tbuckley/cabot-search huggingface dataset:
Noncanonical Inflammasome Activation of Caspase-4/Caspase-11 Mediates Epithelial Defenses against Enteric Bacterial Pathogens
Authors: Leigh A. Knodler, Shauna M. Crowley, Ho Pan Sham, Hyungjun Yang, Marie Wrande, Caixia Ma, Robert K. Ernst, Olivia Steele-Mortimer, Jean Celli, Bruce A. Vallance
Journal: Cell Host & Microbe (2014)

Inflammasome-mediated host defenses have been extensively studied in innate immune cells. Whether inflammasomes function for innate defense in intestinal epithelial cells, which represent the first line of defense against enteric pathogens, remains unknown. We observed enhanced Salmonella enterica serovar Typhimurium colonization in the intestinal epithelium of caspase-11-deficient mice, but not at systemic sites. In polarized epithelial monolayers, siRNA-mediated depletion of caspase-4, a human ortholog of caspase-11, also led to increased bacterial colonization. Decreased rates of pyroptotic cell death, a host defense mechanism that extrudes S. Typhimurium-infected cells from the polarized epithelium, accounted for increased pathogen burdens. The caspase-4 inflammasome also governs activation of the proinflammatory cytokine, interleukin (IL)-18, in response to intracellular (S. Typhimurium) and extracellular (enteropathogenic Escherichia coli) enteric pathogens, via intracellular LPS sensing. Therefore, an epithelial cell-intrinsic noncanonical inflammasome plays a critical role in antimicrobial defense at the intestinal mucosal surface.
Confronting AIDS: Directions for Public Health, Health Care, and Research
Authors: Mervyn F. Silverman
Journal: JAMA (1987)

One need only walk through the health section of a bookstore to see the plethora of books on almost every aspect of the acquired immunodeficiency syndrome (AIDS). Most are informative, but many fall short in one way or another of meeting the current needs of someone looking for an objective review of the many complex issues embodied in the AIDS epidemic. Better than any other book,<i>Confronting AIDS</i>succeeds in doing this. Using a committee of nationally and internationally respected scientists, scholars, and clinicians, the Institute of Medicine—National Academy of Sciences—held two public meetings and also invited a number of individuals to provide reports on the broad range of issues raised by the AIDS crisis—not only medical, but issues related to public health, law, economics, ethics, etc. The result is a text that has captured the complexities of the disease in a concise and straightforward manner. Rather than a collection
P1-07-11: Consistency and Control in Clinical Assay Technology over Time: The Oncotype DX Recurrence Score and Assessment of Single Gene Expression Levels.
Authors: FL Baehner, SM Butler, JM Anderson, J Ballard, V Tan, S Shak
Journal: Cancer Research (2011)

Abstract Background: ASCO® and CAP have recently highlighted the importance of consistency and control in clinical assay technology. To date the Oncotype DX® Recurrence Score® (RS) has been ordered to assist in individualized treatment decision making in over 200,000 estrogen receptor positive, early stage breast cancer patients. The assay quantifies gene expression using RT-PCR from fixed paraffin embedded tissue (FPET) and employs a large number of controls and calibrators to enhance precision and reproducibility. Over 6 years of data on the assay presents an opportunity to explore consistency over time in the RS and quantitative single gene levels (ER, PR, HER2). Methods: All tumors successfully analyzed in the Genomic Health Laboratory from 1/1/05-3/31/11 were included. Descriptive statistics for the RS, the average reference gene expression level, and expression levels for quantitative single genes were obtained for each calendar year. This was done for the entire data set as well as for subgroups defined by histological tumor type. The associations by year between HER2 and GRB7, ER and HER2, and ER and PR expression levels were explored including scatterplots and summary statistics. Results: There were a total of 207,691 breast cancer cases, and the number in each calendar year increased over time as shown in the Table. In general the median age increased slightly over time, as did the proportion of patients in the low RS Risk Group. There was no systematic change over time in the average reference gene expression level, or in the expression levels for the individual genes ER, PR or HER2 during the period from 2008 to 2011 when individual gene testing was provided as part of the Oncotype DX assay report. The relationships between HER2 and GRB7, ER and HER2, and ER and PR remained consistent over time. Conclusions: Active monitoring of the Oncotype DX assay as mandated by ASCO/CAP shows a high degree of consistency in results for both the multigene Recurrence Score and the quantitative single gene results. These results and the approaches used for monitoring consistency are relevant to other institutions in their efforts to maintain and improve assay quality control. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-07-11.
Case 42-1974
Authors: J. Warren Harthorne, James B. Caulfield
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 51-year-old woman was admitted to the hospital because of coronary-artery disease.She was well until 13 years previously, when episodic chest pain developed, and a diagnosis of angina pectoris was made. During the ensuing years the chest pain gradually became more frequent and responded less well to nitroglycerin, and dyspnea and orthopnea developed. Two months before admission she entered another hospital because of an episode of severe chest pain. Serial studies revealed no evidence of acute myocardial infarction. A coronary angiographic examination showed complete occlusion of the right coronary artery 1 cm from its origin; it . . .
Abstract 3153: The role of ubiquitin in androgen receptor function in prostate cancer
Authors: Steven Darby, Hollie Lumsden, Luke Gaughan, Craig N. Robson
Journal: Cancer Research (2010)

