tbuckley/cabot-search huggingface dataset:
Lupus autoantibodies target ribosomal P proteins.
Authors: K B Elkon, A P Parnassa, C L Foster
Journal: The Journal of Experimental Medicine (1985)

All nine SLE (systemic lupus erythematosus) sera with antiribosomal antibody activity targeted the same three ribosomal protein antigens, of molecular masses 38 and 17/19 kD when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. One serum reacted with an additional protein of approximately kD. Ribosomal subunit fractionation by composite gel electrophoresis and sucrose density ultracentrifugation showed that these proteins were part of the large subunit. Isoelectric focusing in agarose, and two-dimensional polyacrylamide gel electrophoresis revealed that the antigens had pI between 4.5 and 6.5, but that the 17/19 kD antigens were more acidic than the 38 kD antigen. Similarities in the molecular masses, charges, as well as the presence of highly conserved crossreactive epitopes, failure to bind to carboxymethylcellulose at pH 4.2, and extractability of the 17/19 kD proteins by 400 mM NH4Cl-ethanol at 0 degrees C indicated that these antigens were analogous to the proteins P0 (38 kD) and P1/P2 (17/19 kD) described previously (25, 36). Co-identity was confirmed using reference antibodies and antigen. Although antibodies to these proteins were only found in 5-10% of more than 50 sera screened by radioimmunoassay or Western blotting, the selective production of antibodies to epitopes on three (out of a total of more than 80) ribosomal proteins may provide further clues to autoantibody induction of SLE.
Mechanism-Based Cancer Prevention Approaches: Targets, Examples, and the Use of Transgenic Mice
Authors: S. D. Hursting, T. J. Slaga, S. M. Fischer, J. DiGiovanni, J. M. Phang
Journal: JNCI Journal of the National Cancer Institute (1999)

Humans are exposed to a wide variety of carcinogenic insults, including endogenous and man-made chemicals, radiation, physical agents, and viruses. The ultimate goal of carcinogenesis research is to elucidate the processes involved in the induction of human cancer so that interventions may be developed to prevent the disease, either in the general population or in susceptible subpopulations. Progress to date in the carcinogenesis field, particularly regarding the mechanisms of chemically induced cancer, has revealed several points along the carcinogenesis pathway that may be amenable to mechanism-based prevention strategies. The purpose of this review is to examine the basic mechanisms and stages of chemical carcinogenesis, with an emphasis on ways in which preventive interventions can modify those processes. Possible ways of interfering with tumor initiation events include the following: i) modifying carcinogen activation by inhibiting enzymes responsible for that activation or by direct scavenging of DNA-reactive electrophiles and free radicals; ii) enhancing carcinogen detoxification processes by altering the activity of the detoxifying enzymes; and iii) modulating certain DNA repair processes. Possible ways of blocking the processes involved in the promotion and progression stages of carcinogenesis include the following: i) scavenging of reactive oxygen species; ii) altering the expression of genes involved in cell signaling, particularly those regulating cell proliferation, apoptosis, and differentiation; and iii) decreasing inflammation. In addition, the utility for mechanism-based cancer prevention research of new animal models that are based on the overexpression or inactivation of specific cancer-related genes is examined.
Surveillance, Epidemiology, and End Results Lung Cancer Data Applied to the World Health Organization's Classifications of Lung Tumors&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: C Percy, L Sobin
Journal: JNCI Journal of the National Cancer Institute (1983)

Less than 1% of the lung cancer cases from the Surveillance, Epidemiology, and End Results (SEER) Program changed categories as a result of the World Health Organization's revision of histologic classifications of lung tumors. Of the 28,119 microscopically proved lung cancers reported to SEER in 1977-79, 32% were squamous cell carcinoma, 16% were small cell and/or oat cell carcinoma, 27% were adenocarcinoma, 8% were large cell carcinoma, and 5% were other specified types. A further 12% (approximately 3,500 cases) were reported with such nonspecific terms as bronchogenic carcinoma, carcinoma of the lung, and undifferentiated or anaplastic carcinoma. The magnitude of the use of these nonspecific terms showed the need for greater precision in reporting and recording data.
Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03)
Authors: A. Bamias, U. Dafni, A. Karadimou, E. Timotheadou, G. Aravantinos, A. Psyrri, I. Xanthakis, M. Tsiatas, V. Koutoulidis, C. Constantinidis, C. Hatzimouratidis, E. Samantas, A. Visvikis, M. Chrisophos, K. Stravodimos, C. Deliveliotis, A. Eleftheraki, D. Pectasides, G. Fountzilas, M.A. Dimopoulos
Journal: Annals of Oncology (2012)
The endosomal-lysosomal system: from acidification and cargo sorting to neurodegeneration
Authors: Yong-Bo Hu, Eric B Dammer, Ru-Jing Ren, Gang Wang
Journal: Translational Neurodegeneration (2015)

