tbuckley/cabot-search huggingface dataset:
Comparison of Five Retrovirus Vectors Containing the Human IL-2 Receptor γ Chain Gene for Their Ability to Restore T and B Lymphocytes in the X-Linked Severe Combined Immunodeficiency Mouse Model
Authors: Guillermo J. Avilés Mendoza, Nancy E. Seidel, Makoto Otsu, Stacie M. Anderson, Karen Simon-Stoos, Adrianna Herrera, Shelley Hoogstraten-Miller, Harry L. Malech, Fabio Candotti, Jennifer M. Puck, David M. Bodine
Journal: Molecular Therapy (2001)

X-linked severe combined immunodeficiency (XSCID) is caused by mutations in the IL-2 receptor γ chain (IL2RG) gene, resulting in absent T lymphocytes and nonfunctional B lymphocytes. Recently T lymphocyte production and B lymphocyte function were restored in XSCID patients infused with autologous stem cells transduced with a retrovirus containing the human IL2RG cDNA. To optimize the expression of human IL2RG for future clinical trials, we compared five retroviral vectors expressing human IL2RG from different LTR enhancer–promoter elements in a mouse model. Northern and Southern blot analysis of hematopoietic tissues from repopulated mice revealed that the retroviral vector with the highest expression per copy number was MFG-S-hIL2RG, followed by MND-hIL2RG. All five vectors were capable of restoring lymphopoiesis in irradiated XSCID mice transplanted with transduced IL2RG-deficient hematopoietic stem cells. Transduction of IL2RG-deficient hematopoietic stem cells with all five vectors restored T lymphopoiesis in transplanted stem cell-deficient W/Wv mouse recipients. However, only XSCID stem cells transduced with the MFG-S-hIL2RG vector generated B lymphocytes in W/Wv mice. We conclude that the MFG-S-hIL2RG vector provides the best opportunity for in vivo selection and development of B and T lymphocytes for human XSCID gene therapy.
The PI3K/mTOR inhibitor PF-04691502 induces apoptosis and inhibits microenvironmental signaling in CLL and the Eµ-TCL1 mouse model
Authors: Matthew D. Blunt, Matthew J. Carter, Marta Larrayoz, Lindsay D. Smith, Maria Aguilar-Hernandez, Kerry L. Cox, Thomas Tipton, Mark Reynolds, Sarah Murphy, Elizabeth Lemm, Samantha Dias, Andrew Duncombe, Jonathan C. Strefford, Peter W. M. Johnson, Francesco Forconi, Freda K. Stevenson, Graham Packham, Mark S. Cragg, Andrew J. Steele
Journal: Blood (2015)
Abstract 17377: Tissue-Specific Telomere Length Variability Predicts Vascular Oxidative Stress in Human Arteries and Veins
Authors: Marios Margaritis, Sheena Patel, Chloe Duke, Alexios S Antonopoulos, Laura Herdman, Rana Sayeed, Ravi Desilva, Mario Petrou, Keith M Channon, Charalambos Antoniades
Journal: Circulation (2014)

Background:  Telomere length (TL) shortening has been related to atherogenesis, and in vitro data suggest that oxidative stress reduces TL in vascular cells. We explored the value of TL measurement in peripheral blood as a marker of vascular redox state in humans.   Methods:  We recruited 648 patients undergoing CABG. Superoxide (O2-) production was measured by lucigenin chemiluminescence in vascular segments of internal mammary artery (IMA), saphenous vein (SV) and peripheral blood mononuclear cells (PBMNCs), by using NADPH 100 uM ± NADPH-oxidase inhibitor Vas2870 and ±LNAME (to determine endothelial nitric oxide synthase (eNOS) coupling status). Telomere to single copy gene ratio (T/S) was measured in peripheral blood DNA by qPCR in the entire cohort. In a sub-group of 35 patients T/S was measured also in DNA extracted from SV and IMA segments. Systemic oxidative stress was evaluated by measuring plasma malonyldialdehyde (MDA) levels.   Results:  Whole blood TL was not associated with resting (A) or NADPH-stimulated O2- generation in SVs or IMAs. Similarly, whole blood TL was not associated with NADPH-stimulated or Vas2870-inhibitable O2- in PBMNCs, but significantly with plasma MDA levels (P   Conclusions:  We clearly demonstrate that whole-blood TL is not associated with vascular oxidative stress. On the contrary, TL in human arteries and veins is strongly related to NADPH-oxidase activity and eNOS coupling within the same tissue. These results document significant tissue-specific variability of telomere length, and imply that telomere shortening is more relevant to the biology of the tissue in which it is measured.
A Naturalist on Lake Victoria, with an Account of Sleeping Sickness and the Tse-Tse Fly.
Authors: Carpenter, G. D. Hale , b.
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Antiepiligrin cicatricial pemphigoid represents an autoimmune response to subunits present in laminin 5 (α3β3γ2)
Authors: None Lazarova, None Hsu, None Yee, None Yancey
Journal: British Journal of Dermatology (1998)