Abstract IntroductionProstate cancer (PC) is the most common male cancer in the western world. The androgen receptor (AR) plays a central role in PC development and remains the primary target for therapy. Androgen deprivation therapy is currently the standard treatment for PC. However, following a 2-3 year period, a more aggressive cancer usually recurs that is unresponsive to further androgen deprivation and is termed castrate resistant prostate cancer (CRPC). Several AR interacting proteins are components of the ubiquitin-proteasome degradation system, including Mdm2, CHIP and E6AP E3 ligases implicating proteasomal degradation/activation as a key event in AR function. In this study we have investigated which ubiquitin ligases are involved in AR ubiquitination and whether altered ubiquitination levels play a critical role and subsequent AR function in development of CRPC.MethodsIn vitro ubiquitination assays were performed with AR as the substrate with multiple purified E3 ligase enzymes in conjunction with wild type or mutant ubiquitin (K7R, K48 and K63). A panel of E2 conjugating enzymes were also employed to identify which E2/E3 heterodimers were involved in this process. Ubiquitinated AR fragments were gel excised and digested with trypsin. Fragments were then subjected to proteomic analysis to determine the sites of ubiquitination in AR.ResultsIn vitro ubiquitination assays using lysine null ubiquitin (K7R) revealed monoubiquitination of AR in multiple domains of AR in response to four E3 ligases. Screening of an E2 panel also identified multiple E2 conjugating enzymes implicated in AR ubiquitination. K48 ubiquitin (implicated in proteosomal degradation) and K63 ubiquitin (implicated in substrate activation) incorporated into in vitro assays identified differential poly-ubiquitination chain patterns in AR, dependent on which E3 ligase was used in the assay. Proteomic analysis of ubiquitinated AR fragments identified a novel site of ubiquitination within AR.ConclusionsAR was ubiquitinated by four E3 ligases evaluated in this study. Mono- and poly-ubiquitination of AR was identified. Mass spectroscopy revealed a novel site of ubiquitination in AR. Further experiments are being performed, including site directed mutagenesis to determine the importance of the novel ubiquitination site in AR protein proteosomal turnover and transcriptional activation. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3153.
Using Modified RECIST and Alpha-Fetoprotein Levels to Assess Treatment Benefit in Hepatocellular Carcinoma
Authors: Jean-Luc Raoul, Joong-Won Park, Yoon-Koo Kang, Richard S Finn, Jun Suk Kim, Winnie Yeo, Blasé N Polite, Yee Chao, Ian Walters, Christine Baudelet, Riccardo Lencioni
Journal: Liver Cancer (2014)

