tbuckley/cabot-search huggingface dataset:
Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice.
Authors: S H Zhang, R L Reddick, E Avdievich, L K Surles, R G Jones, J B Reynolds, S H Quarfordt, N Maeda
Journal: Journal of Clinical Investigation (1997)

Dietary administration of probucol (0.5%, wt/wt) efficiently reduced total plasma cholesterol levels in apolipoprotein E-deficient mice (apoE-/-) by 40%, with decreases in high density lipoprotein (HDL) and apoAI by 70 and 50%, respectively. Paradoxically, however, aortic atherosclerotic plaques in the probucol-treated apoE-/- mice formed more rapidly than in the untreated apoE-/- mice, and the lesions were two to four times larger and more mature regardless of sex, age, and genetic background (P < 10(-)6). Histologically, lesions in probucol-treated mice contained increased fibrous materials and cells other than foam cells, and were commonly associated with focal inflammation and aneurysmal dilatation. Probucol treatment also accelerated lesion development in apoE+/- mice fed an atherogenic diet, indicating that the adverse effect is not dependent on the complete absence of apoE. Furthermore, mice lacking apoE and apoAI have plasma lipoprotein profiles very similar to the probucol-treated apoE-/- mice, but do not have accelerated plaque development. Thus, the enhanced atherosclerosis in the probucol-treated animals is unlikely to be caused by the reduction of HDL and apoAI levels. Our data indicate that a reduction in plasma cholesterol caused by probucol does not necessarily lead to an antiatherogenic effect.
Transcriptome Analysis of PPI-Responsive Esophageal Eosinophilia Reveals the Presence of an Eosinophilic Esophagitis Transcriptome Reversible By PPI Mono-Therapy and the Identification of PPI-Response Predictor Genes
Authors: Ting Wen, Evan Dellon, Fouad J. Moawad, Glenn Furuta, Seema Sharma Aceves, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2015)
Adenoidectomy in children with recurrent upper respiratory infections
Authors: K. J. Kvaerner
Journal: BMJ (2011)

Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2K<sup>d</sup> epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2D<sup>d</sup> epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2D<sup>d</sup> specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.
Congenital Bronchopulmonary-Foregut Malformation
Authors: Richard D. Gerle, Alfred Jaretzki, Charles A. Ashley, Alfred S. Berne
Journal: New England Journal of Medicine (1968)

The pathological anatomy and clinical features of three cases of pulmonary sequestration with gastrointestinal communication and of 10 cases reported in the literature suggest that extralobar sequestration, intralobar sequestration and the sequestration communicating with the gut share a common embryogenesis and be collectively identified as "congenital bronchopulmonary-foregut malformation."
Locally Advanced and Inflammatory Breast Cancer
Authors: Stephen Chia, Sandra M. Swain, David R. Byrd, David A. Mankoff
Journal: Journal of Clinical Oncology (2008)

Article Tools Review Articles Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2008.15.0243 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 18258987 Locally Advanced and Inflammatory Breast Cancer Stephen ChiaxStephen ChiaSearch for articles by this author , Sandra M. SwainxSandra M. SwainSearch for articles by this author , David R. ByrdxDavid R. ByrdSearch for articles by this author , David A. MankoffxDavid A. MankoffSearch for articles by this author Show More From the Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Washington Cancer Institute, Washington Hospital Center, Washington, DC; and Departments of Surgery and Radiology, Seattle Cancer Care Alliance and University of Washington, Seattle, WA https://doi.org/10.1200/JCO.2008.15.0243 First Page Full Text PDF Figures and Tables © 2008 by American Society of Clinical Oncology
Exercise-Induced Abdominal Pain
Authors: Bruce R. Leslie
Journal: JAMA (1983)

