tbuckley/cabot-search huggingface dataset:
Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development
Authors: André Boonstra, Carine Asselin-Paturel, Michel Gilliet, Chad Crain, Giorgio Trinchieri, Yong-Jun Liu, Anne O'Garra
Journal: The Journal of Experimental Medicine (2003)

Distinct dendritic cell (DC) subsets have been suggested to be preprogrammed to direct either T helper cell (Th) type 1 or Th2 development, although more recently different pathogen products or stimuli have been shown to render these DCs more flexible. It is still unclear how distinct mouse DC subsets cultured from bone marrow precursors, blood, or their lymphoid tissue counterparts direct Th differentiation. We show that mouse myeloid and plasmacytoid precursor DCs (pDCs) cultured from bone marrow precursors and ex vivo splenic DC subsets can induce the development of both Th1 and Th2 effector cells depending on the dose of antigen. In general, high antigen doses induced Th1 cell development whereas low antigen doses induced Th2 cell development. Both cultured and ex vivo splenic plasmacytoid-derived DCs enhanced CD4+ T cell proliferation and induced strong Th1 cell development when activated with the Toll-like receptor (TLR)9 ligand CpG, and not with the TLR4 ligand lipopolysaccharide (LPS). The responsiveness of plasmacytoid pDCs to CpG correlated with high TLR9 expression similarly to human plasmacytoid pDCs. Conversely, myeloid DCs generated with granulocyte/macrophage colony-stimulating factor enhanced Th1 cell development when stimulated with LPS as a result of their high level of TLR4 expression. Polarized Th1 responses resulting from high antigen dose were not additionally enhanced by stimulation of DCs by TLR ligands. Thus, the net effect of antigen dose, the state of maturation of the DCs together with the stimulation of DCs by pathogen-derived products, will determine whether a Th1 or Th2 response develops.
Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). II. Comparison of hybridomas derived by lipopolysaccharide stimulation and secondary protein immunization.
Authors: M Shlomchik, D Nemazee, J van Snick, M Weigert
Journal: The Journal of Experimental Medicine (1987)

We have obtained the complete variable region mRNA sequences of 11 LPS-derived and 14 secondary immunization-derived monoclonal IgM anti-IgG antibodies (rheumatoid factors, RFs). A comparative analysis of these sequences showed that monoclonal RFs derived after polyclonal activation are structurally very similar to RFs derived after secondary protein immunization. This study was undertaken to evaluate the potential relationship between two previously described phenomena: (a) during a secondary response to a protein antigen, RF is produced in quantities that equal or exceed the immunogen-specific antibody; and (b) the frequency of B cells that make RF after polyclonal activation is quite high; 3-10%. It has been unclear whether LPS-stimulated cells that produce IgM anti-IgG that is detected by an in vitro assay are related to the cells that produce RF after in vivo stimulation. The similarity of the antigen receptors found in the two types of RF, however, suggests that most or all of the RF-producing B cells detected after LPS stimulation would also be stimulated during the secondary immune response. Thus, the presence of relatively large number of B cells that can make RF after nonspecific stimulation provides an explanation for the magnitude of RF production accompanying the secondary immune response.
Oncolytic Activity of p53-Expressing Conditionally Replicative Adenovirus AdΔ24-p53 against Human Malignant Glioma
Authors: Birgit Geoerger, Gilles Vassal, Paule Opolon, Clemens M. F. Dirven, Jackie Morizet, Lysiane Laudani, Jacques Grill, Giuseppe Giaccone, W. Peter Vandertop, Winald R. Gerritsen, Victor W. van Beusechem
Journal: Cancer Research (2004)

Abstract Prognosis of malignant glioma is poor, and results of treatment remain mediocre. Conditionally replicative adenoviruses hold promise as alternative anticancer agents for the treatment of malignant glioma. Here, we evaluated the conditionally replicative adenovirus AdΔ24 and its recently developed derivative AdΔ24-p53, which expresses functional p53 tumor suppressor protein while replicating in cancer cells, for treatment of malignant glioma. In comparison to its parent AdΔ24, AdΔ24-p53 killed most malignant glioma cell lines and primary glioblastoma multiforme short-term cultures more effectively, irrespective of their p53 status. Moreover, AdΔ24-p53 caused more frequent regression and more delayed growth of IGRG121 xenografts derived from a glioblastoma multiforme in vivo. Five intratumoral injections of 107 pfu AdΔ24 gave 24 days median tumor growth delay (P &amp;lt; 0.01), 30% tumor regressions, and 30% animals surviving &amp;gt;120 days tumor-free or with a minimal tumor residual. The same dose of AdΔ24-p53 caused &amp;gt;113 days of median tumor growth delay (P &amp;lt; 0.001), 70% tumor regressions, and 60% animals surviving &amp;gt;120 days tumor-free or with a minimal tumor residual. Antitumor effects in vivo were associated with extensive conditionally replicative adenovirus replication, apoptosis induction, and tumor morphology changes, including dissociation, inflammatory cell infiltration, and necrosis. We conclude that conditionally replicative adenoviruses expressing p53 are promising new agents for treatment of malignant glioma.
Simple and Complex
Authors: Siyang Leng, Brahmajee K. Nallamothu, Sanjay Saint, Leonard J. Appleman, Gregory M. Bump
Journal: New England Journal of Medicine (2013)

