tbuckley/cabot-search huggingface dataset:
Skeletal Plasmacytoma: Progression of disease and impact of local treatment; an analysis of SEER database
Authors: Muhammad Umar Jawad, Sean P Scully
Journal: Journal of Hematology & Oncology (2009)

Previous reports suggest an as yet unidentifiable subset of patients with plasmacytoma will progress to myeloma. The current study sought to establish the risk of developing myeloma and determine the prognostic factors affecting the progression of disease.Patients with plasmacytoma diagnosed between 1973 and 2005 were identified in the SEER database(1164 patients). Patient demographics and clinical characteristics, treatment(s), cause of death, and survival were extracted. Kaplan-Meier, log-rank, and Cox regression were used to analyze prognostic factors.The five year survival among patients initially diagnosed with plasmacytoma that later progressed to multiple myeloma and those initially diagnosed with multiple myeloma were almost identical (25% and 23%; respectively). Five year survival for patients with plasmacytoma that did not progress to multiple myeloma was significantly better (72%). Age > 60 years was the only factor that correlated with progression of disease (p = 0.027).Plasmacytoma consists of two cohorts of patients with different overall survival; those patients that do not progress to systemic disease and those that develop myeloma. Age > 60 years is associated with disease progression. Identifying patients with systemic disease early in the treatment will permit aggressive and novel treatment strategies to be implemented.
Dynamin and Endocytosis*
Authors: JUN-PING LIU, PHILLIP J. ROBINSON
Journal: Endocrine Reviews (1995)

THE transport of proteins, hormones, and nutrients to different locations within a cell is an essential process for many of the functions of eukaryotic cells. It is of particular importance in complex multicellular organisms to enable the cells to communicate with one another. The pathways for transport of materials into and out of cells utilize a variety of large membrane compartments within the cell, which communicate with each other and with the external environment via smaller membrane carriers called transport vesicles, The movement of the transport vesicles between compartments or to the plasma membrane is called membrane or vesicle trafficking. This is a highly ordered and directed process and takes a variety of different forms that are unique for a particular cellular function. Like intercellular communication, intracellular transport pathways are multidirectional in nature, primarily being composed of trafficking between intracellular structures, the exocytptic (secretory) pathway, and the endocytic (vesicle recycling) pathway (Fig. 1).
Interleukin-7–Mediated Inflammation in Unstable Angina
Authors: Jan Kristian Damås, Torgun Wæhre, Arne Yndestad, Kari Otterdal, Aina Hognestad, Nils Olav Solum, Lars Gullestad, Stig S. Frøland, Pål Aukrust
Journal: Circulation (2003)

Background— Atherogenesis and plaque destabilization involve immune-mediated mechanisms, but the actual mediators have not been fully clarified. Interleukin (IL)-7 is a regulator of T-cell homeostasis but also may be involved in inflammation. We hypothesized that IL-7 could be involved in the inflammatory processes observed in atherosclerosis and acute coronary syndromes. Methods and Results— To study the role of IL-7 in coronary artery disease, we analyzed IL-7 levels and the effect of this cytokine on inflammatory mediators in patients with stable and unstable angina and in healthy control subjects. Our major findings were (1) Plasma levels of IL-7 were significantly increased in patients with stable (n=30) and unstable angina (n=30) comparing healthy control subjects (n=20), particularly in those with unstable disease. (2) Increased release from activated platelets appeared to be a major contributor to the raised IL-7 levels in patients with angina. (3) IL-7 enhanced the expression of several inflammatory chemokines in peripheral blood mononuclear cells from both healthy control subjects and patients with angina, particularly in those with unstable disease. Similar effects were seen in monocytes but not in T cells. (4) MIP-1α further increased the release of IL-7 from platelets in a dose-dependent manner. (5) Aspirin reduced both the spontaneous and the SFLLRN-stimulated release of IL-7 from platelets, and when administered to healthy control subjects for 7 days (160 mg qd), it reduced plasma levels of IL-7. Conclusions— Our findings suggest a role for IL-7-driven inflammation in atherogenesis and the promotion of clinical instability in coronary artery disease involving interactions between platelets, monocytes, and chemokines.
Microsatellite Markers Reveal a Spectrum of Population Structures in the Malaria Parasite Plasmodium falciparum
Authors: Timothy J. C. Anderson, Bernhard Haubold, Jeff T. Williams, Jose G. Estrada-Franco§, Lynne Richardson, Rene Mollinedo, Moses Bockarie, John Mokili, Sungano Mharakurwa, Neil French, Jim Whitworth, Ivan D. Velez, Alan H. Brockman, Francois Nosten, Marcelo U. Ferreira, Karen P. Day
Journal: Molecular Biology and Evolution (2000)

Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3–0.4) were less than half those observed in African locations (0.76–0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51–0.65). Furthermore, variation was distributed among locations in South America (FST = 0.364) and within locations in Africa (FST = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.
The molecular organization of the beta-globin complex of the deer mouse, Peromyscus maniculatus.
Authors: R W Padgett, D D Loeb, L R Snyder, M H Edgell, C A Hutchison
Journal: Molecular Biology and Evolution (1987)

Recombinant DNA clones have been isolated that contain 80 kb of the beta-globin complex from the deer mouse, Peromyscus maniculatus. Comparisons of this complex with that from the laboratory mouse, Mus domesticus (with an order 5'-Hbby, Hbb-bhO, Hbb-bhl, Hbb-bh2, Hbb-bh3, Hbb-bl, Hbb-b2 3') highlight organizational trends in the beta-globin complex since the two species diverged. Unlike other mammals studied thus far, the deer mouse possesses three adult genes. Partial sequence analysis indicates that each of the three adult genes is intact and hence may be functional. Hybridization of one of the two Mus pseudogenes, Hbb-bh3, to genomic blots from Peromyscus reveals that it has a homologous counterpart in Peromyscus. Homologous genes to the two gamma-like Mus genes, Hbb-bhO and Hbb-bhl, are also found in Peromyscus. The strong hybridization between the Hbb-bhl genes and significant nucleotide similarity between the Hbb-bhO genes suggest that both pairs are important for the ontogeny of these mice although no known product has been identified for the Hbb-bhO genes. The presence of Hbb-bhO and Hbb-bhl in Peromyscus suggests that the duplication that created this related gene set occurred before the two lineages diverged. A single gene for Hbb-y has been isolated from Peromyscus. The adult region in Peromyscus has undergone significant divergence from the same region in Mus, having three rather than two adult genes, the acquisition of at least 15 kb of extra DNA relative to Mus, and possibly the loss of the Hbb-bh2 pseudogene. The nonadult region of the complex, in contrast, contains the same set of genes apparently distributed over the same amount of DNA as in the Mus beta-globin complex. This observation suggests that the embryonic region of the complex is more evolutionarily stable than the adult region.
P09 Validation of a novel biomarker model for the prediction of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease
Authors: S. Tanwar, P. Trembling, I. N. Guha, J. Parkes, P. Kaye, A. D. Burt, S. D. Ryder, G. P. Aithal, C. P. Day, W. M. Rosenberg
Journal: Gut (2011)

