tbuckley/cabot-search huggingface dataset:
Constitutive expression of parathyroid hormone-related protein gene in human T cell leukemia virus type 1 (HTLV-1) carriers and adult T cell leukemia patients that can be trans-activated by HTLV-1 tax gene.
Authors: T Watanabe, K Yamaguchi, K Takatsuki, M Osame, M Yoshida
Journal: The Journal of Experimental Medicine (1990)

Adult T cell leukemia (ATL) is associated with human T cell leukemia virus type 1 (HTLV-1) infection, and almost all ATL patients have the complication of hypercalcemia. To understand the mechanism of the high incidence of hypercalcemia in ATL, we studied the expression of a parathyroid hormone-related protein (PTHrP) gene that has been proposed as a causative factor of hypercalcemia in some solid tumors. The polymerase chain reaction coupled with reverse transcription of mRNA was applied to RNA from peripheral blood mononuclear cells. Cells from all 13 ATL patients examined showed abundant expression of the PTHrP gene, while cells from uninfected normal subjects did not. Significant expression of PTHrP gene was also detected in HTLV-1 carriers without any symptoms and in patients with HTLV-1-associated myelopathy or tropical spastic paraparesis. PTHrP mRNA levels correlated with the number of infected cells that were estimated by the integrated HTLV-1 DNA. These results suggest that HTLV-1-infected cells are expressing the PTHrP gene. This concept was further supported by the finding that the HTLV-1 trans-activator, the tax gene product, caused trans-activation of the PTHrP gene promoter linked to the CAT gene. These observations might explain the general expression of the PTHrP gene in ATL patients and the high incidence of hypercalcemia in ATL.
Comparative immunotoxicology of ultraviolet B exposure I. Effects of<i>in vitro</i>and<i>in situ</i>ultraviolet B exposure on the functional activity and morphology of Langerhans cells in the skin of different species
Authors: None Goettsch, None Hurks, None Garssen, None Mommaas, None Slob, None Hoekman, None Pierik, None Roholl, None Van Loveren
Journal: British Journal of Dermatology (1998)

Ultraviolet (UV) B-induced morphological and functional changes in the skin of mice, rats and humans were investigated. Changes in the morphological structure of Langerhans cells (LC), the major antigen-presenting cells in the skin, using confocal laser scanning microscopy, were found in mouse and rat skin after in situ exposure to high doses of UVB radiation (FS40) (3–9 kJ/m2). Similar UVB doses failed to induce alterations in the morphological structure of human LC. Alterations in the function of epidermal cells (especially LC) were studied, using the mixed skin lymphocyte response (MSLR). In vitro UVB exposure of epidermal cells (EC), derived from the skin of the different species, revealed that low doses of UVB radiation impaired the stimulatory capacity of these cells dose-dependently; mouse epidermal cells were most UVB-susceptible, while human cells were least UVB susceptible. For suppression of the stimulatory capacity of EC after in situ UVB exposure of skin tissue, higher doses of UVB radiation than the in vitro UVB exposure were needed in all species tested. Also in this in situ set-up mouse epidermal cells were most UVB-susceptible, and human epidermal cells were least UVB-susceptible. The magnitude of differences in susceptibility for UVB-induced changes in the stimulatory capacity of EC after in situ and after in vitro exposure experiments was similar. Firstly, it may be concluded that UVB impairs the functional activity of LC at a lower dose than that which alters the morphology of these cells. Secondly, it is clear that epidermal cells, especially LC, from the skin of rodents are more susceptible to UVB than epidermal cells derived from human skin. It is important to account for these differences in susceptibility when data on the effects of UVB radiation on the immune system in rodents are extrapolated to humans.
Lung Master Protocol (Lung-MAP)—A Biomarker-Driven Protocol for Accelerating Development of Therapies for Squamous Cell Lung Cancer: SWOG S1400
Authors: Roy S. Herbst, David R. Gandara, Fred R. Hirsch, Mary W. Redman, Michael LeBlanc, Philip C. Mack, Lawrence H. Schwartz, Everett Vokes, Suresh S. Ramalingam, Jeffrey D. Bradley, Dana Sparks, Yang Zhou, Crystal Miwa, Vincent A. Miller, Roman Yelensky, Yali Li, Jeff D. Allen, Ellen V. Sigal, David Wholley, Caroline C. Sigman, Gideon M. Blumenthal, Shakun Malik, Gary J. Kelloff, Jeffrey S. Abrams, Charles D. Blanke, Vassiliki A. Papadimitrakopoulou
Journal: Clinical Cancer Research (2015)

