tbuckley/cabot-search huggingface dataset:
Reciprocal Changes in Tumor Antigenicity and Antigen-specific T Cell Function during Tumor Progression
Authors: Gang Zhou, Zhengbin Lu, John D. McCadden, Hyam I. Levitsky, Aimee L. Marson
Journal: The Journal of Experimental Medicine (2004)

Two seemingly incompatible models exist to explain the progression of cancers in immunocompetent hosts. The cancer immunosurveillance hypothesis posits that recognition of transformed cells by the immune system results in the generation of an effector response that may impede tumor growth. Clinically detectable cancer results from the emergence of tumor variants that escape this selective pressure. Alternatively, induction of immune tolerance to tumor antigens may enable cancer progression. We established a model where changes in the function of tumor-specific T cells and in tumor antigen expression could be followed during cancer progression. Early recognition of antigen led to activation, expansion, and effector function in tumor-specific CD4+ T cells resulting in the outgrowth of tumors expressing substantially reduced levels of antigen. Antigen loss was not complete, however, and levels remained above the threshold required for tumor-specific T cell recognition in vivo. In the face of persisting antigen, T cell tolerance ensued, leading to an impaired ability to mediate further antigen loss. Together, these studies establish that the processes of immunosurveillance and tumor editing coexist with a process in which the functional tumor-specific T cell repertoire is also “edited,” reconciling two hypotheses historically central to our attempts to understand host antitumor immunity.
Tenure is a necessary – not a sufficient – condition for controversial research
Authors: Kevin MacDonald
Journal: Behavioral and Brain Sciences (2006)

The Ceci et al. article is consistent with tenure being a necessary condition for controversial research. In the absence of tenure, as in the United Kingdom, professors have been fired and suspended for politically controversial issues. There are a variety of reasons why tenure does not ensure that professors will engage in controversial research, including career interests and the desire to be liked.
Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome
Authors: Elaine R. Mardis, Li Ding, David J. Dooling, David E. Larson, Michael D. McLellan, Ken Chen, Daniel C. Koboldt, Robert S. Fulton, Kim D. Delehaunty, Sean D. McGrath, Lucinda A. Fulton, Devin P. Locke, Vincent J. Magrini, Rachel M. Abbott, Tammi L. Vickery, Jerry S. Reed, Jody S. Robinson, Todd Wylie, Scott M. Smith, Lynn Carmichael, James M. Eldred, Christopher C. Harris, Jason Walker, Joshua B. Peck, Feiyu Du, Adam F. Dukes, Gabriel E. Sanderson, Anthony M. Brummett, Eric Clark, Joshua F. McMichael, Rick J. Meyer, Jonathan K. Schindler, Craig S. Pohl, John W. Wallis, Xiaoqi Shi, Ling Lin, Heather Schmidt, Yuzhu Tang, Carrie Haipek, Madeline E. Wiechert, Jolynda V. Ivy, Joelle Kalicki, Glendoria Elliott, Rhonda E. Ries, Jacqueline E. Payton, Peter Westervelt, Michael H. Tomasson, Mark A. Watson, Jack Baty, Sharon Heath, William D. Shannon, Rakesh Nagarajan, Daniel C. Link, Matthew J. Walter, Timothy A. Graubert, John F. DiPersio, Richard K. Wilson, Timothy J. Ley
Journal: New England Journal of Medicine (2009)

The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known.We used massively parallel DNA sequencing to obtain a very high level of coverage (approximately 98%) of a primary, cytogenetically normal, de novo genome for AML with minimal maturation (AML-M1) and a matched normal skin genome.We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome. All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample. Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested. Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 gene, was present in 15 of 187 additional AML genomes tested and was strongly associated with normal cytogenetic status; it was present in 13 of 80 cytogenetically normal samples (16%). The other was a nongenic mutation in a genomic region with regulatory potential and conservation in higher mammals; we detected it in one additional AML tumor. The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis.By comparing the sequences of tumor and skin genomes of a patient with AML-M1, we have identified recurring mutations that may be relevant for pathogenesis.
Parents’ Experiences With Pediatric Care at Retail Clinics
Authors: Jane M. Garbutt, Kathy M. Mandrell, Melissa Allen, Randall Sterkel, Jay Epstein, Katherine Kreusser, Jerome O’Neil, Blaine Sayre, Harold Sitrin, Kristin Stahl, Robert C. Strunk
Journal: JAMA Pediatrics (2013)

