tbuckley/cabot-search huggingface dataset:
Different phenotypes in recessive dystrophic epidermolysis bullosa patients sharing the same mutation in compound heterozygosity with two novel mutations in the type VII collagen gene
Authors: R. Gardella, N. Zoppi, G. Zambruno, S. Barlati, M. Colombi
Journal: British Journal of Dermatology (2002)

Dystrophic epidermolysis bullosa (DEB) is a bullous skin disease caused by mutations in the type VII collagen gene (COL7A1).To elucidate the mutations shown by two patients with DEB and understand the clinical phenotypes that they displayed.We have characterized two patients, one affected by the severe recessive Hallopeau-Siemens variant of DEB (HS-RDEB) and the other by a milder recessive DEB form.In both patients we identified the R2063W missense mutation. The second mutation, in the HS-RDEB patient, was a novel 344insG, leading to a premature termination codon of translation (PTC) in exon 3, while, in the other patient, it was a novel 4965C-->T transition, which creates a new donor splice site in exon 53. The effect of this anomalous splice site leads to the maturation of a 17-nucleotides-deleted mRNA containing a PTC. In addition to this aberrant transcript, a certain amount of full-length mRNA is also generated from the mutated pre-mRNA through splicing at the canonical site.In these patients therefore the severity of the phenotype depends on the second mutation. In the patient with the 344insG mutation, leading to a PTC, type VII collagen (COLVII) molecules are exclusively composed of chains containing the R2063W substitution; as a consequence, all anchoring fibrils (AF) are abnormal and the phenotype is severe. In the other patient, the 4965C-->T splicing mutation allows the synthesis of a certain quantity of normal chains and the consequent assembly of partially functional COLVII molecules and AF, thus explaining the mild phenotype.
Pancreatic cancer risk after treatment of Hodgkin lymphoma
Authors: G.M. Dores, R.E. Curtis, F.E. van Leeuwen, M. Stovall, P. Hall, C.F. Lynch, S.A. Smith, R.E. Weathers, H.H. Storm, D.C. Hodgson, R.A. Kleinerman, H. Joensuu, T.B. Johannesen, M. Andersson, E.J. Holowaty, M. Kaijser, E. Pukkala, L. Vaalavirta, S.D. Fossa, F. Langmark, L.B. Travis, J.F. Fraumeni, B.M. Aleman, L.M. Morton, E.S. Gilbert
Journal: Annals of Oncology (2014)
Vigorous Premalignancy-specific Effector T Cell Response in the Bone Marrow of Patients with Monoclonal Gammopathy
Authors: Madhav V. Dhodapkar, Joseph Krasovsky, Keren Osman, Matthew D. Geller
Journal: The Journal of Experimental Medicine (2003)

Most approaches targeting the immune system against tumors have focused on patients with established tumors. However, whether the immune system can recognize preneoplastic stages of human cancer is not known. Here we show that patients with preneoplastic gammopathy mount a vigorous T cell response to autologous premalignant cells. This preneoplasia-specific CD4+ and CD8+ T cell response is detected in freshly isolated T cells from the BM. T cells from myeloma marrow lack this tumor-specific rapid effector function. These data provide direct evidence for tumor specific immune recognition in human preneoplasia and suggest a possible role for the immune system in influencing the early growth of transformed cells, long before the development of clinical cancer.
CD antigens 2002
Authors: David Mason, Pascale André, Armand Bensussan, Chris Buckley, Curt Civin, Edward Clark, Masja de Haas, Sanna Goyert, Martin Hadam, Derek Hart, Václav Hořejšı́, Stefan Meuer, James Morrissey, Reinhard Schwartz-Albiez, Stephen Shaw, David Simmons, Mariagrazia Uguccioni, Ellen van der Schoot, Eric Vivier, Heddy Zola
Journal: Blood (2002)
Combination Antifungal Therapy for Cryptococcal Meningitis
Authors: Jeremy N. Day, Tran T.H. Chau, Marcel Wolbers, Pham P. Mai, Nguyen T. Dung, Nguyen H. Mai, Nguyen H. Phu, Ho D. Nghia, Nguyen D. Phong, Cao Q. Thai, Le H. Thai, Ly V. Chuong, Dinh X. Sinh, Van A. Duong, Thu N. Hoang, Pham T. Diep, James I. Campbell, Tran P.M. Sieu, Stephen G. Baker, Nguyen V.V. Chau, Tran T. Hien, David G. Lalloo, Jeremy J. Farrar
Journal: New England Journal of Medicine (2013)

Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.
Th2 signals induce epithelial injury in mice and are compatible with the biliary atresia phenotype
Authors: Jun Li, Kazuhiko Bessho, Pranavkumar Shivakumar, Reena Mourya, Sujit Kumar Mohanty, Jorge L. dos Santos, Irene K. Miura, Gilda Porta, Jorge A. Bezerra
Journal: Journal of Clinical Investigation (2011)

Biliary atresia (BA) is a destructive cholangiopathy of childhood in which Th1 immunity has been mechanistically linked to the bile duct inflammation and obstruction that culminate in liver injury. Based on reports of decreased Th1 cytokines in some patients and the development of BA in mice lacking CD4+ T cells, we hypothesized that Th1-independent mechanisms can also activate effector cells and induce BA. Here, we tested this hypothesis using Stat1–/– mice, which lack the ability to mount Th1 immune responses. Infection of Stat1–/– mice with rhesus rotavirus type A (RRV) on postnatal day 1 induced a prominent Th2 response, duct epithelial injury and obstruction within 7 days, and atresia shortly thereafter. A high degree of phosphorylation of the Th2 transcription factor Stat6 was observed; however, concurrent inactivation of Stat1 and Stat6 in mice did not prevent BA after RRV infection. In contrast, depletion of macrophages or combined loss of Il13 and Stat1 reduced tissue infiltration by lymphocytes and myeloid cells, maintained epithelial integrity, and prevented duct obstruction. In concordance with our mouse model, humans at the time of BA diagnosis exhibited differential hepatic expression of Th2 genes and serum Th2 cytokines. These findings demonstrate compatibility between Th2 commitment and the pathogenesis of BA, and suggest that patient subgrouping in future clinical trials should account for differences in Th2 status.
<i>MECP2</i>Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism That Mimics the Role of Activated RAS in Malignancy
Authors: Manish Neupane, Allison P. Clark, Serena Landini, Nicolai J. Birkbak, Aron C. Eklund, Elgene Lim, Aedin C. Culhane, William T. Barry, Steven E. Schumacher, Rameen Beroukhim, Zoltan Szallasi, Marc Vidal, David E. Hill, Daniel P. Silver
Journal: Cancer Discovery (2015)

Abstract An unbiased genome-scale screen for unmutated genes that drive cancer growth when overexpressed identified methyl cytosine-guanine dinucleotide (CpG) binding protein 2 (MECP2) as a novel oncogene. MECP2 resides in a region of the X-chromosome that is significantly amplified across 18% of cancers, and many cancer cell lines have amplified, overexpressed MECP2 and are dependent on MECP2 expression for growth. MECP2 copy-number gain and RAS family member alterations are mutually exclusive in several cancer types. The MECP2 splicing isoforms activate the major growth factor pathways targeted by activated RAS, the MAPK and PI3K pathways. MECP2 rescued the growth of a KRASG12C-addicted cell line after KRAS downregulation, and activated KRAS rescues the growth of an MECP2-addicted cell line after MECP2 downregulation. MECP2 binding to the epigenetic modification 5-hydroxymethylcytosine is required for efficient transformation. These observations suggest that MECP2 is a commonly amplified oncogene with an unusual epigenetic mode of action. Significance: MECP2 is a commonly amplified oncogene in human malignancies with a unique epigenetic mechanism of action. Cancer Discov; 6(1); 45–58. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 1
Neuronal Guidance Protein Netrin-1 Induces Differentiation in Human Embryonal Carcinoma Cells
Authors: Mario Mancino, Claudia Esposito, Kazuhide Watanabe, Tadahiro Nagaoka, Monica Gonzales, Caterina Bianco, Nicola Normanno, David S. Salomon, Luigi Strizzi
Journal: Cancer Research (2009)

