tbuckley/cabot-search huggingface dataset:
Abstract P143: Circulating Level of Hepatocyte Growth Factor and Incidence of Diabetes Mellitus: The Multi-Ethnic Study of Atherosclerosis
Authors: Michael P Bancks, Suzette J Bielinski, Paul A Decker, Naomi Q Hanson, Nicholas B Larson, Hugues Sicotte, Christina L Wassel, James S Pankow
Journal: Circulation (2015)

Introduction: Increased levels of hepatocyte growth factor (HGF), active in cell growth, motility, and morphogenesis, are associated with the presence of obesity, poor metabolic health, and cardiovascular disease. Hypothesis: We assessed the hypothesis that higher baseline levels of HGF will be associated with increased risk of diabetes. Methods: We examined the association between HGF and incident diabetes in MESA, including 5395 men and women 45-84 years of age at enrollment (2000-02). Fasting serum HGF was measured at baseline and on a subsample of participants at exam 2 (n = 1915). From 2000-11, incidence of diabetes was ascertained over 4 follow-up examinations, determined by new use of insulin or oral hypoglycemic medication or fasting glucose ≥ 126 mg/dL. Cox regression was used to estimate hazard ratios (HR) for incident diabetes according to 1 standard deviation unit (SDU) of HGF (1 SDU =256 pg/mL), before and after adjustment for age, sex, race/ethnicity, education, study center, smoking status, alcohol consumption, BMI, WC, fasting glucose and insulin, CRP, and IL-6 levels. Similarly, hazard ratios for incident diabetes were estimated according to change in HGF levels from exam 1 to exam 2 in the subsample. Results: At baseline, older age, male sex, current smoking, and higher body mass index (BMI), waist circumference (WC), fasting glucose and insulin, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were all associated with higher levels of HGF, while greater education and physical activity were associated with lower serum HGF. Incidence of diabetes in this analytic sample was 12% (n cases = 670). Per 1 SDU increase in baseline HGF level, unadjusted risk for diabetes increased 1.46 fold (95% CI=1.37, 1.56). After adjustment, diabetes risk per 1 SDU increase in HGF was attenuated but remained significantly increased (HR=1.22; 95% CI=1.12, 1.32). No association was found between change in HGF level between exam 1 and exam 2 and incidence of diabetes. There was no evidence of effect modification by race/ethnicity for either analysis. Conclusion: In conclusion, in this ethnically diverse U.S. adult population, higher levels of serum HGF were independently associated with increased incidence of diabetes.
Measles pneumonia. Bacterial suprainfection as a complicating factor
Authors: R. W. Olson
Journal: JAMA (1975)

During a 3 1/2-month period, 32 previously healthy young men were first seen with typical prodromal symptoms and signs of measles. On admission or within 48 hours of admission, 16 patients (50%) manifested physical signs and roentgenographic evidence of pneumonia. Of these 16 patients, ten (63%) were found to have bacterial suprainfection or colonization confirmed by culture of transtracheal aspirates. From six of these ten patients,<i>Neisseria meningitidis</i>serogroup Y was isolated as the sole organism responsible for suprainfection. In the other four patients,<i>Haemophilus</i>species,<i>Neisseria</i>species (not<i>N gonorrheae</i>or<i>N meningitidis</i>),<i>Streptococcus pneumoniae</i>, and β-hemolytic<i>Streptococcus</i>(not group A or D) were isolated alone or in combination. The data suggest that bacterial suprainfection associated with measles pneumonia is not unusual in adults and<i>N meningitidis</i>serogroup Y is a potential pathogen of the lower respiratory tract. (<i>JAMA</i>232:363-365, 1975)
Ionising radiation in the workplace
Authors: Mark P Little
Journal: BMJ (2015)

Low risk but not no risk

Information on radiation risk for cancer has come from several sources,1 in particular the Japanese atomic bomb survivors that comprise the Life Span Study cohort.2 It remains a controversial question whether there is a risk at low doses and low dose rates; although some have suggested the existence of thresholds below which there is no excess radiation risk or even beneficial (hormetic) effects of radiation exposure,3 this evidence has been disputed.4 The International Commission on Radiological Protection5 assumes, for regulatory purposes, that cancer risks can be linearly extrapolated from high radiation doses and high dose rates to low radiation doses and low dose rates by applying a dose and dose rate effectiveness factor (DDREF) of 2. However, the use of DDREF is controversial, and there is some evidence to suggest that excess cancer risks per unit dose do not fall in the lowest ranges of dose rate.6

