tbuckley/cabot-search huggingface dataset:
APC, β-catenin and E-cadherin protein expression in colon crypts in the Markers of Adenomatous Polyps II (MAP II) study
Authors: Chiranjeev Dash, Valerie Kennedy, Roberd M. Bostick
Journal: Cancer Research (2006)

688   The  APC Pathway , a major pathway in colorectal cancers, involves functional alterations in the components of the  Wnt  signaling system. The “gateway” gene,  APC , functions to degrade β-catenin which is pro-proliferative and regulates E-cadherin, a cell adhesion molecule integral for colon crypt structure and function. Quantification of these biomarkers in crypts in normal-appearing colon mucosa may help us better understand the phenotypic changes associated with the genetic alterations in the APC pathway. MAP II is a community, colonoscopy-based, case-control study (49 cases, 154 controls) of incident sporadic colorectal adenoma, in which adult residents aged 30-74 years residing in Columbia, SC were enrolled. APC, β-catenin and E-cadherin levels were detected and quantified in the cells lining the colon crypt, by automated immunohistochemical methods and image analysis, in biopsies of normal-appearing rectal tissue, for 20 cases and 20 controls, from the MAP II study. We divided the colon crypt into deciles of height from base to apex and measured the signal intensity of biomarker expression in each decile to construct biomarker distribution profiles along the crypt.  APC distribution : In controls, expression of APC was highest in the upper 30% of the crypts, whereas in cases it was highest in the lower 20% and upper 20%. The cases, relative to the controls, had lower expression of APC at all levels of the crypt.  β-catenin distribution : Expression of β-catenin was lowest at the very bottom and the very top of the crypt for both cases and controls. No difference in the amount or shape of the distribution was evident between cases and controls.  E-cadherin distribution : E-cadherin expression was lowest at the two ends of the crypt with a relatively stable distribution in-between. Although the shape of the distribution was the same for both cases and controls, cases had lower expression of E-cadherin at all levels. We also measured the total expression of these biomarkers in the colon crypt. Proportional difference in crude means between cases and controls were: APC:  −24.6%, p=0.18 ; β-catenin:  -4.3%, p=0.73 ; E-cadherin:  -8.4%, p=0.77 . Further analyses comparing the ratio of APC to β-catenin and E-cadherin also revealed case-control differences (APC/β-catenin:  -29.5%, p=0.14 ; APC/E-cadherin:  -40.3%, p=0.15 ). APC, β-catenin, and E-cadherin distribution in the colon crypt based on fully quantitative image analysis procedures are being presented for the first time. Cases had decreased levels of APC and E-cadherin but the pattern varied along the crypt axis from base to apex. Contrary to expectations, we did not find an elevated level of β-catenin among cases. These findings suggest phenotypic differences that cannot be predicted solely from the genetic model of the APC pathway in colorectal adenoma, and further studies to investigate changes in phenotypic expression of biomarkers are needed.
A research roadmap for next-generation sequencing informatics
Authors: Russ B. Altman, Snehit Prabhu, Arend Sidow, Justin M. Zook, Rachel Goldfeder, David Litwack, Euan Ashley, George Asimenos, Carlos D. Bustamante, Katherine Donigan, Kathleen M. Giacomini, Elaine Johansen, Natalia Khuri, Eunice Lee, Xueying Sharon Liang, Marc Salit, Omar Serang, Zivana Tezak, Dennis P. Wall, Elizabeth Mansfield, Taha Kass-Hout
Journal: Science Translational Medicine (2016)

Next-generation sequencing technologies are fueling a wave of new diagnostic tests. Progress on a key set of nine research challenge areas will help generate the knowledge required to advance effectively these diagnostics to the clinic.
Analgesic and Mood Effects of Heroin and Morphine in Cancer Patients with Postoperative Pain
Authors: Robert F. Kaiko, Stanley L. Wallenstein, Ada G. Rogers, Patricia Y. Grabinski, Raymond W. Houde
Journal: New England Journal of Medicine (1981)