Sera from 20 patients with antiepiligrin cicatricial pemphigoid were studied to define the specific reactivity of their IgG autoantibodies. IgG from all patients bound exclusively to the dermal side of 1 mol/L NaCl split skin and immunoprecipitated laminin 5 (alpha3beta3gamma2) from extracts of human keratinocytes (HKs). Immunoblot studies on purified laminin 5 subunits demonstrated that patient IgG bound alpha3 alone in 16 patients. In two patients, IgG autoantibodies were directed predominantly to the gamma2 subunit, yet showed trace reactivity to alpha3 as well. Sera from two patients did not immunoblot any laminin 5 subunits, their IgG presumably immunoprecipitating laminin 5 via a conformational epitope. Sera from patients with alpha3 subunit-specific IgG immunoprecipitated all subunits of laminin 5 as well as polypeptides of 190 and 200 kDa from the conditioned media of HKs. Preclearance studies and experiments utilizing affinity-purified patient IgG demonstrated that the latter signified laminin 6 (alpha3beta1gamma1) that was bound by cross-reactive alpha3 subunit-specific patient IgG. Sera from patients with gamma2 subunit-specific IgG showed no reactivity to laminin 6, except for faint reactivity provided by low levels of their alpha3 subunit-specific IgG. Taken together, these findings indicate that antiepiligrin cicatricial pemphigoid signifies an autoimmune response to subunits present in laminin 5.
Abstract 11617: Proangiogenic Hematopoietic Progenitor-Derived Eotaxins Promote Pathological Angiogenesis and Airway Inflammation in Asthma
Authors: Kewal Asosingh, Collin Venner, Aaron Tipton, Kimberly Queisser, Amit Vasanji, Bela Anand-Apte, Marc Rothenberg, Serpil Erzurum
Journal: Circulation (2014)

Emerging evidence shows a critical role for pathological angiogenesis in asthma. Eosinophils are key effector cells in severe asthma and are recruited into the airways by a family of eosinophil specific chemoattractants called eotaxins. Eotaxins are expressed by structural cells of the lungs including endothelial cells, smooth muscles cells and airway epithelial cells, and by hematopoietic cells. We recently demonstrated that proangiogenic hematopoietic progenitors in the OVA mouse model of allergic airway inflammation express high levels of eotaxin-1 which is released upon contact with endothelial cells in allergen exposed lung resulting in migration of eosinophils from the blood circulation into the lung tissue. However, the contribution of bone marrow-derived eotaxins to airway inflammation and angiogenesis relative to eotaxins secreted by structural cells of the lungs remains unknown. Here we used bone marrow transplantation and adoptive proangiogenic hematopoietic progenitor cell transfer in eotaxin-1/-2 double knockout (KO) mouse to address this question. Wild type (WT) mice transplanted with eotaxin deficient, but not WT, bone marrow had significantly reduced eosinophilic airway inflammation. Adoptive transfer of proangiogenic progenitors from WT asthmatic mice, but not naive mice, into eotaxin1/2 knockout mice induced angiogenesis and eosinophilic allergic lung disease. Lung endothelial cells in asthma exhibited up-regulated expression of eotaxin receptor CCR3 and  ex-vivo  stimulation of endothelial cells with eotaxins induced migration and angiogenic sprouting. Bone marrow engraftment of eGFP proangiogenic progenitors showed differentiation into all hematopoietic lineages, demonstrating that the eotaxin-expressing cells were multipotent hematopoietic progenitors. Eotaxin expression by these progenitors was induced via Th2-dependent mechanism. The data reveal that Th2-polarized hematopoietic progenitor cell-derived eotaxins have a critical dual role in asthma by promoting airway eosinophilia and pathological angiogenesis.
Lactulose vs Polyethylene Glycol for Treatment of Hepatic Encephalopathy
Authors: Elliot B. Tapper
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Influence of pretreatment systolic blood pressure on the effect of carvedilol in patients with severe chronic heart failure
Authors: Jean L Rouleau, Ellen B Roecker, Michal Tendera, Paul Mohacsi, Henry Krum, Hugo A Katus, Michael B Fowler, Andrew J.S Coats, Alain Castaigne, Armin Scherhag, Terry L Holcslaw, Milton Packer
Journal: Journal of the American College of Cardiology (2004)
DRUG REACTIOXS VII.
Authors: G. M. Levene, I. A. Magnus
Journal: British Journal of Dermatology (1969)

