tbuckley/cabot-search huggingface dataset:
Rare Variant Mutations in Pregnancy-Associated or Peripartum Cardiomyopathy
Authors: Ana Morales, Thomas Painter, Ran Li, Jill D. Siegfried, Duanxiang Li, Nadine Norton, Ray E. Hershberger
Journal: Circulation (2010)

The term peripartum cardiomyopathy (PPCM) describes dilated cardiomyopathy (DCM) without known cause that occurs during the last month of pregnancy to 5 months postpartum. A related term, pregnancy-associated cardiomyopathy (PACM), refers to DCM onset earlier in pregnancy. Multiple studies have focused on inflammatory, immunologic, and environmental causes. An alternative hypothesis is that PPCM and PACM result, in part, from a genetic cause. In this study, we sought to test the hypothesis that rare DCM-associated mutations underlie a proportion of PACM or PPCM cases.A systematic search of our DCM database designed for family-based genetic studies was undertaken for cases associated with pregnancy and the postpartum period; in the identified cases, clinical and molecular genetic data, including exonic and near intron/exon boundaries of DCM genes, were analyzed. Of 4110 women from 520 pedigrees in the Familial Dilated Cardiomyopathy Research Project database, we identified 45 cases of PPCM/PACM. Evidence of familial clustering with DCM was present in 23 unrelated cases. Of the 45 cases, 19 had been resequenced for known DCM genes, and 6 carried mutations. Five had PPCM, of which 3 were familial with mutations found in MYH7, SCN5A, and PSEN2, and 2 were sporadic with mutations in MYH6 and TNNT2. One case had PACM and carried a mutation in MYBPC3.These findings suggest that a proportion of PPCM/PACM cases results from a genetic cause.
Anti- 2-glycoprotein I IgG antibodies from 1-year-old healthy children born to mothers with systemic autoimmune diseases preferentially target domain 4/5: might it be the reason for their 'innocent' profile?
Authors: L. Andreoli, C. Nalli, M. Motta, G. L. Norman, Z. Shums, S. Encabo, W. L. Binder, M. Nuzzo, M. Frassi, A. Lojacono, T. Avcin, P.-L. Meroni, A. Tincani
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Anti-β<sub>2</sub>-glycoprotein-I (anti-β<sub>2</sub>GPI) were demonstrated to be pathogenic in the antiphospholipid syndrome (APS). However, they can be detected in patients with no features of APS, especially those affected by systemic autoimmune diseases (SAD), and so in healthy children. It has been suggested that anti-β<sub>2</sub>GPI against domain 1 (D1) associate with thrombosis, while those recognising domain 4/5 (D4/5) are present in non-thrombotic conditions. <h3>Objective</h3> To evaluate the fine specificity of anti-β<sub>2</sub>GPI in adults and infants. <h3>Methods</h3> Three groups were examined—group A: 57 1-year-old healthy children born to mothers with SAD; group B: 33 children with atopic dermatitis; group C: 64 patients with APS. Subjects were selected based on positive anti-β<sub>2</sub>GPI IgG results. Serum samples were tested for anti-β<sub>2</sub>GPI IgG D1 and D4/5 using research ELISAs containing recombinant β<sub>2</sub>GPI domain antigens. <h3>Results</h3> Children (A and B) displayed preferential IgG reactivity for D4/5, whereas patients with APS were mainly positive for D1. No thrombotic events were recorded in groups A and B. <h3>Conclusions</h3> The specificity for D4/5 suggests that anti-β2GPI IgG production in children born to mothers with SAD is a process neither linked to systemic autoimmunity nor related to the maternal autoantibody status. This unusual fine specificity might, at least partially, account for the 'innocent' profile of such antibodies.