We designed a study to determine the relative analgesic potency of intramuscular heroin and morphine and to compare mood and side effects in 166 cancer patients with postoperative pain. Heroin was about twice as potent as morphine (95 per cent confidence limits, 1.6 to 2.6 times) in graded-dose, twin-crossover assays. Heroin provided an analgesic peak effect earlier than morphine (1.2±0.08 and 1.5±0.10 hours, respectively [mean ±S.E.M.]). Doses with equal analgesic effects provided comparable improvements in various elements of mood, particularly feelings of peacefulness. Peak mood improvement occurred earlier after heroin than after morphine (1.2±0.10 and 1.8±0.13 hours, respectively). Both analgesia and mood improvement were less sustained after heroin at doses providing equal peak analgesic effects. The drugs shared the most common side effects, with no marked differences in their occurrence; sleepiness was the most frequent side effect after both drugs (46 per cent with each). Heroin has no apparent unique advantages or disadvantages for the relief of pain in patients with cancer. (N Engl J Med. 1981; 304:1501–5.)
P6 Early Clinical Experience With Nintedanib – a two centre review
Authors: E Nuttall, M Crooks, S Gudur, C Leonard, C Major, S Hart, N Chaudhuri
Journal: Thorax (2015)

<h3>Introduction</h3> Clinical trials of pirfenidone and nintedanib have shown similar reduced rates of lung function decline in patients with idiopathic pulmonary fibrosis (IPF). In 2013 NICE approved pirfenidone for use in IPF patients with forced vital capacity (FVC) between 50% and 80% predicted. More recently, nintedanib has been available on an individual patient supply program (IPSP). <h3>Aims</h3> Reporting early experience of nintedanib in two tertiary referral centres, focussing on characterising the treated population, assessing the indications for use, and evaluating adverse effects. <h3>Method</h3> All IPF patients attending two tertiary referral centre ILD clinics who were commenced on nintedanib as part of the IPSP were included. Data were collected retrospectively from clinical records and local clinical databases. Data are presented as mean (range). <h3>Results</h3> 75 patients (mean age 70.8 years (50–85), 76% male). The FVC was 79.2% predicted (35% - 123%) and transfer factor (DLCO) 45.8% predicted (13% - 74%) prior to commencing treatment. 54% of patients were prescribed nintedanib because they did not meet FVC criteria for pirfenidone (FVC &gt;80% in 41% of patients and FVC &lt;50% in 13%). Other indications included refusal of pirfenidone due to the side effect profile (15%) or adverse effects requiring pirfenidone discontinuation (13%). 39 patients (52%) experienced adverse effects on nintedanib, the most common being diarrhoea (25%), nausea (13%), abnormal liver function tests (8%) and lethargy (11%). Adverse effects required nintedanib to be discontinued in 7 (9%) patients (diarrhoea (n = 3), abnormal LFTs (n = 2) and patient choice (n = 2)), dose reduction in 13 (17%) patients, and temporarily stopped and restarted in 9 (12%) patients. <h3>Conclusion</h3> Nintedanib is a relatively new medication and although there are modest numbers in this review only 9% had to discontinue treatment. Diarrhoea is the most quoted side effect from trial data (63% of patients in INPULSIS-2), but in our observational data only one quarter suffered diarrhoea and only 3 patients stopping due to this. Although the data is from early experience the discontinuation rate is favourable compared with published and local data on pirfenidone (drop out rate 15%). This needs continued review to further evaluate drug tolerability and real world efficacy.
The effect of breastfeeding on lung function at 12 and 18 years: a prospective cohort study
Authors: Nilakshi T. Waidyatillake, Julie A. Simpson, Katrina J. Allen, Caroline J. Lodge, Shyamali C. Dharmage, Michael J. Abramson, Alysha M. De Livera, Melanie C. Matheson, Bircan Erbas, David J. Hill, Adrian J. Lowe
Journal: European Respiratory Journal (2016)