Abstract Pluripotent cells within embryonal carcinoma (EC) can differentiate in vivo or in vitro on treatment with specific agents. Differentiating EC cells express lower levels of stem cell–related genes, such as Cripto-1. We show that migration of human EC cells (NTERA/2 and NCCIT) can be reduced following treatment with the guidance molecule Netrin-1. Moreover, Netrin-1 treatment increased the levels of β-III tubulin, glial filament acidic protein, Nestin, and γ-aminobutyric acid and reduced the expressions of Cripto-1, Nanog, and Oct4 in EC cells. These Netrin-1–induced effects in the EC cells were mediated via binding of Netrin-1 to the Neogenin receptor and activation of SHP-2, resulting in increased levels of inactive phosphorylated c-src(Y527). These results suggest that Netrin-1 can induce neuroectodermal-like differentiation of human EC cells by affecting c-src signaling via SHP-2 activation and regulation of Nanog, Oct4, and Cripto-1 expressions. [Cancer Res 2009;69(5):1717–21]
Effectiveness of supervised training program about spirometry in primary care
Authors: Cristina Represas-Represas, Virginia Leiro-Fernández, Maribel Botana-Rial, Ana Isabel González-Silva, Alberto Fernández-Villar
Journal: European Respiratory Journal (2011)

Spirometry is an essential technique for diagnosing respiratory diseases but it is underused at Primary Care (PC) level. Training could help to improve the situation.   Objectives:  To analyze the effectiveness of 2 months supervised training program about spirometry performance and interpretation.   Methodology:  Interventional study, with measurements before and after, to improve the quality. Target population: doctors and nurses team, of 26 PC centers. Teachers: pulmonologists from our hospital (CHUVI). We designed a structured program showed in figure 1.  To assess the effectiveness of the course, students were evaluated with a test-exam composed of 5 spirometries with 2 questions each one, at three diferents times: before initial training (test 1), at the end of the first working day (test 2), and on the 2nd working day (final test).   Results:  Of 74 students, 72 (97.2%) completed training and 90% passed the exam. The mean punctuation in the different tests were: 4.1±1.9 in test 1, 7.5±1.6 in test 2 and 8.9±1.3 in the final test (p    Conclusions:  An spirometry training program based on theoretical and practical workshops, and practical monitoring improves significantly the competence of PC professionals in the performance and interpretation of this technique.
Does HLA-G prevent tissue destruction in psoriasis?
Authors: C. Sweeney, B. Kirby
Journal: British Journal of Dermatology (2011)

Journal Article Does HLA‐G prevent tissue destruction in psoriasis? Get access C. Sweeney, C. Sweeney Department of Dermatology, St Vincent’s University Hospital, University College Dublin, Elm Park, Dublin 4, Ireland E‐mail: chsweene@tcd.ie Search for other works by this author on: Oxford Academic Google Scholar B. Kirby B. Kirby Department of Dermatology, St Vincent’s University Hospital, University College Dublin, Elm Park, Dublin 4, Ireland E‐mail: chsweene@tcd.ie Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 5, 1 May 2011, Pages 1118–1119, https://doi.org/10.1111/j.1365-2133.2011.10222.x Published: 01 May 2011
The role of superoxide anion and hydrogen peroxide in phagocytosis-associated oxidative metabolic reactions.
Authors: R L Baehner, S K Murrmann, J Davis, R B Johnston
Journal: Journal of Clinical Investigation (1975)

The contribution of hydrogen peroxide (H2O2) and one of its unstable intermediates, superoxide anion (O2), to the oxidative reactions that occur in phagocytizing leukocytes was explored by depleting these cells of O2. This was accomplished by allowing them to phagocytize latex particles coated with superoxide dismutase (SOD), which catalyzes the generation of H2O2 from O2. Although the rate and extent of phagocytosis of latex coated with bovine serum albumin was similar to latex coated with SOD, the rate of oxygen consumption, [14C]formate oxidation, [1-14C]glucose oxidation, and iodination of zymosan particles was significantly enhanced by SOD. In contrast, the rate and extent of reduction of nitroblue tetrazolium (NBT) was diminished by 60%. These studies indicate that the majority of NBT reduction by leukocytes is due to O2, whereas stimulation of the hexose monophosphate shunt and iodination of ingested particles requires H2O2 generated from the increased reduction of oxygen by phagocytizing leukocytes.
Regulated tissue- and cell-specific expression of the human renin gene in transgenic mice.
Authors: C D Sigmund, C A Jones, C M Kane, C Wu, J A Lang, K W Gross
Journal: Circulation Research (1992)