To the Editor.—  In the QUESTIONS AND ANSWERS section of the June 10 issue of JAMA , 1 a 32-year-old woman with exercise-induced right upper quadrant abdominal pain is discussed. I wish to add to the explanation an additional diagnosis—that of a movable kidney.  Report of a Case.—  A 28-year-old woman had right-sided abdominal pain on exertion for one year. She was a professional dancer, whose symptoms began with dull, nonradiating right flank pain while she was dancing. The discomfort was accompanied by tenderness of the middle of the right side of the abdominal wall. She subsequently noted pain and tenderness in the right side of the abdomen while walking long distances. There was no history of recent weight loss or pregnancy. Results of physical examination while she was in the supine position were entirely normal. When she stood, there appeared a 2×3-cm, firm, movable mass in the middle of the
On the lack of response to catecholamine stimulation by the adenyl cyclase system in psoriatic lesions*
Authors: K. YOSHIKAWA, K. ADACHI, K.M. HALPRIN, V. LEVINE
Journal: British Journal of Dermatology (1975)

Journal Article On the lack of response to catecholamine stimulation by the adenyl cyclase system in psoriatic lesions Get access K. YOSHIKAWA, K. YOSHIKAWA Dermatology Service, Voterans Administration Hospital and Department of Dermatology, University of Miami School ol Medicine, Miami, Florida 33125, U.S.A Search for other works by this author on: Oxford Academic Google Scholar K. ADACHI, K. ADACHI Dermatology Service, Voterans Administration Hospital and Department of Dermatology, University of Miami School ol Medicine, Miami, Florida 33125, U.S.A address: K. Adacbi, VA Hospital 1201 NW, I6th Street, Miami, Florida 33125, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar K.M. HALPRIN, K.M. HALPRIN Dermatology Service, Voterans Administration Hospital and Department of Dermatology, University of Miami School ol Medicine, Miami, Florida 33125, U.S.A Search for other works by this author on: Oxford Academic Google Scholar V. LEVINE V. LEVINE Dermatology Service, Voterans Administration Hospital and Department of Dermatology, University of Miami School ol Medicine, Miami, Florida 33125, U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 92, Issue 6, 1 June 1975, Pages 619–624, https://doi.org/10.1111/j.1365-2133.1975.tb03140.x Published: 01 June 1975 Article history Accepted: 04 November 1974 Published: 01 June 1975
Glucagon-Like Peptide I Enhances the Insulinotropic Effect of Glibenclamide in NIDDM Patients and in the Perfused Rat Pancreas
Authors: Mark K Gutniak, Lisa Juntti-Berggren, Per M Hellström, Amel Guenifi, Jens J Holst, Suad Efendic
Journal: Diabetes Care (1996)

