tbuckley/cabot-search huggingface dataset:
Specialization, Tolerance, Memory, Competition, Latency, and Strife among T Cells
Authors: N. A. Mitchison
Journal: Annual Review of Immunology (1992)

Over the last four decades much insight has been gained into the working of T cells. This survey offers an interpretation of regulatory T-cell function in terms of epitope linkage and the need to free B cells of responsibility for self-tolerance. These functions dictate specialized forms of antigen presentation, by separate populations of dendritic cells. Tolerance induction among T cells occurs at a threshold of antigen concentration which is close to that required for positive stimulation, as would be expected for the efficient workingo f the immunsey stem. Certain self-proteins, especially those located on cell surfaces, also induce tolerance among B cells, thus reducing the danger of activating latent epitopes. Memory among T cells is attributed to two components, one of hyperreactivity of activated cells, and the other of clonal expansion. Examples of competition and buffering between T-cell activities are given. A brief discussion of autoimmune disease focusses on the importance of disease remission, protective HLA genes, and immunoinhibitory genes in animal models. The mechanism underlying all three may be a balance between competing subsets of T cells.
Disease prevention: what's really important?
Authors: Gordon O Matheson, Holly O Witteman, Terry G Mochar
Journal: British Journal of Sports Medicine (2015)

Preventable chronic disease has proven to be a stubborn problem, responsible for 60% of deaths worldwide, and its associated morbidity and mortality has not changed in 40 years. The real issue in disease prevention is the lack of progress and the seeming absence of innovation.1

Beedie et al 's2 recent editorial reminds us of the importance of phase IV trials to study effectiveness, not just efficacy, of exercise, arguing that what matters to those who make funding decisions are health outcomes, not proxy measures. We argue that these are also the outcomes that matter to the people whom these interventions are supposed to help: patients and members of the public. It is well past time to include them in solving this long-standing problem.

Disease prevention is not a problem for which the core issue is a lack of scientific evidence for and against exercise, regardless of the phase of research. Restricting our perspective to what can be accomplished by continuing to accumulate scientific evidence in the fight against chronic disease relegates us to the fringes of a complex problem when …
When does amphetamine-induced psychosis become schizophrenia? [clinical conference]
Authors: M Flaum, S K Schultz
Journal: American Journal of Psychiatry (1996)

The patient was a 36-year-old single white man. He lived with his parents in a small rural town in the same house in which he was raised. He was the youngest of six children, all of whom had passed the expeded age of risk for schizophrenia onset and appeared to be leading healthy and productive lives. One would be hard-pressed to predict from childhood family photographs (1) that the patient would be the one who would become ill as an adult: he had a bright smile, was often pic-
Cancer chemotherapy: ethical dilemmas.
Authors: M B Van Scoy-Mosher
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.5.687 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2468747 Cancer chemotherapy: ethical dilemmas. M B Van Scoy-MosherxM B Van Scoy-MosherSearch for articles by this author https://doi.org/10.1200/JCO.1989.7.5.687 PDF "Cancer chemotherapy: ethical dilemmas.." Journal of Clinical Oncology, 7(5), p. 687© 1989 by American Society of Clinical Oncology
Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency: an update
Authors: I. Blanco, D. Lipsker, B. Lara, S. Janciauskiene
Journal: British Journal of Dermatology (2015)

Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency (AATD) is a very rare disease. Its estimated prevalence is 1 in 1000 subjects with severe AATD (usually white individuals with a Pi*ZZ genotype). It is manifested clinically by painful recurrent ulcerating subcutaneous nodules, and characterized histologically by dense infiltrates of neutrophils in the deep dermis and connective-tissue septae, with secondary lobular panniculitis. It may be the only clinical manifestation of AATD, although it can also occur together with the classical pulmonary or hepatic manifestations of the disease. AATD-associated panniculitis is not only very rare but may also be significantly underdiagnosed. The physician managing a case of panniculitis with a clinical presentation suggestive of AATD and a compatible skin biopsy should measure serum AAT concentration and, if low, determine the AAT phenotype by isoelectric focusing. If uncertainty remains, the SERPINA1 gene should be sequenced to identify the genotype. If AATD is diagnosed, AATD testing of first-degree family members should be performed in order to take appropriate preventive and therapeutic measures, including genetic counselling, education on inheritance, risk arising from tobacco smoke, occupational exposure to pollutants and hepatotoxic substances, and the provision of information on clinical management. Cases of panniculitis in which conventional therapy with dapsone has failed may be managed with intravenous augmentative therapy using human AAT. The current manuscript addresses the fundamental concepts of the pathogenesis of AATD-associated panniculitis and describes the clinical presentation and management of cases in order to reduce underdiagnosis and improve outcomes.
Abstract 16047: Decreased Plasma Levels of Active Glucagon-Like Peptide-1 Correlate With Coronary Artery Disease and Coronary Plaque Complexity in High-Risk Patients
Authors: Eiichi Akiyama, Seigo Sugiyama, Yasushi Matsuzawa, Masaaki Konishi, Toshimitsu Nozaki, Keisuke Ohba, Junichi Matsubara, Hitoshi Sumida, Koichi Kaikita, Kazuo Kimura, Satoshi Umemura, Hisao Ogawa
Journal: Circulation (2011)

Background: Glucagon-like peptide-1 (GLP-1) plays an important role in pathogenesis of diabetes mellitus (DM). Involvement of GLP-1 in cardiovascular diseases remains unclear. We investigate the as...
Impact of oncogenic BRAF mutations and p16 expression on the growth rate of early melanomas and naevi<i>in vivo</i>
Authors: P. Tschandl, A.S. Berghoff, M. Preusser, J. Pammer, H. Pehamberger, H. Kittler
Journal: British Journal of Dermatology (2015)

It is important to know what drives and arrests melanocytic growth in vivo but observations linking oncogenic mutations to growth rates of melanocytic neoplasms in vivo are sparse.To clarify the relationship between BRAF(V) (600E) mutations and p16 expression and the growth rate of melanocytic neoplasms in vivo.We measured the growth rate of 54 melanocytic lesions (26 melanomas, 28 naevi) in vivo with digital dermatoscopy and correlated it with BRAF(V) (600E) and p16 expression, and with dermatoscopic and histological patterns.Melanomas grew faster than naevi (mean 2·7 vs. 0·8 mm(2) /year; P < 0·001) and the growth rate was faster in lesions with more nests (> 25% nests: 2·0 mm(2) /year vs. < 25% nests: 1·0 mm(2) /year; P = 0·036). Melanomas with the BRAF(V) (600E) mutation grew significantly faster than melanomas without the mutation (mean 3·36 vs. 1·60 mm(2) /year, P = 0·018). This effect of the BRAF(V) (600E) mutation on the growth rate was not observed in melanocytic naevi (mean 1·01 vs. 0·47 mm(2) /year, P = 0·274). Histopathologically, extensive nesting, larger nests and larger cell sizes were more common in melanocytic neoplasms with the BRAF(V) (600E) mutation than in those without the mutation. Melanomas expressing p16 had a slower growth rate than melanomas without p16 expression (2·27 vs. 4·34 mm(2) /year, P = 0·047). This effect was not observed in naevi (0·81 vs. 0·68 mm(2) /year, P = 0·836).The expression of BRAF(V) (600E) and the loss of p16 accelerate the growth rate of early melanomas in vivo but not in melanocytic naevi. In comparison to melanocytic proliferations that lack the mutation, the epidermal melanocytes in lesions that harbour BRAF(V) (600E) mutations are larger and more frequently arranged in large nests.
Clinical Implication of Exhaled Breath Temperature in Pediatric Asthma
Authors: Yoon Ki Han, Yoon Hee Kim, Hyun Bin Park, Min Jung Kim, Hwan Soo Kim, Hee Seon Lee, Hyun Hee Lee, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim
Journal: Journal of Allergy and Clinical Immunology (2013)
Breast feeding may cut risk of diabetes in high risk women
Authors: Jacqui Wise
Journal: BMJ (2015)

Women with gestational diabetes should be encouraged to breast feed exclusively for at least two months to reduce their risk of developing type 2 diabetes, say researchers.

A prospective cohort study published in the Annals of Internal Medicine 1 found that breast feeding exclusively for two months halved the risk of diabetes in women with gestational diabetes.