The endosomal-lysosomal system is made up of a set of intracellular membranous compartments that dynamically interconvert, which is comprised of early endosomes, recycling endosomes, late endosomes, and the lysosome. In addition, autophagosomes execute autophagy, which delivers intracellular contents to the lysosome. Maturation of endosomes and/or autophagosomes into a lysosome creates an unique acidic environment within the cell for proteolysis and recycling of unneeded cellular components into usable amino acids and other biomolecular building blocks. In the endocytic pathway, gradual maturation of endosomes into a lysosome and acidification of the late endosome are accompanied by vesicle trafficking, protein sorting and targeted degradation of some sorted cargo. Two opposing sorting systems are operating in these processes: the endosomal sorting complex required for transport (ESCRT) supports targeted degradation and the retromer supports retrograde retrieval of certain cargo. The endosomal-lysosomal system is emerging as a central player in a host of neurodegenerative diseases, demonstrating potential roles which are likely to be revealed in pathogenesis and for viable therapeutic strategies. Here we focus on the physiological process of endosomal-lysosomal maturation, acidification and sorting systems along the endocytic pathway, and further discuss relationships between abnormalities in the endosomal-lysosomal system and neurodegenerative diseases, especially Alzheimer’s disease (AD).
Stimulation of Megakaryocyte and Platelet Production by a Single Dose of Recombinant Human Thrombopoietin in Patients with Cancer
Authors: Saroj Vadhan-Raj, Lesley J. Murray, Carlos Bueso-Ramos, Shreyaskumar Patel, Saraswati P. Reddy, William K. Hoots, Taren Johnston, Nicholas E. Papadopolous, Walter N. Hittelman, Dennis A. Johnston, Timothy A. Yang, Virginia E. Paton, Robert L. Cohen, Susan D. Hellmann, Robert S. Benjamin, Hal E. Broxmeyer
Journal: Annals of Internal Medicine (1997)

Background: Thrombocytopenia is frequently encountered in patients with cancer. It is associated with an increased risk for clinically important bleeding episodes, which increases the demand for platelet transfusion. Objective: To assess hematopoietic response to and clinical tolerance of recombinant human thrombopoietin, a recently cloned novel cytokine. Design: Phase I and II clinical cohort study. Setting: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Patients: 12 patients with sarcoma who had high risk for severe chemotherapy-induced thrombocytopenia. Intervention: A single intravenous dose of thrombopoietin (0.3 to 2.4 µg/kg of body weight) 3 weeks before chemotherapy. Measurements: Peripheral blood and bone marrow evaluation before and after thrombopoietin administration. Results: A single dose of thrombopoietin was associated with an increase in platelet counts (mean increase from baseline, 61% to 213%; P = 0.002) in a dose-related manner. This increase began by day 4 in most patients and peaked on a median of day 12. This sustained response was associated with a prolonged serum thrombopoietin half life (20 to 30 hours). The platelets appeared morphologically normal and showed normal aggregation in response to various agonists. Platelet response was accompanied by a dose-related increase in bone marrow megakaryocytes (as much as 4-fold); the expansion of the bone marrow progenitors of myeloid, erythroid, multipotential, and megakaryocytic lineages; and the marked mobilization of progenitors (maximum, 5.7-fold to 10-fold) of multiple cell lineages in the peripheral blood. Treatment was well tolerated, and no serious adverse events occurred. Conclusions: Thrombopoietin, administered as a single dose, is a potent stimulus for prolonged platelet production in humans. It merits further evaluation for the prevention and treatment of thrombocytopenia.
Randomized Double-Blind Placebo-Controlled Trial of Bestatin in Patients With Resected Stage I Squamous-Cell Lung Carcinoma
Authors: Y. Ichinose, K. Genka, T. Koike, H. Kato, Y. Watanabe, T. Mori, S. Iioka, A. Sakuma, M. Ohta
Journal: JNCI Journal of the National Cancer Institute (2003)