Heterogeneity for Stem Cell–Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer
Authors: So Yeon Park, Hee Eun Lee, Hailun Li, Michail Shipitsin, Rebecca Gelman, Kornelia Polyak
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To evaluate the expression of stem cell–related markers at the cellular level in human breast tumors of different subtypes and histologic stage. Experimental Design: We performed immunohistochemical analyses of 12 proteins [CD44, CD24, ALDH1, vimentin, osteonectin, EPCR, caveolin 1, connexin 43, cytokeratin 18 (CK18), MUC1, claudin 7, and GATA3] selected based on their differential expression in breast cancer cells with more differentiated and stem cell–like characteristics in 47 cases of invasive ductal carcinoma (IDC) only, 135 cases of IDC with ductal carcinoma in situ (DCIS), 35 cases of DCIS with microinvasion, and 58 cases of pure DCIS. We also analyzed 73 IDCs with adjacent DCIS to determine the differences in the expression of markers by histology within individual tumors. CD44+/CD24− and CD24−/CD24+ cells were detected using double immunohistochemistry. Results: CD44 and EPCR expression was different among the four histologic groups and was lower in invasive compared with in situ tumors, especially in luminal A subtype. The expression of vimentin, osteonectin, connexin 43, ALDH1, CK18, GATA3, and MUC1 differed by tumor subtype in some histologic groups. ALDH1-positive cells were more frequent in basal-like and HER2+ than in luminal tumors. CD44+/CD24− cells were detected in 69% of all tumors with 100% of the basal-like and 52% of HER2+ tumors having some of these cells. Conclusions: Our findings suggest that in breast cancer, the frequency of tumor cells positive for stem cell–like and more differentiated cell markers varies according to tumor subtype and histologic stage. Clin Cancer Res; 16(3); 876–87
Temporal Target Restriction of Olfactory Receptor Neurons by Semaphorin-1a/PlexinA-Mediated Axon-Axon Interactions
Authors: Lora B. Sweeney, Africa Couto, Ya-Hui Chou, Daniela Berdnik, Barry J. Dickson, Liqun Luo, Takaki Komiyama
Journal: Neuron (2007)
Cytokine Removal during Continuous Hemofiltration in Septic Patients
Authors: AN S. DE VRIESE, FRANCIS A. COLARDYN, JAN J. PHILIPPÉ, RAYMOND C. VANHOLDER, JOHAN H. DE SUTTER, NORBERT H. LAMEIRE
Journal: Journal of the American Society of Nephrology (1999)

Abstract. A potential application of the continuous renal replacement therapies is the extracorporeal removal of inflammatory mediators in septic patients. Cytokine elimination with continuous renal replacement therapies has been demonstrated in several clinical studies, but so far without important effects on their serum concentrations. Improved knowledge of the cytokine removal mechanisms could lead to the development of more efficient treatment strategies. In the present study, 15 patients with septic shock and acute renal failure were observed during the first 24 h of treatment with continuous venovenous hemofiltration (CVVH) with an AN69 membrane. After 12 h, the hemofilter was replaced and the blood flow rate ( Q B ) was switched from 100 ml/min to 200 ml/min or vice versa . Pre- and postfilter plasma and ultrafiltrate concentrations of selected inflammatory and anti-inflammatory cytokines were measured at several time points allowing the calculation of a mass balance. Cytokine removal was highest 1 h after the start of CVVH and after the change of the membrane (ranging from 25 to 43% of the prefilter amount), corresponding with a significant fall in the serum concentration of all cytokines. The inhibitors of inflammation were removed to the same extent as the inflammatory cytokines. Adsorption to the AN69 membrane appeared to be the main clearance mechanism, being most pronounced immediately after installation of a new membrane and decreasing steadily thereafter, indicating rapid saturation of the membrane. A Q B of 200 ml/min was associated with a 75% increase of the ultrafiltration rate and a significantly higher convective elimination and membrane adsorption than at a Q B of 100 ml/min. The results indicate that optimal cytokine removal with CVVH with an AN69 membrane could be achieved with a combination of a high Q B /ultrafiltration rate and frequent membrane changes.
