tbuckley/cabot-search huggingface dataset:
OC-019 Altered trail, CASPASE12, BAK and FAS-l expressions are associated with increased susceptibility to radiation induced intestinal epithelial apoptosis in NF-κ b1-null and NF-κ b2-null mice
Authors: A Hanedi, M D Burkitt, C A Duckworth, R Dimaline, J H Caamano, D M Pritchard
Journal: Gut (2012)

<h3>Introduction</h3> The Nuclear Factor κ B (NFκB) family is composed of five members, RelA, c-Rel, NFκB1, RelB and NFκB2. The first three members signal via the classical pathway and the last two via the alternative pathway to regulate several cellular processes including apoptosis. NFκB1 has previously been shown to regulate radiation-induced apoptosis in the murine small intestine, but the underlying mechanisms have not been defined. The roles of other family members, particularly those involved in alternative pathway signalling, in regulating intestinal epithelial apoptosis in vivo have not previously been investigated. <h3>Aims</h3> To assess susceptibility to intestinal apoptosis and the associated molecular changes in mice with germline deletions of three individual NFκB family members. <h3>Methods</h3> Intestinal apoptosis was induced in male c-Rel-null, NFκB1-null and NFκB2-null mice and their wild-type (C57BL/6) counterparts by 8Gy γ-irradiation (n=6 per group). Apoptosis was assessed on a cell positional basis from H/E stained sections. The mRNA expression of 10 key apoptosis regulating genes in the small intestine and colon (TRAIL, Caspase12, BAK, FAS-L, FAS, p53, BCL2, BCL-XL, c-IAP2 and XIAP) was assessed by real time PCR (n=4 per group). Statistical comparisons were by ANOVA with Bonferroni post-hoc tests. <h3>Results</h3> Basal small intestinal crypt apoptosis was significantly increased in NFκB2-null relative to C57BL/6 mice. In addition, small intestinal and colonic crypt apoptotic indices were both significantly increased (up to threefold) in NFκB1-null and NFκB2-null mice 4.5 h after 8Gy γ-irradiation relative to wild-type and c-Rel-null mice. Untreated NFκB1-null and NFκB2-null small intestine showed reduced mRNA expression of the anti-apoptotic genes BCL2, BCL-XL, c-IAP2 and XIAP. Following irradiation, NFκB1-null mice showed significant increases in the mRNA of the pro-apoptotic genes TRAIL, Caspase12 (in both small intestine and colon) and BAK (small intestine only) compared to wild-type mice. Significant increases in the mRNA of the pro-apoptotic genes Caspase12 and FAS-L were also seen in irradiated NFκB2-null small intestine and colon relative to wild-type mice. <h3>Conclusion</h3> c-Rel expression does not appear to regulate susceptibility to intestinal epithelial apoptosis in vivo. NFκB1 and NFκB2 deletion both caused increased susceptibility to intestinal apoptosis and this was associated with altered expression of TRAIL, Caspase12, BAK and FAS-L. These NFκB family members may therefore also regulate the susceptibility of intestinal epithelia to other consequences of DNA damage such as cancer. <h3>Competing interests</h3> None declared.
Effect of dexamethasone on autoantibody levels and arthritis development in patients with arthralgia: a randomised trial
Authors: W H Bos, B A C Dijkmans, M Boers, R J van de Stadt, D van Schaardenburg
Journal: Annals of the Rheumatic Diseases (2009)