Transgenic mice containing the human renin gene were constructed with the aim of examining the tissue- and cell-specific expression of human renin. The human renin transgene used consisted of a genomic sequence extending approximately 900 bp upstream and 400 bp downstream of the coding region and included all exon and intron sequences. Two assays were developed to differentiate human renin transcripts from endogenous mouse renin transcripts at the whole-tissue level. High level human renin expression was evident in the kidney, adrenal gland, ovary, testis, lung, and adipose tissue of all four transgenic lines examined. Human renin mRNA could also be detected at lower levels in the submandibular gland and heart of two different individual lines. No expression was evident in the liver or brain of any line tested. In situ hybridization revealed the human renin mRNA to be localized and exquisitely restricted to renal juxtaglomerular cells. Treatment of transgenic mice with captopril resulted in an increase in the accumulation of renal renin mRNAs derived from both the mouse and human renin genes. Plasma renin activity assays using synthetic human renin substrate clearly demonstrated the elaboration of active human renin into the systemic circulation of transgenic mice. These data strongly suggest that the human renin transgene exhibits both tissue- and cell-specific expression in transgenic mice. Its expression is entrained to the same regulatory signals as the endogenous renin gene in kidney, and active human renin is released into the plasma of the transgenic mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Carcinoembryonic Antigen–Targeted Selective Gene Therapy for Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors
Authors: Toshihiro Tanaka, Jianhua Huang, Sachie Hirai, Motomu Kuroki, Masahide Kuroki, Naoki Watanabe, Kei Tomihara, Kazunori Kato, Hirofumi Hamada
Journal: Clinical Cancer Research (2006)

Abstract Purpose: A major problem when using the adenoviral vectors for gene therapy applications is thought to be related to low transduction efficiency in cancer cells or to side effects in normal cells. There is an urgent requirement to improve the specificity of gene delivery in the context of cancer gene therapy. Experimental Design: We constructed a genetically modified adenovirus incorporating an IgG Fc-binding motif from the Staphylococcus protein A, Z33, within the HI loop (Adv-FZ33). A remarkable degree of targeted gene delivery to gastric cancer cells was obtained with Adv-FZ33 with the fully human anti–carcinoembryonic antigen (CEA) monoclonal antibody, C2-45. Results: In vitro LacZ or EGFP gene expression after Adv-FZ33 infection via C2-45 was 20 times higher than control monoclonal antibody in MKN-45 at 1,000 viral particles/cell. We generated Ax3CAUP-FZ33 (UP-FZ33), which is an Adv-FZ33 derivative vector expressing a therapeutic gene (i.e., Escherichia coli uracil phosphoribosyltransferase), which converts 5-fluorouracil (5-FU) directly to 5-fluoro-UMP. UP-FZ33 with C2-45 enhanced the cytotoxicity of 5-FU by 10.5-fold in terms of IC50 against MKN-45 compared with control IgG4. In a nude mouse peritoneal dissemination model, tumor growth in mice treated with UP-FZ33/C2-45/5-FU was significantly suppressed, and tumor volumes were less than one-fourth of those of the control IgG4 group (P &amp;lt; 0.05). The median survival time of the UP-FZ33/C2-45/5-FU group was significantly longer than those treated with PBS or 5-FU only (P &amp;lt; 0.01). Conclusions: These data suggest that CEA-targeted FZ33 mutant adenovirus-mediated gene delivery offers a strong and selective therapeutic modality against CEA-producing cancers.
Vertical Targeting of the Phosphatidylinositol-3 Kinase Pathway as a Strategy for Treating Melanoma
Authors: Saadia A. Aziz, Lucia B. Jilaveanu, Christopher Zito, Robert L. Camp, David L. Rimm, Patricia Conrad, Harriet M. Kluger
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Melanoma is relatively resistant to chemotherapy; improved targeting of molecules critical for cell proliferation and survival are needed. Phosphatidylinositol-3 kinase (PI3K) is an important target in melanoma; however, activity of PI3K inhibitors (PI3KI) is limited. Our purpose was to assess mTOR as a cotarget for PI3K. Methods: Using a method of quantitative immunofluorescence to measure mTOR expression in a large melanoma cohort, we studied associations with PI3K subunits, p85 and p110α. We assessed addition of the mTOR inhibitor rapamycin to 2 PI3KIs, NVP-BKM120 and LY294002. We studied in vitro activity of a novel dual PI3K/mTOR inhibitor NVP-BEZ235 and activity of the combination of NVP-BEZ235 and the MAP/ERK kinase (MEK) inhibitor AZD6244. Results: Strong coexpression of mTOR and p110α was observed (ρ = 0.658; P &amp;lt; 0.0001). Less coexpression was seen with p85 (ρ = 0.239; P &amp;lt; 0.0001). Strong synergism was shown between rapamycin and both PI3KIs. Activity of both PI3KIs was similarly enhanced with all rapamycin concentrations used. The dual PI3K/mTOR inhibitor effectively inhibited viability in 23 melanoma cell lines (IC50 values in the nanomolar range), regardless of B-Raf mutation status, with resultant reduction in clonogenicity and downregulation of pAkt and pP70S6K. Synergism was seen when combining NVP-BEZ235 and AZD6244, with resultant increases in poly(ADP-ribose) polymerase and caspase-2 cleavage. Conclusions: mTOR and p110α are coexpressed in melanoma. Rapamycin concentrations as low as 1 nmol/L enhance activity of PI3KIs. The dual PI3K/mTOR inhibitor NVP-BEZ235 is highly active in melanoma cells in vitro, suggesting that concurrent PI3K and mTOR targeting in melanoma warrants further investigation, both alone and in combination with MEK inhibitors.
Temporal Trends in Infective Endocarditis
Authors: Imad M. Tleyjeh, James M. Steckelberg, Hani S. Murad, Nandan S. Anavekar, Hassan M. K. Ghomrawi, Zaur Mirzoyev, Sherif E. Moustafa, Tanya L. Hoskin, Jayawant N. Mandrekar, Walter R. Wilson, Larry M. Baddour
Journal: JAMA (2005)

