tbuckley/cabot-search huggingface dataset:
17β-Hydroxysteroid Dehydrogenase 14 Affects Estradiol Levels in Breast Cancer Cells and Is a Prognostic Marker in Estrogen Receptor–Positive Breast Cancer
Authors: Agneta K. Jansson, Cecilia Gunnarsson, Maja Cohen, Tove Sivik, Olle Stål
Journal: Cancer Research (2006)

Abstract Estrogens have an important role in the progression of breast cancer. The 17β-hydroxysteroid dehydrogenase (17HSD) family has been identified to be of significance in hormone-dependent tissues. 17HSD1 and 17HSD2 are the main 17HSD enzymes involved in breast cancer investigated this far, but it is possible that other hormone-regulating enzymes have a similar role. 17HSD5 and 17HSD12 are associated with sex steroid metabolism, and 17HSD14 is a newly discovered enzyme that may be involved in the estrogen balance. The mRNA expression of 17HSD5, 17HSD12, and 17HSD14 were analyzed in 131 breast cancer specimens by semiquantitative real-time PCR. The results were compared with recurrence-free survival and breast cancer-specific survival of the patients. The breast cancer cell lines MCF7, SKBR3, and ZR75-1 were transiently transfected with 17HSD14 to investigate any possible effect on estradiol levels. We found that high 17HSD5 was related to significantly higher risk of late relapse in estrogen receptor (ER)–positive patients remaining recurrence-free later than 5 years after diagnosis (P = 0.02). No relation to 17HSD12 expression was found, indicating that 17HSD12 is of minor importance in breast cancer. Patients with ER-positive tumors with high expression levels of 17HSD14 showed a significantly better prognosis about recurrence-free survival (P = 0.008) as well as breast cancer-specific survival (P = 0.01), confirmed by multivariate analysis (P = 0.04). Transfection of 17HSD14 in the human breast cancer cells MCF7 and SKBR3 significantly decreased the levels of estradiol, presenting an effect of high expression levels of the enzyme. (Cancer Res 2006; 66(23): 11471-7)
Selective Arterial Embolization
Authors: Nanette Manhoff Clare, John J. Ghidoni
Journal: JAMA (1978)

<h3>To the Editor.—</h3> We have read the article by Bachman et al entitled "Selective Renal Artery Embolization: Treatment of Acute Renovascular Hypertension" (238:1534, 1977) and would like to emphasize their comments concerning the potential hazards of transcatheter embolization. <h3>Report of a Case.—</h3> A 39-year-old woman, a known abuser of alcohol, was seen with diffuse abdominal pain and hematemesis. Her blood pressure was 110/60 mm Hg, pulse rate was 80 beats per minute, and she had hepatomegaly. Laboratory data include a hemoglobin level of 8.2 g/dl; prothrombin time, 13 seconds (control, 11); partial thromboplastin time, 33 seconds (control, 33); serum amylase level, 90 units (normal, 38 to 264); and two-hour urine amylase level, 45 units (normal, 60 to 160). The serum amylase level remained normal through hospital day 15, after which it was not obtained. Her 21-day hospital course was complicated with sepsis and alcoholic hepatitis. During her hospitalization there was
Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response
Authors: Andrew T. Gewirtz, Peter O. Simon, Clare K. Schmitt, Laura J. Taylor, Curt H. Hagedorn, Alison D. O’Brien, Andrew S. Neish, James L. Madara
Journal: Journal of Clinical Investigation (2001)