Background Rheumatoid arthritis is characterised by antibodies to citrullinated proteins (ACPA) and rheumatoid factor (RF) in the preclinical phase. Objective To determine whether an intervention aimed at decreasing autoantibody levels in people at risk may be effective in preventing progression to arthritis. Methods 83 patients with arthralgia positive for ACPA or IgM-RF were randomly allocated to intramuscular injections of 100 mg dexamethasone or placebo at baseline and 6 weeks. The primary end point was a 50% antibody reduction or normalisation at 6 months. Results The primary end point was reached in one patient in each group. Patients treated with dexamethasone had reductions of antibody levels after 1 month (ACPA 222% and IgM-RF 214%), which persisted at 6 months for ACPA. During a median follow-up of 26 months, arthritis development in both groups was similar (20% vs 21%). Conclusion In autoantibody-positive patients with arthralgia, dexamethasone treatment decreases ACPA and IgM-RF levels, but does not prevent arthritis development. Trial registration number: ISRCTN73232918.
Local Recurrences and Distant Metastases After Conservative Breast Cancer Treatments: Partly Independent Events
Authors: U. Veronesi, E. Marubini, M. D. Vecchio, A. Manzari, S. Andreola, M. Greco, A. Luini, M. Merson, R. Saccozzi, F. Rilke, B. Salvadori
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Local Recurrences and Distant Metastases After Conservative Breast Cancer Treatments: Partly Independent Events Get access Umberto Veronesi, Umberto Veronesi 1 *Istituto Nazionale TumoriMilan, Italy Correspondence to: Professor Eltore Maribini, Istituto di Statistica Medica e Biometria, Via G. Venezian, 1, 20133 Milan, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ettore Marubini, Ettore Marubini 1Istitudo di Statistica Medica e BiometriaMilan Search for other works by this author on: Oxford Academic PubMed Google Scholar Marcella Del Vecchio, Marcella Del Vecchio *Istituto Nazionale TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Antonia Manzari, Antonia Manzari *Istituto Nazionale TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Salvatore Andreola, Salvatore Andreola *Istituto Nazionale TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Marco Greco, Marco Greco *Istituto Nazionale TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Alberto Luini, Alberto Luini *Istituto Nazionale TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Mirella Merson, Mirella Merson *Istituto Nazionale TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Roberto Saccozzi, Roberto Saccozzi *Istituto Nazionale TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Franco Rilke, Franco Rilke 1Istitudo di Statistica Medica e BiometriaMilan Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Bruno Salvadori Bruno Salvadori *Istituto Nazionale TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 1, 4 January 1995, Pages 19–27, https://doi.org/10.1093/jnci/87.1.19 Published: 04 January 1995 Article history Received: 08 March 1994 Revision received: 01 September 1994 Accepted: 28 September 1994 Published: 04 January 1995
The Next Influenza Pandemic
Authors: Jeffery K Taubenberger, David M Morens, Anthony S Fauci
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Flow cytometric analysis of gut mucosal lymphocytes supports an impaired Th1 cytokine profile in spondyloarthropathy
Authors: N Van Damme
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To quantify the fraction of gut mucosal lymphocytes expressing the T helper type 1 (Th1) cytokines, interferon γ (IFNγ) and interleukin (IL)2, and the Th2 cytokines, IL4 and IL10, at the single cell level in patients with spondyloarthropathy (SpA) in comparison with healthy controls. <h3>METHODS</h3> An improved extraction protocol was used for the enrichment of intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) from colonic and ileal biopsy specimens obtained from patients with SpA (n=20) and healthy controls (n=13). After stimulation with phorbol ester/ionomycin, expression of the intracellular cytokines IFNγ, IL2, IL4, and IL10 was determined in CD3+, CD3+CD8+ and CD3+CD8− T cells by flow cytometry. <h3>RESULTS</h3> In colonic LPLs, a significant decrease in IFNγ-producing CD3+ cells was observed (p=0.02) in patients with SpA. In the CD3+CD8− subset, the proportion of cells producing IFNγ and IL2 was decreased in patients with SpA (p=0.021 and p=0.027 respectively). In ileal LPLs, the percentage of IL10-producing CD3+CD8− cells was significantly increased (p=0.046). <h3>CONCLUSION</h3> An impaired Th1 cytokine profile is observed in gut mucosal lymphocytes from patients with SpA. This adds to the existing evidence that the gut mucosal immune apparatus is involved in the pathogenesis of SpA.
PHYSICAL FITNESS OF CHILDREN FROM DIFFERENT ECONOMIC LEVELS IN CHICAGO
Authors: MARTHA CRUMPTON HARDY
Journal: JAMA (1941)