The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell carcinoma (SCC) of the lung. There are no approved targeted therapies specific to advanced lung SCC, although The Cancer Genome Atlas project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCC, some of which are targetable by investigational agents. However, the frequency of these changes is low (5%-20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here, we describe our approach to development of a biomarker-driven phase II/II multisubstudy "Master Protocol," using a common platform (next-generation DNA sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care.
Interaction of a 17q12 variant with both fetal and infant smoke exposure in the development of childhood asthma‐like symptoms
Authors: R. J. P. van der Valk, L. Duijts, M. Kerkhof, S. P. Willemsen, A. Hofman, H. A. Moll, H. A. Smit, B. Brunekreef, D. S. Postma, V. W. V. Jaddoe, G. H. Koppelman, J. C. de Jongste
Journal: Allergy (2012)

Abstract Background Gene variants on chromosome 17q12‐21 are associated with an increased risk of childhood‐onset asthma, a risk known to be modified by environmental tobacco smoke ( ETS ). Objectives To assess whether the association of rs2305480 on chromosome 17q12 in the GSDML gene with asthma‐like symptoms in the first 4 years of life is modified by smoke exposure during fetal and early postnatal life. Methods We used data from two independent prospective cohort studies from fetal life onwards in the N etherlands. We genotyped rs2305480 and assessed maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma‐like symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal cough, were reported by parents when the children were 1, 2, 3, and 4 years. Analyses were based on a total group of 4461 C aucasian children. Results The G risk‐allele of rs2305480 was associated with asthma‐like symptoms [overall odds ratio 1.17 (1.11, 1.24), 2.66E‐9]. The effect of rs2305480 on asthma‐like symptoms was stronger among children who were exposed to smoke during fetal life ( P ‐interaction = 0.04). Smoke exposure in early postnatal life was also associated with an increased effect of the 17q12 single nucleotide polymorphism ( SNP ) on asthma‐like symptoms ( P ‐interaction = 5.06E‐4). These associations were consistent in both cohorts. Conclusion A 17q12 variant, rs2305480, was associated with asthma‐like symptoms in preschool children, and this association was modified by smoke exposure already during fetal life, and in infancy. Further investigation regarding SNP s in linkage disequilibrium with rs2305480 in relation to pathophysiological pathways is needed.
Identification of Novel Alternative Splice Isoforms of Circulating Proteins in a Mouse Model of Human Pancreatic Cancer
Authors: Rajasree Menon, Qing Zhang, Yan Zhang, Damian Fermin, Nabeel Bardeesy, Ronald A. DePinho, Chunxia Lu, Samir M. Hanash, Gilbert S. Omenn, David J. States
Journal: Cancer Research (2008)

To assess the potential of tumor-associated, alternatively spliced gene products as a source of biomarkers in biological fluids, we have analyzed a large data set of mass spectra derived from the plasma proteome of a mouse model of human pancreatic ductal adenocarcinoma. MS/MS spectra were interrogated for novel splice isoforms using a nonredundant database containing an exhaustive three-frame translation of Ensembl transcripts and gene models from ECgene. This integrated analysis identified 420 distinct splice isoforms, of which 92 did not match any previously annotated mouse protein sequence. We chose seven of those novel variants for validation by reverse transcription-PCR. The results were concordant with the proteomic analysis. All seven novel peptides were successfully amplified in pancreas specimens from both wild-type and mutant mice. Isotopic labeling of cysteine-containing peptides from tumor-bearing mice and wild-type controls enabled relative quantification of the proteins. Differential expression between tumor-bearing and control mice was notable for peptides from novel variants of muscle pyruvate kinase, malate dehydrogenase 1, glyceraldehyde-3-phosphate dehydrogenase, proteoglycan 4, minichromosome maintenance, complex component 9, high mobility group box 2, and hepatocyte growth factor activator. Our results show that, in a mouse model for human pancreatic cancer, novel and differentially expressed alternative splice isoforms are detectable in plasma and may be a source of candidate biomarkers.
Studying associations between variants in<i>TRAF1-C5</i>and<i>TNFAIP3-OLIG3</i>and the progression of joint destruction in rheumatoid arthritis in multiple cohorts
Authors: R Knevel, D P de Rooy, P K Gregersen, E Lindqvist, A G Wilson, G Gröndal, A Zhernakova, J A van Nies, R E Toes, R Tsonaka, J J Houwing-Duistermaat, K Steinsson, T W Huizinga, T Saxne, A H van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2012)

