tbuckley/cabot-search huggingface dataset:
Preoperative abdominopelvic computed tomographic prediction of optimal cytoreduction in epithelial ovarian carcinoma.
Authors: B E Nelson, A T Rosenfield, P E Schwartz
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study was undertaken to assess the ability of computed tomography (CT) to predict the likelihood of optimal primary tumor cytoreduction in women with epithelial ovarian carcinoma. PATIENTS AND METHODS Fifty-one women with preoperative CT and a histologic diagnosis of epithelial ovarian carcinoma following primary tumor operation by a gynecologic oncologist were identified. Forty-two CT scans were retrospectively analyzed. CT findings of attachment of the omentum to the spleen or disease greater than 2 cm on the diaphragm, liver surface, or parenchyma, pleura, mesentery, gallbladder fossa, or suprarenal paraaortic nodes were coded to represent unresectable disease. CT results were compared with surgical outcome. RESULTS Twenty-nine of 42 (69%) patients underwent optimal cytoreduction to less than 2 cm residual disease. Successful cytoreduction was accomplished in 23 of 24 patients who fulfilled CT criteria for cytoreduction and six of 18 with CT criteria predictive of inability to perform cytoreduction. CT was highly sensitive for detection of ascites, mesenteric, and omental disease, but was poor for detection of liver involvement, omental attachment to the spleen, gallbladder fossa disease, and peritoneal nodules smaller than 2 cm. The CT findings accurately predicted surgical outcome with a sensitivity of 92.3% and specificity of 79.3%. The positive predictive value was 67% and the negative predictive value was 96%. CONCLUSION CT scan is an accurate method for the prediction of successful surgical cytoreduction and may have utility in the decision to offer neoadjuvant chemotherapy to certain medically disabled patients, a hypothesis currently under evaluation.
Differential expression of vascular endothelial growth factor A, its receptors VEGFR-1, -2, and -3 and co-receptors neuropilin-1 and -2 does not predict bevacizumab response in human astrocytomas
Authors: Peter Baumgarten, Anna-Eva Blank, Kea Franz, Elke Hattingen, Maika Dunst, Pia Zeiner, Katharina Hoffmann, Oliver Bähr, Lisa Mäder, Benjamin Goeppert, Marcia Machein, Volker Seifert, Joachim P. Steinbach, Karl H. Plate, Patrick N. Harter, Michel Mittelbronn
Journal: Neuro-Oncology (2015)

A major hallmark of malignant progression in human astrocytomas is the formation of new blood vessels. Antiangiogenic therapy using the anti-vascular endothelial growth factor (VEGF)-antibody bevacizumab leads to increased progression-free survival in glioblastoma patients but does not influence their overall survival. To date, it is unclear why antiangiogenic therapy fails in many glioblastoma patients, while a small subpopulation profits considerably from this treatment. The aim of our study was to determine the expression of VEGF-A and its (co-) receptors by immunohistochemistry and to test the association with patient survival in 350 glioma patients. Additionally, VEGF-A expression was analyzed by in-situ hybridization. In 18 patients, the protein expression was compared with the bevacizumab response according to extended and modified RANO criteria. We found a heterogeneous expression pattern of VEGF and its receptors in glioblastoma patients with significantly lower levels in WHO grade II and III tumors and normal-appearing brain tissue (P < .001). Pilocytic astrocytomas (WHO grade I) showed significantly higher VEGFR-1, -2 and neuropilin-1 levels as compared to WHO grade II and III astrocytomas (P < .01) but at lower levels than glioblastomas. The expression of neuropilin-2 was low in all tumors. There was neither a significant correlation between protein expression and patient survival nor between protein levels and bevacizumab response after modified RANO criteria. Since our data indicate that beneficial response to bevacizumab treatment is independent of the expression of VEGF-A and its (co-) receptors, further investigation is needed to decipher the underlying mechanisms of antiangiogenic treatment response.
Comparison of the bindin proteins of Strongylocentrotus franciscanus, S. purpuratus, and Lytechinus variegatus: sequences involved in the species specificity of fertilization.
Authors: J E Minor, D R Fromson, R J Britten, E H Davidson
Journal: Molecular Biology and Evolution (1991)

