tbuckley/cabot-search huggingface dataset:
Comparison of CA-125 and Standard Definitions of Progression of Ovarian Cancer in the Intergroup Trial of Cisplatin and Paclitaxel Versus Cisplatin and Cyclophosphamide
Authors: Gordon J.S. Rustin, Petra Timmers, Ann Nelstrop, Gavin Shreeves, Soeren M. Bentzen, Benoit Baron, Martine J. Piccart, Kamma Bertelsen, Gavin Stuart, James Cassidy, Elizabeth Eisenhauer
Journal: Journal of Clinical Oncology (2005)

Purpose A definition for progression of ovarian cancer has been proposed based on either a confirmed doubling of CA-125 levels from the upper limit of normal or from the nadir level if levels are persistently elevated. Retrospectively, we determined whether the use of this CA-125 definition in a randomized trial would have shown the same magnitude of difference between the treatment arms as was shown when the standard progression definition was used. Patients and Methods A retrospective analysis was performed on 680 patients in the Taxol Intergroup Trial with advanced epithelial ovarian carcinoma, of whom 628 were assessable according to CA-125. The date of progression according to clinical or radiologic criteria was compared with the date of progression according to CA-125. Results Of the 628 patients assessable for both definitions, 556 clinical or radiologic progressions were determined compared with 389 according to the CA-125 definition. There was a highly significant difference in the hazard of progression between the paclitaxel and cisplatin arm (TP) compared with the cyclophosphamide and cisplatin arm (CP) when either standard or CA-125 criteria were used to define progression (standard, P = .002; CA-125, P = .011). The hazard ratio of TP/CP over time was similar when comparing the different methods of defining progression. Conclusion The results of this analysis show that the magnitude of the therapeutic benefit was similar whether CA-125 or standard criteria were used to define progression.
ADJUVANT TAMOXIFEN IN EARLY BREAST CANCER: OCCURRENCE OF NEW PRIMARY CANCERS
Authors: Tommy Fornander, Björn Cedermark, Anders Mattsson, Lambert Skoog, Tolle Theve, Jutta Askergren, LabsE. Rutqvist, Ulla Glas, Claes Silfverswärd, Anders Somell, Nils Wilking, Marie-Louise Hjalmar
Journal: The Lancet (1989)
Overexpression of Stromal Cell–Derived Factor 1 and Its Receptor CXCR4 Induces Autocrine/Paracrine Cell Proliferation in Human Pituitary Adenomas
Authors: Federica Barbieri, Adriana Bajetto, Ralf Stumm, Alessandra Pattarozzi, Carola Porcile, Gianluigi Zona, Alessandra Dorcaratto, Jean-Louis Ravetti, Francesco Minuto, Renato Spaziante, Gennaro Schettini, Diego Ferone, Tullio Florio
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Hypothalamic or locally produced growth factors and cytokines control pituitary development, functioning, and cell division. We evaluated the expression of the chemokine stromal cell–derived factor 1 (SDF1) and its receptor CXCR4 in human pituitary adenomas and normal pituitary tissues and their role in cell proliferation. Experimental Design: The expression of SDF1 and CXCR4 in 65 human pituitary adenomas and 4 human normal pituitaries was determined by reverse transcription-PCR, immunohistochemistry, and confocal immunofluorescence. The proliferative effect of SDF1 was evaluated in eight fibroblast-free human pituitary adenoma cell cultures. Results: CXCR4 mRNA was expressed in 92% of growth hormone (GH)-secreting pituitary adenomas (GHoma) and 81% of nonfunctioning pituitary adenomas (NFPA), whereas SDF1 was identified in 63% and 78% of GHomas and NFPAs, respectively. Immunostaining for CXCR4 and SDF1 showed a strong homogenous labeling in all tumoral cells in both GHomas and NFPAs. In normal tissues, CXCR4 and SDF1 were expressed only in a subset of anterior pituitary cells, with a lower expression of SDF1 compared with its cognate receptor. CXCR4 and SDF1 were not confined to a specific cell population in the anterior pituitary but colocalized with discrete subpopulations of GH-, prolactin-, and adrenocorticorticotropic hormone–secreting cells. Conversely, most of the SDF1-containing cells expressed CXCR4. In six of eight pituitary adenoma primary cultures, SDF1 induced a statistically significant increase in DNA synthesis that was prevented by the treatment with the CXCR4 antagonist AMD3100 or somatostatin. Conclusions: CXCR4 and SDF1 are overexpressed in human pituitary adenomas and CXCR4 activation may contribute to pituitary cell proliferation and, possibly, to adenoma development `in humans.
Transcutaneous Doppler ultrasound measurement of superior mesenteric artery blood flow in man.
Authors: M I Qamar, A E Read, R Skidmore, J M Evans, P N Wells
Journal: Gut (1986)

