tbuckley/cabot-search huggingface dataset:
FREQUENT H3F3A K27M MUTATIONS IN THALAMIC GLIOMAS FROM YOUNG ADULT PATIENTS
Authors: A. Mukasa, K. Aihara, K. Gotoh, K. Saito, G. Nagae, S. Tsuji, K. Tatuno, S. Yamamoto, S. Takayanagi, Y. Narita, S. Shibui, H. Aburatani, N. Saito
Journal: Neuro-Oncology (2014)

BACKGROUND: Mutations in the H3F3A gene, which encodes histone H3.3, were recently reported in cases of pediatric glioblastoma. H3F3A K27M mutations occur in gliomas that arise at midline locations, including the pons, thalamus, and spine; moreover, this particular mutation is found mainly in tumors in children and adolescents. In this study, we aimed to determine the association between H3F3A mutations and adult thalamic glioma. METHODS: Genomic H3F3A was sequenced from 20 separate thalamic gliomas. Additionally, for 14 of the 20 gliomas, 639 genes—including cancer-related genes and chromatin-modifier genes—were sequenced, and the Infinium HumanMethylation450K BeadChip was used to examine DNA methylation across the genome. RESULTS: Of the 20 tumors, 18 were high-grade thalamic gliomas, and of these 18, 11 were from patients under 50 years of age (median age, 38 years; range, 17–46), and seven were from patients more than 50 years of age. Among the 18 high-grade thalamic gliomas, the H3F3A K27M mutation was present in 10 (91%) of the 11 tumors from patients under 50 years of age, and was absent in all seven tumors from patients over 50 years of age. The H3F3A K27M mutation was not detected in two diffuse astrocytomas. By additional sequencing, recurrent mutations were identified in TP53, ATRX, NF1 and EGFR. In addition, a KDM6A mutation was found in one case of diffuse astrocytoma and a CREBBP mutation was identified in one case of glioblastoma with the H3F3A K27M mutation. Gliomas with H3F3A K27M from pediatric or young-adult patients had similar, characteristic DNA methylation profiles. In contrast, thalamic gliomas with wild-type H3F3A had DNA methylation profiles similar to those of hemispheric glioblastomas. The patients with high-grade thalamic gliomas harboring the H3F3A K27M mutation that occur frequently in young adults had a poor prognosis similar to those with wild-type H3F3A tumors that occur mainly in older adults. CONCLUSIONS: We found that high-grade thalamic gliomas from young adults, like those from children and adolescents, frequently had H3F3A K27M. SECONDARY CATEGORY: Neuropathology & Tumor Biomarkers.
IL-17A and IL-17F induce an invasive phenotype in human rheumatoid synoviocytes through the same signaling pathway and the CXCR4/SDF1 axis
Authors: Arnaud Hot, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> IL-17A is implicated in rheumatoid arthritis (RA) pathogenesis; but the contribution of IL-17F remains to be clarified. This report analyses the effects IL-17A versus IL-17F on gene expression, signaling and invasiveness in human RA synoviocytes. <h3>Methods</h3> The comparison between IL-17A and F effects on RA synoviocytes was assessed at the mRNA level by microarrays (Affymetrix U133 +2). Western blotting, qRT-PCR, and DNA binding assay were used to evaluate their signaling pathways. The capacities of IL-17A and F alone or in combination with TNF to induce synoviocyte migration and invasion were tested using transwell Matrigel invasion chambers. A functional DNA binding assay was used to evaluate the regulation of Hypoxia Induced Factor 1 (HIF1-α) activation. <h3>Results</h3> In microarrays, IL-17A and IL-17F alone had very similar but not identical regulatory effects, IL-17F being less active, with a synergistic pattern in the presence of TNF. This synergistic effect was linked in part to the enhancing expression of TNF RII by IL-17A and F. Regarding their signaling pathway, virtually all IL17A and F inducible genes were dependent on NF-κB activation, whereas a minor number was modulated by p38. Hypoxia-induced pathway was activated by IL-17A and F. Among the hypoxia-induced genes, IL-17A and F alone or combined with TNF induced CXCR4 mRNA (289 fold for IL17A, 34 fold for IL-17F, 450 fold for the combination of IL-17A with TNF). Over expression of CXCR4 at the surface of synoviocytes was confirmed by IF staining. IL-17A and TNF induced in synergy synoviocyte migration and invasion through CXCR4 (6 vs 67 migrated cells/HPF, p≤0.05). Blockade of CXCR4 decreased synoviocyte migration (− 10 fold, p&lt;0.05). The combination of IL-17A or F with TNF induced activation of HIF1-α under normoxic conditions (2 fold, p=0.003). <h3>Conclusion</h3> When combined with TNF, IL-17A and F induced very similar but not identical expression pattern in RA synoviocytes, may contribute to the progression of RA through increased synoviocyte aggressiveness. Part of this effect results from a mediated CXCR4/SDF1 pathway. These results are in line with IL-17A and F targeting in RA.
Sweet Success — A Treatment for McArdle's Disease
Authors: Anthony A. Amato
Journal: New England Journal of Medicine (2003)