&lt;b&gt;&lt;i&gt;Background and Aims: &lt;/i&gt;&lt;/b&gt;Assessing treatment responses in hepatocellular carcinoma (HCC) is challenging, and alternative radiologic methods of measuring treatment response are required. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC and alpha-fetoprotein (AFP) levels were assessed in a post hoc analysis of a phase II study of brivanib, a selective dual inhibitor of fibroblast growth factor and vascular endothelial growth factor signaling. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;HCC patients were treated with first-line (cohort A; n = 55) or second-line (cohort B; n = 46) brivanib alaninate 800 mg once daily. Outcomes were compared between World Health Organization (WHO) criteria and (retrospectively by) mRECIST by independent review. The relationship between on-study AFP changes and outcome was analyzed in patients with elevated AFP at baseline. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;Response rates were higher with mRECIST versus WHO criteria in cohorts A (25.5% vs. 7.3%) and B (10.9% vs. 4.3%). Progressive disease (PD) as assessed by mRECIST was associated with a very short median overall survival (OS; cohort A, 2.8 months; cohort B, 5.3 months); PD as assessed by WHO criteria reflected a mixed population of patients with better outcomes. mRECIST responders tended to have a&gt;50% AFP decrease during therapy. In cohorts A and B pooled, an early AFP response (&gt;20%or &gt;50% decline from baseline within the first 4 weeks) was not associated with longer median OS. &lt;b&gt;&lt;i&gt;Conclusions: &lt;/i&gt;&lt;/b&gt;Tumor response as assessed by mRECIST differed from that by WHO criteria, with mRECIST possibly identifying true nonresponders with a poor prognosis. Many patients had AFP decreases correlating with tumor shrinkage, yet an association with long-term benefit was unclear. mRECIST and on-treatment AFP levels are being explored further with brivanib in HCC.
TCT-490 Coronary Artery Disease and Tako-tsubo Cardiomyopathy: a Possible Association
Authors: Guido Parodi, Rodolfo Citro, Benedetta Bellandi, Eduardo Bossone, Stefano Del Pace, Marco Marrani, Fausto Rigo, Francesco Bovenzi, Renato Valenti, David Antoniucci
Journal: Journal of the American College of Cardiology (2012)
Medical Students and Smoking
Authors: O. P. Arya
Journal: BMJ (1970)

SIR,-The problems of lung transplanta- tion have been reviewed in your leading article (12 September, p. 600).The combi- nation of infection and rejection are a par- ticular hazard in an organ that is exposed to the atmosphere, and it must be expected that prospects of success cannot improve until there are advances in medical manage- ment.However, not all the current evidence is unfavourable and some points are worth noting.Mucus transport may be severely curtailed in animals after lung reimplantation, but recovery probably occurs after 90 to 120 days.'Lymphatics are rapidly reconstituted, and loss of bronchial circulation does not appear to cause problems.Denervation is likely to become an impor- tant problem only if the cough reflex from both lungs is lost or if the upper airway reflexes are interrupted.A lung homograft provides a large vas- cular bed as well as a ventilation organ, and pulmonary hypertension may be improved as in F. Derom's patient.The use of enhancing serum has been shown in animals2 to be capable of prevent- ing rejection without increasing the subject's susceptibility to infection.The chance of a successful lung transplant may be considerably higher now than in the recent past.Like many of our colleagues, we believe that the most favourable cases to consider for this opera- tion are cases of advanced pulmonary fibrosis or of primary pulmonary hyperten- sion.-Weare, etc.,
Histologic and Imaging Features of Mural Nodules in Mucinous Pancreatic Cysts
Authors: Ning Zhong, Lizhi Zhang, Naoki Takahashi, Vladislav Shalmiyev, Marcia Irene Canto, Jonathan E. Clain, John C. Deutsch, John DeWitt, Mohamad A. Eloubeidi, Ferga C. Gleeson, Michael J. Levy, Shawn Mallery, Massimo Raimondo, Elizabeth Rajan, Tyler Stevens, Mark Topazian
Journal: Clinical Gastroenterology and Hepatology (2011)
Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma.
Authors: R J Cahill, C Kilgallen, S Beattie, H Hamilton, C O'Morain
Journal: Gut (1996)