This study investigated whether soluble paracrine factors mediated Salmonella-induced IL-8 expression in polarized model intestinal epithelia. We found that the basolateral media of model epithelia that had been apically infected with Salmonella typhimurium for a short period (10 minutes) could activate IL-8 secretion in virgin model epithelia, demonstrating that a proinflammatory factor (PIF) was indeed present. Initial characterization found that PIF was a heat-stable protein with a molecular mass of about 50 kDa that acts on the basolateral, but not apical, surface of model intestinal epithelia to elicit IL-8 secretion. PIF was not present in the media of model epithelia stimulated with other inducers of IL-8 secretion (TNF-α or carbachol) but was present in S. typhimurium supernatants, indicating PIF is of bacterial origin. PIF was purified from bacterial culture supernatants by anion/cation exchange chromatography and SDS-PAGE and found by using microsequencing to be the protein flagellin. In support of this finding, flagellin-deficient S. typhimurium mutants did not secrete detectable levels of PIF (i.e., a bioactivity that induced IL-8 secretion when placed basolaterally on model epithelia). Furthermore, viable flagellin-deficient mutant organisms (fliC/fljB and flhD) failed to elicit IL-8 secretion when added apically to model intestinal epithelia. These findings indicate that translocation of flagellin across epithelia, subsequent to apical epithelial–S. typhimurium interaction, is likely a major means of activating a mucosal inflammatory response.
Role reversal: infiltrating T cells protect the brain
Authors: Lawrence Steinman
Journal: Journal of Clinical Investigation (2015)

Inflammatory conditions intensify and then resolve, often sparing and recovering some of the injured tissue. While the ebb and flow of inflammation can be followed in many tissues, there is not a great deal of information on how inflammation regresses in the brain. In this issue of the JCI, Walsh, Hendrix, and colleagues illuminate a cellular mechanism whereby T cells that infiltrate the brain after nerve crush or contusion actually protect neurons from injury. These infiltrating T cells produce IL-4 and do so independently of a classic adaptive T cell immune response. The T cells respond to mediators produced by damaged neurons, without the classic three-way interaction among antigen, the major histocompatibility complex, and the T cell receptor. After brain injury, these protective T cells produce IL-4, which attenuates damage via IL-4 receptors on neurons.
Quarterly Visits With Glycated Hemoglobin Monitoring: The Sweet Spot for Glycemic Control in Youth With Type 1 Diabetes
Authors: Thao-Ly Phan, Jobayer Hossain, Stephen Lawless, Lloyd Neil Werk
Journal: Diabetes Care (2013)

To evaluate the association between the frequency of visits and glycated hemoglobin (GHb) measurements on glycemic control in youth with type 1 diabetes.A retrospective longitudinal cohort study of 1,449 youth with type 1 diabetes (mean age 11.4 years, 50% female, 74% Caucasian, 24% with Medicaid) followed at five pediatric endocrinology clinics from the years 2008-2011 was conducted. By hierarchical cluster analysis, three homogeneous groups of patients were generated: those with a relative increase in GHb (worsened [n = 237]), no change in GHb (stable [n = 842]), and a decrease in GHb (improved [n = 370]) over the study period. The number of visits and GHb measurements per year were compared among the three groups by multinomial logistic regression analysis using one visit or GHb test per year as a reference and controlling for patient demographic and baseline characteristics.Patients with quarterly visits were least likely to have worsened glycemic control (odds ratio 0.33, P < 0.05) and were most likely to have improved glycemic control (3.48, P < 0.01). Patients with four GHb tests a year (0.53, P < 0.05) were least likely to have worsened glycemic control.Quarterly visits and GHb testing are associated with glycemic control in youth with type 1 diabetes.
Critical Pathway for Chest Pain
Authors: Xavier Bosch
Journal: Annals of Internal Medicine (1998)

Letters1 July 1998Critical Pathway for Chest PainXavier Bosch, MD, PhDXavier Bosch, MD, PhDHospital Casa Maternitat; 08028-Barcelona, SpainSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-1-199807010-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In developing a critical pathway for emergency-department management of low-risk patients with chest pain to improve quality and efficiency of care, Nichol and colleagues [1] used a single normal creatine kinase-MB level (obtained at least 4 hours after the onset of pain) to complement clinical observations. Other markers for myocardial injury, such as troponin T and troponin I, were not used in the pathway because their role was considered unclear or because no controlled trials had shown the effects of their use on clinical outcomes.Only a few days after this paper was published, a prospective study ...References1. Nichol G, Walls R, Goldman L, Pearson S, Hartley LH, Antman E, et al. A critical pathway for management of patients with acute chest pain who are at low risk for myocardial ischemia: recommendations and potential impact. Ann Intern Med. 1997; 127:996-1005. Google Scholar2. Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med. 1997; 337:1648-53. Google Scholar3. Lindahl B, Venge P, Wallentin L. Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. Circulation. 1996; 93:1651-7. Google Scholar4. Ravkilde J, Nissen H, Horder M, Thygesen K. Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction: analysis of 28 months of follow-up in 196 patients. J Am Coll Cardiol. 1995; 25:574-81. Google Scholar5. Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996; 335:1342-9. Google Scholar Author, Article, and Disclosure InformationAffiliations: Hospital Casa Maternitat; 08028-Barcelona, Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1998Volume 129, Issue 1Page: 70KeywordsCreatineDecision makingHospitalizationsIschemiaMonoclonal antibodiesMyocardial infarctionProspective studiesQualitative studiesTroponinTroponin T Issue Published: 1 July 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 4126: Optimization of clinical sample collection for detection of c-Met phosphorylation
Authors: Takayuki Nakagawa, Namita Kumar, Galina Kuznetsov
Journal: Cancer Research (2011)