The severity of joint destruction in rheumatoid arthritis (RA) is highly variable between patients. Recent twin and population studies indicated that the severity of joint destruction is influenced by genetic factors.1 ,2 Previously, we reported the association of rs10818488 ( TRAF1-C5 ) and rs675520 ( TNFAIP3-OLIG3 ) with progression of joint destruction.3 ,4 The genes near these loci encode for tumour necrosis factor receptor-associated factor-1 ( TRAF1 ), complement component-5 ( C5 ) and tumour necrosis factor α-induced protein-3 ( TNFAIP3 ; a protein that inhibits NF-κ B activation). A basic principle in genetic association studies is to evaluate multiple cohorts to validate observed findings. We therefore studied both single-nucleotide polymorphisms in several RA cohorts with radiological follow-up data.

Six thousand two hundred and eighty-two x-rays of 2666 RA patients were studied: 147 patients from Lund (Sweden), 385 patients from Sheffield (UK), 285 patients from Iceland, 384 patients from the North American Rheumatoid Arthritis Consortium (NARAC), 756 patients from the National Databank of Rheumatic Diseases (NDB), 113 patients from Wichita and 596 patients from the Leiden Early Arthritis Clinic (Leiden-EAC) cohort (table 1). Detailed information on these datasets is provided elsewhere.2 ,5,–,10 …
Disabling injuries of the cervical spine in Argentine rugby over the last 20 years
Authors: F P Secin, E J Poggi, F Luzuriaga, H A Laffaye
Journal: British Journal of Sports Medicine (1999)

To investigate the incidence and risk factors of disabling injuries to the cervical spine in rugby in Argentina.A retrospective review of all cases reported to the Medical Committee of the Argentine Rugby Union (UAR) and Rugby Amistad Foundation was carried out including a follow up by phone. Cumulative binomial distribution, chi 2 test, Fisher test, and comparison of proportions were used to analyse relative incidence and risk of injury by position and by phase of play (Epi Info 6, Version 6.04a).Eighteen cases of disabling injury to the cervical spine were recorded from 1977 to 1997 (0.9 cases per year). The forwards (14 cases) were more prone to disabling injury of the cervical spine than the backs (four cases) (p = 0.03). Hookers (9/18) were at highest risk of injury (p < 0.01). The most frequent cervical injuries occurred at the 4th, 5th, and 6th vertebrae. Seventeen of the injuries occurred during match play. Set scrums were responsible for most of the injuries (11/18) but this was not statistically significant (p = 0.44). The mean age of the injured players was 22. Tetraplegia was initially found in all cases. Physical rehabilitation has been limited to the proximal muscles of the upper limbs, except for two cases of complete recovery. One death, on the seventh day after injury, was reported.The forwards suffered a higher number of injuries than the backs and this difference was statistically significant. The chance of injury for hookers was statistically higher than for the rest of the players and it was particularly linked to scrummaging. However, the number of injuries incurred in scrums was not statistically different from the number incurred in other phases of play.
Loss of Lung Health from Young Adulthood and Cardiac Phenotypes in Middle Age
Authors: Michael J. Cuttica, Laura A. Colangelo, Sanjiv J. Shah, Joao Lima, Satoru Kishi, Alexander Arynchyn, David R. Jacobs, Bharat Thyagarajan, Kiang Liu, Donald Lloyd-Jones, Ravi Kalhan
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Chronic lung diseases are associated with cardiovascular disease. How these associations evolve from young adulthood forward is unknown. Understanding the preclinical history of these associations could inform prevention strategies for common heart-lung conditions.
Pica and Nutrition
Authors: Darla Erhard Danford
Journal: Annual Review of Nutrition (1982)