IFN-α-2b–Induced Signal Transduction and Gene Regulation in Patient Peripheral Blood Mononuclear Cells Is Not Enhanced by a Dose Increase from 5 to 10 Megaunits/m2
Authors: Jason M. Zimmerer, Amy M. Lehman, Amy S. Ruppert, Carl W. Noble, Thomas Olencki, Michael J. Walker, Kari Kendra, William E. Carson
Journal: Clinical Cancer Research (2008)

The precise molecular targets of IFN-alpha therapy of melanoma are unknown but likely involve signal transducer and activator of transcription (STAT) 1 signal transduction within host immune effector cells. We hypothesized that intermediate and high doses of IFN-alpha would be equally effective in activating patient immune cells.Eleven metastatic melanoma patients who were enrolled in a clinical trial of bevacizumab in combination with escalating doses of IFN-alpha-2b (5 megaunits/m(2) and then 10 megaunits/m(2)) were included in the study. Peripheral blood mononuclear cells (PBMC) were procured from patient blood just before therapy and again 1 h after each dose of IFN-alpha-2b and analyzed for the presence of phosphorylated STAT1, phosphorylated STAT2, and the induction of IFN-stimulated gene (ISG) transcripts.Phosphorylated STAT1 was significantly greater at the 5 megaunits/m(2) dose compared with the 10 megaunits/m(2) dose of IFN-alpha-2b (P = 0.02). In contrast, no significant difference in phosphorylated STAT2 was observed at a dose of 5 megaunits/m(2) compared with 10 megaunits/m(2) (P = 0.20). There were also no significant differences in the induction of ISGs within PBMCs between the two doses (P > 0.4 for all ISGs). Suppressor of cytokine signaling 1 and 3 (two inhibitors of IFN-alpha signaling) transcripts were significantly higher among patient PBMCs following the 10 megaunits/m(2) dose of IFN-alpha (P < 0.001).These results suggest that lower doses of IFN-alpha-2b are as effective as higher doses with respect to the induction of Janus-activated kinase-STAT signal transduction and the transcription of ISGs within immune effector cells.
Pentosan Polysulfate Prevents Glomerular Hypertension and Structural Injury Despite Persisting Hypertension in 5/6 Nephrectomy Rats
Authors: NORMA A. BOBADILLA, IVAN TACK, EDILIA TAPIA, LAURA G. SÁNCHEZ-LOZADA, JOSÉ SANTAMARÍA, FABIOLA JIMÉNEZ, LILIANE J. STRIKER, GARY E. STRIKER, JAIME HERRERA-ACOSTA
Journal: Journal of the American Society of Nephrology (2001)

Five/six nephrectomy induces systemic and glomerular hypertension, glomerulosclerosis, proteinuria, and tubulointerstitial fibrosis. Polysulfate pentosan (PPS) decreases mesangial proliferation and extracellular matrix accumulation. The aim of this study was to determine whether PPS prevents glomerular hemodynamic changes and renal damage. Micropuncture studies were performed in three groups of eight male Wistar rats. Two groups included rats with 5/6 nephrectomy—one of which was treated with PPS in drinking water (100 mg/kg body wt) and the second of which received normal drinking water—and the third group consisted of normal rats that served as controls. Five/six nephrectomy produced systemic hypertension, a 50% reduction in GFR, and a 67% increase in single-nephron GFR due to elevated glomerular pressure and single-nephron plasma flow as well as proteinuria. Hypertension persisted in PPS-treated animals. Despite a similar reduction in GFR, PPS prevented the rise in single-nephron GFR, glomerular capillary hydrostatic pressure, and proteinuria. By morphometry, glomerular volume was increased by 46% and mesangial area by 94%. Fractional glomerular capillary area decreased by 24%. PPS prevented these changes. Tubular dilatation, epithelial cell atrophy, and increased interstitial area were largely prevented by PPS, as was the interstitial inflammatory infiltrate. These results suggest that the renal protection conferred by PPS was mediated both by prevention of glomerular hypertension as well as suppression of the inflammatory response. It was postulated that this was partly due to the preservation of a greater fraction of functional nephrons.