Bindin is the sea urchin sperm acrosomal protein that is responsible for the species-specific adhesion of the sperm to the egg. Two new bindin cDNA sequences that contain the entire open reading frame for the binding precursor are reported: one for Strongylocentrotus franciscanus and one for Lytechinus variegatus. Both contain inverted repetitive sequences in their 3' untranslated regions, and the S. franciscanus cDNA contains an inverted repetitive sequence match between the 5' untranslated region and the coding region. The middle third of the mature bindin sequence is highly conserved in all three species, and the flanking sequences share short repeated sequences that vary in number between the species. Cross-fertilization data are reported for the species S. purpuratus, S. franciscanus, L. variegatus, and L. pictus. A barrier to cross-fertilization exists between the sympatric Strongylocentrotus species, but there is no barrier between the allopatric Lytechinus species.
Recovering phylogenetic signal from DNA sequences: relationships within the corvine assemblage (class aves) as inferred from complete sequences of the mitochondrial DNA cytochrome-b gene.
Authors: K Helm-Bychowski, J Cracraft
Journal: Molecular Biology and Evolution (1993)

Phylogenetic analysis of cytochrome-b sequences and cranial osteological characters for nine genera of corvine passerine birds supports the hypothesis that the two major groups of birds of paradise, the manucodines and paradisaeinines, constitute a monophyletic group and that their postulated sister group is the Corvidae (crows, jays, and allies). The data are also consistent with the hypothesis that the bowerbirds are not closely related to the birds of paradise but instead lie near the base of the corvine assemblage. The corvine radiation exemplifies a case of multiple star phylogenies embedded within a major clade, with the branching pattern characterized by very short internodal divergence times. Such histories are difficult to resolve no matter what type of data is employed, because little change accumulates between branching events. With respect to sequence data, reconstructed tree topologies are sensitive to the choice of outgroup and to the method of analysis (e.g., transversion vs. global parsimony). In such cases, assessing the "reliability" of a best-fit or most-parsimonious tree inferred from any particular data set becomes problematic. Statistical tests of tree topologies that depend on random sampling of characters will generally be inconclusive in that all cladistic components will tend to be poorly supported because relatively few character-state changes will be recorded between branching events. It is suggested, on the other hand, that congruence in cladistic signal across different data sets may be a potentially more useful method for evaluating the reliability of the signal of any one data set. Resolution of star phylogenies will probably be possible only if DNA sequence and morphological characters are combined in a single analysis.
Clinical outcomes following stent placement in refractory benign esophageal stricture: a systematic review and meta-analysis
Authors: Lorenzo Fuccio, Cesare Hassan, Leonardo Frazzoni, Rossella Miglio, Alessandro Repici
Journal: Endoscopy (2015)

<b>Background and aims:</b> The management of refractory benign esophageal strictures (RBESs) is challenging. Stent placement has been proposed as a possible rescue strategy. We performed a systematic review and meta-analysis to examine the efficacy of this strategy in the long-term resolution of dysphagia. <b>Methods: </b>PubMed, SCOPUS, and Google Scholar were searched (up to January 2015). Studies recruiting adults with RBES treated with stent placement were eligible. The success, adverse event, and migration rates were pooled by means of a random-effect model to obtain odds with a 95 % confidence interval (CI). <b>Results: </b>Eighteen studies (444 patients) were eligible for inclusion. The pooled clinical success rate was 40.5 % (95 %CI 31.5 % – 49.5 %), yielding odds of 0.68 (95 %CI 0.46 – 0.98) with high heterogeneity (I<sup>2</sup> = 65.0 %). The meta-regression analysis showed stricture etiology as the only influencing factor. Treatment with self-expanding plastic (SEPSs) and metal stents (SEMSs) did not result in significantly higher success rates than treatment with biodegradable stents (BDSs) (46.2 % vs. 40.1 % vs. 32.9 %, respectively). The migration rate was 28.6 % (95 %CI 21.9 % – 37.1 %), yielding odds of 0.40 (95 %CI 0.28 – 0.59), with migration rates for SEPSs and SEMSs reported as being not significantly higher than BDSs (33.3 % vs. 31.5 % vs. 15.3 %, respectively). The adverse event rate was 20.6 % (95 %CI 15.3 % – 28.1 %), yielding odds of 0.26 (95 %CI 0.18 – 0.39) with no significant difference between stent types (19.4 % vs. 21.9 % vs. 21.9 %, respectively). <b>Conclusions: </b>Stent placement in patients with RBES is effective in about 40 % of cases. Further studies should investigate whether the clinical success rate varies according to the stricture etiology. (PROSPERO registration number: CRD42015019017.)
Patterns of Treatment and Rates of Admission in a Specialist Oncology Clinic
Authors: M. Doherty, L. Keenan, J. McHugh, M.M. O'Brien, A. O'Reilly, C. Reilly, E. Hannan, P.La Harpe De Golden, E. O'Connor, D. Hannon, N. Tierney, R. Henderson, P. Doyle, C. McHugh, W.M. Grogan, B. Hennessy, P. Morris, O.S. Breathnach
Journal: Annals of Oncology (2014)
CD30+ expression in Peripheral T-cell lymphomas (PTCLs): A subset analysis from the international, prospective T-Cell Project.
Authors: Massimo Federico, Monica Bellei, Stefano Luminari, Steven M. Horwitz, Silvia Montoto, Emanuele Zucca, Stefano A Pileri, Young-Hyeh Ko, Pier Luigi Zinzani, Joseph M. Connors, Francine M. Foss, Aaron Polliack, Maria Elena Cabrera, Won Seog Kim, Michele Spina, Carmino Antonio De Souza, Sabela Bobillo Varela, Ivan Dlouhy, Ranjana H. Advani, Julie Vose
Journal: Journal of Clinical Oncology (2015)