Little is known about the use of retail clinics (RCs) for pediatric care.To describe the rationale and experiences of families with a pediatrician who also use RCs for pediatric care.Cross-sectional study with 19 pediatric practices in a Midwestern practice-based research network.Parents attending the pediatrician’s office.Parents’ experience with RC care for their children.In total, 1484 parents (91.9% response rate) completed the self-administered paper survey. Parents (23.2%) who used the RC for pediatric care were more likely to report RC care for themselves (odds ratio, 7.79; 95% CI, 5.13-11.84), have more than 1 child (2.16; 1.55-3.02), and be older (1.05; 1.03-1.08). Seventy-four percent first considered going to the pediatrician but reported choosing the RC because the RC had more convenient hours (36.6%), no office appointment was available (25.2%), they did not want to bother the pediatrician after hours (15.4%), or they thought the problem was not serious enough (13.0%). Forty-seven percent of RC visits occurred between 8 am and 4 pm on weekdays or 8 am and noon on the weekend. Most commonly, visits were reportedly for acute upper respiratory tract illnesses (sore throat, 34.3%; ear infection, 26.2%; and colds or flu, 19.2%) and for physicals (13.1%). While 7.3% recalled the RC indicating it would inform the pediatrician of the visit, only 41.8% informed the pediatrician themselves.Parents with established relationships with a pediatrician most often took their children to RCs for care because access was convenient. Almost half the visits occurred when the pediatricians’ offices were likely open.
The markers of inflammatory process activity and fybrogenesis activity in patients with idiopathic pulmonary fibrosis
Authors: O.V. Karas'ova, E.S. Khmel, E.N. Kovalenko, V.V. Rodionova
Journal: European Respiratory Journal (2012)

Purpose: to define the inflammatory markers and severity of idiopathic pulmonary fibrosis (IPF).

Design:There were examined 29 patients with IPF (men - 21, women - 8) in the age of 35 - 57 years. Duration of disease was from 2-3 months till 2-3 years. Control group included 10 practically healthy persons (donors). Methods: common clinical methods, X-ray examination, definition of hemostasis parameters. The hardphase method of immune analysis was used for measuring level of plasma fibronectin (PFN) and lavage fibronectin (LFN). Patients had been examined during the period of disease aggravation. Results: Patients with IPF had increased level of PFN and decreased activated blood recalcification time (ABRT) (p<0,05). The level of PFN was 319,211±14,769 mkg/ml, LFN - 0,055±0,011 mkg/ml and didn't depend on both sex and age. There existed straight connection between level of PFN and ABRT (r = 0,4335; p<0,05) and reverse connections between levels of PFN and LFN and level of plasma fibrin (r =-0,5482 and r=-0,4969; p<0,05). Severity of patients condition correlated with increased level of PFN. Conclusions: Revealed inflammatory markers and changes in hemostasis system testify about activation of fybrogenesis and forming of chronic disseminated intravascular coagulation.
ELECTRON MICROSCOPIC STUDY OF DERMATITIS HERPETIFORMIS
Authors: LIONEL FRY, F. R. JOHNSON
Journal: British Journal of Dermatology (1969)

SUMMARY.— Biopsy specimens from 2 patients with dermatitis herpetiformis have been studied by electron microscopy. The basal lamina showed considerable alteration. In some regions it was completely absent. Where present it showed breaks, considerable thickening, and increase in electron density; it may or may not be applied to the epidermis. The cells of the stratum basale showed changes in their basal regions, but the superficial regions appeared normal. Pseudopodium-like processes extended into the dermis. The cytoplasm within these processes had a low electron density and contained few organelles, but glycogen was frequently present both in the processes and elsewhere in the cytoplasm. Half-desmosomes were absent where the basal lamina was lacking, and where it was present they were decreased in number or absent. The dermis showed little alteration apart from infiltration with leucocytes.
Injuries of the upper body extremities in recreational climbers: incidence and risk factors
Authors: M van Middelkoop, S Rakhshandehroo, M L Bruens, B W Koes, S M A Bierma-Zeinstra
Journal: British Journal of Sports Medicine (2011)