Increased epithelial cell proliferation is associated with an increased risk of adenocarcinoma and is associated with Helicobacter pylori infection. The aim of this study was to assess both gastric epithelial cell proliferation and the influence of H pylori infection on cell kinetics in the progression from normal mucosa to gastric carcinoma. One hundred and forty four subjects were assigned to study groups based on diagnosis and H pylori status: microscopically normal mucosa and H pylori negative (n = 28); chronic active gastritis and H pylori positive (n = 83); atrophic gastritis (n = 9); intestinal metaplasia (n = 19); gastric carcinoma (n = 12). Gastric antral epithelial cell proliferation was assessed using the in vitro bromodeoxyuridine immunohistochemical technique and expressed as the labelling index per cent (LI%). Subjects with chronic atrophic gastritis, intestinal metaplasia or gastric cancer have increased gastric epithelial cell proliferation compared with normal mucosa (LI% mean (SEM): 5.14 (0.6), 4.68 (0.3), 6.50 (0.5) v 3.08 (0.2), p < 0.001). This increase in gastric epithelial cell proliferation was not influenced by H pylori status. Gastritis associated with H pylori had an increased LI% compared with normal controls or subjects with H pylori negative gastritis (4.98 (0.2) v 3.08 (0.2), 3.83 (0.2), p < 0.01). H pylori infection although associated with an increased epithelial cell proliferation in subjects with chronic gastritis, does not influence the increased epithelial cell proliferation seen in subjects with precancerous lesions or gastric carcinoma. This is further evidence that H pylori may be an initiating step in gastric carcinogenesis.
Folic Acid and Prevention of Colorectal Adenomas—Reply
Authors: Bernard F. Cole, John A. Baron, Leila A. Mott
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Urticarial and anaphylactoid reactions following ethanol intake
Authors: M. STICHERLING, J. BRASCH, H. BRUNING, E. CHRISTOPHERS
Journal: British Journal of Dermatology (1995)

Ingestion of ethyl alcohol may be associated with a number of adverse reactions. Apart from toxicological effects, intolerance syndromes occur, which are caused by genetic or acquired defects in alcohol metabolism and are manifest clinically as flushing. In addition to these abnormalities, rare cases of generalized urticaria and anaphylactoid reactions after ingestion of ethyl alcohol have been reported, the pathogenesis of which is still a matter of debate. We describe three patients who presented with recurrent generalized urticaria, which developed within minutes of consumption of small amounts of ethyl alcohol. Common causes of chronic recurrent urticaria were excluded by case history, physical examination and laboratory investigations, and by comprehensive allergy testing. All patients produced positive prick tests with acetic acid, and developed urticaria after oral challenge with small amounts of highly purified ethyl alcohol. The symptoms are most probably caused by an intolerance to ethyl alcohol or its metabolites, whereas an allergy sensu strictu seems unlikely.
Dr. Reuben D. Mussey.
Authors: F. M. Green
Journal: JAMA (1896)

Lexington, Ky., April 20, 1896. <h3>To the Editor:</h3> —My attention was called to your very interesting and able address contained in theJournalof April 4 several days after I had written you acknowledging the receipt of a number of copies of theJournal of the American Medical Association. I was a student under Dr. R. D. Mussey when he was a professor of surgery in Miami Medical College in 1856 and 1857, and he was my first teacher in surgery. He used to exhibit the specimen of the neck of fractured femur with bony union within the capsular ligament, the same that he took to Europe with him and showed to Sir Astley Cooper. Our class was always of the impression that he was the first to call attention to the fact, and I believe he so stated in his lectures. I saw in the lastJournalthat Dr.
Abstract 1873: Delayed progression to hormone-independent prostate cancer through modulation of mTOR by omega-3 fatty acids
Authors: Shruti Apte, William Friedrichs, Stephen Hursting, David Cavazos, Leticia Nogueira, Susan Perkins, Linda A. deGraffenried
Journal: Cancer Research (2010)