To investigate the acute effects of glibenclamide and glucagon-like peptide I (GLP-I) and their combination in perfused isolated rat pancreas and in patients with secondary failure to sulfonylureas.Rat islets were perfused with 10 nmol/l GLP-I in combination with 2 mumol/l glibenclamide. In human experiments, GLP-I (0.75 pmol. kg-1.min-1) was given as a continuous infusion during 240 min, while glibenclamide (3.5 mg) was administered orally. Eight patients participated in the study (age 57.6 +/- 2.7 years, BMI 28.7 +/- 1.5 kg/m2, mean +/- SE). In all subjects, blood glucose was first normalized by insulin infusion administered by an artificial pancreas (Biostator).GLP-I increased the insulinotropic effect of glibenclamide fourfold in the perfused rat pancreas. In human experiments, treatment with GLP-I alone and in combination with glibenclamide significantly decreased basal glucose levels (5.1 +/- 0.4 and 4.5 +/- 0.1 vs. 6.0 +/- 0.3 mmol/l, P < 0.01), while with only glibenclamide, glucose concentrations remained unchanged. GLP-I markedly decreased total integrated glucose response to the meal (353 +/- 60 vs. 724 +/- 91 mmol.l-1. min-1, area under the curve [AUC] [-30-180 min], P < 0.02), whereas glibenclamide had no effect (598 +/- 101 mmol.l-1. min-1, AUC [-30-180 min], NS). The combined treatment further enhanced the glucose lowering effect of GLP-I (138 +/- 24 mmol. l-1.min, AUC [-30-180 min], P < 0.001). GLP-I, glibenclamide, and combined treat-stimulated meal-induced insulin release as reflected by insulinogenic indexes (control 1.44 +/- 0.4; GLP-I 6.3 +/- 1.6, P < 0.01; glibenclamide 6.8 +/- 2.1, P < 0.01; combination 20.7 +/- 5.0, P < 0.001). GLP-I inhibited basal but not postprandial glucagon responses. Using paracetamol as a marker for gastric emptying rate of the test meal, treatment with GLP-I decreased gastric emptying at 180 min by approximately 50% compared with the control subjects (P < 0.01).In acute experiments on overweight patients with NIDDM, GLP-I exerted a marked antidiabetogenic action on the basal and postprandial state. The peptide stimulated insulin, suppressed basal glucagon release, and prolonged gastric emptying. The glucose-lowering effect of GLP-I was further enhanced by glibenclamide. This action may be at least partially accounted for by a synergistic effect of these two compounds on insulin release. Glibenclamide per se enhanced postprandial but not basal insulin release and exerted a less pronounced antidiabetogenic effect compared with GLP-I.
Accentuated T Helper Type 2 Airway Response after Allergen Challenge in Cyclooxygenase-1<sup>−/−</sup>but Not Cyclooxygenase-2<sup>−/−</sup>Mice
Authors: Michelle A. Carey, Dori R. Germolec, J. Alyce Bradbury, Rebecca A. Gooch, Michael P. Moorman, Gordon P. Flake, Robert Langenbach, Darryl C. Zeldin
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Acute pharmacologic inhibition of cyclooxygenase (COX)-1 or -2 during allergen sensitization and exposure leads to enhanced T helper type 2 (Th2) airway responses. COX-1 and -2 play functionally distinct roles in lymphocyte development, and consequently, genetic deficiency of either enzyme, as opposed to acute pharmacologic inhibition, may modulate Th2-mediated allergic airway disease differently. An ovalbumin-induced mouse model of allergic airway disease was used. The immunophenotype of bronchoalveolar lavage lymphocytes was assessed by flow cytometry, bronchoalveolar lavage cytokines, and chemokines were measured by enzyme-linked immunosorbent assay, adhesion molecule expression was assessed by immunoblotting in combination with immunohistochemistry, and bronchoconstriction was assessed by whole body plethysmography. The airways of COX-1-/- mice contained increased numbers of CD4+ and CD8+ T cells, exaggerated levels of the Th2 cytokines interleukin-4, -5, and -13, and increased levels of eotaxin and thymus- and activation-regulated chemokine. Allergen-induced bronchoconstriction was also increased in COX-1-/- mice. Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 levels were increased in lungs of both COX-1-/- and COX-2-/- mice relative to wild type. These data suggest that genetic deficiency of COX-1 but not COX-2 modulates T cell recruitment, Th2 cytokine secretion, and lung function in the allergic airway.
Charges in General Practice
Authors: H. B. Minchom
Journal: BMJ (1970)

MEDAL5hconsider such representations at a later date.The profession's negotiators should be well able to ensure that the question of the inclusion of public health doctors is raised without prejudicing what has already been gained in the dispute.It is sophism to argue that public health doctors are not part of the National Health Service, when the 1946 Act itself and the steady development of co-operation and close relations in the working of the Service show otherwise.It is not legalistic views which will determine whether public health doctors are to be included but a sense of fairness, a desire to preserve the community health services on the part of the Government and the local authorities, and, above all, readiness of the medical profession to show unity.The demonstration of unity should be made easier on this occasion by the knowledge that public health doctors have suffered for their willingness not to stand in the way of their colleagues when the Review Body was first set up, that they supported them again in the recent dispute, and that in any case mere self-interest on the part of the profes- sion as a whole requires that no section of it should be left in a position in which it is a source of weakness to the remainder.-Weare, etc.,
A Lecture on Inversion of the Uterus: With Ten Cases Succesftully Treated by the Sigmoid Repositor
Authors: J. H. Aveling
Journal: BMJ (1886)

Recent inversion includes the period between the occurrence of the displament and involution of tihe uterus Chronic inversion is so called during the existence of the displacement after involution has been completiedFrequatcy of Isversion.-Puerperalinversion is far more commoa than non-puerperal.Of 400 cases notedlbyCrosse, he found that in 350 it occurred as a sequel to parturition, in 40 from polypus, and in 10 from other causes.Dr. Atthill doubts the correctness of the view com-
ASTROCYTIC TUMORS WITH GAIN ON 7Q AND THOSE WITH GAIN OF WHOLE CHROMOSOME 7 BELONG TO DISTINCT SUBGROUPS CHARACTERIZED BY VARIOUS GENETIC FACTORS INCLUDING IDH1 AND TP53
Authors: Y. Hirose, H. Sasaki
Journal: Neuro-Oncology (2014)