A duplex scanner which consists of a real time two dimensional scanner and a pulsed Doppler flowmeter was used to measure superior mesenteric blood flow in 70 healthy subjects. By processing the Doppler shift signals, the instantaneous average Doppler shift frequency and then the instantaneous average velocity of the flow rate were calculated. Both diameter of the vessel and angle between vessel and beam were measured from real time imaging. The mean (+/- standard error of the mean) of the superior mesenteric blood flow was 517 +/- 19 ml/min. There was neither significant difference in flow between sexes, nor correlation between flow and age (r = 0.042). The mean of coefficients of variability were 6.8% over the short term, and 8.2% in long term studies.
Effect of the p38 kinase inhibitor, SB 203580, on sephadex induced airway inflammation in the rat
Authors: M. Birrell, D. Hele, K. McCluskie, S. Webber, M. Foster, M.G. Belvisi
Journal: European Respiratory Journal (2000)

SB 203580 is a pyridinyl imidazole compound which inhibits the release of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), in vitro and in vivo by inhibiting p38 mitogen-activated protein kinase (MAPK). The present study investigated the effects of SB 203580 in a model of airway inflammation induced by the topical administration of Sephadex into the rat airways. This inflammatory response is characterized by the development of lung oedema, airway tissue inflammatory cell recruitment and an increase in lung TNF-alpha and IL-1beta levels. Sephadex-induced lung oedema was accompanied by a significant increase in lung tissue TNF-alpha but not IL-1beta levels. There was also a significant increase in lung tissue macrophages and an increase in eosinophils which did not reach significance. SB 203580 administration significantly inhibited lung oedema (ED50=18 mg x kg(-1)) in a dose-related manner but was without significant effect on lung tissue cell recruitment or cytokine levels. These data suggest that the increase in tumour necrosis factor-alpha and lung oedema are separate processes which both contribute to Sephadex pathology. Furthermore, the inhibitory effect of SB 203580 on Sephadex-induced lung oedema suggests that p38 kinase inhibitors may be of use in pulmonary pathologies in which lung oedema is a feature.
Assessment of a Retrovirus Sequence and Other Possible Risk Factors for the Chronic Fatigue Syndrome in Adults
Authors: Ali S. Khan
Journal: Annals of Internal Medicine (1993)

To assess whether the human T-lymphotropic virus type II (HTLV-II) gag gene sequence, a purportedly new laboratory marker of the chronic fatigue syndrome (CFS), and other possible risk factors for CFS, particularly those associated with retroviral transmission, are associated with well-characterized CFS.Two matched case-control studies.The metropolitan Atlanta area.Twenty-one patients with CFS who were identified by the Centers for Disease Control and Prevention CFS surveillance system; 21 CDC employee controls (laboratory study) and 42 neighborhood controls (risk-factor study) who were matched to patients by age, race, and gender.Peripheral blood lymphocytes and leukocytes were assayed for the HTLV-II gag gene sequence by polymerase chain reaction and specific Southern blot hybridization. Questionnaires elicited demographic and clinical information and a history of exposures associated with retrovirus transmission (for example, blood transfusions, sexual practices, intravenous drug use).All patients were white and 86% were female. The median age at illness onset was 34 years (range, 16 to 51 years). The HTLV-II gag gene sequence was not identified in the blood of any patient or control under conditions in which the appropriate assay controls were positive. No statistical differences were observed between patients and controls in frequency of blood transfusions (10% compared with 7%), median number of sex partners before illness (3 compared with 3), bisexual or homosexual behavior (14% compared with 7%), intravenous drug use (0% compared with 0%), and other factors associated with retroviral infection.The HTLV-II gag gene sequence was not a marker for CFS in this small study of well-defined patients, nor did other characteristics of the patients and controls support the hypothesis that a retrovirus, transmitted by usual modes, was a cause of CFS.
Fibronectin mediates Treponema pallidum cytadherence through recognition of fibronectin cell-binding domain.
Authors: D D Thomas, J B Baseman, J F Alderete
Journal: The Journal of Experimental Medicine (1985)