Psychological Hypothesis . . . .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . . . . . . . . Cultural Hypothesis .... .. .. ... ...... .... ... ... .. ... .. ... .. .. ..... ...... ..... ... ... .. ...... .. . .. .. .. . .. .. ..   . Other Hypotheses .. ... . ... ... . ... .. .. .. . ... .. . .. .. .. . .. .... .. . .. ,   ..
Elevated 1,25-dihydroxyvitamin D plasma levels in normal human pregnancy and lactation.
Authors: R Kumar, W R Cohen, P Silva, F H Epstein
Journal: Journal of Clinical Investigation (1979)

Plasma 1,25-dihydroxyvitamin D levels are elevated in early pregnancy and continue to increase throughout pregnancy. They remain elevated postpartum in lactating women. The elevated levels probably represent a physiological response to increased calcium requirements.
Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity
Authors: Thomas Stratmann, Natalia Martin-Orozco, Valérie Mallet-Designe, Laurent Poirot, Dorian McGavern, Grigoriy Losyev, Cathleen M. Dobbs, Michael B.A. Oldstone, Kenji Yoshida, Hitoshi Kikutani, Diane Mathis, Christophe Benoist, Kathryn Haskins, Luc Teyton
Journal: Journal of Clinical Investigation (2003)

To detect and characterize autoreactive T cells in diabetes-prone NOD mice, we have developed a multimeric MHC reagent with high affinity for the BDC-2.5 T cell receptor, which is reactive against a pancreatic autoantigen. A distinct population of T cells is detected in NOD mice that recognizes the same MHC/peptide target. These T cells are positively selected in the thymus at a surprisingly high frequency and exported to the periphery. They are activated specifically in the pancreatic LNs, demonstrating an autoimmune specificity that recapitulates that of the BDC-2.5 cell. These phenomena are also observed in mouse lines that share with NOD the H-2g7 MHC haplotype but carry diabetes-resistance background genes. Thus, a susceptible haplotype at the MHC seems to be the only element required for the selection and emergence of autoreactive T cells, without requiring other diabetogenic loci from the NOD genome.
Relative efficiencies of the maximum parsimony and distance-matrix methods in obtaining the correct phylogenetic tree.
Authors: J Sourdis, M Nei
Journal: Molecular Biology and Evolution (1988)

The relative efficiencies of the maximum parsimony (MP) and distance-matrix methods in obtaining the correct tree (topology) were studied by using computer simulation. The distance-matrix methods examined are the neighbor-joining, distance-Wagner, Tateno et al. modified Farris, Faith, and Li methods. In the computer simulation, six or eight DNA sequences were assumed to evolve following a given model tree, and the evolutionary changes of the sequences were followed. Both constant and varying rates of nucleotide substitution were considered. From the sequences thus obtained, phylogenetic trees were constructed using the six tree-making methods and compared with the model (true) tree. This process was repeated 300 times for each different set of parameters. The results obtained indicate that when the number of nucleotide substitutions per site is small and a relatively small number of nucleotides are used, the probability of obtaining the correct topology (P1) is generally lower in the MP method than in the distance-matrix methods. The P1 value for the MP method increases with increasing number of nucleotides but is still generally lower than the value for the NJ or DW method. Essentially the same conclusion was obtained whether or not the rate of nucleotide substitution was constant or whether or not a transition bias in nucleotide substitution existed. The relatively poor performance of the MP method for these cases is due to the fact that information from singular sites is not used in this method. The MP method also showed a relatively low P1 value when the model of varying rate of nucleotide substitution was used and the number of substitutions per site was large. However, the MP method often produced cases in which the correct tree was one of several equally parsimonious trees. When these cases were included in the class of "success," the MP method performed better than the other methods, provided that the number of nucleotide substitutions per site was small.
An Interleukin (IL)-10/IL-12 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease
Authors: Benjamin M. Segal, Bonnie K. Dwyer, Ethan M. Shevach
Journal: The Journal of Experimental Medicine (1998)