Overexpression, Amplification, and Androgen Regulation of TPD52 in Prostate Cancer
Authors: Mark A. Rubin, Sooryanarayana Varambally, Rameen Beroukhim, Scott A. Tomlins, Daniel R. Rhodes, Pamela L. Paris, Matthias D. Hofer, Martina Storz-Schweizer, Rainer Kuefer, Jonathan A. Fletcher, Bae-Li Hsi, Jennifier A. Byrne, Kenneth J. Pienta, Colin Collins, William R. Sellers, Arul M. Chinnaiyan
Journal: Cancer Research (2004)

Abstract Gains in the long arm of chromosome 8 (8q) are believed to be associated with poor outcome and the development of hormone-refractory prostate cancer. Based on a meta-analysis of gene expression microarray data from multiple prostate cancer studies (D. R. Rhodes et al., Cancer Res 2002;62:4427–33), a candidate oncogene, Tumor Protein D52 (TPD52), was identified in the 8q21 amplicon. TPD52 is a coiled-coil motif-bearing protein, potentially involved in vesicle trafficking. Both mRNA and protein levels of TPD52 were highly elevated in prostate cancer tissues. Array comparative genomic hybridization and amplification analysis using single nucleotide polymorphism arrays demonstrated increased DNA copy number in the region encompassing TPD52. Fluorescence in situ hybridization on tissue microarrays confirmed TPD52 amplification in prostate cancer epithelia. Furthermore, our studies suggest that TPD52 protein levels may be regulated by androgens, consistent with the presence of androgen response elements in the upstream promoter of TPD52. In summary, these findings suggest that dysregulation of TPD52 by genomic amplification and androgen induction may play a role in prostate cancer progression.
Predictive factors of total hip replacement due to primary osteoarthritis: a prospective 2 year study of 505 patients
Authors: L Gossec
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To determine the 2 year total hip replacement (THR) rate and to identify factors predictive of THR due to primary osteoarthritis (OA). <b>Methods:</b> A 2 year prospective cohort study. Inclusion criteria were primary hip OA, with a history of pain for 6 months, and patients' pain assessment of ⩾30 mm on a visual analogue scale (0–100 mm). Predictive factors of THR were identified by univariate then multivariate analysis using logistic regression. Potential predictors considered were demographic, radiographic (localisation and severity of OA), and patients' assessment of symptomatic severity of OA. <b>Results:</b> Of the 741 patients enrolled, 505 (68.2%) patients, mean (SD) age 64.0 (10.1) years, mean (SD) disease duration 4.7 (5.2) years, had complete 2 year data. There was no difference between the completer and non-completer groups. During follow up, 189/505 (37.4%) patients had a first THR. By multivariate analysis, predictors of THR were Kellgren-Lawrence radiographic grade (grade III: odds ratio (OR) = 3.3 (95% confidence interval (95% CI) 1.7 to 6.4); grade IV: OR = 5.3 (95% CI 2.6 to 10.8)), high mean patient global assessment during the first 6 months (OR = 2.2 (95% CI 1.4 to 3.2)), and previous non-steroidal anti-inflammatory drug (NSAID) intake (OR = 1.5 (95% CI 1.0 to 2.4)). For two of these factors together, OR = 3.0 (95% CI 1.6 to 5.9), for three factors together, OR = 5.6 (95% CI 2.6 to 12.2). <b>Conclusion:</b> The 2 year rate of THR was high in this group of patients with painful hip OA: 37.4%. Radiological grade, mean patient global assessment, and the need for NSAIDs were predictive of THR.