Carbohydrates are often stored as glycogen in the body. Pathways for the synthesis and breakdown of glycogen (see Figure) permit the maintenance of a steady blood glucose level and provide a source of energy. There are 14 recognized glycogen storage diseases, most of which are “dynamic” in nature, in that the major symptoms are related to exercise intolerance; these symptoms are attributable to an inability to break down glycogen and its metabolites to form ATP. Glycogen storage disease types II, III, and IV are considered to be “static” in nature in that they are associated with fixed weakness, rather than . . .
Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitor
Authors: Martin Bickel, Karl-Heinz Baringhaus, Martin Gerl, Volkmar Günzler, Jiri Kanta, Ludwig Schmidts, Michael Stapf, Georg Tschank, Klaus Weidmann, Ulrich Werner
Journal: Hepatology (1998)

Fibrosis and cirrhosis of the liver are often the result of chronic liver damage by a variety of different agents. Pathological accumulation of collagen, disruption of the lobular structure, and impaired hepatocellular function frequently lead to systemic involvement and fatal complications. Drugs inhibiting collagen hydroxylation and accumulation are expected to improve this situation, making prolyl 4-hydroxylase (P4H), the key enzyme of intracellular collagen processing, a rational target for pharmacological intervention. S 4682, a novel inhibitor of purified P4H (Ki = 155 nmol/L), reduced hydroxyproline (Hyp) synthesis in chicken embryo calvaria (IC50 = 8.2 micromol/L) and in cultured hepatic stellate cells (HSC) (IC50 = 39 micromol/L). S 4682 inhibited hepatic collagen hydroxylation in vivo after metabolic labeling with [14C]proline. In the CCl4 model of chronic hepatic injury, characterized by histologically and biochemically evident fibrosis and highly elevated levels of serum procollagen type III N-peptide, S 4682 reduced hepatic collagen accumulation, decreased prevalence of ascites, and lowered serum procollagen type III N-peptide (PIIINP) levels. The hepatic Hyp content of drug-treated animals was closely correlated with serum levels of PIIINP S 4682 had no influence on Hyp content of heart, lung, and kidney.
Acquisition of an additional antigen specificity after mouse CD4 gene transfer into a T helper hybridoma.
Authors: W G Ballhausen, A B Reske-Kunz, B Tourvieille, P S Ohashi, J R Parnes, T W Mak
Journal: The Journal of Experimental Medicine (1988)

We have transfected the mouse CD4 gene into a beef insulin (BI)-specific murine T helper hybridoma that lacks CD4 surface expression. The CD4-expressing transfectants have acquired an additional reactivity for pork insulin (PI), which was not detectable in the original recipient cell. The transfectants' response to PI can be completely abrogated by anti-CD4 antibodies. The transfected clone showed a 50-fold increased sensitivity towards BI in comparison to the same CD4- hybridoma. These experiments suggest that CD4 may be important in determining the antigen fine specificity and, therefore, may also play a role in altering the T cell repertoire.
Serum beta-2-microglobulin and angiotensin-converting enzyme activity in sarcoidosis.
Authors: R W Parrish, J D Williams, B H Davies
Journal: Thorax (1982)