Abstract Prostate cancer is the second leading cause of cancer related deaths in men. The primary obstacle in effective treatment of prostate cancer is the progression of the disease from a hormone-dependent to a hormone-independent state. Previous studies indicate that activation of the mammalian Target of Rapamycin (mTOR) signaling pathway may be involved in progression of prostate cancer. Several studies have demonstrated a significant role for mTOR in promoting androgen independence. Recent data indicate that the combination of androgen deprivation with mTOR inhibition provides an additive anti-tumor effect in vivo. mTOR is directly involved in regulating cell survival, growth, proliferation, and differentiation. Many dietary and lifestyle interventions that reduce cancer risk and progression mediate their effects through regulation of mTOR signaling. Epidemiological studies indicate an inverse relation between dietary intake of omega-3 fatty acids and prostate cancer risk. Omega-3 fatty acids have been shown to inhibit prostate cell growth both in vitro and in vivo. Preliminary data from our laboratory demonstrated that treatment of LNCaP prostate cancer cells with omega-3 fatty acids, specifically docosahexaonoic acid (DHA), delayed development of androgen independence in vitro. This delay correlated with a decrease in protein expression of downstream targets of mTOR regulation, including phosphorylated S6, Bcl-2, and cyclin D. We hypothesize that omega-3 fatty acids may prevent prostate cancer progression to a hormone independent phenotype in part through modulation of mTOR. To test this hypothesis, we transiently transfected LNCaP cells to express a constitutively active mTOR. Our results showed that expression of the constitutively active mTOR correlated with a reduction in response to hormone deprivation, resembling that observed in our previously generated hormone refractory LNCaP cell line. When exposed to hormone-ablation conditions, the proliferation rates observed compared to the that of the vector-only control cells were 64% higher in the constitutively active mTOR cells, and 55% higher in the hormone-refractory cell. Ongoing studies are using a stable transfectant of constitutively active mTOR to determine if modulation of mTOR signaling is one mechanism by which the omega-3 fatty acids delay the progression to hormone-independence. These studies suggest that inhibition of mTOR is critical for cellular response to hormone ablation, and that mTOR may be a viable target for delaying progression to a hormone refractory disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1873.
Effect of secretion on intracellular pH regulation in isolated rat bile duct epithelial cells.
Authors: D Alvaro, W K Cho, A Mennone, J L Boyer
Journal: Journal of Clinical Investigation (1993)

The effects of secretin on ion transport mechanisms involved in regulation of intracellular pH (pHi) and HCO3- excretion were characterized in bile duct epithelial (BDE) cells isolated from normal rat liver. pHi was measured with 2,7-bis(carboxy-ethyl)-5(6)-carboxy-fluorescein-acetomethylester (BCECF-AM) using a microfluorimetric method. Basal pHi of BDE was 7.04 +/- 0.06 in Hepes and 7.16 +/- 0.10 in KRB and was unaffected by secretin (50-200 nM). Recovery rates from an acid load in Hepes or in KRB media (with and without amiloride) were also not altered by secretin, indicating that Na+/H+ exchange and Na+/HCO3- cotransport were not affected by this hormone. After acute Cl- removal, pHi rose 0.24 +/- 0.08 pHU at a maximal rate of 0.125 +/- 0.06 pHU/min (H+ flux rates = 6.02 +/- 3.27 mM/min) and recovered after Cl- readmission (0.188 +/- 0.08 pHU/min; H+ flux rates = 11.82 +/- 5.34 mM/min). Pretreatment with 1 mM DIDS inhibited the effects of Cl- removal, while valinomycin, which induces cell depolarization, enhanced these effects, probably by stimulating electrogenic HCO3- influx. Secretin significantly increased both the maximal rate of alkalinization after Cl- removal (P < 0.012) and of pHi recovery after Cl- readmission (P < 0.025), indicating stimulation of Cl-/HCO3- exchange activity. These findings were reproduced with N6,2'-O-Dibutyryladenosine-3',5'-cyclic monophosphate (DBcAMP). The Cl- channel blocker 5-nitro-2'-(3-phenylpropylamino)-benzoate (NPPB, 10 microM) significantly decreased the effects of secretin and DBcAMP on the pHi changes promoted by acute Cl- removal/readmission. These findings establish that secretin stimulates the activity of the Cl-/HCO3- exchanger in BDE cells, probably by activating Cl- channels via the intracellular messenger cAMP. This in turn depolarizes the cell, stimulating electrogenic Na+/HCO3- symport. The cell depolarization induced by Cl- channel activation should enhance HCO3- entrance through electrogenic Na+/HCO3- symport, which in turn stimulates the Cl-/HCO3- exchange. These mechanisms could account for secretin stimulated bicarbonate secretion in bile.