BACKGROUND: Many genetic studies on gliomas have reported the utility of DNA copy number aberrations (CNAs) in tumor classification, and we have previously shown that grade II–III adult supratentorial gliomas could be classified into clinically relevant subgroups based on the CNAs. The major CNAs in astrocytic tumors of these grades were gain of whole chromosome 7 (+7) and that on chromosomal arm 7q (+7q), and tumors with +7 had a worse outcome than tumors with 7q. However, it was not confirmed that the former could develop from the latter; that is, it is not clear that a stepwise DNA copy number gain on chromosome 7, beginning as partial gain of 7q, develops along with glioma progression. We then aimed to establish glioma development pathway model by combining information on CNAs and other genetic information. METHODS: We analyzed the chromosomal DNA copy number aberrations of 160 adult supratentorial gliomas using comparative genomic hybridization as well as mutational status of IDH1 and TP53 by PCR-based direct sequencing. We also performed immunohistochemistry for c-Met whose gene is located in 7q34, that is included in the region with copy number gain in both +7 and +7q tumors. RESULTS: The most frequent aberration in IDH1 mutant tumors was -1p/19q followed by +7q, and, in contrast, IDH1 wild-type tumors showed +7 and, less frequently in grade II-III tumors, -10q. Kaplan-Meier estimates for progression free survival showed that the tumors with mutant IDH1, -1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wildtype IDH1, +7, or -10q. Furthermore, +7q tumors showed TP53 mutation and c-Met overexpression whereas +7 tumors did not show these features. Paired analysis of astrocytic tumors for primary and recurrent disease showed that the majority of +7q tumors progressed without additional gain of 7p. In contrast to tumors with gain on chromosome 7, there is a lack of evidence to indicate that tumors with 1p/19q loss are composed of multiple lineages. CONCLUSIONS: We found +7q tumors were distinct tumor lineage from tumors with whole 7 gain, and, although associated with CNA in common region of the chromosome, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management. SECONDARY CATEGORY: n/a.
Martin Delany, Thomas Hodgkin, and the Black Nationalist Movement
Authors: Amalie M. Kass, Edward H. Kass
Journal: New England Journal of Medicine (1981)

THE return to an African homeland has had a continuing appeal to many American blacks since the inception of slavery.1 The Black Nationalist movement gained particular prominence in the decade preceding the Civil War.2 , 3 Two physicians had important roles in this movement.Dr. Martin R. Delany (1812–1885), a free black man, studied with physicians in Pittsburgh, Pennsylvania, practiced as a cupper, leecher, and bleeder, and was commended for his skill as a physician during an outbreak of cholera in Pittsburgh in 1854.4 5 6 He was also a fervent participant in reform, especially in abolitionism. He edited his own newspaper, joined with . . .
Unrestrained p38 MAPK Activation in <i>Dusp1/4</i> Double-Null Mice Induces Cardiomyopathy
Authors: Mannix Auger-Messier, Federica Accornero, Sanjeewa A. Goonasekera, Orlando F. Bueno, John N. Lorenz, Jop H. van Berlo, Robert N. Willette, Jeffery D. Molkentin
Journal: Circulation Research (2012)