A 44-year-old man presented to the emergency department with chest pain that had started 1 hour earlier and had awakened him from sleep. The pain was severe, substernal, burning, radiating to the left arm, and accompanied by nausea and vomiting.
Postoperative Complications and Mortality Following Colectomy for Ulcerative Colitis
Authors: Shanika de Silva, Christopher Ma, Marie–Claude Proulx, Marcelo Crespin, Belle S. Kaplan, James Hubbard, Martin Prusinkiewicz, Andrew Fong, Remo Panaccione, Subrata Ghosh, Paul L. Beck, Anthony MacLean, Donald Buie, Gilaad G. Kaplan
Journal: Clinical Gastroenterology and Hepatology (2011)
α4β7 independent pathway for CD8+ T cell–mediated intestinal immunity to rotavirus
Authors: Nelly A. Kuklin, Lusijah Rott, Jama Darling, James J. Campbell, Manuel Franco, Ningguo Feng, Werner Müller, Norbert Wagner, John Altman, Eugene C. Butcher, Harry B. Greenberg
Journal: Journal of Clinical Investigation (2000)

Rotavirus (RV), which replicates exclusively in cells of the small intestine, is the most important cause of severe diarrhea in young children worldwide. Using a mouse model, we show that expression of the intestinal homing integrin α4β7 is not essential for CD8+ T cells to migrate to the intestine or provide immunity to RV. Mice deficient in β7 expression (β7–/–) and unable to express α4β7 integrin were found to clear RV as quickly as wild-type (wt) animals. Depletion of CD8+ T cells in β7–/– animals prolonged viral shedding, and transfer of immune β7–/– CD8+ T cells into chronically infected Rag-2–deficient mice resolved RV infection as efficiently as wt CD8+ T cells. Paradoxically, α4β7hi memory CD8+ T cells purified from wt mice that had been orally immunized cleared RV more efficiently than α4β7low CD8+ T cells. We explained this apparent contradiction by demonstrating that expression of α4β7 on effector CD8+ T cells depends upon the site of initial antigen exposure: oral immunization generates RV-specific CD8+ T cells primarily of an α4β7hi phenotype, but subcutaneous immunization yields both α4β7hi and α4β7low immune CD8+ T cells with anti-RV effector capabilities. Thus, α4β7 facilitates normal intestinal immune trafficking to the gut, but it is not required for effective CD8+ T cell immunity.
Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression
Authors: Helen Court, Marc Amoyel, Michael Hackman, Kyoung Eun Lee, Ruliang Xu, George Miller, Dafna Bar-Sagi, Erika A. Bach, Martin O. BergÃ¶, Mark R. Philips
Journal: Journal of Clinical Investigation (2013)

RAS is the most frequently mutated oncogene in human cancers. Despite decades of effort, anti-RAS therapies have remained elusive. Isoprenylcysteine carboxylmethyltransferase (ICMT) methylates RAS and other CaaX-containing proteins, but its potential as a target for cancer therapy has not been fully evaluated. We crossed a Pdx1-Cre;LSL-KrasG12D mouse, which is a model of pancreatic ductal adenocarcinoma (PDA), with a mouse harboring a floxed allele of Icmt. Surprisingly, we found that ICMT deficiency dramatically accelerated the development and progression of neoplasia. ICMT-deficient pancreatic ductal epithelial cells had a slight growth advantage and were resistant to premature senescence by a mechanism that involved suppression of cyclin-dependent kinase inhibitor 2A (p16INK4A) expression. ICMT deficiency precisely phenocopied Notch1 deficiency in the Pdx1-Cre;LSL-KrasG12D model by exacerbating pancreatic intraepithelial neoplasias, promoting facial papillomas, and derepressing Wnt signaling. Silencing ICMT in human osteosarcoma cells decreased Notch1 signaling in response to stimulation with cell-surface ligands. Additionally, targeted silencing of Ste14, the Drosophila homolog of Icmt, resulted in defects in wing development, consistent with Notch loss of function. Our data suggest that ICMT behaves like a tumor suppressor in PDA because it is required for Notch1 signaling.
Th1 and Th17 Cells Induce Proliferative Glomerulonephritis
Authors: Shaun A. Summers, Oliver M. Steinmetz, Ming Li, Joshua Y. Kausman, Timothy Semple, Kristy L. Edgtton, Dorin-Bogdan Borza, Hal Braley, Stephen R. Holdsworth, A. Richard Kitching
Journal: Journal of the American Society of Nephrology (2009)

Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1(-/-) mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against alpha3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 +/- 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies.
Effectiveness of Psychotherapy for Personality Disorders
Authors: J. Christopher Perry, Elisabeth Banon, Floriana Ianni
Journal: American Journal of Psychiatry (1999)

The authors examined the evidence for the effectiveness of psychotherapy for personality disorders in psychotherapy outcome studies.Fifteen studies were located that reported data on pretreatment-to-posttreatment effects and/or recovery at follow-up, including three randomized, controlled treatment trials, three randomized comparisons of active treatments, and nine uncontrolled observational studies. They included psychodynamic/interpersonal, cognitive behavior, mixed, and supportive therapies.All studies reported improvement in personality disorders with psychotherapy. The mean pre-post effect sizes within treatments were large: 1.11 for self-report measures and 1.29 for observational measures. Among the three randomized, controlled treatment trials, active psychotherapy was more effective than no treatment according to self-report measures. In four studies, a mean of 52% of patients remaining in therapy recovered--defined as no longer meeting the full criteria for personality disorder--after a mean of 1.3 years of treatment. A heuristic model based on these findings estimated that 25.8% of personality disorder patients recovered per year of therapy, a rate sevenfold larger than that in a published model of the natural history of borderline personality disorder (3.7% recovered per year, with recovery of 50% of patients requiring 10.5 years of naturalistic follow-up).Psychotherapy is an effective treatment for personality disorders and may be associated with up to a sevenfold faster rate of recovery in comparison with the natural history of disorders. Future studies should examine specific therapies for specific personality disorders, using more uniform assessment of core pathology and outcome.
The Textbook of Rheumatology.
Authors: C. DEIGHTON, P. PERKINS
Journal: Annals of the Rheumatic Diseases (1997)

The Textbook of Rheumatology. Edited by William N Kelley, et al . (Pp 1792; £179) Philadelphia, PA: WB Saunders, 1997. 5th ed. ISBN0-7216-5692-7.

CMD was given the honour of reviewing the fourth edition of this encyclopaedic textbook (Ann Rheum Dis 1994;53:89). He had the following criticisms to make on that occasion:

(1) Huge tomes go quickly out of date, particularly when CD roms and computer literature searches are readily available.

(2) Some chapters were unpalatable to a wide rheumatology audience and there was unnecessary overlap between chapters.

(3) Summaries, conclusions, tables instead of text, and diagrams and pictures were …
The state of health in the Arab world, 1990–2010: an analysis of the burden of diseases, injuries, and risk factors
Authors: Ali H Mokdad, Sara Jaber, Muna I Abdel Aziz, Fadia AlBuhairan, Abduljabbar AlGhaithi, Nawal M AlHamad, Suad N Al-Hooti, Adel Al-Jasari, Mohammad A AlMazroa, Ahmed Mohamed AlQasmi, Shirina Alsowaidi, Majed Asad, Charles Atkinson, Alaa Badawi, Talal Bakfalouni, AbdelAziz Barkia, Stan Biryukov, Charbel El Bcheraoui, Farah Daoud, Mohammad Hossein Forouzanfar, Diego Gonzalez-Medina, Randah R Hamadeh, Mohamed Hsairi, Seifeddin Saleh Hussein, Nadim Karam, Shams Eldin Ali Hassan Khalifa, Tawfik A M Khoja, Faris Lami, Katherine Leach-Kemon, Ziad A Memish, Ali A Mokdad, Mohsen Naghavi, Jamal Nasher, M Bassam Hijawi Qasem, Mohammad Shuaib, Al Anoud M Al Thani, Mohamed H Al Thani, Mohammed Zamakhshary, Alan D Lopez, Christopher J L Murray
Journal: The Lancet (2014)
Incidence of cancer in the general population and in patients with or without atopic dermatitis in the U.K.
Authors: A. Arana, C.E. Wentworth, C. Fernández-Vidaurre, R.G. Schlienger, E. Conde, F.M. Arellano
Journal: British Journal of Dermatology (2010)