8552 Background: CD30 is a member of TNF-alpha receptor family that might have important therapeutic implications with the advent of targeted therapies. Several PTCLs subtypes have been reported in literature to be associated to variable CD30 expression. We investigated the frequency of CD30 expression among PTCLs subtypes registered in the T-Cell Project and correlated it with clinical features and outcome. Methods: The T-cell Project is a prospective, international study in patients (pts) with newly diagnosed aggressive PTCLs. Clinical, laboratory and disease localization data at diagnosis as well as therapy details and follow-up information are collected at a dedicated website via secure HTTP protocols. Central review of diagnostic biopsy is planned. Results: From Sept 2006 to Jan 2015, 1308 pts were registered in the T-Cell Project by 73 sites from 14 countries world-wide. As from the 792 pathology forms filled out by site local staff CD30 expression was tested in 490 pts (62%) and reported as CD30+ in 349 (71%) and CD30- in 141 (29%). Frequency of CD30 expression in different subtypes is shown in the Table. CD30+ pts tended to be younger (54 vs 58 yrs, P = .03) with less extranodal involvement (65% vs 78%, P = .01) than CD30-. CHOP like regimens were the most common irrespective of CD30 status (63% in both groups, P = 1.0). In the group of pts with any histology but ALCL, no difference in CR rate (44% vs 51%, P = .26), 5-yr PFS (29% vs 22%, P = .57) and OS (44% vs 29%, P = .17) was observed between CD30+ and CD30- pts. Brentuximab use in first line was noted in only 5 pts enrolled in clinical trials. Conclusions: Data from the T-cell project confirm that CD30 is expressed in many PTCLs other than ALCL, thus suggesting a routine assessment for all PTCLs. Again, this analysis suggests that CD30 expression has no prognostic significance. The very limited use of anti CD30 targeted therapy in this sample doesn't allow to establish the predictive value of CD30 expression in PTCLs. CD30- N, % CD30+ N, % PTCL,NOS 85, 41 120, 59 AITL 16, 42 50, 76 ALCL 0, 0 145, 100 NKTCL 13, 48 14, 52 EATL 11, 46 13, 54 Other 16, 70 7, 30
Humoral immune responses in CD40 ligand-deficient mice.
Authors: B R Renshaw, W C Fanslow, R J Armitage, K A Campbell, D Liggitt, B Wright, B L Davison, C R Maliszewski
Journal: The Journal of Experimental Medicine (1994)

