance.rs58542926 is a low-frequency variant with a modest effect on NAFLD, suggesting that carriers of the T allele are slightly more likely to accumulate fat in the liver and develop nonalcoholic steatohepatitis than those without. TM6SF2 appears to play a significant role in disease biology.
Activin A Suppresses Neuroblastoma Xenograft Tumor Growth via Antimitotic and Antiangiogenic Mechanisms
Authors: Ekaterini Panopoulou, Carol Murphy, Heidi Rasmussen, Eleni Bagli, Einar K. Rofstad, Theodore Fotsis
Journal: Cancer Research (2005)

Abstract The tumor suppressor function of activin A, together with our findings that activin A is an inhibitor of angiogenesis, which is down-regulated by the N-MYC oncogene, prompted us to investigate in more detail its role in the malignant transformation process of neuroblastomas. Indeed, neuroblastoma cells with restored activin A expression exhibited a diminished proliferation rate and formed smaller xenograft tumors with reduced vascularity, whereas lung metastasis rate remained unchanged. In agreement with the decreased vascularity of the xenograft tumors, activin A inhibited several crucial angiogenic responses of cultured endothelial cells, such as proteolytic activity, migration, and proliferation. Endothelial cell proliferation, activin A, or its constitutively active activin receptor-like kinase 4 receptor (ALK4T206D), increased the expression of CDKN1A (p21), CDKN2B (p15), and CDKN1B (p27) CDK inhibitors and down-regulated the expression of vascular endothelial growth factor receptor-2, the receptor of a key angiogenic factor in cancer. The constitutively active forms of SMAD2 and SMAD3 were both capable of inhibiting endothelial cell proliferation, whereas the dominant-negative forms of SMAD3 and SMAD4 released the inhibitory effect of activin A on endothelial cell proliferation by only 20%. Thus, the effects of activin A on endothelial cell proliferation seem to be conveyed via the ALK4/SMAD2-SMAD3 pathways, however, non-SMAD cascades may also contribute. These results provide novel information regarding the role of activin A in the malignant transformation process of neuroblastomas and the molecular mechanisms involved in regulating angiogenesis thereof.
Deferred use of bevacizumab for recurrent glioblastoma is not associated with diminished efficacy
Authors: David E. Piccioni, Julia Selfridge, Reema R. Mody, Reshmi Chowdhury, Sichen Li, Shadi Lalezari, James Wawrzynski, Jennifer Quan, Mira Zurayk, Arthur P. Chou, Desiree E. Sanchez, Linda M. Liau, Benjamin M. Ellingson, Whitney B. Pope, Phioanh L. Nghiemphu, Richard M. Green, He-jing Wang, William H. Yong, Robert Elashoff, Timothy F. Cloughesy, Albert Lai
Journal: Neuro-Oncology (2014)

The optimal timing to initiate bevacizumab (BV) therapy for recurrent glioblastoma (GBM) is currently unclear. To address this issue, we examined progression-free survival (PFS) and survival time (ST) in a large retrospective cohort of GBM patients treated with BV at different recurrences. We identified 468 primary GBM patients who underwent biopsy or surgery followed by radiation therapy and temozolomide (RT/TMZ), and then received BV. PFS and ST were compared between patients stratified by the recurrence that BV was initiated (upfront, first recurrence, second recurrence, or 3+ recurrences). We also examined the effect on PFS and ST of the addition of chemotherapy to BV. In a larger cohort of GBM patients, we determined overall treatment continuation rates at each recurrence and identified variables predictive of inability to continue treatment. BV PFS was similar for all 3 recurrence groups (median, 4.1 months). There were no differences in BV ST (median, 9.8 months). The addition of chemotherapy to BV improved PFS but not ST. Analysis of treatment continuation rates indicated that the number of patients unable to undergo further treatments is modest, and that patients unable to tolerate BV delay can be identified by age ≥60 years and low extent of resection. Deferred use of bevacizumab is not associated with diminished efficacy. Analysis of treatment continuation rates identified patients who may be unable to delay BV therapy. Our findings suggest that there is a fixed survival after BV initiation and that delayed BV treatment is preferable for most patients.
Renal Na/H exchanger NHE-3 and Na-PO4 cotransporter NaPi-2 protein expression in glucocorticoid excess and deficient states.
Authors: J Loffing, M Lötscher, B Kaissling, J Biber, H Murer, M Seikaly, R J Alpern, M Levi, M Baum, O W Moe
Journal: Journal of the American Society of Nephrology (1998)