The Study of Women, Infant Feeding and Type 2 Diabetes …
TNF-a + IFN-g suppress SDF-1 expression in endothelial cells
Authors: Ombretta Salvucci, Mark Basik, Rosella Bianchi, Rita Rezzani, Luigi Rodella, Giovanna Tosato
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4786 

Tumor-associated endothelial cells are increasingly seen as critical targets of effective anticancer therapy. For instance, radiotherapy as well as combined high-dose cytokine therapy (tumor necrosis factor-alpha (TNF-a) and interferon gamma (IFN-g) have been shown to destroy cancers through the targeted destruction of endothelial cells. An important factor regulating endothelial cell growth and morphogenesis is the chemokine, stromal cell-derived factor 1 (SDF-1). Little is known of the regulation of SDF-1 expression in vascular endothelial cells. We studied the effects of proinflammatory cytokines on SDF-1 expression in endothelial cells. We found that, contrary to treatment with TNF-a alone, treatment of human umbilical with both TNF-a and IFN-g markedly decreased SDF-1 expression by endothelial cells. Both RNA and protein levels of SDF-1 were decreased by cytokine treatment. Previously, we provide evidence that SDF-1 and CXCR-4 mediate critical signaling for endothelial cell assembly into tubular structures on extracellular matrix. To this end, we tested the effects of TNF-a and IFN-g in an in vitro morphogenesis assay. TNF-a and IFN -g added to HUVEC on Matrigel prevented the formation of characteristic tubular structures assembled in a branching reticular network. Incubation of TNF-a and IFN-g-treated HUVEC with recombinant human SDF-1 in order to increase levels on the HUVEC cell surface, can reconstitute tube formation. This was observed also in vivo in an angiogenesis assay. DNA microarray analysis of the effects of combined cytokine treatment of HUVECs is being used to further explore the effects of TNF-a together with IFN-g on endothelial cells. Thus the regulation of endothelial cell production of SDF-1 may play a role in the anticancer therapies directed at endothelial cells.
Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis
Authors: A.K. Ekman, C. Enerbäck
Journal: British Journal of Dermatology (2015)

Journal Article Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis Get access A.K. Ekman, A.K. Ekman Department of Clinical and Experimental Medicine Ingrid Asp Psoriasis Research Center Faculty of Health Sciences Linköping University Linköping Sweden Search for other works by this author on: Oxford Academic Google Scholar C. Enerbäck C. Enerbäck Department of Clinical and Experimental Medicine Ingrid Asp Psoriasis Research Center Faculty of Health Sciences Linköping University Linköping Sweden Correspondence: Charlotta Enerbäck. E‐mail: charlotta.enerback@liu.se Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 2, 1 February 2016, Pages 424–426, https://doi.org/10.1111/bjd.14021 Published: 01 February 2016
Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL)
Authors: Ajay K. Gopal, Brad S. Kahl, Sven de Vos, Nina D. Wagner-Johnston, Stephen J. Schuster, Wojciech Jurczak, Ian W. Flinn, Christopher R. Flowers, Peter Martin, Andreas Viardot, Kristie A. Blum, Andre Goy, Andrew Davies, Pier Luigi Zinzani, Martin H. Dreyling, Leanne M. Holes, Bess Sorensen, Wayne R. Godfrey, Gilles Andre Salles
Journal: Blood (2014)
Predicting mortality in bronchiectasis using bronchiectasis severity index and FACED scores: a 19-year cohort study
Authors: Huw C. Ellis, Steven Cowman, Michele Fernandes, Robert Wilson, Michael R. Loebinger
Journal: European Respiratory Journal (2015)

The clinical course of bronchiectasis is unpredictable, posing a challenge both in clinical practice and in research. Two mortality prediction scores, the bronchiectasis severity index (BSI) and FACED scores, have recently been developed. The aim of this study was to assess the ability of these scores to predict long-term mortality and to compare the two scores. The study was a single-centre retrospective cohort analysis consisting of 91 subjects originally recruited in 1994. BSI and FACED scores were calculated at the time of enrolment and long-term mortality ascertained. Data was available for 74 patients with a median of 18.8 years of follow-up. Both scoring systems had similar predictive power for 5-year mortality (area under receiver operator characteristic curve (AUC) 0.79 for BSI and 0.8 for FACED). Both scores were able to predict 15-year mortality with the FACED score showing slightly superior predictive power (AUC 0.82 versus 0.69, p=0.0495). This study provides further validation of the FACED and BSI scores for the prediction of mortality in bronchiectasis and demonstrates their utility over a longer period than originally described. Whilst both scores had excellent predictive power, the FACED score was superior for 15-year mortality.
Transepithelial Transport of Immunoglobulins
Authors: Keith E. Mostov
Journal: Annual Review of Immunology (1994)