Mitogen-activated protein kinases (MAPKs) are activated in the heart by disease-inducing and stress-inducing stimuli, where they participate in hypertrophy, remodeling, contractility, and heart failure. A family of dual-specificity phosphatases (DUSPs) directly inactivates each of the MAPK terminal effectors, potentially serving a cardioprotective role.To determine the role of DUSP1 and DUSP4 in regulating p38 MAPK function in the heart and the effect on disease.Here, we generated mice and mouse embryonic fibroblasts lacking both Dusp1 and Dusp4 genes. Although single nulls showed no molecular effects, combined disruption of Dusp1/4 promoted unrestrained p38 MAPK activity in both mouse embryonic fibroblasts and the heart, with no change in the phosphorylation of c-Jun N-terminal kinases or extracellular signal-regulated kinases at baseline or with stress stimulation. Single disruption of either Dusp1 or Dusp4 did not result in cardiac pathology, although Dusp1/4 double-null mice exhibited cardiomyopathy and increased mortality with aging. Pharmacological inhibition of p38 MAPK with SB731445 ameliorated cardiomyopathy in Dusp1/4 double-null mice, indicating that DUSP1/4 function primarily through p38 MAPK in affecting disease. At the cellular level, unrestrained p38 MAPK activity diminished cardiac contractility and Ca2+ handling, which was acutely reversed with a p38 inhibitory compound. Poor function in Dusp1/4 double-null mice also was partially rescued by phospholamban deletion.Our data demonstrate that Dusp1 and Dusp4 are cardioprotective genes that play a critical role in the heart by dampening p38 MAPK signaling that would otherwise reduce contractility and induce cardiomyopathy.
Microtubule Associated Protein-Tau (MAPT) Is Influenced by ER: ICI182,780, a Selective ER Inhibitor, Down-Regulates MAPT Expression and Reverses Resistance to Taxanes in MAPT- and ER-Positive Breast Cancer Cells.
Authors: H. Ikeda, N. Taira, F. Hara, T. Nogami, T. Shien, H. Doihara
Journal: Cancer Research (2009)

Abstract Background: Taxanes are important drugs in treatment of breast cancer. These drugs bind to tubulin and suppress spindle microtubule dynamics, which leads to cell cycle arrest in the G2/M phase followed by apoptosis. However, resistance to taxane therapy prevents some patients from benefiting from these drugs. Several mechanisms of taxane resistance have been described, including the involvement of microtubule-associated protein-tau (MAPT). MAPT binds to the same pocket as taxanes in microtubules and obstructs the function of the drug. Estrogen receptors (ER) are transcriptional factors that play an important role in the development and progression of breast cancer. However, the relationship between ER and MAPT in breast cancer is not entirely clear. In this study we examined the correlation between MAPT expression and the sensitivity of human breast cancer cells to taxanes, and the relationship between ER and MAPT at the protein level in these cells. We also examined combination therapy with hormone drugs and taxanes.Methods: The correlation between MAPT expression and sensitivity to taxanes was examined in 12 human breast cancer cell lines using real time PCR, western blotting analysis and an MTS assay. Following small interfering RNA (siRNA) knockdown of MAPT expression, the alteration of cellular sensitivity to taxanes was examined by MTS assay, flow cytometry and immunofluorescence. To examine the relationship between ER and MAPT, ER expression was knocked down with siRNA or stimulated with 17-β-estradiol in MAPT- and ER-positive cell lines (MCF-7 and ZR75.1, respectively). The cells were also treated with hormone drugs (tamoxifen and ICI182,780) and changes in MAPT protein expression were examined.Results: Six cell lines showed high MAPT mRNA expression and four showed high MAPT protein expression; that is, expression at the mRNA level did not always correlate with that at the protein level. MAPT mRNA expression did not correlate with taxane resistance, but expression of MAPT protein isoforms under 70 kDa correlated with taxane resistance. Downregulation of MAPT increased sensitivity to taxanes. MAPT protein expression was decreased by ER knockdown and increased by 17-β-estradiol stimulation. The MAPT protein level was also increased by tamoxifen, but decreased by ICI182,780. Combination treatment of taxanes with ICI182,780 showed a strong synergistic effect, but similar treatment with tamoxifen had an antagonistic effect in both cell lines.Conclusions: Expression of MAPT protein isoforms under 70 kDa correlates with taxane resistance in breast cancer cells. MAPT expression is influenced by ER in breast cancer and ICI182,780, a selective ER inhibitor, can reverse the resistance to taxanes in both MAPT- and ER-positive breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2118.
Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT
Authors: Judith Feucht, Kathrin Opherk, Peter Lang, Simone Kayser, Lena Hartl, Wolfgang Bethge, Susanne Matthes-Martin, Peter Bader, Michael H. Albert, Britta Maecker-Kolhoff, Johann Greil, Hermann Einsele, Paul-Gerhardt Schlegel, Friedhelm R. Schuster, Bernhard Kremens, Claudia Rossig, Bernd Gruhn, Rupert Handgretinger, Tobias Feuchtinger
Journal: Blood (2015)