In a linked article,7 the International Nuclear Workers Study (INWORKS) suggests significant risks associated with low dose rate occupational exposure to radiation in a combined cohort of 308 297 radiation workers from France, the United Kingdom, and the United States. This important study extends the follow-up of parts of a previous pooled analysis of nuclear …
Urinary Placental Growth Factor and Risk of Preeclampsia
Authors: Richard J. Levine
Journal: JAMA (2005)

Preeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and low levels of placental growth factor (PlGF), a proangiogenic protein, predict subsequent development of preeclampsia. In the absence of glomerular disease leading to proteinuria, sFlt1 is too large a molecule to be filtered into the urine, while PlGF is readily filtered.To test the hypothesis that urinary PlGF is reduced prior to onset of hypertension and proteinuria and that this reduction predicts preeclampsia.Nested case-control study within the Calcium for Preeclampsia Prevention trial of healthy nulliparous women enrolled at 5 US university medical centers during 1992-1995. Each woman with preeclampsia was matched to 1 normotensive control by enrollment site, gestational age at collection of the first serum specimen, and sample storage time at -70 degrees C. One hundred twenty pairs of women were randomly chosen for analysis of serum and urine specimens obtained before labor.Cross-sectional urinary PlGF concentrations, before and after normalization for urinary creatinine.Among normotensive controls, urinary PlGF increased during the first 2 trimesters, peaked at 29 to 32 weeks, and decreased thereafter. Among cases, before onset of preeclampsia the pattern of urinary PlGF was similar, but levels were significantly reduced beginning at 25 to 28 weeks. There were particularly large differences between controls and cases of preeclampsia with subsequent early onset of the disease or small-for-gestational-age infants. After onset of clinical disease, mean urinary PlGF in women with preeclampsia was 32 pg/mL, compared with 234 pg/mL in controls with fetuses of similar gestational age (P<.001). The adjusted odds ratio for the risk of preeclampsia to begin before 37 weeks of gestation for specimens obtained at 21 to 32 weeks, which were in the lowest quartile of control PlGF concentrations (<118 pg/mL), compared with all other quartiles, was 22.5 (95% confidence interval, 7.4-67.8).Decreased urinary PlGF at mid gestation is strongly associated with subsequent early development of preeclampsia.
A Survivin-Associated Adaptive Response in Radiation Therapy
Authors: David J. Grdina, Jeffrey S. Murley, Richard C. Miller, Helena J. Mauceri, Harold G. Sutton, Jian Jian Li, Gayle E. Woloschak, Ralph R. Weichselbaum
Journal: Cancer Research (2013)

Abstract Adaptive responses can be induced in cells by very low doses of ionizing radiation resulting in an enhanced resistance to much larger exposures. The inhibitor of apoptosis protein, survivin, has been implicated in many adaptive responses to cellular stress. Computerized axial tomography used in image-guided radiotherapy to position and monitor tumor response uses very low radiation doses ranging from 0.5 to 100 mGy. We investigated the ability of these very low radiation doses administered along with two 2 Gy doses separated by 24 hours, a standard conventional radiotherapy dosing schedule, to initiate adaptive responses resulting in the elevation of radiation resistance in exposed cells. Human colon carcinoma (RKO36), mouse sarcoma (SA-NH), along with transformed mouse embryo fibroblasts, wild type or cells lacking functional tumor necrosis factor receptors 1 and 2 were used to assess their relative ability to express an adaptive response when grown either to confluence in vitro or as tumors in the flank of C57BL/6 mice. The survival of each of these cells was elevated from 5% to 20% (P ≤ 0.05) as compared to cells not receiving a 100 mGy or lesser dose. In addition, the cells exposed to 100 mGy exhibited elevations in survivin levels, reductions in apoptosis frequencies, and loss of an adaptive response if transfected with survivin siRNA. This survivin-mediated adaptive response has the potential for affecting outcomes if regularly induced throughout a course of image guided radiation therapy. Cancer Res; 73(14); 4418–28. ©2013 AACR.
Lifetime Risk for Development of Atrial Fibrillation
Authors: Donald M. Lloyd-Jones, Thomas J. Wang, Eric P. Leip, Martin G. Larson, Daniel Levy, Ramachandran S. Vasan, Ralph B. D’Agostino, Joseph M. Massaro, Alexa Beiser, Philip A. Wolf, Emelia J. Benjamin
Journal: Circulation (2004)