The objective was to assess associations between duration of total and exclusive breastfeeding and lung function up to adolescence. A birth cohort (Melbourne Atopy Cohort Study) of 620 infants with a family history of allergic disease was recruited. Mothers were encouraged to breastfeed exclusively for 6 months. Lung function was assessed at 12 and 18 years of age. Associations between breastfeeding and lung function were investigated using multivariable linear regression and path analysis was used to assess the potential mediating factors. Duration of breastfeeding (total and exclusive) was not associated with most assessed lung function outcomes. However, there was a trend for increased pre-bronchodilator mid-expiratory flow (MEF) at both 12 (adjusted mean difference (95% CI) per week of breastfeeding of 10 (−1–20) mL·s −1 ) and 18 years (11 (−1–22) mL·s −1 ) (p-values of 0.07 and 0.08, respectively). There was a strong indirect effect of height on these observed associations. Duration of breastfeeding does not appear to greatly influence lung function outcomes in children with a family history of allergic diseases. Longer duration of exclusive breastfeeding may be associated with an increase in MEF, partly due to greater attained height of the child.
Abstract 5475: Cancer exosome promotes cisplatin resistance In bladder cancer and inhibition of exosome sensitizes bladder cancer cells to cisplatin chemotherapy
Authors: Chiahao Wu, Chris Silvers, Elizabeths Guancial, Jong-Wei Hsu, Edward Messing, Yi-Fen Lee
Journal: Cancer Research (2015)

Abstract Exsosomes are nano-vesicles secreted by most types of cells, and substantially increased secretion in cancer cells. Their role in tumorigenesis/cancer progression have been extensively studied but their role in regulating therapy response have been suggested without in depth investigation. We are particularly interested in exosome's roles in cisplatin resistant, since cisplatin is one of the most widely used chemodrugs for many cancer types. To investigate the role of exosomes in cisplatin resistance in bladder cancer, we examined the cisplatin sensitivity among five bladder cancer cell lines. The expression levels of exosome associated genes that are involved in exosome biogenesis and secretion/internalization were examined by quantative PCR. Interestingly, cisplatin resistant bladder cancer cells express relative high level of exosome associated genes as compared to cisplatin sensitive cells. More importantly, cisplatin treatment induces the expression of exosome associated genes’ expression in cisplatin resistant cells, but not in sensitive cell. Among all those genes, we are particularly interested in Rab gene family, and mechanistic study of targeting those Rab proteins is undergoing. The correlative exosome genes profiles with cisplatin resistance suggested exosome production might facilitate cancer cells escaping from cisplatin-induced cell death; thereby, inhibition of exosome might sensitize cancer cells response to cisplatin. To test this, we have screened several compounds that are known to inhibit exosome biogenesis and uptake, and. found that inhibition of exosomes by dynasore + NSC23766, indeed can sensitize bladder cancer cells to cisplatin. In summary, we concluded that cancer exosome play a critical role of promoting cisplatin resistance in bladder cancer, and inhibition of exosomes sensitizes bladder cancer cell response to cisplain. The exosome related profiles potentially can serve as therapy biomarkers Citation Format: Chiahao Wu, Chris Silvers, Elizabeths Guancial, Jong-Wei Hsu, Edward Messing, Yi-Fen Lee. Cancer exosome promotes cisplatin resistance In bladder cancer and inhibition of exosome sensitizes bladder cancer cells to cisplatin chemotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5475. doi:10.1158/1538-7445.AM2015-5475
P240 Validation of the Leicester Cough Questionnaire in pulmonary tuberculosis
Authors: RD Turner, GH Bothamley, SS Birring
Journal: Thorax (2015)