Angiotensin-converting enzyme activity in sarcoidosis is regarded both as a diagnostic feature and as an index of disease activity. Increased activity of this enzyme is thought to parallel macrophage and epithelioid cell activity. Beta-2-microglobulin, a low-molecular-weight protein associated with the histocompatibility antigens, is thought to reflect activation of immunocompetent cells, particularly lymphocytes. In 132 patients with known sarcoidosis no close association was found to exist between the results of the two assays (r = 0.53). Angiotensin-converting enzyme activity was raised in 33% and beta 2-microglobulin concentrations in 63% of patients with sarcoidosis. When analysed prospectively, the results of the two assays showed no correlation in 29 patients over periods of up to 19 months. Stage, duration of disease, and corticosteroid treatment showed no significant effect on levels of either angiotensin-converting enzyme or beta 2-microglobulin. The disparity between indices of macrophage and lymphocyte activation requires further study in sarcoidosis.
Muscarinic receptors in gastric mucosa are increased in peptic ulcer disease.
Authors: A Pfeiffer, W Kromer, J Friemann, M Ruge, M Herawi, M Schatzl, U Schwegler, B May, H Schatz
Journal: Gut (1995)

Muscarinic receptors stimulate the secretion of acid pepsinogen and mucous in gastric mucosa. Whether muscarinic receptors are involved in the pathogenesis of benign gastric disease is unknown. Receptor changes in these conditions were therefore sought. An autoradiographic technique was developed to determine quantitatively muscarinic receptors in microtome sections of biopsy specimens obtained during gastroscopy. Muscarinic receptor density was mean (SEM) 18.4 (1.2) fmol/mg protein in the corpus and 8.9 (0.7) fmol/mg protein in the antrum (n = 53). Neither chronic nor active gastritis was associated with receptor changes in the antrum but chronic gastritis was associated with a receptor loss in the corpus. Patients with acute or recent duodenal or antral ulcers (n = 23) had significantly higher levels of muscarinic receptors in the corpus than controls (n = 25) (22.2 (1.5) v 16.9 (1.7) fmol/mg protein respectively (p &lt; 0.025). These results suggest that muscarinic M3 receptor is overexpressed in duodenal ulcer disease and may play a part in its pathogenesis.
Biochemical and morphological correlates of cardiac ischaemia: contractile proteins
Authors: Y. S. REDDY, L. WYBORNY, R. M. LEWIS, A. SCHWARTZ
Journal: Cardiovascular Research (1976)

Journal Article Biochemical and morphological correlates of cardiac ischaemia: contractile proteins Get access Y. SURENDRANATH REDDY, Y. SURENDRANATH REDDY From the Department of Cell Biophysics, Division of Myocardial Biology, Baylor College of Medicine, Fondren-Brown Cardiovascular Research and Training Center, The Methodist and Veterans Administration Hospitals, Houston, Texas 77025, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar LEIGH WYBORNY, LEIGH WYBORNY From the Department of Cell Biophysics, Division of Myocardial Biology, Baylor College of Medicine, Fondren-Brown Cardiovascular Research and Training Center, The Methodist and Veterans Administration Hospitals, Houston, Texas 77025, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar ROBERT M. LEWIS, ROBERT M. LEWIS From the Department of Cell Biophysics, Division of Myocardial Biology, Baylor College of Medicine, Fondren-Brown Cardiovascular Research and Training Center, The Methodist and Veterans Administration Hospitals, Houston, Texas 77025, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar ARNOLD SCHWARTZ ARNOLD SCHWARTZ From the Department of Cell Biophysics, Division of Myocardial Biology, Baylor College of Medicine, Fondren-Brown Cardiovascular Research and Training Center, The Methodist and Veterans Administration Hospitals, Houston, Texas 77025, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 10, Issue 1, January 1976, Pages 129–135, https://doi.org/10.1093/cvr/10.1.129 Published: 01 January 1976
CARDIOPULMONARY FITNESS IS ASSOCIATED WITH LOWER CARDIOVASCULAR MORTALITY IN A COMMUNITY-BASED COHORT
Authors: Abhijeet Dhoble, Brian Lahr, Thomas G. Allison, Iftikhar Kullo, Francisco Lopez-Jimenez, Ray W. Squires, Gerald Gau, Randal J. Thomas, Stephen L. Kopecky
Journal: Journal of the American College of Cardiology (2010)
A piece of my mind. Father's day
Authors: A. J. Herrmann
Journal: JAMA (1990)