Amiloride-insensitive Na+-H+ exchange
Authors: G Zerbini, A Maestroni, R Mangili, G Pozza
Journal: Journal of the American Society of Nephrology (1998)

Erythrocyte Na+-Li+ countertransport shows an increased activity in essential hypertension and diabetic nephropathy, but its nature remains unknown. This amiloride-insensitive membrane transport may not be a mode of operation of the amiloride-sensitive NHE1, the only Na+-H+ exchange isoform found in human erythrocytes. Whether an independent, although unknown, amiloride-insensitive isoform mediates Na+-Li+ countertransport is unclear. Na+-H+ exchange activity was measured in acid-loaded erythrocytes. Dimethylamiloride, a specific inhibitor of Na+-H+ exchange and phloretin, a known inhibitor of Na+-Li+ countertransport, gave a reduction in H+-driven Na+ influx (by 31 and 37%, respectively). This effect was additive, and a 66% reduction in H+-driven Na+ influx was found in the presence of both inhibitors. Internal acidification, a stimulus for Na+-H+ exchange, enhanced Na+-Li+ countertransport activity (from 287 +/- 55 to 1213 +/- 165 micromol x Lcell(-1) h(-1), mean +/- SEM, P = 0.003). This transport remained sensitive to phloretin under both conditions. Conversely, external acidification decreased Na+-Li+ countertransport activity (as expected for a Na+-H+ exchanger). Competition between internal H+ and Li+ or Na+ for a common binding site was present. Finally, similar kinetic parameters for external Na+ characterized Na+-Li+ countertransport and the phloretin-sensitive component of H+-driven Na+ influx. These findings suggest that both Na+-Li+ countertransport and the amiloride-insensitive, phloretin-sensitive component of H+-driven Na+ influx can be mediated by a previously unrecognized novel amiloride-insensitive Na+-H+ exchange isoform in human erythrocytes.
Ewing Sarcomas With <i>p53</i> Mutation or <i>p16/p14ARF</i> Homozygous Deletion: A Highly Lethal Subset Associated With Poor Chemoresponse
Authors: Hsuan-Ying Huang, Peter B. Illei, Zhiquan Zhao, Madhu Mazumdar, Andrew G. Huvos, John H. Healey, Leonard H. Wexler, Richard Gorlick, Paul Meyers, Marc Ladanyi
Journal: Journal of Clinical Oncology (2005)

EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES.We studied 60 patients with ES (stage: localized in 54, metastatic in six). All cases were confirmed to contain the EWS-FLI1 (29 type 1, 12 type 2, 14 other types) or EWS-ERG fusions (five cases). Homozygous deletion of p16/p14ARF, and p53 mutations were determined by fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) p53 GeneChip microarray hybridization, respectively.Eight cases (13.3%) contained point mutations of p53, and eight cases (13.3%) showed p16/p14ARF deletion, including one case with both alterations. Among 32 cases with data on histologic chemoresponse, all 10 with alterations in p53 or p16/p14ARF showed a poor chemoresponse (P = .03). Variables predicting poorer overall survival included p53 mutation alone (P < .001), either p53 or p16/p14ARF alteration (P < .001), and stage (P < .01). In multivariate analysis, alterations of p53 and/or p16/p14ARF as a single variable, was the most adverse prognostic factor (P < .001), followed by stage (P = .04). In a multivariate analysis with alterations of p53 and p16/p14ARF as separate variables, both were significant (P < .001 and P = .03, respectively). Six cases with p16/p14ARF deletion were also studied for co-deletion of the contiguous methylthioadenosine phosphorylase gene, and this was detected in four cases.Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse.
Gulstonian Lectures on Certain Points in the Study and Classification of Diseases of the Nervous System
Authors: J. H. Jackson
Journal: BMJ (1869)

AFTER some introductory remarks, the Lecturer urged that, whenever it is possible, we should study each case of nervous disease in a three-fold manner:-I, as it shows damage at a certain point in a sensori-motor tract (Organ); 2, as it is an instance of local change of some wide-spread Tissue; and, 3, as it is one of disorder of Function.He took the word organ to imply not only nervous centres, but-illustrating by motor or- gans-the nerves to the mnuscles which they are known to governi.He remarked, too, on the importance of considering the relations parts have by their arterial supply.Artelies give to parts which have no relation- ship by continuity of duties a relationship by community of nutrition.