Bestatin is a potent aminopeptidase inhibitor that has immunostimulant and antitumor activity. We conducted a prospective randomized, double-blind, placebo-controlled trial to determine whether postoperative adjuvant treatment with bestatin could prolong the survival of patients with completely resected stage I squamous-cell lung carcinoma.Patients with confirmed, resected stage I squamous-cell lung carcinoma were randomly assigned to receive either bestatin (30 mg) or placebo daily by mouth for 2 years. We assessed whether bestatin treatment was associated with overall survival and 5-year cancer-free survival and assessed its safety. All statistical tests were two-sided.From July 8, 1992, through March 30, 1995, 402 patients were entered in the study, 202 in the bestatin group and 198 in the placebo group. The median follow-up for surviving patients was 76 months (range = 58-92 months). The 5-year overall survival was 81% in the bestatin group and 74% in the placebo group for a difference of 7% (95% confidence interval [CI] = -1.4% to 15.0%). The 5-year cancer-free survival was 71% in the bestatin group and 62% in the placebo group for a difference of 9% (95% CI = -0.7% to 17.8%). Overall survival (P =.033, log-rank test) and cancer-free survival (P =.017, log-rank test) were statistically significantly different by Kaplan-Meier analysis. Few adverse events were observed in either group.Survival was statistically significantly better for patients with completely resected stage I squamous-cell lung carcinoma who were treated with bestatin as a postoperative adjuvant therapy than for those who received a placebo. This result requires confirmation in other phase III trials.
Daily Life Activity and Risk of Developing Cardiovascular Risk Factors
Authors: Noriyuki Nakanishi, Toshio Takatorige, Kenji Suzuki
Journal: Diabetes Care (2005)

Because of the epidemic of sedentary lifestyle worldwide, there has been a secular decline in the amount of daily life energy expenditure (1). Daily life activities represent the accumulation of complex behaviors in daily life, and few middle-aged individuals engage in physical training or physical activity at their jobs or during leisure time. Thus, it is important to examine whether overall physical activity in daily life contributes to a reduction of the risk of cardiovascular risk factors (2,3). Because BMI has been previously identified as an effect modifier of physical fitness on the risk of cardiovascular risk factors (4), we prospectively examined the relationship between daily life activities (expressed in terms of energy expenditure) and the development of cardiovascular risk factors (i.e., hypertension, type 2 diabetes, hypercholesterolemia, and the metabolic syndrome) according to BMI.

A survey of the incidence of cardiovascular risk factors was done between 1994 and 2001 at one of the biggest building contractors in Japan. All Japanese male office workers aged 35–59 years in May 1994 were invited to participate in annual health examinations ( n = 3,694). Subjects for this study were 3,607 men who did not have a history of cardiovascular disease and who completed the activity record. Details …
Familial Pheochromocytoma Associated With Cerebellar Hemangioblastoma
Authors: S. Grant Mulholland
Journal: JAMA (1969)

The association of pheochromocytoma with neurocutaneous diseases and tumors of neuroectodermal origin has recently been recognized. The case reported here provides evidence to suggest that there is more than a random relationship between pheochromocytoma and these tumors of the primitive ectodermal tissue. In addition to similar etiology and pathology, it is likely that a common origin may be postulated.
Defining the Metabolic Syndrome Construct
Authors: Dhananjay Vaidya, Moyses Szklo, Kiang Liu, Pamela J. Schreiner, Alain G. Bertoni, Pamela Ouyang
Journal: Diabetes Care (2007)

