tbuckley/cabot-search huggingface dataset:
CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO
Authors: Marc Feldmann, Antony Basten
Journal: The Journal of Experimental Medicine (1972)

The role of soluble factors in cell collaboration was investigated by means of a tissue culture system in which populations of T and B cells were either incubated together or separated from each other by cell impermeable membranes. Histoincompatible T cells were found to augment antibody responses to both thymus-dependent and thymus-independent antigens, whether they were in contact with B cells or not. The properties of the factor released by the T cells in the allogeneic mixture were compared with those of the previously reported antigen-specific mediator found in syngeneic collaborative antibody responses. Unlike the latter, the factor made in allogeneic responses failed to display any degree of antigen specificity either in its induction or in its action, enhancing responses to all the antigens present in the cultures to a similar degree. It was of lower molecular weight than the antigen-specific factor, because it could pass through dialysis membranes as well as nuclepore membranes, whereas the antigen-specific factor could only penetrate nuclepore membranes. Furthermore, the factor made in allogeneic reactions had a different site of action. It acted directly on B lymphocytes, whereas the antigen-specific component acts through macrophages. Although antigen in the presence of the allogeneic factor did not initiate antibody production, it augmented responses once they had been induced by a matrix of antigenic determinants, either mediated by the antigen-specific factor or directly by a thymus-independent antigen. It was therefore considered to act at a later stage of the antibody response, probably as a nonspecific stimulator of immune B cell proliferation. Observations that the effect on the allogeneic factor are more pronounced 2 days after the beginning of the response are in keeping with this interpretation.
A case of secondary Sjogren's syndrome with a swollen thigh
Authors: A. A Deodhar, M. G Bruce, K. D Krohn, R. M Bennett
Journal: Annals of the Rheumatic Diseases (1997)

A 73 year old English woman with seropositive, nodular, severe destructive rheumatoid arthritis (RA) and secondary Sjogren’s syndrome was seen with a 10 day history of pain and five day history of swelling in the left thigh.

She reported that she got out of bed 10 days ago, and felt pain in her left thigh, which she presumed to be a pulled muscle. She had difficulty in weight bearing and walking, but continued her already limited daily activities in a sheltered accommodation. Five days after this episode she noticed generalised swelling of her left thigh and developed fever (38.5°C), chills, headache, and malaise. The fever and associated symptoms resolved with high doses of acetaminophan, but the thigh pain and swelling progressively worsened to where she became bedridden. She had no history of swelling in her calves, recent surgery, prolonged immobilisation or any injury to her left thigh before the onset of pain.

Her past medical history was notable for debilitating RA of 30 years duration. Over the years, she had had bilateral hip arthroplasties and hand surgeries. She had developed a severe secondary Sjogren’s syndrome (diagnosis based on clinical criteria only) with corneal ulcerations despite regular use of artificial tears and protective glasses. She had lost all of her teeth except five; she wore dentures and used artificial saliva. Over the past eight years her RA was stable with prednisone 5 mg per day, methotrexate 7.5 mg orally per week, and nabumetone 500 mg twice a day. She was a widow and lived alone in a sheltered accommodation. She did not smoke. Her son and daughter in law who lived in the same town, helped her …
INDUCTION OF CYTOCHROME P4501A1
Authors: James P. Whitlock
Journal: The Annual Review of Pharmacology and Toxicology (1999)

▪ Abstract Cytochrome P4501A1 is a substrate-inducible microsomal enzyme that oxygenates polycyclic aromatic hydrocarbons, such as the carcinogen benzo(a)pyrene, as the initial step in their metabolic processing to water-soluble derivatives. Enzyme induction reflects increased transcription of the cognate CYP1A1 gene. The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin is the most potent known cytochrome P4501A1 inducer. Two regulatory proteins, the aromatic (aryl) hydrocarbon receptor (AhR) and the AhR nuclear translocator (Arnt), mediate induction. AhR and Arnt are prototypical members of the basic helix-loop-helix/Per-Arnt-Sim class of transcription factors. Mechanistic analyses of cytochrome P4501A1 induction provide insights into ligand-dependent mammalian gene expression, basic helix-loop-helix/Per-Arnt-Sim protein function, and dioxin action; such studies also impact public health issues concerned with molecular epidemiology, carcinogenesis, and risk assessment.
BCL6 is critical for the development of a diverse primary B cell repertoire
Authors: Cihangir Duy, J. Jessica Yu, Rahul Nahar, Srividya Swaminathan, Soo-Mi Kweon, Jose M. Polo, Ester Valls, Lars Klemm, Seyedmehdi Shojaee, Leandro Cerchietti, Wolfgang Schuh, Hans-Martin Jäck, Christian Hurtz, Parham Ramezani-Rad, Sebastian Herzog, Hassan Jumaa, H. Phillip Koeffler, Ignacio Moreno de Alborán, Ari M. Melnick, B. Hilda Ye, Markus Müschen
Journal: The Journal of Experimental Medicine (2010)