For a number of years the Elizabeth McCormick Memorial Fund has been interested in the accumulation of a body of factual information on the general health and dietary practices of preschool and school age children in the Chicago area. Its regular health education program centers around a periodic examination by a pediatrician, followed by family consultations with a nutritionist. Approximately 1,500 children from six hundred families, largely from the low income levels, are examined each year in connection with this program. In 1939, with the assistance of the Work Projects Administration,<sup>1</sup>a study was begun of the records of 10,000 children who had been enrolled in the Fund's health supervision classes during the preceding decade, and plans were made for examining during the next two years a large number of children from widely different economic levels. Since then more than 7,200 children from three thousand nine hundred families have
Up-regulation of Mcl-1 Is Critical for Survival of Human Melanoma Cells upon Endoplasmic Reticulum Stress
Authors: Chen Chen Jiang, Keryn Lucas, Kelly A. Avery-Kiejda, Margaret Wade, Charles E. deBock, Rick F. Thorne, John Allen, Peter Hersey, Xu Dong Zhang
Journal: Cancer Research (2008)

Abstract We have previously shown that most melanoma cell lines are insensitive to endoplasmic reticulum (ER) stress–induced apoptosis, and this involves activation of the mitogen-activated protein/extracellular signal-regulated kinase (MEK)/ERK signaling pathway and expression of the apoptosis repressor with caspase recruitment domain (ARC) protein in the cells. In the present study, we show that up-regulation of the antiapoptotic Bcl-2 family member Mcl-1 is another mechanism critical for protection of melanoma cells against ER stress–induced apoptosis. Inhibition of Mcl-1 by small interference RNA (siRNA) rendered melanoma cells sensitive to apoptosis induced by the ER stress inducers thapsigargin and tunicamycin, but this sensitization was partially reversed by siRNA knockdown of PUMA or Noxa, as shown in Mcl-1–deficient melanoma cells. Both PUMA and Noxa were increased by ER stress through transcriptional up-regulation, but only up-regulation of Noxa was dependent on p53, whereas up-regulation of PUMA seemed to be mediated by a p53-independent mechanism(s). Up-regulation of Mcl-1 was also due to increased transcription that involved the IRE1α and activating transcription factor 6 signaling pathways of the unfolded protein response. In addition, activation of the MEK/ERK signaling pathway seemed to be necessary for optimal up-regulation of Mcl-1. Taken together, these results reveal the mechanisms of resistance of melanoma cells to apoptosis induction mediated by BH3-only proteins upon ER stress, and identify Mcl-1 as a target for the treatment of melanoma in combination with therapeutics that induce ER stress. [Cancer Res 2008;68(16):6708–17]
Understanding the regulation of surfactant gene expression
Authors: W. Jacot, J. Bousquet
Journal: European Respiratory Journal (2003)

Among a number of biochemical and morphological criteria, alveolar type-II epithelial cells are defined by the synthesis of surfactant proteins. These molecules are implicated in numerous human diseases such as neonatal respiratory distress syndrome 1 and possibly acute respiratory distress syndrome (ARDS) 2, where a better understanding could lead to new therapeutic modalities via a targeted induction of surfactant synthesis. The synthesis of surfactant proteins (SPs) is under the control of a variety of potential developmental and hormonal regulators, however, two transcription factors, thyroid transcription factor (TTF)‐1 and hepatocyte nuclear factor (HNF)‐3, have a crucial role in mediating the expression of SPs 3. The promoter region of the SP‐B gene has been studied extensively 4. In the human SP‐B gene, a region located at the immediate 5′ flanking region of the basal promoter TATA box between 80–110 contains two cis-acting elements for TTF‐1 and HNF‐3 binding 4. These two elements are important for the specificity and activation of SPs gene expression in the lung.