<h3>Introduction and objective</h3> Cough is prominent in pulmonary tuberculosis (TB) and transmits infection, yet no tool has been validated for assessing cough symptoms. We evaluated the Leicester Cough Questionnaire (LCQ) for measuring cough-related quality of life (QOL) in TB. <h3>Method</h3> The face validity of the LCQ was evaluated by structured interviews with patients and a multi-disciplinary team (MDT) discussion (respiratory physicians and nurses). Consecutive patients with TB completed the LCQ just before or within 7 days of starting therapy; a subgroup completed a repeat questionnaire approximately two weeks after the first. Internal reliability (inter-relatedness between items), concurrent validity (association with cough severity visual analogue scale [VAS] score and 24-hour cough frequency measured with the Leicester Cough Monitor), and responsiveness were evaluated. <h3>Results</h3> The MDT and patients thought the LCQ to be relevant, comprehensive and useful in TB and no modifications were suggested. Forty patients completed the questionnaire before (n = 29) or just after (n = 11) the start of treatment. Internal reliability of responses was high (Cronbach’s α = 0.93). LCQ scores were correlated with both the VAS (Spearman’s ρ = -0.69 [95% confidence intervaI -0.83 to -0.46], <i> p &lt; 0 </i>0.0001) and 24-hour cough frequency (ρ = -0.36 [-0.62 to -0.04], <i> p = 0 </i>.023), and were worse pre-treatment in culture-positive compared to culture-negative disease (median 12.4 [IQR 8.5–17.4] <i>vs </i>18.7 [17.8–19.6] respectively, <i> p = 0 </i>.052). There was no evidence of association with other markers of disease severity (sputum smear positivity, lung cavities and radiographic extent of disease), but a trend towards worse LCQ scores amongst current smokers than non-smokers (12.6 [8.3–14.4] <i>vs </i>17.1 [11.1–21.0] respectively, <i> p = 0 </i>.075). All patients who repeated the questionnaire appeared adherent to TB medication. There were substantial improvements in LCQ responses after a median of 14 (10–14) days’ treatment (n = 12; median [IQR] score 9.1 [8.1–14.5] at baseline, 18.3 [14.5–19.4] at two weeks, median improvement 5.1 [1.8–9.7], <i> p = 0 </i>.003; Figure 1). The effect size of the change in LCQ scores was 1.17. <h3>Conclusion</h3> The LCQ is a valid instrument for evaluating cough-related QOL in TB and may be a useful outcome measure to evaluate therapy.
Lymphomatosis cerebri: a rare form of primary central nervous system lymphoma. Analysis of 7 cases and systematic review of the literature
Authors: Cristina Izquierdo, Roser Velasco, Noemí Vidal, Juan José Sánchez, Andreas A. Argyriou, Sarah Besora, Francesc Graus, Jordi Bruna
Journal: Neuro-Oncology (2015)

Primary central nervous system lymphomas may present as diffuse, nonenhancing infiltrative lesions. This rare variant is termed lymphomatosis cerebri (LC). We did a systematic review and analysis of the literature, adding our own cases, to better characterize LC in order to improve early diagnosis and treatment. PubMed, ISI Web of Knowledge, and hospital databases were reviewed. Information was extracted regarding demographic, clinical, histological, cerebrospinal fluid (CSF), neuroimaging, and treatment variables. The impact of single parameters on overall survival (OS) was determined by applying univariate and multivariate analyses. Forty-two patients were included (median age: 58 y; range: 28–80 y). At consultation, 52% of patients had a poor KPS. The most common presenting symptom was cognitive decline (59.5%). Imaging studies showed supratentorial and infratentorial infiltration in 55% of patients and bilateral hemispheric involvement in 95%. CSF pleocytosis was present in 51.5% of the patients. Median time to diagnosis was 4.5 (range: 1–30) months, and the diagnosis was not established until autopsy for 33% of patients. The median OS was 2.95 (range: 0.33–56) months; however, those patients who received methotrexate had a median OS of 13.8 (range: 0.7–56) months. Analysis identified KPS ≥ 70 (HR: 0.32; 95% CI: 0.114–0.894; P = .03) and treatment with methotrexate (HR: 0.19; 95% CI: 0.041–0.886; P = .034) as independent favorable prognostic factors, whereas T-cell lymphoma was independently related with a worse outcome (HR: 6.62; 95% CI: 1.317–33.316; P = .022). LC is a misdiagnosed entity associated with considerable diagnostic delay. MRI evidence of bilateral hemispheric involvement and CSF pleocytosis should be alerts for this diagnosis. Treatment with methotrexate-based chemotherapy must be considered, especially for patients with good KPS.
Transition from childhood to adulthood in coeliac disease: the Prague consensus report
Authors: Jonas F Ludvigsson, Lars Agreus, Carolina Ciacci, Sheila E Crowe, Marilyn G Geller, Peter H R Green, Ivor Hill, A Pali Hungin, Sibylle Koletzko, Tunde Koltai, Knut E A Lundin, M Luisa Mearin, Joseph A Murray, Norelle Reilly, Marjorie M Walker, David S Sanders, Raanan Shamir, Riccardo Troncone, Steffen Husby
Journal: Gut (2016)