BCL6 protects germinal center (GC) B cells against DNA damage–induced apoptosis during somatic hypermutation and class-switch recombination. Although expression of BCL6 was not found in early IL-7–dependent B cell precursors, we report that IL-7Rα–Stat5 signaling negatively regulates BCL6. Upon productive VH-DJH gene rearrangement and expression of a μ heavy chain, however, activation of pre–B cell receptor signaling strongly induces BCL6 expression, whereas IL-7Rα–Stat5 signaling is attenuated. At the transition from IL-7–dependent to –independent stages of B cell development, BCL6 is activated, reaches expression levels resembling those in GC B cells, and protects pre–B cells from DNA damage–induced apoptosis during immunoglobulin (Ig) light chain gene recombination. In the absence of BCL6, DNA breaks during Ig light chain gene rearrangement lead to excessive up-regulation of Arf and p53. As a consequence, the pool of new bone marrow immature B cells is markedly reduced in size and clonal diversity. We conclude that negative regulation of Arf by BCL6 is required for pre–B cell self-renewal and the formation of a diverse polyclonal B cell repertoire.
<i>In vitro</i> Induction of Myeloid Leukemia–Specific CD4 and CD8 T Cells by CD40 Ligand – Activated B Cells Gene Modified to Express Primary Granule Proteins
Authors: Hiroshi Fujiwara, J. Joseph Melenhorst, Frank El Ouriaghli, Sachiko Kajigaya, Matthias Grube, Giuseppe Sconocchia, Katayoun Rezvani, David A. Price, Nancy F. Hensel, Daniel C. Douek, A. John Barrett
Journal: Clinical Cancer Research (2005)

Abstract The primary granule proteins (PGP) of myeloid cells are a source of multiple antigens with immunotherapeutic potential for myeloid leukemias. Therefore, we developed a method to induce T-cell responses to PGP protein sequences. We found that gene-transfected antigen-presenting cells efficiently expand functionally competent PGP-specific CD4 and CD8 T cells. The system was optimized using T-cell responses to autologous CD40-activated B cells (CD40-B) transfected with a cytomegalovirus pp65-encoding expression vector. To generate leukemia-specific T cells, expression vectors encoding the PGP proteinase 3 (PR3), human neutrophil elastase, and cathepsin-G were transfected into CD40-B cells to stimulate postallogeneic stem cell transplantation T cells from five patients with myeloid and three with lymphoid leukemias. T-cell responses to PGP proteinase 3 and human neutrophil elastase were observed in CD8+ and CD4+ T cells only in patients with myeloid leukemias. T-cell responses against cathepsin-G occurred in both myeloid and lymphoblastic leukemias. T cells from a patient with chronic myelogenous leukemia (CML) and from a posttransplant CML patient, expanded against PGP, produced IFN-γ or were cytotoxic to the patient's CML cells, demonstrating specific antileukemic efficacy. This study emphasizes the clinical potential of PGP for expansion and adoptive transfer of polyclonal leukemia antigen-specific T cells to treat leukemia.
Lentigo maligna and lentigo maligna melanoma
Authors: Robert H. Johr, Wilhelm Stolz
Journal: Journal of the American Academy of Dermatology (1997)