<h3>Introduction</h3> The detection of non-alcoholic steatohepatitis (NASH) within non-alcoholic fatty liver disease (NAFLD) is important both for ascertaining prognosis and the stratification of patients for existing interventions and emerging therapies. Liver biopsy is considered the reference standard for assessing NASH. The aim of this study was to develop a biomarker of NASH which would be able to detect NASH prior to the development of significant hepatic fibrosis. Candidate biomarkers of hepatic inflammation, apoptosis and liver fibrosis were selected on the basis of biological plausibility and previous association with NAFLD. <h3>Method</h3> 172 patients with NAFLD and no evidence of other liver disease were consecutively recruited from two centres. 84 patients from the first centre were included as a training cohort and 88 patients from the second centre as a validation cohort. Liver biopsies were performed on all patients and scored using the NAFLD activity score (NAS). 36 patients with advanced fibrosis were excluded from the analysis. Serum samples were taken on all patients and tested for five matrix proteins (HA, P3NP, TIMP-1, Procollagen 4 and YKL-40) and 19 haematological and biochemical parameters including HOMA-IR. Stepwise multiple linear regression was used to determine the relationship of the multiple variables to the NAS score. <h3>Results</h3> A model combining terminal peptide of pro-collagen III (P3NP) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) was found to significantly correlate with the NAS score in the training cohort (R=0.643, R2=0.413, p&lt;0.0000001). The regression model was then validated in the second patient cohort. AUROC were calculated for the ability of the model to discriminate between differing degrees of NAS. <h3>Conclusion</h3> This model appears to have good diagnostic performance for the detection of NASH in both the training and validation cohorts. Our results appear promising and if confirmed in further studies this model will be of clinical utility in detecting the minority of patients with NAFLD who have NASH and are at risk of developing progressive liver disease.
Plasminogen Activator Inhibitor-1 Antagonist TM5441 Attenuates N <sup>ω</sup> -Nitro- <scp>l</scp> -Arginine Methyl Ester–Induced Hypertension and Vascular Senescence
Authors: Amanda E. Boe, Mesut Eren, Sheila B. Murphy, Christine E. Kamide, Atsuhiko Ichimura, David Terry, Danielle McAnally, Layton H. Smith, Toshio Miyata, Douglas E. Vaughan
Journal: Circulation (2013)

Long-term inhibition of nitric oxide synthase by L-arginine analogues such as N(ω)-nitro-l-arginine methyl ester (L-NAME) has been shown to induce senescence in vitro and systemic hypertension and arteriosclerosis in vivo. We previously reported that plasminogen activator inhibitor-1 (PAI-1)-deficient mice (PAI-1(-/-)) are protected against L-NAME-induced pathologies. In this study, we investigated whether a novel, orally active PAI-1 antagonist (TM5441) has a similar protective effect against L-NAME treatment. Additionally, we studied whether L-NAME can induce vascular senescence in vivo and investigated the role of PAI-1 in this process.Wild-type mice received either L-NAME or L-NAME and TM5441 for 8 weeks. Systolic blood pressure was measured every 2 weeks. We found that TM5441 attenuated the development of hypertension and cardiac hypertrophy compared with animals that had received L-NAME alone. Additionally, TM5441-treated mice had a 34% reduction in periaortic fibrosis relative to animals on L-NAME alone. Finally, we investigated the development of vascular senescence by measuring p16(Ink4a) expression and telomere length in aortic tissue. We found that L-NAME increased p16(Ink4a) expression levels and decreased telomere length, both of which were prevented with TM5441 cotreatment.Pharmacological inhibition of PAI-1 is protective against the development of hypertension, cardiac hypertrophy, and periaortic fibrosis in mice treated with L-NAME. Furthermore, PAI-1 inhibition attenuates the arterial expression of p16(Ink4a) and maintains telomere length. PAI-1 appears to play a pivotal role in vascular senescence, and these findings suggest that PAI-1 antagonists may provide a novel approach in preventing vascular aging and hypertension.
All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists
Authors: L. Carmona, M. A. Descalzo, E. Perez-Pampin, D. Ruiz-Montesinos, A. Erra, T. Cobo, J. J Gomez-Reino
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> Mortality is increased in rheumatoid arthritis (RA), mainly because of cardiovascular (CV) events, cancer and infections. Recent data suggest that treatment with tumour necrosis factor (TNF) antagonists may affect this trend. <b>Objective:</b> To assess whether treatment with TNF antagonists is associated with reduction in CV events, cancer and infection rates, and in mortality in patients with RA treated and not treated with TNF antagonists. <b>Methods:</b> BIOBADASER is a registry for active long-term follow-up of safety of biological treatments in patients with RA. It includes 4459 patients with RA treated with TNF antagonists. EMECAR is an external RA cohort (n = 789) established to define the characteristics of the disease in Spain and to assess comorbidity. The incidence density (ischaemic heart disease) of CV events, cancer and infections was estimated and compared. The standardised mortality ratio was compared with the rate in the general population. A propensity score was used to match cohorts by the probability of being treated. <b>Results:</b> Rates of CV and cancer events are significantly higher in EMECAR than in BIOBADASER (RR 5–7 for different CV events, and RR 2.9 for cancer), whereas the rate of serious infections is significantly higher in BIOBADASER (RR 1.6). Mortality ratio of BIOBADASER by EMECAR is 0.32 (0.20–0.53) for all causes of death, 0.58 (0.24–1.41) for CV events, 0.52 (0.21–1.29) for infection and 0.36 (0.10–1.30) for cancer-related deaths. <b>Conclusion:</b> Morbidity, other than infection, and mortality are not higher than expected in patients with RA treated with TNF antagonists.
Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression
Authors: Xuchao Zhang, Shirley Zhang, Xuening Yang, Jinji Yang, Qing Zhou, Lucy Yin, Shejuan An, Jiaying Lin, Shiliang Chen, Zhi Xie, Mike Zhu, Xiaolin Zhang, Yi-long Wu
Journal: Molecular Cancer (2010)