OBJECTIVE—It is controversial whether the clustering of certain metabolic abnormalities should be separately designated as the metabolic syndrome. We operationalized the “syndrome” concept and tested whether the metabolic syndrome was compatible with these operational constructs. RESEARCH DESIGN AND METHODS—The baseline cross-section of the Multi-Ethnic Study of Atherosclerosis recruited a population-based cohort of 6,781 individuals, aged 45–84 years, from six communities in the U.S. Metabolic syndrome components (waist circumference, blood pressure, fasting serum HDL cholesterol, triglycerides, and plasma glucose), homeostasis model assessment (HOMA) of insulin resistance (fasting glucose × insulin), and intimal-medial thickness (IMT) in the common and internal carotid arteries by B-mode ultrasound were measured. RESULTS—Higher syndrome component count is associated with higher HOMA levels (trend P &amp;lt; 0.001). Given the prevalence of individual components, the nonprevalence of any component or the co-prevalence of four or five components is greater than expected (χ2 P &amp;lt; 0.001). After accounting for the additive association of each component, the current definition of metabolic syndrome (co-prevalence of three or more components) does not have supra-additive association with thicker IMT in the common carotid (men: P = 0.075, women: P = 0.949) or internal carotid artery (men: P = 0.106, women: P = 0.121). CONCLUSIONS—The metabolic syndrome did not have supra-additive association with IMT, but its components clustered greater than chance expectation and a higher component count was associated with greater insulin resistance. The metabolic syndrome was compatible with two of three “syndrome” constructs tested.
Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis
Authors: Y. Yoshihara
Journal: Annals of the Rheumatic Diseases (2000)

OBJECTIVE Matrix metalloproteinases (MMPs) are expressed in joint tissues of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The objective of this study was to define the steady state levels of seven different MMPs and two tissue inhibitors of metalloproteinases (TIMPs) as well as the potential metalloproteinase activity in the synovial fluid (SF) to provide more insight into the role of MMPs in cartilage destruction in RA and OA. METHODS Levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, TIMP-1, and TIMP-2 in SF aspirated from knee joints of 97 patients with RA and 103 patients with OA were measured by the corresponding one step sandwich enzyme immunoassays. Proteolytic activity of MMPs in these SFs was examined in an assay using [3H]carboxymethylated transferrin substrate in the presence of inhibitors of serine and cysteine proteinases after activation with p -aminophenylmercuric acetate (APMA). Destruction of RA knee joints was radiographically evaluated. RESULTS Levels of MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9 were significantly higher in RA SF than in OA SF. MMP-7 and MMP-13 were detectable in more than 45% of RA SFs and in less than 20% of OA SFs, respectively. Among the MMPs examined, MMP-3 levels were extremely high compared with those of other MMPs. Direct correlations were seen between the levels of MMP-1 and MMP-3 and between those of MMP-8 and MMP-9 in RA SF. Although the levels of MMP-1 and MMP-3 increased even in the early stage of RA, those of MMP-8 and MMP-9 were low in the early stage and increased with the progression of RA. Molar ratios of the total amounts of the MMPs to those of the TIMPs were 5.2-fold higher in patients with RA than in OA, which was significant. APMA-activated metalloproteinase activity in SF showed a similar result, and a direct correlation was seen between the molar ratios and the activity in RA SF. CONCLUSIONS Our results show that high levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and TIMP-1 are present in RA SF and suggest that once these MMPs are fully activated, they have an imbalance against TIMPs, which may contribute to the cartilage destruction in RA.
GSK-3β phosphorylation of functionally distinct tau isoforms has differential, but mild effects
Authors: Kellen Voss, T Chris Gamblin
Journal: Molecular Neurodegeneration (2009)

Tau protein exists as six different isoforms that differ by the inclusion or exclusion of exons 2, 3 and 10. Exon 10 encodes a microtubule binding repeat, thereby resulting in three isoforms with three microtubule binding repeats (3R) and three isoforms that have four microtubule binding repeats (4R). In normal adult brain, the relative amounts of 3R tau and 4R tau are approximately equal. These relative protein levels are preserved in Alzheimer's disease, although in other neurodegenerative tauopathies such as progressive supranuclear palsy, corticobasal degeneration and Pick's disease, the ratio of 3R:4R is frequently altered. Because tau isoforms are not equally involved in these diseases, it is possible that they either have inherently unique characteristics owing to their primary structures or that post-translational modification, such as phosphorylation, differentially affects their properties. We have determined the effects of phosphorylation by a kinase widely believed to be involved in neurodegenerative processes, glycogen synthase kinase-3β (GSK-3β), on the microtubule binding and inducer-initiated polymerization of these isoforms in vitro. We have found that each isoform has a unique microtubule binding and polymerization profile that is altered by GSK-3β. GSK-3β phosphorylation had differential effects on the isoforms although there were similarities between isoforms and the effects were generally mild. These results indicate that tau phosphorylation by a single kinase can have isoform specific outcomes. The mild nature of these changes, however, makes it unlikely that differential effects of GSK-3β phosphorylation on the isoforms are causative in neurodegenerative disease. Instead, the inherent differences in the isoform interactions themselves and local conditions in the diseased cells are likely the major determinant of isoform involvement in various neurodegenerative disorders.
Unemployment and suicides during the recession in Italy
Authors: R. De Vogli
Journal: BMJ (2013)