Cells of the innate immune system secrete cytokines early in immune responses that guide maturing T helper (Th) cells along appropriate lineages. This study investigates the role of cytokine networks, bridging the innate and acquired immune systems, in the pathogenesis of an organ specific autoimmune disease. Experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is widely used as an animal model for multiple sclerosis. We demonstrate that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon γ. The disease-promoting effects of IL-12 are antagonized by IL-10 produced by an antigen nonspecific CD4+ T cell which, in turn, is regulated by the endogenous production of IL-12. This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease.
Tolerance of Baked Milk in a Subset of Patients with Cow's Milk-Mediated Eosinophilic Esophagitis
Authors: John Leung, Aubrey J. Katz, Qian Yuan, Rajashri Shuba Iyengar, Perdita Permaul, Jolan E. Walter, Jyoti Ramakrishna, Navneet Hundal, Theadora Swenson, Alexandra R. Alejos, Wayne G. Shreffler, Paul E. Hesterberg
Journal: Journal of Allergy and Clinical Immunology (2013)
Bodily Pain, Poor Physical Functioning, and Poor Glycemic Control in Adults With Diabetes
Authors: Cathy Sinnott, Mary A.M. Rogers, David Lehmann, Ruth S. Weinstock
Journal: Diabetes Care (2005)

In the January issue of Diabetes Care , Krein et al. (1) reported that the presence of chronic pain was associated with poor diabetes self-management. Their study was performed in a primarily male veteran population, and glycemic control was not addressed. We examined psychosocial factors associated with poor glycemic control in a largely female population followed in an urban, underserved, primary care medical clinic and found that the presence of pain and poor physical functioning were associated with poor glycemic control.

Medical records of adults with diabetes ( n = 236, 76% female, mean age 62 years) were reviewed. Mean HbA1c was 8.1%, and 52.5% had HbA1c …
Actinic keratosis: epidemiology and progression to squamous cell carcinoma
Authors: M. Lebwohl
Journal: British Journal of Dermatology (2003)

Journal Article Actinic keratosis: epidemiology and progression to squamous cell carcinoma Get access M. Lebwohl M. Lebwohl Mark Lebwohl E‐mail: sinaiderm@aol.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue s66, 1 November 2003, Pages 31–33, https://doi.org/10.1046/j.0366-077X.2003.05621.x Published: 01 November 2003
Abnormalities of the Extracellular Degradation of Collagen Type I in Essential Hypertension
Authors: Concepción Laviades, Nerea Varo, Javier Fernández, Gaspar Mayor, María J. Gil, Ignacio Monreal, Javier Díez
Journal: Circulation (1998)

This study was designed to investigate whether collagen type I degradation is altered in patients with essential hypertension and whether this alteration could be related to disturbances in the serum matrix metalloproteinase pathway of collagen degradation. A second aim of the study was to assess whether some relation exists between serum markers of collagen type I degradation and left ventricular hypertrophy in hypertensive patients.We measured serum concentrations of carboxy-terminal telopeptide of collagen type I (CITP) as a marker of extracellular collagen type I degradation, of total matrix metalloproteinase-1 (MMP-1), or collagenase, of total tissue inhibitor of metalloproteinases 1 (TIMP-1), and of MMP-1/TIMP-1 complex in 37 patients with never-treated essential hypertension and in 23 normotensive control subjects. Serum concentrations of free MMP-1 and free TIMP-1 were calculated by subtracting the values of MMP-1/TIMP-1 complex from the values of total MMP-1 and total TIMP-1, respectively. Measurements were repeated in 26 hypertensive patients after 1 year of treatment with the ACE inhibitor lisinopril. Baseline free MMP-1 was decreased (P<0.001) and baseline free TIMP-1 was increased (P<0.001) in hypertensives compared with normotensives. No significant differences were observed in the baseline values of CITP between the 2 groups of subjects. Hypertensive patients with baseline left ventricular hypertrophy exhibited lower values of free MMP-1 (P<0.01) and CITP (P<0.05) and higher (P<0.001) values of free TIMP-1 than hypertensive patients without baseline left ventricular hypertrophy. Treated patients attained an increase (P<0.001) in free MMP-1 and a decrease (P<0.05) in free TIMP-1. In addition, serum CITP was increased (P<0.05) in treated hypertensives compared with normotensive subjects.These findings suggest that systemic extracellular degradation of collagen type I is depressed in patients with essential hypertension and can be normalized by treatment with lisinopril. A depressed degradation of collagen type I may facilitate organ fibrosis in hypertensive patients, namely, in those with left ventricular hypertrophy.