Abstract The receptor tyrosine kinase c-Met is being investigated as a target for cancer chemotherapy. c-Met and its ligand HGF (hepatocyte growth factor) play important roles in cell growth, survival and migration. Dysregulation of the HGF-c-Met pathway (overexpression, constitutive activation, gene amplification, ligand-dependent activation, mutation or epigenetic mechanisms) can lead to oncogenic changes, and has been described in multiple types of cancer including lung, gastric, and colorectal cancer. For cancer therapies targeting the HGF-c-Met signaling pathway, elevated levels of c-Met expression and increased phosphorylation of c-Met have been explored as both the predictive and PD biomarkers. However, detection of c-Met phosphorylation by IHC in human clinical cancer samples has proven to be extremely challenging. We have conducted a study aimed at finding a way to detect phosphorylation of c-Met in clinical samples. In the first attempt, we have acquired a set of 30 gastric cancer samples which were fixed in formalin in the presence of phosphatase inhibitors (PhosphoGuardTM fixation kit). While this approach has helped us to improve detection of several other phospho-proteins in tissues, it did not help with the detection of phospho-c-Met. We then hypothesized that this is a very labile phosphorylation which is rapidly lost during the cold ischemia time occurring between the surgical excision of the tissue and its placement in formalin for fixation (which could last 30-60 minutes or longer in the operating room). Studies with xenograft tissues showed that a 15 minute delay in fixation resulted in approximately 50% decrease in c-Met phosphorylation, while a 30 minute delay resulted in almost complete disappearance of phospho-c-Met. We therefore acquired a set of colorectal cancer samples which were placed into formalin within 5 minutes of surgical excision. Using these rapidly fixed samples, we were able to detect strong phosphorylation of c-Met in a small number of samples. The staining pattern for phospho-c-Met correlated with that of phospho-ERK (a downstream signaling molecule in the c-Met pathway) suggesting that the relatively low occurrence of c-Met phosphorylation may reflect the status of activation of this pathway in vivo at a given time point. This work suggests that rapid fixation of human tissues facilitates detection of phospho-c-met and its use as a PD and predictive biomarker in clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4126. doi:10.1158/1538-7445.AM2011-4126
Psychological Well-Being Revisited: Advances in the Science and Practice of Eudaimonia
Authors: Carol D. Ryff
Journal: Psychotherapy and Psychosomatics (2013)

This article reviews research and interventions that have grown up around a model of psychological well-being generated more than two decades ago to address neglected aspects of positive functioning such as purposeful engagement in life, realization of personal talents and capacities, and enlightened self-knowledge. The conceptual origins of this formulation are revisited and scientific products emerging from 6 thematic areas are examined: (1) how well-being changes across adult development and later life; (2) what are the personality correlates of well-being; (3) how well-being is linked with experiences in family life; (4) how well-being relates to work and other community activities; (5) what are the connections between well-being and health, including biological risk factors, and (6) via clinical and intervention studies, how psychological well-being can be promoted for ever-greater segments of society. Together, these topics illustrate flourishing interest across diverse scientific disciplines in understanding adults as striving, meaning-making, proactive organisms who are actively negotiating the challenges of life. A take-home message is that increasing evidence supports the health protective features of psychological well-being in reducing risk for disease and promoting length of life. A recurrent and increasingly important theme is resilience - the capacity to maintain or regain well-being in the face of adversity. Implications for future research and practice are considered.
Up-regulation of 14-3-3ζ in Lung Cancer and Its Implication as Prognostic and Therapeutic Target
Authors: Tao Fan, Ruiyun Li, Nevins W. Todd, Qi Qiu, Hong-Bin Fang, Huijun Wang, Jianjun Shen, Richard Y. Zhao, Nancy P. Caraway, Ruth L. Katz, Sanford A. Stass, Feng Jiang
Journal: Cancer Research (2007)