SP‐B is a 79-amino acid peptide critical to postnatal respiratory adaptation. SP‐B is the only surfactant-associated protein required for postnatal lung function and survival. Complete deficiency of SP‐B in mice and humans results in lethal neonatal respiratory distress syndrome and is characterised by a virtual absence of lung compliance, highly disorganised lamellar bodies, and greatly diminished levels of SP‐C mature …
THE ROLE OF INTESTINAL BACTERIA IN THE RECOVERY FROM WHOLE BODY RADIATION
Authors: Chester B. Rosoff
Journal: The Journal of Experimental Medicine (1963)

Non-absorbable antibiotics, neomycin sulfate or polymyxin B, prevent death from an otherwise lethal dose of whole body radiation by suppressing the activity of the Gram-negative bacterial flora of the intestinal tract. The protective effect of such suppression has been evaluated over a range of radiation exposure from 325 to 675 r. Coliform-free animals uniformly survive exposure to 550 r, a dose which is regularly lethal for coliform bearing animals. When antibiotic treatment is begun within 1 hour after 550 r whole body radiation, survival is the rule. Delay in starting treatment is critical, for the longer the delay, the higher the mortality, even though the stool cultures meanwhile become coliform-free. When antibiotic is started prior to or immediately after radiation exposure, it must be continued for at least 3 weeks if maximum effectiveness is to be obtained. The shorter the postradiation period of treatment, the greater the mortality. This suggests that the defense systems involved require protection for at least 3 weeks in order to permit return of maximal function. The non-absorbable intestinal antibiotics are effective only when cultural data demonstrate successful elimination of the coliform flora in the gut.
Characterizing Bias in Population Genetic Inferences from Low-Coverage Sequencing Data
Authors: Eunjung Han, Janet S. Sinsheimer, John Novembre
Journal: Molecular Biology and Evolution (2013)

The site frequency spectrum (SFS) is of primary interest in population genetic studies, because the SFS compresses variation data into a simple summary from which many population genetic inferences can proceed. However, inferring the SFS from sequencing data is challenging because genotype calls from sequencing data are often inaccurate due to high error rates and if not accounted for, this genotype uncertainty can lead to serious bias in downstream analysis based on the inferred SFS. Here, we compare two approaches to estimate the SFS from sequencing data: one approach infers individual genotypes from aligned sequencing reads and then estimates the SFS based on the inferred genotypes (call-based approach) and the other approach directly estimates the SFS from aligned sequencing reads by maximum likelihood (direct estimation approach). We find that the SFS estimated by the direct estimation approach is unbiased even at low coverage, whereas the SFS by the call-based approach becomes biased as coverage decreases. The direction of the bias in the call-based approach depends on the pipeline to infer genotypes. Estimating genotypes by pooling individuals in a sample (multisample calling) results in underestimation of the number of rare variants, whereas estimating genotypes in each individual and merging them later (single-sample calling) leads to overestimation of rare variants. We characterize the impact of these biases on downstream analyses, such as demographic parameter estimation and genome-wide selection scans. Our work highlights that depending on the pipeline used to infer the SFS, one can reach different conclusions in population genetic inference with the same data set. Thus, careful attention to the analysis pipeline and SFS estimation procedures is vital for population genetic inferences.
Association between peripheral muscle strength and daily physical activity in patients with COPD - a meta-analysis
Authors: Anne-Kathrin Rausch-Osthoff, Jan Taeymans, Jan Kool, Valentine Marcar, Arnoldus J.R. Van Gestel
Journal: European Respiratory Journal (2014)

Background:   Patients with chronic obstructive pulmonary disease have skeletal muscle dysfunction and reduced daily physical activity (PA). Whether the reduction in quadriceps strength (QS) is directly linked to physical inactivity remains to be elucidated.   Methods:   A systematic review and a meta-analysis were conducted to determine the potential relationship between QS and the level of PA. The overall estimate of the correlation coefficient (  r  *) was calculated, and a subgroup analysis was conducted to analyze the association between QS and indices of PA separately.   Results:   A total of 8 studies were included in the meta-analysis. The overall association between QS and PA was low but highly significant (  r  * = 0.288, 95% CI = 0.180-0.389;  P   r  = 0.260; 95% CI = 0.060-0.440) and the association between QS and the time spent walking was moderate (  r  = 0.418; 95% CI = 0.229-0.576).   Conclusion:   Peripheral muscle strength is associated with PA as assessed by the number of steps per day and the time spent walking in patients with chronic obstructive pulmonary disease. The overall association between QS and PA was low to moderate and highly significant.
Users' Guides to the Medical Literature
Authors: Roman Jaeschke
Journal: JAMA (1994)