Background In recent years sport climbing is increasing in popularity, due to the improvements of climbing facilities. This sport has a spectrum of associated injuries which involve most frequently overuse injuries of the hand and the finger. Objective To determine the incidence of climbing related injuries in Dutch recreational climbers and to identify possible risk factors that are associated with these injuries. Design A prospective cohort study. Setting Indoor climbing halls. Participants 426 recreational climbers in four different climbing halls were recruited. Assessment of risk factors All climbers filled in a baseline questionnaire including potential risk factors such as age, gender, body mass index, education level, finger strength, climbing level/experience/time, main climbing activity, earlier injury, training with campus board, performing warming-up/cooling down and other sport activities. Finger strength was measured with the DIGITSgrip. A physical examination was performed to examine the shoulders, elbow, wrist, hand and fingers. Main outcome measurements Follow-up questionnaires were sent to all climbers at 3, 6, 9 and 12 months follow-up and reported on new injuries occurred due to climbing. Results A total of 178 (41.8%) climbers reported a new injury during the 1-year follow-up period. Fingers were the most reported injuries, followed by the elbow and shoulder. A climbing level &gt;6a, climbing more than 40 h per 3 months, bouldering and those who train with a campus board and perform warming-up and cooling-down exercises are univariately associated with a higher injury risk. Only a climbing level &gt;6a (OR 2.00, 95%CI 1.25 to 3.19) remained in the multivariate regression model as being associated with climbing injuries. Conclusion Climbing injuries of the upper body extremities in Dutch recreational climbers are very frequent. The most common site of an injury is the finger. A climbing level &gt;6a is a risk factor for climbing injuries in this recreational climbing population.
Evolution of the primary and secondary structures of the E1a mRNAs of the adenovirus.
Authors: D A Konings, P Hogeweg, B Hesper
Journal: Molecular Biology and Evolution (1987)

In this paper we investigate and compare (evolutionary) patterns in the primary and secondary structure of four homologous E1a mRNAs of the adenovirus. Our main results are as follows: (1) The similarity of the coding regions of the mRNA sequences reflects both similarity in function (i.e., oncogenicity) and evolutionary divergence. (2) The similarity of the leader and the trailer regions reflects host specificity (i.e., human or simian) and must therefore arise from convergence. (3) Minimal energy foldings of the mRNAs show similar secondary structures (in particular around the splice sites). The conservation of pre-mRNA secondary structure shows that mRNAs are subject to selection constraints in addition to those associated with proteins. (4) The conserved secondary (helical) structures consist of nonhomologous subsequences, i.e., shifts have occurred. The observed shifts near the splice sites seem to be the simplest way of dealing with the dual constraints.
A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability
Authors: Francesca Zalfa, Boris Eleuteri, Kirsten S Dickson, Valentina Mercaldo, Silvia De Rubeis, Alessandra di Penta, Elisabetta Tabolacci, Pietro Chiurazzi, Giovanni Neri, Seth G N Grant, Claudia Bagni
Journal: Nature Neuroscience (2007)
Acute Intravenous <scp>l</scp> -Arginine Infusion Decreases Endothelin-1 Levels and Improves Endothelial Function in Patients With Angina Pectoris and Normal Coronary Arteriograms
Authors: PierMarco Piatti, Gabriele Fragasso, Lucilla D. Monti, Emanuela Setola, Pietro Lucotti, Isabella Fermo, Rita Paroni, Elena Galluccio, Guido Pozza, Sergio Chierchia, Alberto Margonato
Journal: Circulation (2003)

Background— We tested the hypothesis that asymmetric dimethylarginine (ADMA) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X (CSX). In addition, we evaluated whether an intravenous infusion of l -arginine would improve endothelial function in these subjects. Methods and Results— Nine patients with CSX and 14 control subjects underwent a continuous infusion of l -arginine (0.125 g/min) or saline for 120 minutes. Sixty minutes after l -arginine or saline infusions, an intravenous insulin bolus (0.1 U/kg) combined with a euglycemic clamp was performed. Basal ADMA and endothelin-1 levels were higher in patients with CSX than in controls. At the end of the first hour of infusion, compared with saline, l -arginine infusion increased basal forearm blood flow, nitrite and nitrate (NOx), and forearm cGMP release and decreased endothelin-1. After insulin bolus, during saline, insulin-induced NOx, endothelin-1, and forearm cGMP release was almost abolished. Conversely, l -arginine restored a physiological profile of all endothelial variables compared with control subjects. In control subjects, compared with saline infusion, l -arginine infusion did not modify any parameter. ADMA levels were positively correlated with basal endothelin-1 levels and negatively correlated with insulin-induced incremental levels of NOx and forearm cGMP release. Conclusions— Plasma ADMA levels are increased in patients with CSX, and they are correlated with increases in endothelin-1 and reductions in insulin-induced increments in plasma NOx and cGMP, effects that are reversed by intravenous l -arginine. These data suggest that increased ADMA levels play a role in the abnormal vascular reactivity that is observed in patients with CSX.
Morphological and Functional Alterations in Ventricular Myocytes From Male Transgenic Mice With Hypertrophic Cardiomyopathy
Authors: M. Charlotte Olsson, Bradley M. Palmer, Brian L. Stauffer, Leslie A. Leinwand, Russell L. Moore
Journal: Circulation Research (2003)