Abstract A functional genomic approach integrating microarray and proteomic analyses done in our laboratory has identified 14-3-3ζ as a putative oncogene whose activation was common and driven by its genomic amplification in lung adenocarcinomas. 14-3-3ζ is believed to function in cell signaling, cycle control, and apoptotic death. Following our initial finding, here, we analyzed its expression in lung tumor tissues obtained from 205 patients with various histologic and stage non–small cell lung cancers (NSCLC) using immunohistochemistry and then explored the effects of specific suppression of the gene in vitro and in a xenograft model using small interfering RNA. The increased 14-3-3ζ expression was positively correlated with a more advanced pathologic stage and grade of NSCLCs (P = 0.001 and P = 0.006, respectively) and was associated with overall and cancer-specific survival rates of the patients (P = 0.022 and P = 0.018, respectively). Down-regulation of 14-3-3ζ in lung cancer cells led to a dose-dependent increased sensitivity to cisplatin-induced cell death, which was associated with the inhibition of cell proliferation and increased G2-M arrest and apoptosis. The result was further confirmed in the animal model, which showed that the A549 lung cancer cells with reduced 14-3-3ζ grew significantly slower than the wild-type A549 cells after cisplatin treatment (P = 0.008). Our results suggest that 14-3-3ζ is a potential target for developing a prognostic biomarker and therapeutics that can enhance the antitumor activity of cisplatin for NSCLC. [Cancer Res 2007;67(16):7901–6]
NHS framework reintroduces target of treating 92% of patients within 18 weeks
Authors: H. Mooney
Journal: BMJ (2011)

NHS trusts in England should treat 92% of patients waiting for treatment within 18 weeks, the government’s NHS Operating Framework for 2012-13 has specified.

The Department of Health has also ordered hospitals with patients on their books who have already been waiting longer than 18 weeks to review their “planned waiting lists” for all areas and specialties by the end of December.

Although the framework fails to stipulate an absolute maximum waiting time for patients, it says that “92% of patients on an incomplete pathway should have been waiting no more than 18 weeks” and that less than 1% of patients should …
CULPRIT AND NON-CULPRIT PCI COMPARED TO CULPRIT ONLY PCI IN MULTI-VESSEL CORONARY ARTERY DISEASE PATIENTS WITH ACUTE ST ELEVATION MYOCARDIAL INFARCTION TREATED BY PRIMARY PERCUTANEOUS CORONARY INTERVENTION: A SYSTEMATIC REVIEW
Authors: Naji Alhulaimi, William Midodzi, Robert C. Welsh
Journal: Journal of the American College of Cardiology (2010)
Screening for hemochromatosis in children of homozygotes: Prevalence and cost-effectiveness
Authors: Paul C. Adams, Ann E. Kertesz, Leslie S. Valberg
Journal: Hepatology (1995)

Although hereditary hemochromatosis is an autosomal recessive disease, most homozygotes are concerned with the genetic implications for their children. The optimal age for testing children and the cost implications of screening their children have not been clearly established. A clinical database consisting of 255 children from families with at least one homozygote is used to assess the prevalence of homozygotes among children of homozygous parents and to review the biochemical abnormalities and life-threatening symptoms in these young adults. Decision analysis is used to estimate the cost and utility of screening children of a homozygous parent. Eleven homozygotes were discovered among children of homozygotes. Only one male had a life-threatening event, cirrhosis. Decision analysis estimated cost saving of $12 per child screened ($ net present value) and a saving of 10 quality-adjusted days per child screened at age 10 years compared with not screening. If screening began at age 20 years, there is a cost saving of $65 per child screened. Sensitivity analysis showed that the major factors influencing cost savings were the cost of venesections, sensitivity and specificity of the screening tests, and prevalence of disease. Because the prevalence of hemochromatosis is higher in children of homozygotes than in the general population, screening with transferrin saturation and ferritin as early as age 10 years is recommended. Savings are augmented if the cost per venesection is eliminated by allowing hemochromatosis patients to become voluntary blood donors.
Ethics review in research
Authors: Martin McKee
Journal: BMJ (2004)