The specificity of the interaction between Treponema pallidum and fibronectin was demonstrated. Treatment of host cells with only antifibronectin sera and not anticollagen or antilaminin sera, inhibited treponemal cytadsorption. Incubation of fibronectin-coated coverslips with monoclonal antibody to the cell-binding domain of fibronectin reduced treponemal attachment to the same extent as antifibronectin serum. Both iodinated fibronectin and iodinated cell-binding domain bound to T. pallidum in a saturable manner. Specificity of the T. pallidum association with the cell-binding domain was the most effective inhibitor of the binding of either radioiodinated cell-binding domain or fibronectin to T. pallidum. Scatchard analysis gave Kd on the order of 10(-7) M for both cell-binding domain and fibronectin binding to T. pallidum, consistent with the high affinity interaction of these organisms with host cell surfaces. Finally, the same level of attachment of treponemes was achieved on coverslips coated with cell-binding domain as that observed for organisms incubated with fibronectin, indicating that the cell-binding domain polypeptide is functionally identical to fibronectin in mediating T. pallidum adherence.
CXCL12 Does Not Attract CXCR4+ Human Metastatic Neuroblastoma Cells: Clinical Implications
Authors: Irma Airoldi, Lizzia Raffaghello, Erich Piovan, Claudia Cocco, Barbara Carlini, Alberto Amadori, Maria Valeria Corrias, Vito Pistoia
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The role of CXCR4 in bone marrow localization of neuroblastoma cells has been recently proposed. The aim of this study was to investigate the expression and chemotactic functionality of CXCR4 in human metastatic neuroblastoma cells isolated from the bone marrow and, for comparison, in a panel of neuroblastoma cell lines. Experimental Design: CXCR4 expression and chemotactic functionality were investigated in metastatic neuroblastoma cells isolated from patient bone marrow and in neuroblastoma cell lines. The former cells were isolated as CD45− or GD2+ cells by immunomagnetic bead manipulation. Chemotactic assays were done in a transwell system. Regulator of G protein signaling expression was investigated by reverse transcription-PCR. Results: Metastatic neuroblastoma cells consistently expressed CXCR4, which was also detected in 5 of 10 neuroblastoma cell lines. CXCL12 did not stimulate the chemotaxis of primary tumor cells or cell lines in either normoxia or hypoxia, irrespective of CXCR4 up-regulation detected under the latter condition. Accordingly, neuroblastoma cells failed to modulate filamentous actin and to activate mitogen-activated protein kinase upon treatment with CXCL12. RGS16 mRNA was consistently expressed in primary tumor cells and cell lines, but its down-regulation by RNA interference did not restore CXCR4 chemotactic functionality. Conclusions: These results show unambiguously that CXCR4 expressed in human metastatic neuroblastoma cells is not functional and do not support the clinical use of CXCR4 antagonists to prevent neuroblastoma metastasis.
Allergen‐avoidance measures in homes of house‐dust‐mite‐allergic asthmatic patients: effects of acaricides and mattress encasings
Authors: S. van der Heide, H. F. Kauffman, A. E. J. Dubois, J. G. R. de Monchy
Journal: Allergy (1997)

This double‐blind, placebo‐controlled study investigated whether the application of an acaricide (Acarosan®) on mattresses and on textile floor coverings in living rooms and bedrooms can contribute to improvement in lung function and airway hyperresponsiveness in 40 adult asthmatic patients sensitized to house‐dust mite. In a second group of 19 patients who refused chemical intervention, the clinical effects of application of allergen‐impermeable mattress encasings were studied. In all three treatment groups, Der p 1 levels in mattress dust were statistically significantly decreased after 12 months. However, this decrease was much greater in the group who received mattress encasings (final mean level 430 ng/g) than in groups with acaricide‐ or placebo‐treated mattresses (final mean levels 1730 and 2100 ng/g, respectively). Treatment of textile floors with either Acarosan or placebo chemical caused a statistically significant decrease in the level of the house‐dust‐mite allergen Der p 1 in floor dust. In the group with mattress encasings, no significant changes of floor dust Der p 1 were found. Airway hyperresponsiveness (as measured by the PC 20 histamine) improved significantly in the mattress cover group after 6 months. The Acarosan group also showed a small but statistically significant improvement after 12 months.
Peanut T Cell Epitope Discovery: Ara h1 and Ara h3
Authors: Manish Ramesh, Madhan Masilamani, George N. Konstantinou, Jay A. Lieberman, Hugh A. Sampson, Madhundra Sivakumar, Araya Yuenyongviwat, Mariona Pascal
Journal: Journal of Allergy and Clinical Immunology (2014)