Familial hypertrophic cardiomyopathy (FHC) is a human genetic disorder caused by mutations in sarcomeric proteins. It is generally characterized by cardiac hypertrophy, fibrosis, and myocyte disarray. A transgenic mouse model of FHC with mutations in the actin-binding domain of the alpha-myosin heavy chain (MyHC) gene displays many phenotypes similar to human FHC. At 4 months, male transgenic (TG) mice present with concentric cardiac hypertrophy that progresses to dilation with age. Accompanying this latter morphological change is systolic and diastolic dysfunction. Left ventricular (LV) myocytes from male TG and wild-type (WT) littermates at 5 and 12 months of age were isolated and used for morphological and functional studies. Myocytes from 5- and 12-month-old TG animals had shorter sarcomere lengths compared with WT. This sarcomere length difference was abolished in the presence of 2,3-butanedione monoxime, suggesting that the basal level of contractile element activation was increased in TG myocytes. Myocytes from 12-month-old TG mice were significantly longer than those from age-matched WT controls, and TG myocytes exhibited Z-band disorganization. When cells were paced at 0.5 Hz, TG myocyte relengthening and the fall in intracellular [Ca2+] were slowed when compared with cells from age-matched WT controls. Moreover, an increased amount of beta-myosin heavy chain protein was found in hearts from TG compared with WT. Thus, myocytes from the alpha-MyHC TG mouse model display many morphological and functional abnormalities that may help explain the LV dysfunction seen in this TG mouse model of FHC.
Overexpression and Amplification of Aurora-A in Hepatocellular Carcinoma
Authors: Yung-Ming Jeng, Shian-Yang Peng, Chiao-Ying Lin, Hey-Chi Hsu
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Aurora-A/STK15/BTAK, a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation. The purpose of this study was to investigate the expression and amplification of Aurora-A in hepatocellular carcinoma (HCC). Experimental Design: Aurora-A mRNA levels were measured in 224 HCCs and 199 paired nontumorous liver tissues by reverse transcription-PCR. Aurora-A mRNA and protein levels of 8 were also measured by reverse transcription-PCR and Western blot hybridization in 8 liver cancer cell lines. Amplification of Aurora-A was determined by Southern blot hybridization in 99 cases. Results: Aurora-A was overexpressed in 137 of 224 (61%) HCCs and all 8 of the cell lines. Overexpression of Aurora-A was associated with high-grade (grade II-IV), and high-stage (stage IIIB-IV) tumors, p53 mutation, infrequent β-catenin mutation, and poor outcome. Aurora-A overexpression and p53 mutation acted synergistically toward poor prognosis. Amplification of Aurora-A was detected only in 3 HCCs. Conclusion: The results show that Aurora-A is overexpressed frequently in HCC, and correlated with high grade and high stage, indicating that overexpression of Aurora-A plays a role in the development and progression of HCC.
Compensatory Functions and Interdependency of the DNA-Binding Domain of BRCA2 with the BRCA1–PALB2–BRCA2 Complex
Authors: Muthana Al Abo, Donniphat Dejsuphong, Kouji Hirota, Yasukazu Yonetani, Mitsuyoshi Yamazoe, Hitoshi Kurumizaka, Shunichi Takeda
Journal: Cancer Research (2013)