Background— Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated. Methods and Results— We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%. Conclusions— Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.
Radioimmunotherapy of CD22-Expressing Daudi Tumors in Nude Mice with a 90Y-Labeled Anti-CD22 Monoclonal Antibody
Authors: Daniel A. Vallera, Martin W. Brechbiel, Linda J. Burns, Angela Panoskaltsis-Mortari, Katie E. Dusenbery, Dennis R. Clohisy, Ellen S. Vitetta
Journal: Clinical Cancer Research (2005)

Abstract A study was undertaken to investigate the efficacy of a high affinity, rapidly internalizing anti-CD22 monoclonal antibody for selectively delivering high-energy 90Y radioactivity to B lymphoma cells in vivo. The antibody, RFB4, was readily labeled with 90Y using the highly stable chelate, 1B4M-diethylenetriaminepentaacetic acid. Labeled RFB4 selectively bound to the CD22+ Burkitt's lymphoma cell line Daudi, but not to CD22− control cells in vitro as compared with a control antibody, and was more significantly bound (P = 0.03) to Daudi solid tumors growing in athymic nude mice. Biodistribution data correlated well with the antitumor effect. The therapeutic effect of 90Y-labeled anti-CD22 (Y22) was dose-dependent, irreversible, and the best results were achieved in mice receiving a single i.p. dose of 196 μCi. These mice displayed a significantly better (P &amp;lt; 0.01) antitumor response than control mice and survived &amp;gt;200 days with no evidence of tumor. Histology studies showed no significant injury to kidney, liver, or small intestine. Importantly, tumor-bearing mice treated with Y22 had no radiologic bone marrow damage compared with tumor-bearing mice treated with the control-labeled antibody arguing that the presence of CD22+ tumor protected mice from bone marrow damage. When anti-CD22 radioimmunotherapy was compared to radioimmunotherapy with anti-CD19 and anti-CD45 antibodies, all three antibodies distributed significantly high levels of radioisotope to flank tumors in vivo compared with controls (P &amp;lt; 0.05), induced complete remission, and produced long-term, tumor-free survivors. These findings indicate that anti-CD22 radioimmunotherapy with Y22 is highly effective in vivo against CD22-expressing malignancies and may be a useful therapy for drug-refractory B cell leukemia patients.
Agalactosyl IgG in inflammatory bowel disease: correlation with C-reactive protein.
Authors: R Dube, G A Rook, J Steele, R Brealey, R Dwek, T Rademacher, J Lennard-Jones
Journal: Gut (1990)

The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine (GlcNAc) rather than galactose is increased in rheumatoid arthritis and tuberculosis, and in sera from patients with Crohn9s disease, probably because of decreased activity of a galactosyltransferase in B lymphocytes. We have assayed the prevalence of agalactosyl oligosaccharides on IgG in sera from 67 patients with inflammatory bowel disease (32 ulcerative colitis and 35 Crohn9s disease). The prevalence of agalactosyl IgG significantly increases in the majority of Crohn9s patients (19/35 patients), and correlates with the level of C-reactive protein (r = 0.79), and inversely with the concentration of serum albumin. Sera from ulcerative colitis patients show less frequent (nine of 32) and less marked rises in agalactosyl IgG, and sera with high C-reactive protein values can contain normal levels. Thus in ulcerative colitis no correlation was seen between the two assays. The diseases in which the percentage of agalactosyl IgG is raised (rheumatoid arthritis, tuberculosis, Crohn9s disease and some ulcerative colitis) are characterised by simultaneous T cell mediated granulomatous tissue damage, and acute phase responses. Levels are normal in less tissue damaging granulomatous conditions, including sarcoidosis, and leprosy (except during episodes of erythema nodosum leprosum). We suggest therefore that a raised percentage of agalactosyl IgG is a correlate of a particular type of T cell mediated pathology which may be relevant to the pathogenesis of inflammatory bowel disease.
Induction of IgG in young nude mice by lipid A or thymus grafts.
Authors: C Kolb, R Di Pauli, E Weiler
Journal: The Journal of Experimental Medicine (1976)

Postnatal serum concentrations of IgG2a of paternal allotype, measured in congenitally thymusless nude mice, increase with kinetics and titers comparable to their normal congeneic counterparts. Lipid A, the mitogenic part of LPS, stimulates IgG synthesis in nude mice when it is given 7 days after birth. IgG concentrations at 15 days of age are 6- to 8-fold higher than in untreated control nudes; this is considerably lower, however, than in normal mice, which show up to 45-fold higher IgG2ab levels after lipid A treatment. A thymus graft from nearly congeneic donors of the same age, transplanted at 4 days after birth, also stimulates long-lasting IgG synthesis in the nude recipients. If the grafted nudes are injected with lipid A 3 days later, IgG synthesis is further stimulated 8- to 16-fold. The data are discussed in relation to the thymus dependency of IgG production and the conditions for lipid A stimulation.
αβ T cell receptors as predictors of health and disease
Authors: Meriem Attaf, Eric Huseby, Andrew K Sewell
Journal: Cellular and Molecular Immunology (2015)