Individuals with X-linked hyper-IgM syndrome fail to express functional CD40 ligand (CD40L) and, as a consequence, are incapable of mounting protective antibody responses to opportunistic bacterial infections. To address the role of CD40L in humoral immunity, we created, through homologous recombination, mice deficient in CD40L expression. These mice exhibited no gross developmental deficiencies or health abnormalities and contained normal percentages of B and T cell subpopulations. CD40L-deficient mice did display selective deficiencies in humoral immunity; basal serum isotype levels were significantly lower than observed in normal mice, and IgE was undetectable. Furthermore, the CD40L-deficient mice failed to mount secondary antigen-specific responses to immunization with a thymus-dependent antigen, trinitrophenol-conjugated keyhole limpet hemocyanin (TNP-KLH). By contrast, the CD40L-deficient mice produced antigen-specific antibody of all isotypes except IgE in response to the thymus-independent antigen, DNP-Ficoll. These results underscore the requirement of CD40L for T cell-dependent antibody responses. Moreover, Ig class switching to isotypes other than IgE can occur in vivo in the absence of CD40L, supporting the notion that alternative B cell signaling pathways regulate responses to thymus-independent antigens.
Loss of parkin promotes lipid rafts-dependent endocytosis through accumulating caveolin-1: implications for Parkinson’s disease
Authors: Seon-Heui Cha, Yu Ree Choi, Cheol-Ho Heo, Seo-Jun Kang, Eun-Hye Joe, Ilo Jou, Hwan-Myung Kim, Sang Myun Park
Journal: Molecular Neurodegeneration (2015)

Parkinson's disease (PD) is characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor dysfunctions. While most PD is sporadic in nature, a significant subset can be linked to either autosomal dominant or recessive mutations. PARK2, encoding the E3 ubiquitin ligase, parkin, is the most frequently mutated gene in autosomal recessive early onset PD. It has recently been reported that PD-associated gene products such as PINK1, α-synuclein, LRRK2, and DJ-1, as well as parkin associate with lipid rafts, suggesting that the dysfunction of these proteins in lipid rafts may be a causal factor of PD. Therefore here, we examined the relationship between lipid rafts-related proteins and parkin. We identified caveolin-1 (cav-1), which is one of the major constituents of lipid rafts at the plasma membrane, as a substrate of parkin. Loss of parkin function was found to disrupt the ubiquitination and degradation of cav-1, resulting in elevated cav-1 protein level in cells. Moreover, the total cholesterol level and membrane fluidity was altered by parkin deficiency, causing dysregulation of lipid rafts-dependent endocytosis. Further, cell-to-cell transmission of α-synuclein was facilitated by parkin deficiency. Our results demonstrate that alterations in lipid rafts by the loss of parkin via cav-1 may be a causal factor of PD, and cav-1 may be a novel therapeutic target for PD.
Renal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced Hypertension
Authors: Rebecca A. Lazelle, Belinda H. McCully, Andrew S. Terker, Nina Himmerkus, Katharina I. Blankenstein, Kerim Mutig, Markus Bleich, Sebastian Bachmann, Chao-Ling Yang, David H. Ellison
Journal: Journal of the American Society of Nephrology (2015)

Tacrolimus is a widely used immunosuppressive drug that inhibits the phosphatase calcineurin when bound to the 12 kDa FK506-binding protein (FKBP12). When this binding occurs in T cells, it leads to immunosuppression. Tacrolimus also causes side effects, however, such as hypertension and hyperkalemia. Previously, we reported that tacrolimus stimulates the renal thiazide-sensitive sodium chloride cotransporter (NCC), which is necessary for the development of hypertension. However, it was unclear if tacrolimus-induced hypertension resulted from tacrolimus effects in renal epithelial cells directly or in extrarenal tissues, and whether inhibition of calcineurin was required. To address these questions, we developed a mouse model in which FKBP12 could be deleted along the nephron. FKBP12 disruption alone did not cause phenotypic effects. When treated with tacrolimus, however, BP and the renal abundance of phosphorylated NCC were lower in mice lacking FKBP12 along the nephron than in control mice. Mice lacking FKBP12 along the nephron also maintained a normal relationship between plasma potassium levels and the abundance of phosphorylated NCC with tacrolimus treatment. In cultured cells, tacrolimus inhibited dephosphorylation of NCC. Together, these results suggest that tacrolimus causes hypertension predominantly by inhibiting calcineurin directly in cells expressing NCC, indicating thiazide diuretics may be particularly effective for lowering BP in tacrolimus-treated patients with hypertension.
Lamin B autoantibodies in sera of certain patients with systemic lupus erythematosus.
Authors: W H Reeves, N Chaudhary, A Salerno, G Blobel
Journal: The Journal of Experimental Medicine (1987)