970 FREE FATTY ACID INDUCE OXIDATIVE STRESS IN HEPG2-CELL. PROTECTIVE ROLE OF ANTI-OXIDANT SUBSTANCES AND ADIPONECTIN
Authors: G. Soardo, D. Donnini, C. Pagano, C. Milocco, L. Domenis, D. De Silvestri, D. Cappello, A.G. Dibenedetto, L.A. Sechi
Journal: Journal of Hepatology (2008)
<i>Gata2</i> is required for HSC generation and survival
Authors: Emma de Pater, Polynikis Kaimakis, Chris S. Vink, Tomomasa Yokomizo, Tomoko Yamada-Inagawa, Reinier van der Linden, Parham Solaimani Kartalaei, Sally A. Camper, Nancy Speck, Elaine Dzierzak
Journal: The Journal of Experimental Medicine (2013)

Knowledge of the key transcription factors that drive hematopoietic stem cell (HSC) generation is of particular importance for current hematopoietic regenerative approaches and reprogramming strategies. Whereas GATA2 has long been implicated as a hematopoietic transcription factor and its dysregulated expression is associated with human immunodeficiency syndromes and vascular integrity, it is as yet unknown how GATA2 functions in the generation of HSCs. HSCs are generated from endothelial cells of the major embryonic vasculature (aorta, vitelline, and umbilical arteries) and are found in intra-aortic hematopoietic clusters. In this study, we find that GATA2 function is essential for the generation of HSCs during the stage of endothelial-to-hematopoietic cell transition. Specific deletion of Gata2 in Vec (Vascular Endothelial Cadherin)-expressing endothelial cells results in a deficiency of long-term repopulating HSCs and intra-aortic cluster cells. By specific deletion of Gata2 in Vav-expressing hematopoietic cells (after HSC generation), we further show that GATA2 is essential for HSC survival. This is in contrast to the known activity of the RUNX1 transcription factor, which functions only in the generation of HSCs, and highlights the unique requirement for GATA2 function in HSCs throughout all developmental stages.
CONTROVERSIES IN THE TREATMENT OF CANCER OF THE BREAST
Authors: S M Swain, M E Lippman
Journal: Annual Review of Medicine (1987)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Judo, the gentle way
Authors: Nikos Malliaropoulos, Mike Callan, Babette Pluim
Journal: British Journal of Sports Medicine (2013)

<h3>Background</h3> A working projection in coil embolization of a cerebral aneurysm is usually determined using three-dimensional volume rendering digital subtraction angiography (3D VRDSA), in which the boundary between an aneurysm and its parent artery cannot be identified simultaneously on the front and back surfaces of the vessel. A new method was devised to obtain a more optimal working projection. <h3>Methods</h3> 83 patients with aneurysms being treated by embolization were retrospectively evaluated. An aneurysm was accurately distinguished from the parent artery by observation of front, back, proximal and distal sides of the vessel on 3D VRDSA (carving method). An optimal working projection with simultaneous identification of the front and back boundary lines was determined using a translucent vessel complex combined with the carved aneurysm. <h3>Results</h3> In 32 aneurysms (38.6%), the optimal working projection was consistent with the working projection that had been used during the procedure. In terminal type aneurysms, the angle difference between the optimal and actual working projections was significantly smaller than in the other types (p&lt;0.05). Aneurysms with a maximal diameter &lt;5 mm showed a significantly larger angle difference between the optimal and actual working projections than aneurysms with a maximal diameter ≥5 mm (p&lt;0.05). <h3>Conclusion</h3> In more than half of the patients, the actual working projection was inaccurate. The carving method might be useful to determine working projections, especially for aneurysms other than the terminal type and/or those with a maximal diameter &lt;5 mm.