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR 'signatures' raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome.
Identification and cloning of a prethymic precursor T lymphocyte from a population of common acute lymphoblastic leukemia antigen (CALLA)-positive fetal bone marrow cells.
Authors: P Hokland, M Hokland, J Daley, J Ritz
Journal: The Journal of Experimental Medicine (1987)

We have cloned common acute lymphoblastic leukemia (CALLA)-positive cells from human fetal bone marrow containing less than 1 in 10,000 E-RFC in round-bottomed microtiter wells (one cell per well) using the autocloning unit of an EPICS-V cell sorter. Expansion of such cells (with IL-2 and heavily irradiated autologous thymocytes as feeder cells) resulted in growth in 6-14% of the wells (mean, 11%) with cells with mature T lymphocyte phenotype. Two-color fluorescence analysis of outgrowing cultures furthermore ascertained that these cells had differentiated through a phase of simultaneous expression of T4 and T8 antigens and at the same time expression of the thymocyte-associated T6 antigens. Thus, given the fact that 10-20% of T cell acute lymphoblastic leukemia (T-ALLs) are CALLA+, we have been able to identify a human prethymic T lymphocyte population that might be the normal counterpart of precursor cell to the CALLA+ T-ALL cell.
Maternal Antibodies to Dietary Antigens and Risk for Nonaffective Psychosis in Offspring
Authors: Håkan Karlsson, Åsa Blomström, Susanne Wicks, Shuojia Yang, Robert H. Yolken, Christina Dalman
Journal: American Journal of Psychiatry (2012)

The authors analyzed archival dried blood spots obtained from newborns to assess whether levels of immunoglobulin G (IgG) directed at dietary antigens were associated with a later diagnosis of a nonaffective psychotic disorder.The study population consisted of individuals born in Sweden between 1975 and 1985 with verified register-based diagnoses of nonaffective psychoses made between 1987 and 2003 and comparison subjects matched on sex, date of birth, birth hospital, and municipality. A total of 211 case subjects and 553 comparison subjects consented to participate in the study. Data on factors associated with maternal status, pregnancy, and delivery were extracted from the Swedish Medical Birth Register. Levels of IgG directed at gliadin (a component of gluten) and casein (a milk protein) were analyzed in eluates from dried blood spots by enzyme-linked immunosorbent assay. Odds ratios were calculated for levels of IgG directed at gliadin or casein for nonaffective psychosis.Levels of anti-gliadin IgG (but not anti-casein IgG) above the 90th percentile of levels observed among comparison subjects were associated with nonaffective psychosis (odds ratio=1.7, 95% CI=1.1-2.8). This association was not confounded by differences in maternal age, immigrant status, or mode of delivery. Similarly, gestational age at birth, ponderal index, and birth weight were not related to maternal levels of anti-gliadin IgG.High levels of anti-gliadin IgG in the maternal circulation are associated with an elevated risk for the development of a nonaffective psychosis in offspring. Research is needed to identify the mechanisms underlying this association in order to develop preventive strategies.
Perforin expression is upregulated in the epidermis of psoriatic lesions
Authors: M. Kastelan, L. Prpic Massari, F. Gruber, G. Zamolo, G. Zauhar, M. Coklo, D. Rukavina
Journal: British Journal of Dermatology (2004)

Background There are currently very few data regarding the role of cell-mediated cytotoxicity in psoriasis. Both cytotoxic T lymphocytes and natural killer (NK) cells mediate cytotoxicity reactions, mainly by two distinct pathways, the perforin/granzyme and the Fas/Fas ligand pathway. Objectives To study the expression and distribution of perforin, T- and NK-cell subsets in psoriatic lesional and nonlesional skin. Methods Skin biopsy specimens from both lesional and nonlesional skin of 11 patients with chronic plaque psoriasis and eight healthy controls were analysed by immunohistochemistry. Results We found a significant increase in CD4+ and CD8+ cells in psoriatic lesions compared with nonlesional and healthy skin. The expression of CD16+ NK cells was significantly lower in lesions compared with healthy skin. Perforin expression was significantly enhanced in the epidermis of psoriatic lesions. Conclusions Perforin expression is upregulated in the epidermis of psoriatic lesions, suggesting a potential role for perforin in the creation of the psoriatic plaque.