We enjoyed reading the CME article on lentigo maligna and lentigo maligna melanoma by Cohen in the December 1995 issue of the Journal (1995;33:923-36). The article did, however, fail to mention dermatoscopy (skin surface microscopy, epiluminescence microscopy [ELM]) as a tool that is available for clinicians to help differentiate these potentially serious pigmented skin lesions from more banal pathology, such as seborrheic keratosis or lentigines. Dermatoscopy is an in vivo, noninvasive examination of skin lesions with the use of a hand-held microscope (Dermatoscope by Heine USA, Episcope by Welch Allyn), stereomicroscopes, or digital imaging computer systems and some type of oil/fluid immersion. The liquid applied to the lesion eliminates the reflection of light from the surface of the skin and subsurface colors, and structures in the epidermis, dermoepidermal junction, and papillary dermis become visible that cannot be seen with the naked eye, even with normal magnification typically used by clinicians. The major advantages of dermatoscopy are the differentiation of melanocytic from nonmelanocytic pigmented skin lesions, differentiation of benign from malignant skin lesions, minimization of unnecessary surgery, choice of appropriate surgical procedures, and patient reassurance. On the face, one can see with dermatoscopy skin appendages that appear as uniform white circles, often with hyperpigmented rims or borders. When the hyperpigmented borders touch each other, a networklike appearance is seen. This has been defined as the pseudopigment network. Normally, the pseudopigment network appears regular in terms of the color, thickness, and symmetry of the line segments and light areas. By definition, a rhomboid is a parallelogram with unequal sides and angles. The rhomboid pattern is formed when the monomorphous, uniform appearance of the pseudopigment network forms line segments that become thickened, irregular in size and shape, forming rhomboids with loss of symmetry within the lesion. The degree of changes that can be seen with the pseudopigment network vary with each lesion. At times, they can be subtle or pronounced. This pattern, when seen under the dermatoscope, is highly suggestive of lentigo maligna. In addition, if there are discrete structureless areas of hyperpigmentation, the possibility of dermal invasion and lentigo maligna melanoma should be considered. Although no formal studies have been performed on the sensitivity, specificity, and diagnostic accuracy of the rhomboid pattern, in our experience it is not only a helpful sign that a banal-appearing equivocally pigmented skin lesion might be of more importance, but this technique can be useful in localizing more specifically the best area for biopsy.
Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review
Authors: Roberto Stasi, Ameet Sarpatwari, Jodi B. Segal, John Osborn, Maria Laura Evangelista, Nichola Cooper, Drew Provan, Adrian Newland, Sergio Amadori, James B. Bussel
Journal: Blood (2008)
Spanish authorities investigate how nurse contracted Ebola
Authors: A. Gulland
Journal: BMJ (2014)

Spanish authorities are investigating how a nurse contracted Ebola virus disease while caring for a patient in a Madrid hospital.The nurse, who has not been named, was caring for two Spanish missionaries, Manuel Garcia Viejo and Miguel Pajares, who were flown home to Spain for treatment after contracting the disease in west Africa.Garcia Viejo died at the Carlos III Hospital on 25 September and Pajares died in August.
Systemic and Coronary Energetics in the Resting Unanesthetized Dog
Authors: DONALD E. GREGG, EDWARD M. KHOURI, CLAUDIA R. RAYFORD
Journal: Circulation Research (1965)

This report is an initial attempt to study the coronary circulation in the chronic unanesthetized dog. A standardized preparation has been developed in which phasic aortic pressure and flow, phasic left coronary inflow, and myocardial metabolism have been studied for many weeks in the unanesthetized dog under resting conditions. The flow patterns in the main left coronary artery and in its major branches are very similar. In the resting dog, the left coronary inflow during systole is 7 to 45% of that during diastole. We believe that much of this flow into the epicardial arteries penetrates into the myocardium. Stroke coronary flow can change considerably without significant alterations of blood pressure and heart rate. Despite this, the coronary flow values (37 to 58 cc) and oxygen usage values (4.4 cc to 8.6 cc) per 100 grams left ventricle per minute are low. Since, however, these measurements can vary considerably not only in different dogs but also in the same dog on the same day, and from day to day, it is suggested that these animals were in a semiresting state and probably not in a basal state.
Chromosome Analysis of Three Virus-Associated Chicken Tumors: Rous Sarcoma, Erythroleukemia, and RPL12 Lymphoid Tumor&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Jan Pontén
Journal: JNCI Journal of the National Cancer Institute (1963)

Journal Article Chromosome Analysis of Three Virus-Associated Chicken Tumors: Rous Sarcoma, Erythroleukemia, and RPL12 Lymphoid Tumor Get access Jan Pontén, Jan Pontén, The Wistar Institute, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 30, Issue 5, May 1963, Pages 897–921, https://doi.org/10.1093/jnci/30.5.897 Published: 01 May 1963 Article history Received: 17 December 1962 Published: 01 May 1963
Inducible interleukin-1 gene expression in human vascular smooth muscle cells.
Authors: P Libby, J M Ordovas, L K Birinyi, K R Auger, C A Dinarello
Journal: Journal of Clinical Investigation (1986)