Background Atopic dermatitis (AD) affects approximately 20% of children and 1–3% of adults in developed countries. Objective To study the incidence of cancer in patients with AD in the U.K. general population. Methods We conducted a follow-up study in the U.K. using The Health Improvement Network (THIN) database. We calculated the incidence rate (IR) of the first occurrence of overall cancer, lymphoma, melanoma and nonmelanoma skin cancer (NMSC) in the general population, in patients with AD and in individuals without AD. In addition we calculated the IR ratio (IRR) of overall cancer and subtypes of cancer in patients with AD vs. those without. Results The study population included 4 518 131 patients [2 336 230 (51·7%) female]. There were 129 972 subjects [68 688 (52·8%) female] with a diagnosis of cancer (excluding NMSC). The IR (per 10 000 person-years) of cancer (excluding NMSC) was 42·41 [95% confidence interval (CI) 42·18–42·64]; of lymphoma 1·70 (95% CI 1·65–1·74); of skin melanoma 1·71 (95% CI 1·67–1·76) and of NMSC 11·76 (95% CI 11·64–11·88). The age- and sex-adjusted IRR for cancer (excluding NMSC) was 1·49 (95% CI 1·39–1·61); for lymphoma 2·21 (95% CI 1·65–2·98); for melanoma 1·74 (95% CI 1·25–2·41); and for NMSC 1·46 (95% CI 1·27–1·69). Conclusions Our results indicate an increased incidence of cancer overall as well as of specific cancer subtypes, including lymphoma, in patients with AD. Further studies are needed to disentangle the effects of treatment for AD from AD itself.
FAVORABLE EFFECTS OF HIGH DOSE ATORVASTATIN TREATMENT ON ARTERIAL WALL PROPERTIES AND INFLAMMATORY PROCESS IN ISCHEMIC HEART FAILURE
Authors: Evangelos Oikonomou, Gerasimos Siasos, Dimitris Tousoulis, Marina Zaromitidou, Christine Chrysohoou, Konstantinos Maniatis, Stavroula Michalea, Antigoni Miliou, Konstantinos Zisimos, Stamatios Kioufis, Christina Kollia, Athanasios G. Papavassiliou, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2012)
High plasma cardiac natriuretic peptides associated with enhanced cyclic guanosine monophosphate production in preascitic cirrhosis
Authors: Tadashi Iwao, Kazuhiko Oho, Ryohichi Nakano, Teruhiro Sakai, Masahiro Sato, Yasunao Miyamoto, Masafumi Kumamoto, Kenji Sakai, Michio Sata, Atsushi Toyonaga
Journal: Journal of Hepatology (2000)
Rebamipide Suppresses Collagen‐Induced Arthritis Through Reciprocal Regulation of Th17/Treg Cell Differentiation and Heme Oxygenase 1 Induction
Authors: Su‐Jin Moon, Jin‐Sil Park, Yun‐Ju Woo, Mi‐Ae Lim, Sung‐Min Kim, Seon‐Yeong Lee, Eun‐Kyung Kim, Hee Jin Lee, Weon Sun Lee, Sang‐Hi Park, Jeong‐Hee Jeong, Sung‐Hwan Park, Ho‐Youn Kim, Mi‐La Cho, Jun‐Ki Min
Journal: Arthritis & Rheumatology (2013)

Rebamipide, a gastroprotective agent, has the ability to scavenge reactive oxygen radicals. Increased oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to investigate the impact of rebamipide on the development of arthritis and the pathophysiologic mechanisms by which rebamipide attenuates arthritis severity in a murine model of RA.Collagen-induced arthritis (CIA) was induced in DBA/1J mice. Anti-type II collagen antibody titers and interleukin-17 (IL-17) levels were determined using enzyme-linked immunosorbent assay. The expression of transcription factors was analyzed by immunostaining and Western blotting. Frequencies of IL-17-producing CD4+ T cells (Th17 cells) and CD4+CD25+FoxP3+ Treg cells were analyzed by flow cytometry.Rebamipide reduced the clinical arthritis score and severity of histologic inflammation and cartilage destruction in a dose-dependent manner. The joints isolated from rebamipide-treated mice with CIA showed decreased expression of nitrotyrosine, an oxidative stress marker. Rebamipide-treated mice showed lower circulating levels of type II collagen-specific IgG, IgG1, and IgG2a. Whereas the number of Th17 cells in spleens was decreased in rebamipide-treated mice with CIA, a significant increase in the number of Treg cells in spleens was observed. In vitro, rebamipide inhibited Th17 cell differentiation through STAT-3/retinoic acid receptor-related orphan nuclear receptor γt and reciprocally induced Treg cell differentiation through FoxP3. Rebamipide increased Nrf2 nuclear activities in murine CD4+ T cells and LBRM-33 murine T lymphoma cells. Heme oxygenase 1 (HO-1) expression in the spleens was markedly increased in rebamipide-treated mice.The inhibitory effects of rebamipide on joint inflammation are associated with recovery from an imbalance between Th17 cells and Treg cells and with activation of an Nrf2/HO-1 antioxidant pathway.
Pericardial mesothelioma presenting as systemic lupus erythematosus.
Authors: L McGuigan, A Fleming
Journal: Annals of the Rheumatic Diseases (1984)