EDITOR-Glasziou and Chalmers are to be congratulated for their stand on the important issue of ethics review.1For many years MSc students in this school undertook projects considering policy questions facing local trusts and health authorities.These typically entailed a literature review and interviews with managers, clinicians, and other relevant stakeholders.These interviewees are now deemed research subjects,
Visceral Pleural Invasion Classification in Non–Small-Cell Lung Cancer in the 7th Edition of the Tumor, Node, Metastasis Classification for Lung Cancer: Validation Analysis Based on a Large-Scale Nationwide Database
Authors: Akikazu Kawase, Junji Yoshida, Etsuo Miyaoka, Hisao Asamura, Yoshitaka Fujii, Yoichi Nakanishi, Kenji Eguchi, Masaki Mori, Noriyoshi Sawabata, Meinoshin Okumura, Kohei Yokoi
Journal: Journal of Thoracic Oncology (2013)
Canadian panel recommends against PSA screening
Authors: M. McCarthy
Journal: BMJ (2014)

The prostate specific antigen (PSA) test should not be used to screen for prostate cancer, the Canadian Task Force on Preventive Health Care has said. “Available evidence does not conclusively show that PSA screening will reduce prostate cancer mortality, but it clearly shows an increased risk of harm,” the task force said.

The task force is an independent panel established by the Public Health Agency of Canada to develop clinical practice guidelines for preventive services provided in primary care. The panel’s recommendations, which were based on a systematic review, were published online on 27 October by CMAJ , the journal of the Canadian Medical Association.1

“Unfortunately the PSA test is simply not an effective screening tool,” said Neil Bell, chair of the guideline working group …
Testimonial to Dr. Davis.
Authors: Wm. B. Atkinson
Journal: JAMA (1896)

Philadelphia, Pa., July 6, 1896. <h3>To the Editor:</h3> —The note of Dr. Overlock in the number for July 4, relative to a medal demands some information. The medal to which he alludes is that ordered by theAssociationin 1875; see Vol. xxvi, page 35. In accordance with the instructions then given, 1 had a number of the medals struck off and sent to those who forwarded the money. The date on the medal does not mean that when it was issued, but the date of the origin of theAssociation. Although Dr. Davis was quite prominent in the work of organizing theAssociation, yet at that time no thought existed of having a medal issued with his likeness on it. The meeting of the profession to organize a national society was held in New York, as stated in the note in theJournal, but Dr. Lewis Williams was not
CHANGES IN THE PARAOCULAR GLANDS ACCOMPANYING THE OCULAR LESIONS WHICH RESULT FROM A DEFICIENCY OF VITAMINE A
Authors: Robert A. Lambert, Arthur M. Yudkin
Journal: The Journal of Experimental Medicine (1923)

There is evidence suggesting that the ophthalmia which results from a deficiency of vitamine A is secondary to some change outside the eyes, and that this change may lie in the paraocular glands. In rats these glands consist of the lacrimal, with its watery secretion, the Harderian, with a probable fatty product, and the Meibomian glands. A histological study of these structures shows questionable changes in the lacrimal and Meibomian glands, and marked changes in the Harderian gland. The changes in the Harderian gland are both degenerative and inflammatory. The degenerative changes consist of swelling, vacuolation, and occasionally complete epithelial disintegration. The inflammatory lesions may be either acute or chronic. The acute reactions are sometimes diffuse, but are more often focal. Definite suppuration occasionally results. The acute process generally passes over into a chronic inflammation with mononuclear cell infiltration, fibrosis, and atrophy. The changes demonstrated indicate a serious disturbance in the secretion of the Harderian gland, such as may conceivably render the conjunctiva susceptible to infection. Theses studies suggest the importance of investigating the paraocular glands in other types of conjunctival infection. It is possible that they may have a definite relation to the origin and course of such infections.