Peptide-based immunotherapy is a viable modality that circumvents IgE-mediated adverse reactions. Here we identify candidate peptides of Ara h1 and 3 that display promiscuous binding to MHC class II and induce Th2 cytokine production by T cells. A two-step peptide screening process was employed. In silico MHC class II binding prediction was performed using NetMHCIIpan 2.0 (peptide length 15, 1-mer offset) using the most abundant class II alleles in our population. Proimmune Reveal® (in vitro MHC class II peptide reporter) assay was performed using synthesized 15-mer peptides offset by 5-mer spanning the protein. One hundred patients with an unequivocal history of peanut allergy or IgE level >95% predictive of peanut allergy were enrolled, PBMCs collected, and 3H-Thymidine T-cell stimulation assay using pre-selected peptides were performed. IL4, IL13, IL5, IFNg and TNFa were measured in culture supernatants using the luminex platform. Comparison of in vitro and in silico results showed good concordance for both Ara h1 and Ara h3. A pool of 36 Ara h1 peptides was selected for T-cell stimulation assays and confirmed these results. In silico analysis predicted promiscuous binding to different HLA types by several peptides. This was also seen in ex vivo T-cell stimulation assays. In combination with cytokines secreted in T-cell assays, we have identified 4 vaccine candidate Ara h1 peptides. Using a similar approach, we have also identified 4 Ara h3 vaccine candidate peptides. Pre-selection of peptides in combination with conventional methods was an effective strategy for identifying peanut T-cell vaccine candidates.
Changes in Ploidy Distributions in Human Liver Carcinogenesis
Authors: G. Saeter, C.-Z. Lee, P. K Schwarze, S. Ous, D.-S. Chen, J.-L. Sung, P. O. Seglen
Journal: JNCI Journal of the National Cancer Institute (1988)

Cellular and nuclear DNA content was measured by flow cytometry and the fraction of binucleated cells by fluorescence microscopy in normal adult human livers, hepatocellular carcinomas, cirrhotic livers surrounding tumors, and in some benign liver conditions. In five normal livers about one-half of the hepatocytes were polyploid; the majority of these were binucleated tetraploids containing two diploid nuclei. Thus, polyploidization in human liver does not progress as far as, for example, in the rat, where 80%-90% of adult hepatocytes are polyploid, mostly with tetraploid or octoploid nuclei. In five human euploid hepatocellular carcinomas and one investigated case of focal nodular hyperplasia, the percentage of polyploid cells was significantly reduced. Four other carcinomas exhibited a prominent aneuploid (hypotetraploid) peak in addition to the diploid peak. An abnormally low fraction of binucleated cells was also indicated in these tumors. Liver tissue surrounding the tumors had a ploidy distribution similar to that of normal liver. The results suggest that, like in several models of experimental hepatocarcinogenesis, human hepatocellular tumor growth is associated with a decreased polyploidization tendency and a corresponding increase in diploid, divisional growth, which may give the tumors a growth advantage relative to the surrounding liver.
Hematopoietic Stem Cells Are Not the Direct Target of Spontaneous Leukemic Transformation in p18INK4C-Null Reconstituted Mice
Authors: Youzhong Yuan, Hui Yu, Matthew J. Boyer, Xianmin Song, Shaonan Cao, Hongmei Shen, Tao Cheng
Journal: Cancer Research (2006)