Abstract BRCA1, BRCA2, and PALB2 are key players in cellular tolerance to chemotherapeutic agents, including camptothecin, cisplatin, and PARP inhibitor. The N-terminal segment of BRCA2 interacts with PALB2, thus contributing to the formation of the BRCA1–PALB2–BRCA2 complex. To understand the role played by BRCA2 in this complex, we deleted its N-terminal segment and generated BRCA2ΔN mutant cells. Although previous studies have suggested that BRCA1–PALB2 plays a role in the recruitment of BRCA2 to DNA-damage sites, BRCA2ΔN mutant cells displayed a considerably milder phenotype than did BRCA2−/− null-deficient cells. We hypothesized that the DNA-binding domain (DBD) of BRCA2 might compensate for a defect in BRCA2ΔN that prevented stable interaction with PALB2. To test this hypothesis, we disrupted the DBD of BRCA2 in wild-type and BRCA2ΔN cells. Remarkably, although the resulting BRCA2ΔDBD cells displayed a moderate phenotype, the BRCA2ΔN+ΔDBD cells displayed a very severe phenotype, as did the BRCA2−/− cells, suggesting that the N-terminal segment and the DBD play a substantially overlapping role in the functionality of BRCA2. We also showed that the formation of both the BRCA1–PALB2–BRCA2 complex and the DBD is required for efficient recruitment of BRCA2 to DNA-damage sites. Our study revealed the essential role played by both the BRCA1–PALB2–BRCA2 complex and the DBD in the functionality of BRCA2, as each can compensate for the other in the recruitment of BRCA2 to DNA-damage sites. This knowledge adds to our ability to accurately predict the efficacy of antimalignant therapies for patients carrying mutations in the BRCA2 gene. Cancer Res; 74(3); 797–807. ©2013 AACR.
Rosacea, migraine, Dixarit
Authors: W. J. Cunliffe, S. G. Tan, E. Tebbs
Journal: British Journal of Dermatology (1975)

Journal Article Rosacea, migraine, Dixarit Get access W. J. Cunliffe, W. J. Cunliffe The General Infirmary, Leeds Search for other works by this author on: Oxford Academic Google Scholar S. G. Tan, S. G. Tan The General Infirmary, Leeds Search for other works by this author on: Oxford Academic Google Scholar E. Tebbs E. Tebbs The General Infirmary, Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 93, Issue s11, 1 July 1975, Page 11, https://doi.org/10.1111/j.1365-2133.1975.tb06758.x Published: 01 July 1975
The effect of obesity on intrahepatic cytokine and chemokine expression in chronic hepatitis C infection
Authors: C. Palmer, T. Corpuz, M. Guirguis, S. O'Toole, K. Yan, Y. Bu, J. Jorgenson, M. Talbot, K. Loi, A. Lloyd, A. Zekry
Journal: Gut (2009)

Obese subjects with chronic hepatitis C virus (HCV) infection have more rapidly progressive liver disease. Objective In this study, we aimed to compare the hepatic cytokine and chemokine profiles in obese and lean subjects with chronic HCV infection using qRT-PCR and immunohistochemistry.Liver biopsies from 55 subjects were studied, including 20 with chronic hepatitis C, 25 with non-alcoholic fatty liver disease and 10 subjects with non-diseased liver.Compared to the control groups, the liver injury in chronic hepatitis C was characterised by increased expression of several T-helper-1 cytokines including interferon-gamma and tumour necrosis factor-alpha, and chemokines such as RANTES, IP-10 and MCP-1. In particular, in comparison with lean (BMI <or=25 kg/m(2)) HCV infected subjects, obese (BMI>or=30 kg/m(2)) HCV infected subjects had increased hepatic expression of interferon-gamma (p=0.004) and tumour necrosis factor-alpha (p<0.001), as well as increased expression of IP-10 (p=0.009) and MCP-1 (p<0.001). Localisation of these inflammatory chemokines revealed that in comparison to lean-HCV subjects, HCV infected liver from obese subjects exhibited significantly increased expression of IP-10 (p<0.001) and MCP-1 (p=0.02) in the inflammatory infiltrate of the portal tracts. In parallel, there was increased CD3 infiltration in the liver of obese-HCV subjects.The data provide important mechanistic information on the cause of hepatic injury in obese-HCV subjects including: (1) enhanced T helper-1 cytokine response patterns-to promote hepatocellular injury; (2) increased expression of the chemokines IP-10 and MCP-1 at both the mRNA and protein levels-to enhance inflammatory cell recruitment; (3) differing localisation of these chemokines within the liver of obese-HCV versus lean-HCV subjects-implying different inducing stimuli and; (4) increased CD3 expression in the liver of obese-HCV subjects-concordant with the increased expression of T cell chemoattractants.