My father died of lung cancer in 1975. He was a physician. Much has been written about the marriages of physicians— the satisfactions, the discord, the dynamics of these marriages. What of the effect of the physician's life on his or her children? What will they remember of their physician/father? What legacy does his quality of life leave them? I doubt my father would ever have guessed my answer; less would he imagine the profound effect his life has had on mine. The wife chooses her husband; the child knows no choice. One's father is the norm against whom all other fathers are measured. Other children's fathers played ball with them, took them camping and on vacations. They taught their children fair play, an appreciation of nature, and the importance of family. Paradoxically, it was my father's absences that taught me something more, a stratum above: the meaning of responsibility,
Studies on the Osmotic Resistance of Incubated Leptocytes.
Authors: A. Haut
Journal: Annals of Internal Medicine (1963)

s1 April 1963Studies on the Osmotic Resistance of Incubated Leptocytes.A. Haut, M.D. (Associate), G. E. Cartwright, M.D. (Associate), M. M. Wintrobe, M.D., F.A.C.P.A. Haut, M.D. (Associate)Search for more papers by this author, G. E. Cartwright, M.D. (Associate)Search for more papers by this author, M. M. Wintrobe, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-732_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptErythrocytes from patients with thalassemia minor, iron deficiency anemia, liver disease associated with the target cells and an example of elliptocytosis were studied. These red cells are known to generally have a greater than normal osmotic resistance when studied in the fresh condition. We have found them to have an even greater osmotic resistance after their incubation in their own serum, under aseptic conditions for 24 hours, than before incubation. The increase in osmotic resistance was the opposite of the well-known change noted for normal cells under the same conditions. By virtue of this fact, the difference between the osmotic... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: A. Haut, M.D. (Associate); G. E. Cartwright, M.D. (Associate); M. M. Wintrobe, M.D., F.A.C.P.Affiliations: Salt Lake City, Utah (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAutosomal dominant hemolytic anemia characterized by ovalocytosis 1 April 1963Volume 58, Issue 4Page: 732-733KeywordsBeta-thalassemiaCellsIron deficiency anemiaLiver diseases ePublished: 1 December 2008 Issue Published: 1 April 1963 PDF downloadLoading ...
Medical Heuristics: The Silent Adjudicators of Clinical Practice
Authors: Clement J. McDonald
Journal: Annals of Internal Medicine (1996)

Robust scientific conclusions are too sparse to inform fully most of the choices that physicians must make about tests and treatments.Instead, ad hoc rules of thumb, or "heuristics," must guide them, and many of these are problematic. Physicians extrapolate from the small samples studied by clinical trials to general populations, but they do so inconsistently. Many physicians live by rules that dictate "not treating the numbers," correcting abnormalities slowly, achieving diagnostic certainty, and operating now to avoid "greater" risk in the future. Yet in each case, historical trends or statistical realities suggest either doing the opposite or investing in more discriminating heuristics. The heuristics of medicine should be discussed, criticized, refined, and then taught. More uniform use of explicit and better heuristics could lead to less practice variation and more efficient medical care.
Desensitization in delayed drug hypersensitivity reactions – an <scp>EAACI</scp> position paper of the Drug Allergy Interest Group
Authors: K. Scherer, K. Brockow, W. Aberer, J. H. C. Gooi, P. Demoly, A. Romano, B. Schnyder, P. Whitaker, J. S. R. Cernadas, A. J. Bircher
Journal: Allergy (2013)

Abstract Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV ‐positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre‐existent sensitization has not been proven by positive skin tests. Successful re‐administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the D rug H ypersensitivity I nterest G roup of the E uropean A cademy of A llergy and C linical I mmunology.
5-Azacytidine–Induced Methyltransferase-DNA Adducts Block DNA Replication <i>In vivo</i>
Authors: H. Kenny Kuo, Jack D. Griffith, Kenneth N. Kreuzer
Journal: Cancer Research (2007)