Administration of pharmacologic doses of glucocorticoid in vivo increases renal proximal tubule apical membrane Na/H exchange and decreases Na/PO4 cotransport activity (1). Current data suggest that the NHE-3 and NaPi-2 proteins mediate significant fractions of proximal tubule apical membrane Na/H exchange and Na/PO4 cotransport, respectively. This study examines whether glucocorticoid excess or deficiency affects NHE-3 and NaPi-2 protein abundance and the intrarenal distribution of these transporters. Protein abundance of NHE-3 and NaPi-2 in control rats was compared to rats rendered glucocorticoid-deficient by bilateral adrenalectomy, and to rats receiving pharmacologic doses of dexamethasone using immunoblots and immunohistochemistry. Adrenalectomy had modest effects on NHE-3 protein abundance, but dexamethasone administration to either adrenalectomized or sham-operated rats significantly increased NHE-3 protein abundance in both the proximal tubule and thick ascending limb, but not the thin descending limb. Adrenalectomy increased NaPi-2 protein abundance in the proximal tubule, whereas dexamethasone administration dramatically suppressed NaPi-2 protein on the apical membrane in both adrenalectomized and sham-operated animals. No significant reciprocal increase in subapical NaPi-2 staining was seen in the dexamethasone-treated rats. The present study shows that glucocorticoids regulate proximal tubule apical membrane Na/H exchange and NaPi cotransport by changes in protein abundance of NHE-3 and NaPi-2, respectively.
Characterization of the transport of a synthetic bile salt, iodinated cholyl-glycyl-tyrosine, in isolated cultured rat hepatocytes
Authors: John C. Deutsch, Mieko M. Iwahashi, Eileen M. Sutherland, John Mapoles, Francis R. Simon
Journal: Hepatology (1992)

ABSTRPlCT The uptake of tri–hydroxy conjugated bile salts by hepatocytes is principally by a sodium–dependent carrier. We examined the uptake kinetics of the high–specific–activity, hydroxylated, conjugated bile salt 125 I–labeled cholyl–glycyl–tyrosine, to determine whether this synthetic bile salt was transported by the sodium–dependent bile salt system. 125 I–labeled cholyl–glycyl–tyrosine was synthesized, and its transport kinetics were studied in freshly cultured rat hepatocytes. Uptake into hepatocytes was time and temperature dependent and was decreased by the inhibitors diisothiocyanodisulfonic acid stilbene, probenecid and carbonyl cyanide chlorophenyl hydrazone, demonstrating carrier mediation and energy dependence. At concentrations of iodinated cholyl–glycyl–tyrosine less than 10 μmol/L, uptake was 27% ± 5% sodium dependent, whereas at concentrations from 10 μmol/L to 40 μmol/L uptake was 52% ± 4% sodium dependent. The apparent affinity for uptake of 125 I–labeled cholyl–glycyl–tyrosine was 8 ± 2 μmol/L, and the maximal velocity was 50 ± 20 pmol/μg DNA/min. Both taurocholate and indocyanine green inhibited uptake of 125 I–labeled cholyl–glycyl–tyrosine. Indocyanine green inhibited the uptake of 125 I–labeled cholyl–glycyl–tyrosine (K i = 10 μm) more effectively than taurocholate (K i = 20 μm). We conclude that 125 I–labeled cholyl–glycyl–tyrosine is not a specific probe for either sodium–dependent bile salt or sodium–independent organic anion carriers, but appears to use both systems in a concentration–dependent manner in cultured rat hepatocytes. (Hepatology 1992;15:917-922).
Coup d'Etat: An Orphan Takes Control
Authors: Fu-Jung Lin, Jun Qin, Ke Tang, Sophia Y. Tsai, Ming-Jer Tsai
Journal: Endocrine Reviews (2011)

Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) belong to the steroid/thyroid hormone receptor superfamily. Cloning of their cDNAs demonstrated the existence of two distinct but related genes: COUP-TFI (EAR-3, NR2F1) and COUP-TFII (ARP-1, NR2F2). They are referred to as orphan receptors because ligands for COUP-TFs have yet to be identified. Since 1998, extensive studies have demonstrated their physiological importance in cell-fate specification, organogenesis, angiogenesis, and metabolism, as well as a variety of diseases. In this article, we will comprehensively review the biological functions of COUP-TFII and its underlying mechanism in various developmental processes and diseases. In addition, we will briefly summarize some of the current findings of COUP-TFI.
Improved Survival After Lymphadenectomy for Nodal Metastasis From an Unknown Primary Melanoma
Authors: Chris C. Lee, Mark B. Faries, Leslie A. Wanek, Donald L. Morton
Journal: Journal of Clinical Oncology (2008)

No primary lesion is identified in 10% to 20% of patients presenting with palpable evidence of regional metastatic melanoma. Because the prognostic significance of unknown primary melanoma (MUP) is unclear, we compared clinical outcomes of patients with MUP and known primary melanoma (MKP) with regional nodal metastases.We reviewed our 13,000-patient prospective melanoma database (1971 through 2005) to identify patients managed with regional lymphadenectomy for palpable nodal metastases from MUP or MKP. Multivariate analysis identified prognostic factors significant for survival. MUP and MKP were then matched by significant covariates. Overall survival (OS) was estimated by Kaplan-Meier method and compared by log-rank analysis.Multivariate analysis of data from 1,571 study patients identified four significant covariates associated with worse prognosis: age >or= 60 years (hazard ratio [HR] = 1.294; P = .0017), male sex (HR = 1.335; P = .0004), nodal tumor burden >or= one (HR = 1.256; P < .0001), and known primary (HR = 1.507; 95% CI, 1.220 to 1.862; P = .0001). Five-year OS was significantly higher for 262 patients with MUP than for 1,309 patients with MKP (55% +/- 6% v 44% +/- 3%; P = .0021). Computerized matching of MUP and MKP by four significant covariates (age, sex, nodal tumor burden, and decade of diagnosis) yielded 221 matched pairs. Median and 5-year OS rates were 165 months and 58% +/- 7%, respectively, for MUP as compared with 34 months and 40% +/- 7%, respectively, for MKP (P = .0006).Lymphadenectomy is effective for nodal metastasis from MUP. The significantly better postoperative survival for MUP versus MKP suggests a strong endogenous immune response against the primary melanoma. Immunologic studies to identify cell-mediated and antibody components of this response may lead to new approaches for determining melanoma prognosis and treatment.
Treatment of pulmonary hypertension in interstitial lung disease: do not throw out the baby with the bath water
Authors: Vincent Cottin
Journal: European Respiratory Journal (2013)