Immunoglobulins are transported across a variety of epithelial tissues. The best studied example of this is the transport of polymeric IgA and IgM by the polymeric immunoglobulin receptor (pIgR) across many types of epithelial cells. The pIgR binds its ligand at the basolateral surface and is internalized into endosomes. Here it is sorted into vesicles that transcytose it to the apical surface. At the apical surface the pIgR is proteolytically cleaved, and the large extracellular fragment (known as secretory component) is released together with the ligand. The pIgR contains a cytoplasmic domain of 103 amino acids that contains several sorting signals. Targeting from the trans-Golgi network to the basolateral surface is determined by the membrane-proximal 17 residues of this domain. There are two endocytosis signals that contain crucial tyrosine residues. Transcytosis of the pIgR is stimulated by binding of polymeric IgA. Phosphorylation of a cytoplasmic serine promotes transcytosis of the pIgR without ligand bound. Transcytosis may be regulated by the heterotrimeric Gs protein, protein kinase C and calmodulin. IgG is transcytosed from the apical to basolateral surface in several epithelial tissues such as the placenta and the small intestine of newborn rats. The receptor for intestinal transport of IgG is structurally similar to class I MHC molecules.
The role of computed tomography of the chest in the management of small-cell lung cancer.
Authors: C A Griffin, C Lu, E K Fishman, N Khouri, M Markman, S S Siegelman, M D Abeloff
Journal: Journal of Clinical Oncology (1984)

Despite the wide application of computed tomography (CT) in the diagnosis and management of lung cancer, the role of this diagnostic modality in the management of small-cell lung cancer (SCC) has not yet been defined. We therefore compared information gained from routine chest radiography (CXR) and CT scans performed on 32 patients with SCC who were treated on an intensive chemotherapy-radiotherapy protocol. Seventy-nine pairs of CXRs and CT scans were retrospectively reviewed. We found that although CT delineates a greater extent of intrathoracic disease in each of nine anatomic areas evaluated than does CXR, agreement between CT and CXR was significant for all areas except the pericardium. Pericardial thickening was seen only on CT scan and is more frequent in SCC patients than has previously been appreciated, but both its etiology and prognostic significance are unclear at this time. CT also allowed interpretation of disease status in cases where radiation-induced fibrosis made interpretation of the CXR impossible. We do not recommend routine use of chest CT at time of diagnosis of SCC, but we recommend that its use be reserved for evaluation of new symptoms or suspected relapse, or when radiation fibrosis on CXR is severe.
Cancer and tissue-specific reprogramming of hTERT by trans-splicing ribozyme driven by tissue-specific promoter to target hepatocellular carcinoma in vivo
Authors: Jin Jeong, Sang Han, Min Song, Seong Lee, Sang Lee, In Kim
Journal: Cancer Research (2008)