A case of mesothelioma of the pericardium with many features of systemic lupus erythematosus (SLE) is described. We stress that satisfaction of the American Rheumatism Association9s classification criteria for SLE does not confirm the diagnosis, even though their diagnostic sensitivity and specificity has recently been improved.
A Single Nucleotide Polymorphism Chip-Based Method for Combined Genetic and Epigenetic Profiling: Validation in Decitabine Therapy and Tumor/Normal Comparisons
Authors: Eric Yuan, Fatemeh Haghighi, Susan White, Ramiro Costa, Julie McMinn, Kathy Chun, Mark Minden, Benjamin Tycko
Journal: Cancer Research (2006)

Progress on several unresolved issues in cancer epigenetics will benefit from rapid and standardized methods for profiling DNA methylation genome-wide. In the area of epigenetic therapy, the demethylating drug decitabine (5-aza-2'-deoxycytidine) is increasingly used to treat acute myelogenous leukemia and myelodysplastic syndrome, but the mechanisms of its anticancer activity have remained unclear. Given the clinical efficacy of decitabine and the uncertainties about its mode of action, it will be useful to optimize methods for following DNA methylation as a biochemical response in individual patients. Here, we describe a single nucleotide polymorphism (SNP) chip-based method (MSNP) for profiling DNA methylation. Using this procedure, the extent of demethylation in bone marrow aspirates from patients with leukemia receiving decitabine can be assessed genome-wide using commercially available (Affymetrix) SNP chips. We validated the accuracy of MSNP by comparing the results with combined bisulfite restriction analysis and by sequencing cloned PCR products from bisulfite-converted DNA. We further validated MSNP in a Wilms' tumor/normal kidney comparison, comparing the results with methylation-sensitive Southern blotting. MSNP simultaneously detects aberrations in DNA copy number and loss of heterozygosity, making it a generally useful approach for combined genetic and epigenetic profiling in tissue samples from cancer patients.
Empirical Diagnosis of Pneumocystis carinii Pneumonia
Authors: Robert Moskowitz
Journal: JAMA (1988)

To the Editor.  —In a recent Letter to the Editor, Chaisson and Hopewell 1 stated that Pneumocystis carinii pneumonia (PCP) should only be diagnosed by microscopic confirmation. We recently cared for two patients with clinical PCP in whom induced sputum and bronchoalveolar lavage specimens did not reveal P carinii when appropriately stained; however, both had a dramatic response to empirical therapy, which left us with a diagnostic dilemma.  Report of Cases.—Case 1.  —A 35-year-old man who was positive for human immunodeficiency virus antibody and who was a former intravenous drug abuser presented with a localized herpes zoster infection. Three weeks later, fever, headaches, and right-sided focal neurological defects developed. Computed tomography of the head revealed enhancing lesions consistent with toxoplasmosis and therapy with pyrimethamine and a sulfadiazine was begun. A diffuse rash developed that resolved when the sulfadiazine therapy was discontinued, so clindamycin was substituted. A few weeks later, he
Relevant impact of central pathology review on nodal classification in individual breast cancer patients
Authors: J.H.M.J. Vestjens, M.J. Pepels, M. de Boer, G.F. Borm, C.H. M. van Deurzen, P.J. van Diest, J.A.A.M. van Dijck, E.M.M. Adang, J.W.R. Nortier, E.J. Th. Rutgers, C. Seynaeve, M.B.E. Menke-Pluymers, P. Bult, V.C.G. Tjan-Heijnen
Journal: Annals of Oncology (2012)
Glomerular Injury in Patients with Neoplasia
Authors: B. S. Kaplan, J. Klassen, M. H. Gault
Journal: Annual Review of Medicine (1976)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More