Abstract Background The anaplastic lymphoma kinase ( ALK ) gene is frequently involved in translocations that lead to gene fusions in a variety of human malignancies, including lymphoma and lung cancer. Fusion partners of ALK include NPM , EML4 , TPM3 , ATIC , TFG , CARS , and CLTC . Characterization of ALK fusion patterns and their resulting clinicopathological profiles could be of great benefit in better understanding the biology of lung cancer. Results RACE-coupled PCR sequencing was used to assess ALK fusions in a cohort of 103 non-small cell lung carcinoma (NSCLC) patients. Within this cohort, the EML4 - ALK fusion gene was identified in 12 tumors (11.6%). Further analysis revealed that EML4 - ALK was present at a frequency of 16.13% (10/62) in patients with adenocarcinomas, 19.23% (10/52) in never-smokers, and 42.80% (9/21) in patients with adenocarcinomas lacking EGFR and KRAS mutations. The EML4 - ALK fusion was associated with non-smokers ( P = 0.03), younger age of onset ( P = 0.03), and adenocarcinomas without EGFR / KRAS mutations ( P = 0.04). A trend towards improved survival was observed for patients with the EML4 - ALK fusion, although it was not statistically significant ( P = 0.20). Concurrent deletion in EGFR exon 19 and fusion of EML4 - ALK was identified for the first time in a Chinese female patient with an adenocarcinoma. Analysis of ALK expression revealed that ALK mRNA levels were higher in tumors positive for the EML - ALK fusion than in negative tumors (normalized intensity of 21.99 vs. 0.45, respectively; P = 0.0018). However, expression of EML4 did not differ between the groups. Conclusions The EML4 - ALK fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking EGFR / KRAS mutations. The EML4 - ALK fusion appears to be tightly associated with ALK mRNA expression levels. RACE-coupled PCR sequencing is a highly sensitive method that could be used clinically for the identification of EML4 - ALK -positive patients.
Identification of Heme Oxygenase-1 As a Novel BCR/ABL-Dependent Survival Factor in Chronic Myeloid Leukemia
Authors: Matthias Mayerhofer, Stefan Florian, Maria-Theresa Krauth, Karl J. Aichberger, Martin Bilban, Rodrig Marculescu, Dieter Printz, Gerhard Fritsch, Oswald Wagner, Edgar Selzer, Wolfgang R. Sperr, Peter Valent, Christian Sillaber
Journal: Cancer Research (2004)