Sera from four patients with systemic lupus erythematosus containing antibodies that yield nuclear rim staining of HEp-2 cells by indirect immunofluorescence were identified and characterized. Each serum contained autoantibodies reacting strongly with lamin B on western blots. One of the four sera displayed weaker reactivity with lamins A and C, while the other three displayed only minimal reactivity with lamins A and C. Titers of antilamin antibodies ranged from 1:1,250 to 1:36,250. Two of the sera also reacted at a dilution of 1:20 with cytoplasmic filaments of PTK-2 cells, suggesting that a small fraction of the autoantibodies in these sera may bind to alpha-helical domains of the lamins that are homologous to those of intermediate filaments. The majority of the antilamin antibodies in these patients' sera are specific for portions of the lamin B molecule that are not homologous to lamins A and C, however. The findings suggest that autoantibodies to the nuclear lamina may, in some instances, be responsible for a rim pattern in the fluorescent antinuclear antibody assay. In addition, autoantibodies to the nuclear lamina in sera of certain patients with systemic lupus erythematosus may be useful for defining the molecular structure and biological functions of lamin B, as well as for studying mechanisms of autoimmunity.
Relationship between immune gene signatures and clinical response to PD-1 blockade with pembrolizumab (MK-3475) in patients with advanced solid tumors
Authors: Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, Andrew Albright, Jonathan Cheng, S Peter Kang, Scot Ebbinghaus, Jennifer Yearley, Veena Shankaran, Tanguy Seiwert, Antoni Ribas, Terri McClanahan
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immune checkpoint inhibition with anti–PD-1 monoclonal antibodies such as pembrolizumab has demonstrated robust, durable anti-tumor activity against many advanced malignancies. We analyzed immune-related gene expression profiles in pembrolizumab-treated patients with advanced
<i>Boy and the Candle</i>
Authors: Thomas B. Cole
Journal: JAMA (2015)

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Airway Nitric Oxide Diffusion in Asthma
Authors: PHILIP E. SILKOFF, JIMMIE T. SYLVESTER, NOE ZAMEL, SOLBERT PERMUTT
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

If the nitric oxide (NO) diffusing capacity of the airways (DNO) is the quantity of NO diffusing per unit time into exhaled gas (q) divided by the difference between the concentration of NO in the airway wall (Cw) and lumen, then DNO and C(w) can be estimated from the relationship between exhaled NO concentration and expiratory flow. In 10 normal subjects and 25 asthmatic patients before and after treatment with inhaled beclomethasone, DNO averaged 6.8 +/- 1.2, 25.5 +/- 3.8, and 22.3 +/- 2.7 nl/s/ppb x 10(-3), respectively; C(w) averaged 149 +/- 31.9, 255.3 +/- 46.4, and 108.3 +/- 14.3 ppb, respectively; and DNOC(w) (the maximal from diffusion) averaged 1,020 +/- 157.5, 6,512 +/- 866, and 2,416 +/- 208.5 nl/s x 10(-3), respectively. DNO and DNOC(w) in the asthmatic subjects before and after steroids were greater than in normal subjects (p < 0.0001), but C(w) was not different. Within asthmatic subjects, steroids caused C(w) and DNOC(w) to fall (p < 0.0001), but DNO was unchanged. DNOC(w) after steroids, presumably reflecting maximal diffusion of constitutive NO, was positively correlated with methacholine PC(20) and FEV(1)/FVC before or after steroids. The increased DNO measured in asthmatic patients may reflect upregulation of nonadrenergic, noncholinergic, NO-producing nerves in airways in compensation for decreased sensitivity of airway smooth muscle to the relaxant effects of endogenous NO.
Low Rates of Malignancy and Mortality in Asymptomatic Patients With Suspected Neoplastic Pancreatic Cysts Beyond 5 Years of Surveillance
Authors: Wilson T. Kwong, Gordon C. Hunt, Syed M. Fehmi, Gordon Honerkamp-Smith, Ronghui Xu, Robert D. Lawson, Raymond S. Tang, Ingrid Gonzalez, Mary L. Krinsky, Andrew Giap, Thomas J. Savides
Journal: Clinical Gastroenterology and Hepatology (2015)
Retinal blood flow in nonischemic central retinal vein occlusion11The following three letters address an article that appeared in the May 1998 issue of the Journal:Chen H-C, et al. Retinal blood flow in nonischemic central retinal vein occlusion. (Ophthalmology 1998;105:772–5)
Authors: Michael G Quigley
Journal: Ophthalmology (1999)