ristic of the clinical features of infective endocarditis (IE) as described by Osler has undergone a significant change in developed countries. 1,2Previously, IE was a disease that commonly affected patients with predisposing valvular abnormalities caused by rheumatic carditis, with viridans group streptococci the most common causative pathogens. 3This presentation is currently seen in developing countries, where rheumatic heart disease is still prevalent.In developed countries, mitral valve prolapse (MVP) is now thought to be the most common predisposing cardiac condition in patients with IE. 2 Several recent studies from passively reported case series suggest that Staphylococcus aureus is now the most frequently identified causative pathogen. 1These more recent clinical observations of IE characteristics, however, are based on data that come primarily from large, tertiary care centers 4,5 and may not reflect true changes in the epidemiology of IE but rather temporal changes in referral patterns.Thus, population-based investigations are needed to more accurately characterize IE in the United States.Olmsted County, Minnesota, is a setting uniquely qualified for the conduct of population-based studies of dis-See also pp
Massive Pulmonary Carcinoid Tumor Deemed Inoperable until <sup>68</sup>Ga DOTATATE Positron Emission Tomography/Magnetic Resonance Imaging
Authors: K. L. Ordidge, J. M. Brown, L. Succony, N. Navani, G. Hardavella, D. R. Lawrence, F. Fraioli, A. Groves, S. M. Janes
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Risk for Tuberculosis in Child Contacts. Development and Validation of a Predictive Score
Authors: Pei-Chun Chan, Steven Shinn-Forng Peng, Mei-Yu Chiou, Du-Lin Ling, Luan-Yin Chang, Kwei-Feng Wang, Chi-Tai Fang, Li-Min Huang
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Contact investigation of persons exposed to tuberculosis (TB) is resource intensive. To date, no clinical prediction rule for TB risk exists for use as a guide during contact investigation.We sought to develop and validate a simple and easy-to-use predictive score for TB risk, using data routinely available during contact investigation.The derivation cohort consisted of 9,411 children aged 0 to 12 years from 2008 to 2009 national contacts cohort. We used a multivariate Cox proportional hazards model to predict the risk of developing active TB. The validation cohort consisted of 2,405 children from the 2005 national contacts cohort. We calculated area under the receiver operating characteristic curves of the model as well as the predicted risk of TB for contacts with different scores.An 8-point scoring system was developed, including reaction to tuberculin skin test of the contacts, as well as smear-positivity, residence in high-incidence areas, and sex of the index cases. Area under the receiver operating characteristic curve was 0.872 (95% confidence interval, 0.810-0.935) for the derivation cohort and 0.900 (95% confidence interval, 0.830-0.969) for the validation cohort. The risk of developing active TB within 3 years is 100, 7.8, 4.3, 1.0, 0.7, and 0.2% for contacts with risk scores of 7, 6, 5, 4, 3, and 2, respectively.A risk predictive score was developed and validated to identify child contacts aged 0 to 12 years at increased risk for active TB. This predictive score can help to prioritize active case finding or isoniazid preventive therapy among children exposed to TB.