Journal Article DRUG REACTIOXS VII: Photosensitivity to Systemically Administered Drugs Get access G. M. Levene, G. M. Levene Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar I. A. Magnus I. A. Magnus Institute of Dermatology, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 9, 1 September 1969, Pages 712–715, https://doi.org/10.1111/j.1365-2133.1969.tb16216.x Published: 01 September 1969
Abstract 15414: Ablation of Aryl Hydrocarbon Nuclear Translocator (ARNT) in the Heart Leads to Diabetic Cardiomyopathy Phenotype Through PPARα Activity
Authors: Rongxue Wu, Hsiang Chun Chang, Minh Tran, Kusum Chawla, Arineh Khechaduri, Xiaomeng Chai, Mohsen Ghanefar, Marina Bayeva, Cory Wagg, Frank Gonzalez, Gary Lopaschuk, Hossein Ardehali
Journal: Circulation (2014)

Background: Metabolic changes decrease cardiac efficiency and energetics in diabetes. Impaired hypoxia inducible factor (HIF) signaling may contribute to cardiac metabolic abnormalities. ARNT, also known as HIF1β, is a transcription factor that regulates several cellular processes by dimerizing with certain proteins, including HIF-1α or -2α, and its function in the heart is unknown. We hypothesized that cardiac deletion of ARNT leads to metabolic derangement and cardiac dysfunction. Methods and Results: Cardiac-specific ARNT knockout (csARNT-KO) mice were generated by our lab as previously described. ARNT deletion in the heart resulted in dilated cardiomyopathy and significant lipid accumulation, which was determined by electron microscopy, oil-red staining and triglyceride level quantification. We found that loss of ARNT in the heart increased PPARα activity, as confirmed by 2-fold increase in fatty acid oxidation (FAO) in ex-vivo csARNT+/- working hearts, increased PPARα protein content and increased PPARα target gene expression.To study the mechanism by which ARNT regulates PPARα, luciferase reporter assays revealed that ARNT knockdown resulted in increased PPARα promoter activity and deletion of the second hypoxia response element (HRE) upstream of the initiation site removed the inhibitory effect of ARNT on the PPARα promoter, suggesting that this site is likely involved in the regulation of the gene. ARNT binding to this sequence was confirmed by chromatin immunoprecipitation analysis. Moreover, a reduction in HIF-2α, but not HIF-1α or AHR, also significantly increased the levels of PPARα. These results suggest that the effects of ARNT deletion on PPARα are, at least partially, through its association with HIF-2α and through the binding of this complex to the second HRE upstream of the PPARα initiation site. Finally, mice with double deletion of ARNT and PPARα demonstrated rescue of the cardiac dysfunction phenotype, improved survival, and complete reversal of FA accumulation. Conclusion: Reduction in ARNT levels leads to cardiomyopathy by increasing lipid accumulation through a PPARα pathway. Thus, ARNT is a critical regulator of fatty acid metabolism in the heart, and a potential target for the treatment of diabetic cardiomyopathy.
Bmi-1 regulates self-renewal of normal and malignant human mammary stem cells
Authors: Suling Liu, Gabriela Dontu, Shivani Patel, Julie Dutcher, Hayley Smithkort, Max S. Wicha
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3984 

The epithelial components of the mammary gland are thought to arise from stem cells with the capacity for self-renewal and multilineage differentiation. These cells and/or their immediate progeny may be targets for transformation, generating tumors which are driven by cells retaining stem cell properties. We have previously shown that normal mammary stem cell self-renewal is regulated by bi-directional interactions between Hedgehog and Notch pathways with subsequent regulation of the polycomb gene Bmi-1. We have now utilized in vitro suspension based culture systems as well as NOD-SCID mouse models to examine the role of Bmi-1 in regulating human mammary stem cell self-renewal. qRT-PCR demonstrates that Bmi-1 is highly expressed in primitive human mammary cells cultured in mammospheres compared to differentiated cells cultured on collagen substrata. Overexpression of Bmi-1 with a lentivirus vector increases mammosphere initiating cells by 77% and mammosphere size by 61%. In contrast, down regulation of Bmi-1 expression with siRNA lentiviruses reduces mammosphere formation by 80% and mammosphere size by 60%. Inhibiting Bmi-1 expression also abrogates the stimulatory effects of Hedgehog and Notch signaling on mammosphere formation. Modulation of Bmi-1 expression in mammosphere initiating cells altered their mammary gland outgrowth in humanized fat pads of NOD-SCID mice. Interestingly, “tumor stem cells” characterized as CD44+CD24-/lowLin- displayed an 8-fold increase in Bmi-1 expression compared to non-tumorigenic CD44+CD24+Lin- cells isolated from the same human mammary tumor. These studies support a “tumor stem cell model” in which Bmi-1 plays an important role in the self-renewal of both normal and tumorigenic mammary stem cells with disregulation of Bmi-1 promoting carcinogenesis. Since tumor stem cells may drive tumor formation, targeting components of Bmi-1 regulated pathways represents a rationale strategy to eliminate this important cancer cell population.
The art of detecting EML4-ALK gene rearrangements in NSCLC patients - Immediate implications for patient care
Authors: Marina Pekar, Maya Ilouze, Vincent Miller, Doron Lipson, Siraj Ali, Jair Bar, Amir Onn, Dekel Shlomi, Meital Elimelech, Lior Soussan-Gutman, Murry Wynes, Fred R. Hirsch, Nir Peled
Journal: European Respiratory Journal (2013)