Abstract Cell cycle inhibitors are important regulators in normal tissue regeneration and disruption of the regulators are involved in cancer development. Our recent study showed that the absence of the CDK inhibitor p18INK4C (p18) enhances self-renewal of normal hematopoietic stem cell (HSC) in vivo, whereas previous studies by others showed an increased incidence of leukemogenesis in older p18-null mice. Here, we have examined potential leukemogenesis during experimentally induced regeneration of HSC in the absence of p18 in order to gauge the relation between these two processes. Reconstituted mice with p18-deficient HSCs under the condition of repetitive proliferative stress (serial transplantation) were followed for &amp;gt;3 years. T cell leukemia from the p18−/− origin was recapitulated 24 months after secondary transplantation. However, no myeloid leukemia was found in the recipients. The T cell leukemia–initiating cells (mainly in a CD3lo cell subset) did not share the same immunophenotype with normal HSCs and, in fact, the function of HSCs was significantly compromised with decreased abundance in the leukemic mice. Furthermore, we found that the p15 or p16 gene promoters were frequently methylated in the leukemic cells but not in HSCs. Our present study argues against the possibility of overgrowth of p18-null HSCs leading to a leukemic phenotype. The data also support the notion that p18 has an independent role in T cell maintenance such that CD3+CD8+ cells, unlike HSCs, are more accessible to leukemogenic transformation after the loss of p18. (Cancer Res 2006; 66(1): 343-51)
Polymorphism of Angiotensin Converting Enzyme, Angiotensinogen, and Angiotensin II Type 1 Receptor Genes and End-Stage Renal Failure in IgA Nephropathy
Authors: LUC FRIMAT, CHRISTOPHE PHILIPPE, MARIE-NOE[Combining Diaeresis]LLE MAGHAKIAN, PHILIPPE JONVEAUX, BRUNO HURAULT DE LIGNY, FRANCIS GUILLEMIN, MICHE[Combining Grave Accent]LE KESSLER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The impact of renin-angiotensin system (RAS) gene polymorphism on the prognosis of IgA nephropathy (IgAN) is still debated. A longitudinal study of renal prognosis in patients with IgAN was conducted to search retrospectively for a genotype-phenotype association between RAS polymorphisms and end-stage renal failure (ESRF). A classification based on serum creatinine (S cr ) and 24-h proteinuria (24-P) measured at the time of renal biopsy was used to estimate the risk of ESRF in IgAN: stage 1 (S cr ≤ 150 μmol/L and 24-P &lt; 1 g), stage 2 (S cr &gt; 150 μmol/L and 24-P &lt; 1 g or S cr ≤ 150 μmol/L and 24-P ≥ 1 g), stage 3 (S cr &gt; 150 μmol/L and 24-P ≥ 1 g). Deletion/insertion polymorphism ( D/I ) of the angiotensin I converting enzyme gene, M235T polymorphism ( T/M ) of the angiotensinogen gene and A1166C polymorphism ( C/A ) of the angiotensin II type 1 receptor gene were determined in 274 Caucasian men with biopsy-proven IgAN ( n = 86, 112, and 76 in stages 1, 2, and 3, respectively). Mean global follow-up was 6 ± 5 yr after renal biopsy. For stages 1, 2, and 3, ESRF developed in 7 (8.1%), 39 (34.8%), and 49 (64.4%) cases ( P &lt; 0.0001), 11.7 ± 4, 5.4 ± 4, and 2 ± 2 yr, respectively, after renal biopsy ( P &lt; 0.001). The distributions of the three genotypes into the three stages were similar. Different distributions were observed when patients were grouped by stage and genotype: ID + DD : 72% in stage 1 versus 84.6% in stages 2 + 3 ( P = 0.02; κ = 0.14); MT + TT : 66.2% in stages 1 + 2 versus 78.9% in stage 3 ( P = 0.04; κ = 0.09); and AA + AC : 89.9% in stages 1 + 2 versus 97.4% in stage 3 ( P = 0.04; κ = -0.1). However, with the use of the Cox proportional hazard model, none of the three genotypes was found to have predictive value for renal survival. Compared with S cr and 24-P, genotypes DD , TT , and AA are unlikely to serve as clinically useful predictors of ESRF in IgAN.
Repeat pulmonary rehabilitation programmes: Are they beneficial in COPD?
Authors: Karen Ingram, Jane Canavan, Samantha Kon, Claire Nolan, Sarah Jones, Amy Clark, Djeya Kaliaraju, William Man
Journal: European Respiratory Journal (2014)

Recent guidelines indicate that repeat PR should be offered to patients who have completed a course more than one year previously and remain functionally limited. However this is based on a paucity of data and it is not known whether patients who failed to gain benefit from their original PR course improve with repeated PR.

125 patients with COPD completed two separate PR courses at least 1 year apart from Sept 2009-Aug 2013. The Chronic Respiratory Questionnaire (CRQ) and Incremental Shuttle Walk (ISW) were measured pre and post course 1 (PR1) and 2 (PR2). The response to PR within, and between, PR1 and PR2 was assessed using paired t-tests. Subgroup analysis included patients who did not benefit from PR1 (ISW<47.5m, CRQ total <10 point improvement). Data are presented as mean and standard deviation (SD) or mean difference (95%CI).

Mean duration from the end of PR 1 to PR 2 was 555 (268) days, with FEV1% stable over time (0.92 (-1.2 to 3.0) p=0.39). There was a statistically significant improvement in ISW and CRQ with PR1 (64 (50 to 77)m;16.4 (19.9 to 12.9)) and PR2 (46 (36 to 56)m; 11.1 (8.0 to 14.2)) - all p<0.0001. Comparison of the response to PR1 and PR2 identified a statistically but not clinically significant difference for ISW change (PR1 versus PR2: 17.5 (2.3 to 32.7)m; p=0.025) and CRQ total (5.3 (0.92 to 9.6) p=0.02). In those who did not benefit from PR1, 63% showed an improvement in ISW or CRQ with PR2.

Patients with COPD significantly improve health related quality of life and exercise capacity with repeat PR, but response is heterogeneous. A significant proportion of patients who show no benefit with initial PR showed improvement in either exercise capacity or health status with repeated PR.