Abstract 5-Azacytidine (aza-C) and its derivatives are cytidine analogues used for leukemia chemotherapy. The primary effect of aza-C is the prohibition of cytosine methylation, which results in covalent methyltransferase-DNA (MTase-DNA) adducts at cytosine methylation sites. These adducts have been suggested to cause chromosomal rearrangements and contribute to cytotoxicity, but the detailed mechanisms have not been elucidated. We used two-dimensional agarose gel electrophoresis and electron microscopy to analyze plasmid pBR322 replication dynamics in Escherichia coli cells grown in the presence of aza-C. Two-dimensional gel analysis revealed the accumulation of specific bubble and Y molecules, dependent on overproduction of the cytosine MTase EcoRII (M.EcoRII) and treatment with aza-C. Furthermore, a point mutation that eliminates a particular EcoRII methylation site resulted in disappearance of the corresponding bubble and Y molecules. These results imply that aza-C–induced MTase-DNA adducts block DNA replication in vivo. RecA-dependent X structures were also observed after aza-C treatment. These molecules may be generated from blocked forks by recombinational repair and/or replication fork regression. In addition, electron microscopy analysis revealed both bubbles and rolling circles (RC) after aza-C treatment. These results suggest that replication can switch from theta to RC mode after a replication fork is stalled by an MTase-DNA adduct. The simplest model for the conversion of theta to RC mode is that the blocked replication fork is cleaved by a branch-specific endonuclease. Such replication-dependent DNA breaks may represent an important pathway that contributes to genome rearrangement and/or cytotoxicity. [Cancer Res 2007;67(17):8248–54]
Fibrin D-Dimer and Coronary Heart Disease
Authors: John Danesh, Peter Whincup, Mary Walker, Lucy Lennon, Andrew Thomson, Paul Appleby, Ann Rumley, Gordon D.O. Lowe
Journal: Circulation (2001)

Background —It is unknown whether modest increases of fibrin D-dimer, a circulating marker of fibrin turnover, are relevant to coronary heart disease (CHD) in the general population. Methods and Results —We measured serum concentrations of D-dimer antigen in the stored baseline blood samples of 630 CHD cases and 1269 controls “nested” in a prospective cohort of 5661 men who were monitored for 16 years, and we conducted a meta-analysis of previous relevant studies to place our findings in context. In a comparison of men in the top third compared with those in the bottom third of baseline fibrin D-dimer values (tertile cutoffs, &gt;94 versus &lt;49 ng/mL), the odds ratio for CHD was 1.67 (95% CI, 1.31 to 2.13; P &lt;0.0001) after adjustments for age and town. The odds ratio increased slightly after further adjustment for smoking, other classic risk factors, and indicators of socioeconomic status (1.79; 95% CI, 1.36 to 2.36). Strong correlations were observed of fibrin D-dimer values with circulating concentrations of C-reactive protein and serum amyloid A protein but not with smoking, blood lipids, blood pressure, and other risk factors. Conclusion —Although there may be an association between circulating D-dimer values and CHD, further studies are needed to determine the extent to which this is causal.
Which patients should undergo laparoscopy?: Authors' reply
Authors: S. Paterson-Brown, H A F Dudley
Journal: BMJ (1988)

part in autoaggressive diseases, particularly in inflammatory joint disease in predisposed people, so the association between HIV infection and inflammatory joint disease is no longer a surprise.Moreover, the data, although preliminary, may shed some light on the immunopathogenesis of HIV infection and autoaggressive disorders.The investigation of y interferon concentrations in the serum of people with HIV infection has to be extended.The increased y interferon concentrations in HIV infection suggest the presence of pre- activated cellular immunity despite severe immunodeficiency.Thus in these patients im- munodeficiency is, in general, not the result of diminished release of y interferon by T lymphocytes but is caused by persistent exposure ofcells to various immunogens.The reduced ability of T cells in AIDS to release y interferon is, therefore, restricted to in vitro studies.4
THE UPTAKE OF LABELLED THYMIDINE BY LEUCOCYTES OF NICKEL SENSITIVE PATIENTS
Authors: T. M. MACLEOD, F. HUTCHINSON, E. J. RAFFLE
Journal: British Journal of Dermatology (1970)

Journal Article THE UPTAKE OF LABELLED THYMIDINE BY LEUCOCYTES OF NICKEL SENSITIVE PATIENTS Get access T. M. MACLEOD, T. M. MACLEOD Department of Dermatology, University of Dundee, and Regional Physics Department, Dundee Search for other works by this author on: Oxford Academic Google Scholar F. HUTCHINSON, F. HUTCHINSON Department of Dermatology, University of Dundee, and Regional Physics Department, Dundee Search for other works by this author on: Oxford Academic Google Scholar E. J. RAFFLE E. J. RAFFLE Department of Dermatology, University of Dundee, and Regional Physics Department, Dundee Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue 5, 1 May 1970, Pages 487–492, https://doi.org/10.1111/j.1365-2133.1970.tb02209.x Published: 01 May 1970 Article history Accepted: 19 November 1969 Published: 01 May 1970