Arie writes about suicides resulting from the crisis and budget cuts in Italy.1 To date, no study has investigated the impact of austerity on suicides in Italy. To answer this question, I retrieved annual data on suicides and unemployment rates (for people over 15 years) for all Italian regions from the National Institute of Statistics (ISTAT) from 2000 to 2010.2 Then, I obtained data on per capita expenditure on social services and benefits delivered by single and associated municipalities in 2008 from the SocialCohesion.Stat database.3

I investigated the association between change in unemployment …
Congenital cleft sternum
Authors: A. Eijgelaar, J. H. Bijtel
Journal: Thorax (1970)

The embryonic development of the sternum is discussed in an effort to explain the pathogenesis of cleft sternum (fissura sterni congenita). The treatment of one patient with such an anomaly is described. The operative indication, operative technique, and timing of the correction are discussed in some detail.
Effects of Exercise and Ischemia on Mobilization and Functional Activation of Blood-Derived Progenitor Cells in Patients With Ischemic Syndromes
Authors: Marcus Sandri, Volker Adams, Stephan Gielen, Axel Linke, Karsten Lenk, Nicolle Kränkel, Dominik Lenz, Sandra Erbs, Dierk Scheinert, Friedrich Wilhelm Mohr, Gerhard Schuler, Rainer Hambrecht
Journal: Circulation (2005)

Background— Exercise training (ET) has been shown to improve regional perfusion in ischemic syndromes. This might be partially related to a regeneration of diseased endothelium by circulating progenitor cells (CPCs) or CPC-derived vasculogenesis. The aim of the present study was to determine whether ischemic stimuli during ET are required to promote CPC mobilization in patients with cardiovascular diseases. Methods and Results— Patients with peripheral arterial occlusive disease (PAOD) were randomized to 4 weeks of daily ischemic ET or control (group A). Successfully revascularized patients with PAOD were randomized to 4 weeks of daily nonischemic ET or control (group B). Patients with stable coronary artery disease were subjected to 4 weeks of subischemic ET or control (group C). At baseline and after 4 weeks, the number of KDR + /CD34 + CPCs was determined by fluorescence-activated cell sorting analysis. Levels of vascular endothelial growth factor (VEGF) were measured by ELISA. A Matrigel assay was used to quantify CPC integration into vascular structures. Expression of the homing factor CXCR4 was determined by reverse transcription-polymerase chain reaction. In group A only, ischemic ET increased VEGF levels by 310% ( P &lt;0.05 versus control) associated with an increase in CPCs by 440% ( P &lt;0.05 versus control), increased CXCR4 expression, and enhanced integration of CPCs into endothelial networks. In contrast, subischemic ET in groups B and C increased CXCR4 expression and CPC integration. Conclusions— In training programs, symptomatic tissue ischemia seems to be a prerequisite for CPC mobilization. However, ischemic and subischemic ET programs affect CXCR4 expression of CPCs, which might lead to an improved CPC integration into endothelial networks.
Evidence for the involvement of the Ss protein of the mouse in the hemolytic complement system.
Authors: T H Hansen, H S Shin, D C Shreffler
Journal: The Journal of Experimental Medicine (1975)

A significant within-strain correlation has been demonstrated between the levels of Ss and hemolytic complement (C) activity in two Ss-high strains. Mouse serum specifically depleted of Ss by absorption with F(ab')2 fragments of anti-Ss had negligible C activity. In control experiments, Ss-specific antigen-antibody complexes formed with F(ab')2 fragments did not fix rabbit C, and bovine serum albumin-specific antigen-antibody complexes formed with F(ab')2 fragments did not fix mouse C. Therefore the removal of C activity by anti-Ss [F(ab')2] was apparently not due to C fixation. These results suggest that the Ss protein is a necessary component of the C system.