Interleukin-1 (IL-1) mediates many components of generalized host response to injury and may also contribute to local vascular pathology during immune or inflammatory responses. Because altered function of smooth muscle cells (SMC) accompanies certain vascular diseases, we tested whether SMC themselves might produce this hormone. Unstimulated SMC contain little or no IL-1 mRNA. However, exposure to bacterial endotoxin caused accumulation of IL-1 mRNA in SMC cultured from human vessels. Endotoxin maximally increased IL-1 beta mRNA in SMC after 4-6 h. The lowest effective concentration of endotoxin was 10 pg/ml. 10 ng/ml produced maximal increases in IL-1 beta mRNA. Interleukin-1 alpha mRNA was detected when SMC were incubated with endotoxin under "superinduction" conditions with cycloheximide. Endotoxin-stimulated SMC also released biologically functional IL-1, measured as thymocyte costimulation activity inhibitable by anti-IL-1 antibody. Thus, human SMC can express IL-1 beta and IL-1 alpha genes, or very similar ones, and secrete biologically active product in response to a pathological stimulus. Endogenous local production of this inflammatory mediator by the blood vessel wall's major cell type could play an important early role in the pathogenesis of vasculitis and arteriosclerosis.
THE DIFFERENTIATION PATHWAY OF T LYMPHOCYTES
Authors: Alex Matter
Journal: The Journal of Experimental Medicine (1974)

Two experimental models have been used to study T-cell differentiation. The first, a graft-vs.-host reaction, was induced by injecting thymocytes or cortisone-resistant thymocytes into lethally irradiated allogeneic mice. The second was tumor graft rejection in allogeneic hosts. Ultrastructural studies at various time intervals revealed two differentiated T-cell types. One of these (the "pale" cell) is probably high cytotoxic as measured in the chromium-release assay, the other (the "dark" cell) may be an "amplifier" cell, helping in the differentiation of cytotoxic cells.
Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis
Authors: P Harle
Journal: Annals of the Rheumatic Diseases (2004)

Hypoandrogenicity is common in obesity and in chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Adrenal androgens such as androstenedione (ASD) and dehydroepiandrosterone (DHEA) sulphate are low, which partly depends on the influence of TNF in chronic inflammatory diseases. Leptin is stimulated by TNF and is associated with hypoandrogenicity in non-inflammatory conditions.To study the interrelation between serum levels of leptin and adrenal steroids in SLE and RA.In a retrospective study, serum levels of leptin, ASD, DHEA, and 17-hydroxyprogesterone (17OHP) were measured by ELISA, and serum levels of cortisol by radioimmunoassay in 30 patients with RA, 32 with SLE, and 54 healthy control subjects (HS).In SLE and RA but not HS, serum levels of ASD correlated negatively with serum levels of leptin (p<0.01) independently of prior prednisolone treatment in patients with SLE (p = 0.013) and tended to be independent of prednisolone in patients with RA (p = 0.067). In a partial correlation analysis, this interrelation remained significant after controlling for daily prednisolone dose in both patient groups. In both patient groups, serum leptin levels correlated negatively with the molar ratio of serum ASD/serum cortisol and serum ASD/serum 17OHP, and positively with the molar ratio of serum DHEA/serum ASD.The negative correlation of serum leptin and ASD or, particularly, ASD/17OHP, together with its known anti-androgenic effects indicate that leptin is also involved in hypoandrogenicity in patients with SLE and RA. Leptin may be an important link between chronic inflammation and the hypoandrogenic state.
Protein Kinase C-ε Regulates the Apoptosis and Survival of Glioma Cells
Authors: Hana Okhrimenko, Wei Lu, Cunli Xiang, Nathan Hamburger, Gila Kazimirsky, Chaya Brodie
Journal: Cancer Research (2005)

Abstract In this study, we examined the role of protein kinase C (PKC)-ε in the apoptosis and survival of glioma cells using tumor necrosis factor–related apoptosis inducing ligand (TRAIL)-stimulated cells and silencing of PKCε expression. Treatment of glioma cells with TRAIL induced activation, caspase-dependent cleavage, and down-regulation of PKCε within 3 to 5 hours of treatment. Overexpression of PKCε inhibited the apoptosis induced by TRAIL, acting downstream of caspase 8 and upstream of Bid cleavage and cytochrome c release from the mitochondria. A caspase-resistant PKCε mutant (D383A) was more protective than PKCε, suggesting that both the cleavage of PKCε and its down-regulation contributed to the apoptotic effect of TRAIL. To further study the role of PKCε in glioma cell apoptosis, we employed short interfering RNAs directed against the mRNA of PKCε and found that silencing of PKCε expression induced apoptosis of various glioma cell lines and primary glioma cultures. To delineate the molecular mechanisms involved in the apoptosis induced by silencing of PKCε, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that knockdown of PKCε did not affect the expression of Bcl2 and Bax or the phosphorylation and expression of Erk1/2, c-Jun-NH2-kinase, p38, or STAT, whereas it selectively reduced the expression of AKT. Similarly, TRAIL reduced the expression of AKT in glioma cells and this decrease was abolished in cells overexpressing PKCε. Our results suggest that the cleavage of PKCε and its down-regulation play important roles in the apoptotic effect of TRAIL. Moreover, PKCε regulates AKT expression and is essential for the survival of glioma cells.
RAPIDLY LABELED NUCLEAR AND CYTOPLASMIC RENAL RNA
Authors: Ronald A. Malt
Journal: The Journal of Experimental Medicine (1966)