Pulmonary hypertension (PH), group III of the international aetiological classification [1], is a frequent and severe complication of interstitial lung diseases (ILDs), especially idiopathic pulmonary fibrosis (IPF), the syndrome of combined pulmonary fibrosis and emphysema, ILD associated with connective tissue disease, sarcoidosis, pulmonary Langerhans cell histiocytosis and, rarely, other ILDs [2–6]. Although its prevalence varies widely between these conditions, PH, when present, dramatically impacts morbidity and survival.

Despite recent progress with pirfenidone and nintedanib, which reduce the rate of decline in lung function in patients with mild-to-moderate disease [7, 8], management of IPF remains largely supportive, with a relentless progression to respiratory failure and death after a median of only 3 years from the time of diagnosis. Precapillary PH is common in advanced IPF, with a prevalence of 32–46% [9–12] at right heart catheterisation (RHC) at the time of evaluation for lung transplantation. The haemodynamic severity of PH in this context is usually mild, although 2–10% of patients have severe PH with a mean pulmonary artery pressure (mPAP) greater than 35–40 mmHg [9, 10]. PH is associated with increased dyspnoea, decreased exercise capacity as measured by the 6-min walk distance (6MWD) and the peak oxygen uptake at cardiopulmonary exercise testing [9, 13, 14], lower diffusing capacity of the lung for carbon monoxide ( D LCO), greater oxygen requirements and reduced survival [2, 9]. In one study, the 1-year mortality of patients with IPF and associated PH at RHC was 28% versus only 5.5% in those without PH [9]. In subjects with moderate functional impairment, the prevalence of PH is lower and varies depending upon the procedures used. In a recent series of 101 patients who underwent …
Pretargeting of Carcinoembryonic Antigen–Expressing Tumors with a Biologically Produced Bispecific Anticarcinoembryonic Antigen × Anti-Indium–Labeled Diethylenetriaminepentaacetic Acid Antibody
Authors: Frank G. van Schaijk, Egbert Oosterwijk, Annemieke C. Soede, Matthias Broekema, Cathelijne Frielink, William J. McBride, David M. Goldenberg, Frans H.M. Corstens, Otto C. Boerman
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The aim of these studies was to develop a pretargeting strategy for CEA-expressing cancers using biologically produced bispecific monoclonal antibodies (bsMAb). The bsMAbs used in this system have affinity for the carcinoembryonic antigen on the one hand, and for indium-labeled diethylenetriaminepentaacetic acid (DTPA), on the other. Experimental Design: Stable quadroma clones producing bsMAb MN-14xDTIn-1 were isolated. LS174T tumor–bearing mice were injected with 1 to 100 μg of bsMAb followed by 1 to 60 ng of an 111In-labeled bivalent peptide [Ac-Phe-Lys(DTPA)-Tyr-Lys(DTPA)-NH2]. Mice were killed at 24 hours postinjection and the biodistribution of the radiolabel was determined. The biodistribution of diDTPA labeled with four different radionuclides (111In, 99mTc, nonresidualizing 125I, and residualizing 125I) was determined at various time points postinjection following pretargeting of LS174T tumors with bsMAb MN-14xDTIn-1. Results: Optimal tumor targeting was observed when tumors were pretargeted with 10 μg of bsMAb MN-14xDTIn-1 and when 6 ng of a radiolabeled peptide was given 72 hours later. The uptake of the four radiolabels in LS174T tumors at 4 hours postinjection was similar. However, at later time points, the 111In-label and residualizing 125I-label were better retained in the tumor than the nonresidualizing 125I label. Although the absolute uptake in the tumor (in terms of percentage of injected dose per gram of tissue) was 5-fold lower than the uptake obtained with directly labeled MN-14, the pretargeting strategy revealed much higher tumor-to-blood ratios due to the rapid clearance of the radiolabel from the circulation as compared with 111In-MN-14 (445 ± 90 and 5.3 ± 1.1, respectively, at 72 hours postinjection). Conclusions: Effective targeting of carcinoembryonic antigen-expressing tumors was achieved with a newly produced bispecific antibody. The 111In-labeled l-amino acid peptide and 125I-d-amino acid peptide were better retained in the tumor than the 99mTc- and 125I-l-amino acid peptide. Very high tumor-to-blood ratios were obtained due to rapid background clearance.