<h3>CLINICAL SCENARIO</h3> You are back where we put you in the previous article<sup>1</sup>on diagnostic tests in this series on how to use the medical literature: in the library studying an article that will guide you in interpreting ventilation-perfusion (V/Q) lung scans. Using the criteria in Table 1, you have decided that the Prospective Investigation of Pulmonary Diagnosis (PIOPED) study<sup>2</sup>will provide you with valid information. Just then, another physician comes looking for an article to help with the interpretation of V/Q scanning. Her patient is a 28-year-old man whose acute onset of shortness of breath and vague chest pain began shortly after completing a 10-hour auto trip. He experienced several episodes of similar discomfort in the past, but none this severe, and is very apprehensive about his symptoms. After a normal physical examination, electrocardiogram and chest radiograph, and blood gas measurements that show a Pco<sub>2</sub>of
Delay of Postoperative Radiotherapy in Head and Neck Cancer Patients
Authors: Emmanuel Blot, Emilie Astruc, Laurent Bastit
Journal: Journal of Clinical Oncology (2004)

therapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med 334:1356-1361, 1996 6. Bellon J, Come SE, Gelman R, et al: Sequencing of chemotherapy and radiation therapy for patients with early stage breast cancer: Updated results of a prospective randomized trial. Int J Radiat Oncol Biol Phys 51:2-3, 2001 (abstr, suppl 1) 7. Hartsell WF, Recine DC, Griem KL, et al: Delaying the initiation of intact breast irradiation for patients with lymph node positive breast cancer increases the risk of local recurrence. Cancer 76:2497-2503, 1995
EFFECTS OF GROWTH-HORMONE RELEASE-INHIBITING HORMONE ON CIRCULATING GLUCAGON, INSULIN, AND GROWTH HORMONE IN NORMAL, DIABETIC, ACROMEGALIC, AND HYPOPITUITARY PATIENTS
Authors: C.H. Mortimer, D. Carr, T. Lind, S.R. Bloom, C.N. Mallinson, A.V. Schally, W.M.G. Tunbridge, Lynne Yeomans, D.H. Coy, A. Kastin, G.M. Besser, R. Hall
Journal: The Lancet (1974)
An In Vitro Effect of Triiodothyronine on Rat Adipose Tissue*
Authors: Martha Vaughan
Journal: Journal of Clinical Investigation (1967)

Triiodo-L-thyronine (T(3)) added in vitro to fat pads from normal, or propylthiouracil-treated rats enhanced the rate of release of glycerol and free fatty acids (FFA) in the presence of epinephrine. An effect of T(3) was also demonstrated in the presence of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, or glucagon in studies with tissue from normal rats. The minimal effective concentration of T(3) was approximately 2.5 x 10(-5) mole/liter for intact fat pads and 3 x 10(-6) mole/liter for fat cells. With fat pads from propylthiouracil-treated rats the effect of T(3) was not apparent until the 3rd hr of incubation. Enhancement of epinephrine-stimulated lipolysis by T(3) was evident during the 1st hr of incubation of fat pads from normal rats, and fat cells responded almost immediately to the presence of T(3). When added alone or in the presence of theophylline, 3',5'-adenosine monophosphate or its dibutyryl derivative, T(3) had little or no effect on lipolysis. The effect of T(3) was observed with or without glucose in the medium, and was not inhibited by cycloheximide or actinomycin D. It did not persist when tissues, after incubation in the presence of T(3) were transferred to medium without T(3). No effect of T(3) on glucose uptake in the presence of epinephrine, ACTH, or insulin was demonstrated.