Background and aims : Patients with lung adenocarcinoma carrying the EML4-ALK rearrangement show dramatic response to crizotinib. There are several methods for identifying this rearrangement, the currently approved being fluorescence in situ hybridization (FISH). Other methods include: gene sequencing and immunohistochemistry (IHC).The purpose of this study is to examine IHC as an alternative method for detecting EML4-ALK translocation.   Methods : All the slides were tested by FISH and IHC using D5F3 antibody. When the FISH and IHC results were not identical, the samples were sequenced by FoundationOne” next-generation sequencing (NGS) based assay   Results : 58 consecutive NSCLC adenocarcinoma samples referred for ALK FISH testing were included in the study. 52 had sufficient tissue for further ALK IHC study. Four (6.9%) were positive by FISH; Seven (12%) were positive by IHC while three of them were both FISH+ and IHC+. One sample was FISH+ and IHC-. NGS was done for the mismatched samples (IHC(+); FISH(-); N=4) showing positive ALK rearrangement. Two of the samples were found to harbor a unique novel ALK rearrangement at intron 19. One of the patients that harbor this unique rearrangement showed a complete respond.   Conclusion:  This study provides evidence to support change of practice when ALK rearrangement detection is required. We recommend ALK IHC as a first screener and NGS as a validated method when IHC is not diagnostic. Due to the significant clinical benefit for patients whose tumor harbor ALK rearrangement, it is extremely important to keep the clinical senses alert and to combine different methodologies for a better personalized medicine.
Inguinal Hernias in Children
Authors: Arnaud Bonnard, Yves Aigrain
Journal: JAMA (1963)

The inguinal hernia repair account among surgical procedures the most frequently performed in children. Most inguinal hernias in infants and children are indirect due to patent processus vaginalis. Failure of closure of the processus vaginalis accounts for nearly all the inguino scrotal abnormalities seen in infancy and childhood. In little girls, the processus (canal de Nuck) may remain patent and may allow the ovary and fallopian tube to enter the inguinal region. Incarceration represents the most common complications associated (30 per-cent during the first year of life). Consequences concern in the first place the testicular blood supply before to interest the vitality of the incarcerated intestine. The surgically repair is recommended shortly after the diagnosis. The concurrence rate of recurrent inguinal hernia after uncomplicated inguinal hernia repairs is generally reported at 0.5-1 per cent, increasing for premature infant and complicated inguinal hernia.
Differential Role of Transcription-Coupled Repair in UVB–Induced Response of Human Fibroblasts and Keratinocytes
Authors: Mariarosaria D'Errico, Massimo Teson, Angelo Calcagnile, Tiziana Nardo, Naomi De Luca, Chiara Lazzari, Silvia Soddu, Giovanna Zambruno, Miria Stefanini, Eugenia Dogliotti
Journal: Cancer Research (2005)

Abstract Most solar radiation–induced skin cancers arise in keratinocytes. In the human epidermis, protection against cancer is thought to be mediated mainly by nucleotide excision repair (NER) of UVB-induced cyclobutane pyrimidine dimers, and by elimination of the damaged cells by apoptosis. NER consists of two subpathways: global genome repair (GGR) and transcription-coupled repair (TCR). Here, we investigate the impact of defects in NER subpathways on the cellular response to UVB-induced damage by comparing primary human keratinocytes and fibroblasts from normal, XP-C (GGR-defective), and CS-A (TCR-defective) individuals. We show that human keratinocytes are more resistant to UVB killing than fibroblasts and present higher levels of UVB-induced DNA repair synthesis due to a more efficient GGR. The CS-A defect is associated with a strong apoptotic response in fibroblasts but not in keratinocytes. Following an UVB dose of 1,000 J/m2, no p53-mediated transactivation of mdm2 is observed in CS-A fibroblasts, whereas the p53-mdm2 circuit is fully activated in CS-A keratinocytes. Thus, in fibroblasts, the signal for apoptosis originates from DNA photoproducts in the transcribed strand of active genes, whereas in keratinocytes, it is largely TCR-independent. This study shows that the response to UVB radiation is cell type–specific in humans and provides the first evidence that a deficiency in TCR has a different impact depending on the cell type. These findings have important implications for the mechanism of skin cancer protection after UVB damage and may explain the lack of skin cancer in patients with Cockayne syndrome.