1397  Cancer gene therapy in clinical setting depends on the development of control system of transgene expression combined with tissue specific gene delivery systems. Cancer-restricted gene expression through transcriptional targeting is an attractive approach to reduce toxicity and potentially increase efficacy. We developed a new cancer specific therapeutic gene expression system composed of trans-splicing ribozymes (TSR) based on group I intron of Tetrahymena thermophila, targeting and reprogramming cancer specific transcript, hTERT, and inserted suicidal gene, HSVtk. To restrict expression of transgene to liver, we have surveyed liver specific promoters of Apo E, phosphoenolpyruvate carboxykinase (PEPCK), or albumin. PEPCK promoter significantly activated level of transcriptional induction produced by liver enriched transcription factors in hepatoma cells. We constructed adenoviral vectors encoding hTERT targeting TSR with lacZ (Ad-PEPCK-Ribo.LacZ) or HSVtk (Ad-PEPCK-Ribo.Tk), driven by PEPCK promoter. We observed specific and efficient cytotoxicity and antitumor effect of hepatocellular carcinoma (HCC), in vitro and in vivo subcutaneous xenograft and carcinoma peritonei models of hTERT (+) Hep 3B cells. In this study, we investigated the feasibility of transcriptional targeting approach as a tool for HCC gene therapy in intrahepatic tumor model, similar to human, through systemic administration. We injected 2.5x106 of Hep 3B cells under splenic capsule of nude mouse. Multifocal intrahpeaitc HCCs of Hep 3B cells were established within 2 weeks, above 95% of success rate. Two weeks after cell inoculation, we injected 1x1011 vp of Ad-PEPCK-Ribo.LacZ and Ad-MOCK, systemically, for hTERT-tagrgeting specific transgenic induction. After two days, livers were studied with X-gal staining, PCR and RT-PCR. For anti-tumor effect, we injected 2.5x1010 vp adenoviruses (Ad-PEPCK-Ribo.Tk, controls: Ad-Mock, Ad-CMV-Ribo-Tk, Ad-CMV-Tk) i.v. via tail vein. I.p. injection of 50mg/kg gancyclovir was followed, twice per day for 10 days. Two days after, removed livers were evaluated. Tumor specific expression of B-gal. was observed in Ad-PEPCK-Ribo.LacZ group. Semiquantitavely calulated intrahepatic tumor weights (mean ± SD) were 17.1±15.9mg (Ad-PEPCK-Ribo.Tk), 387.3 ±178.8mg(Ad-MOCK), 28.2 ±18.6mg (Ad-CMV-Ribo-Tk) and 26.7± 29.9mg (Adv-CMV-Tk), representing significant antitumor effect of therapeutic groups compared with Ad-MOCK (P=0.0001, Kruskal-Wallis test, MedCalc). Adv-PEPCK-Ribo.Tk-treated group tends to produce better efficiecncy, compared with CMV groups although statistically not meaningful. These results demonstrate that cancer-specific TSR expressed by liver-specific PEPCK promoter can be promising targeting anti-cancer agents in HCC and underlie the basis of cancer gene therapy.
Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 4: Congenital Heart Disease
Authors: George F. Van Hare, Michael J. Ackerman, Juli-anne K. Evangelista, Richard J. Kovacs, Robert J. Myerburg, Keri M. Shafer, Carole A. Warnes, Reginald L. Washington
Journal: Circulation (2015)
A Surgeon’s Guide to Bundled Payment Models for Episodes of Care
Authors: Hannah Alphs Jackson, Brian Walsh, Michael Abecassis
Journal: JAMA Surgery (2015)

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Novel Stat3-regulated genes in prostate cancer identified by microarray analysis.
Authors: Ralf Buettner, Mei Huang, Steve Eschrich, Greg Bloom, Bobby Sprinkle, Steve Enkemann, Alice Lee, Hua Yu, Richard Jove
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2401 

Compared to normal tissues and cells, the transcription factor Stat3 is constitutively activated in a variety of human tumor tissues and cell lines, including prostate cancer. Persistent activity of Stat3 leads to changes in the expression of genes that participate in the control of fundamental cellular processes that are subverted in oncogenesis. We previously reported that direct inhibition of Stat3 activity with antisense oligonucleotides induces apoptosis in the model human prostate cancer cell line DU145. Using Stat3 antisense oligos in three independent experiments, Significance Analysis of Microarrays (SAM) data mining software revealed 176 genes to be significantly altered (174 down/2 up) upon Stat3 inactivation. Gene expression profiling was based on the Affymetrix microarray platform (U133A GeneChip). To evaluate the accuracy of SAM, changes in mRNA expression levels of selected genes were confirmed using real-time PCR. A dominant-negative Stat3 adenoviral construct was used to further validate Stat3 candidate target genes. In addition, luciferase-reporter promoter studies identified a subset of genes that are directly regulated by Stat3, including the cell growth and angiogenesis regulators HER2, IGF1R and VEGF. Interestingly, another candidate gene directly regulated by Stat3 is CD46, an immune regulator that may protect tumor cells from complement-mediated lysis. These studies reveal a molecular signature of novel Stat3-regulated genes in prostate cancer cells that potentially contribute to malignant progression.