Chronic myeloid leukemia (CML) is a stem cell disease in which BCR/ABL promotes the survival of leukemic cells. Heme oxygenase-1 (HO-1) is an inducible stress protein that catalyzes the degradation of heme and has recently been implicated in the regulation of growth and survival of various neoplastic cells. In the present study, we analyzed the expression and role of HO-1 in CML cells. As assessed by Northern and Western blot analysis as well as immunostaining, primary CML cells were found to express HO-1 mRNA and the HO-1 protein in a constitutive manner. Exposure of these cells to the BCR/ABL tyrosine kinase inhibitor STI571 resulted in decreased expression of HO-1 mRNA and protein. In addition, BCR/ABL was found to up-regulate HO-1 promoter activity, mRNA levels, and protein levels in Ba/F3 cells. To investigate the role of HO-1 for survival of primary CML cells, the HO-1 inducer hemin was used. Hemin-induced expression of HO-1 was found to protect CML cells from STI571-induced cell death. In addition, inhibition of HO-1 by zinc-(II)-deuteroporphyrin-IX-2,4-bisethyleneglycol resulted in a substantial decrease of cell viability. Furthermore, overexpression of HO-1 in the CML-derived cell line K562 was found to counteract STI571-induced apoptosis. Together, our data identify HO-1 as a novel BCR/ABL-driven survival molecule and potential target in leukemic cells in patients with CML. The pathogenetic and clinical implications of this observation remain to be elucidated.
Regulation of Marginal Zone B Cell Development by MINT, a Suppressor of Notch/RBP-J Signaling Pathway
Authors: Kazuki Kuroda, Hua Han, Shoichi Tani, Kenji Tanigaki, Tin Tun, Takahisa Furukawa, Yoshihito Taniguchi, Hisanori Kurooka, Yoshio Hamada, Shinya Toyokuni, Tasuku Honjo
Journal: Immunity (2003)
Seronegative rheumatoid arthritis, rheumatoid factor cross reactive idiotype expression, and hidden rheumatoid factors.
Authors: V.R Bonagura, J.F Wedgwood, N Agostino, L Hatam, L Mendez, I Jaffe, B Pernis
Journal: Annals of the Rheumatic Diseases (1989)

The major rheumatoid factor cross reactive idiotype (RCRI), defined by prototypic monoclonal rheumatoid factors (RFs), is expressed as a dominant idiotype by pokeweed mitogen induced plasma cells obtained from seropositive (RF+) patients with rheumatoid arthritis (RA). Some patients who meet clinical diagnostic criteria for RA set by the American Rheumatism Association fail to express RFs at any time during their clinical course. To determine if seronegative (RF-) patients with RA, so designated by the latex fixation, Rose-Waaler classic binding assays, or a RF enzyme linked immunosorbent assay (ELISA), express the RCRI in the absence of detectable RFs we examined pokeweed mitogen plasma cells from these patients by indirect immunofluorescence. In addition, we used an inhibition ELISA to detect RCRI bearing molecules in the sera of RF- patients with RA. Five of 10 RF- patients with RA had a high prevalence of RCRI+ plasma cells (16-49% of total pokeweed mitogen plasma cells in culture). Six of 20 RF- patients with RA had high serum concentrations of molecules marked by the RCRI, equivalent to 21-110 micrograms/ml of RCRI+ reference monoclonal IgM RF. Four of five patients who expressed the RCRI in high prevalence in pokeweed mitogen plasma cells, also demonstrated high concentrations of RCRI in their sera detected by inhibition ELISA. There was significant concordance of RCRI expression determined by the two different assays. Four RF- patients with RA who expressed RCRI in their whole sera had hidden RFs detected in their 19S and, in one case, 7S serum fraction. Detection of RF related molecules in whole sera by the expression of RCRI in RF- patients with RA identifies a subgroup of RF- patients with RA who possess hidden RFs. Some RF- patients with RA can express the major RCRI in pokeweed mitogen plasma cells and in their sera and therefore are related to patients with prototypic Waldenstrom's macroglobulinaemia, who produce RCRI+ 19S IgM monoclonal RFs.
Repeated Sequences with Similar Physicochemical Properties May Account for Cross-Reactions Between Peanuts and Tree Nuts
Authors: Soheila J. Maleki, Tysheena Charles, Casey C. Grimm, Barry K. Hurlburt, Maksymilian Chruszcz, Hsiaopo Cheng, Catherine Schein
Journal: Journal of Allergy and Clinical Immunology (2013)