Much of the RNA in mouse kidneys is not recovered when they are extracted with phenol-SDS at 60°C. Better recovery is achieved by extracting in hypertonic buffer with phenol-SDS, chloroform, and isoamyl alcohol after treatment with DNase. 1. Among the polydisperse RNA in the renal nuclei are small amounts of 45S RNA and large amounts of 32S RNA; the latter first appear when 18S RNA is detectable in the cytoplasm 10 min after administration of undine-H3. 2. In the cytoplasm rapidly labeled 18S RNA is transported as part of a 45S particle to which mRNA is attached. 3. Compared to HeLa cells in culture, normal mouse kidney is poor in the polydisperse nuclear precursors of rRNA and rich in the cytoplasmic polydisperse RNA that sediments like mRNA.
Endothelial Sirtuin 1 Deficiency Perpetrates Nephrosclerosis through Downregulation of Matrix Metalloproteinase-14
Authors: Radovan Vasko, Sandhya Xavier, Jun Chen, Chi Hua Sarah Lin, Brian Ratliff, May Rabadi, Julien Maizel, Rina Tanokuchi, Frank Zhang, Jian Cao, Michael S. Goligorsky
Journal: Journal of the American Society of Nephrology (2013)

Sirtuin 1 (SIRT1) depletion in vascular endothelial cells mediates endothelial dysfunction and premature senescence in diverse cardiovascular and renal diseases. However, the molecular mechanisms underlying these pathologic effects remain unclear. Here, we examined the phenotype of a mouse model of vascular senescence created by genetically ablating exon 4 of Sirt1 in endothelial cells (Sirt1endo−/−). Under basal conditions, Sirt1endo−/− mice showed impaired endothelium-dependent vasorelaxation and angiogenesis, and fibrosis occurred spontaneously at low levels at an early age. In contrast, induction of nephrotoxic stress (acute and chronic folic acid–induced nephropathy) in Sirt1endo−/− mice resulted in robust acute renal functional deterioration followed by an exaggerated fibrotic response compared with control animals. Additional studies identified matrix metalloproteinase-14 (MMP-14) as a target of SIRT1. In the kidneys of Sirt1endo−/− mice, impaired angiogenesis, reduced matrilytic activity, and retention of the profibrotic cleavage substrates tissue transglutaminase and endoglin accompanied MMP-14 suppression. Furthermore, restoration of MMP-14 expression in SIRT1-depeleted mice improved angiogenic and matrilytic functions of the endothelium, prevented renal dysfunction, and attenuated nephrosclerosis. Our findings establish a novel mechanistic molecular link between endothelial SIRT1 depletion, downregulation of MMP-14, and the development of nephrosclerosis.
Identifying Predictive Features in Drug Response Using Machine Learning: Opportunities and Challenges
Authors: Mathukumalli Vidyasagar
Journal: The Annual Review of Pharmacology and Toxicology (2014)

This article reviews several techniques from machine learning that can be used to study the problem of identifying a small number of features, from among tens of thousands of measured features, that can accurately predict a drug response. Prediction problems are divided into two categories: sparse classification and sparse regression. In classification, the clinical parameter to be predicted is binary, whereas in regression, the parameter is a real number. Well-known methods for both classes of problems are briefly discussed. These include the SVM (support vector machine) for classification and various algorithms such as ridge regression, LASSO (least absolute shrinkage and selection operator), and EN (elastic net) for regression. In addition, several well-established methods that do not directly fall into machine learning theory are also reviewed, including neural networks, PAM (pattern analysis for microarrays), SAM (significance analysis for microarrays), GSEA (gene set enrichment analysis), and k-means clustering. Several references indicative of the application of these methods to cancer biology are discussed.