The process of transition from childhood to adulthood is characterised by physical, mental and psychosocial development. Data on the transition and transfer of care in adolescents/young adults with coeliac disease (CD) are scarce. In this paper, 17 physicians from 10 countries (Sweden, Italy, the USA, Germany, Norway, the Netherlands, Australia, Britain, Israel and Denmark) and two representatives from patient organisations (Association of European Coeliac Societies and the US Celiac Disease Foundation) examined the literature on transition from childhood to adulthood in CD. Medline (Ovid) and EMBASE were searched between 1900 and September 2015. Evidence in retrieved reports was evaluated using the Grading of Recommendation Assessment, Development and Evaluation method. The current consensus report aims to help healthcare personnel manage CD in the adolescent and young adult and provide optimal care and transition into adult healthcare for patients with this disease. In adolescence, patients with CD should gradually assume exclusive responsibility for their care, although parental support is still important. Dietary adherence and consequences of non-adherence should be discussed during transition. In most adolescents and young adults, routine small intestinal biopsy is not needed to reconfirm a childhood diagnosis of CD based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) or North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria, but a biopsy may be considered where paediatric diagnostic criteria have not been fulfilled, such as, in a patient without biopsy at diagnosis, additional serology (endomysium antibody) has not been performed to confirm 10-fold positivity of tissue transglutaminase antibodies or when a no biopsy strategy has been adopted in an asymptomatic child.
Frozen Autologous Platelet Transfusion for Patients with Leukemia
Authors: Charles A. Schiffer, Joseph Aisner, Peter H. Wiernik
Journal: New England Journal of Medicine (1978)

Platelets were removed from 25 patients with leukemia during remission and were frozen for subsequent transfusion. With 5 per cent dimethyl sulfoxide as a cryoprotective agent, we froze 3 to 5 units of pooled platelet concentrate by simply placing the platelets in the vapor phase of a liquid nitrogen freezer. Ninety-one transfusions of platelets stored for 13 to 400 days were administered. The mean freeze-thaw loss was 13 per cent, and the corrected one-hour increment in platelet count was 13,700 per microliter, corresponding to a recovery of 53 per cent of the predicted value. In many patients most or all of the transfusion requirements were met with frozen platelets. Our results indicate that frozen platelets can circulate and function hemostatically. Autologous frozen platelets are of particular value in the management of alloimmunized patients and have become an integral part of our transfusion support program. (N Engl J Med 299:7–12, 1978)
Cheyne-Stokes Breathing
Authors: Neil S. Cherniack, Guy S. Longobardo
Journal: New England Journal of Medicine (1973)

TWO dominant but apparently conflicting theories explain the regular waxing and waning of tidal volume and respiratory frequency that characterize Cheyne-Stokes breathing. This difference of opinion reflects the two diseases in which Cheyne-Stokes breathing is most often observed: cerebrovascular disease and heart failure.1 , 2 One theory attributes Cheyne-Stokes respiration to a neurologic abnormality; in dispute is whether this neurologic abnormality is an excessively depressed respiratory center or an excessively excitable one. The other theory ascribes Cheyne-Stokes breathing to the prolongation of the circulation time produced by congestive heart failure. Since patients with Cheyne-Stokes respiration frequently have both cardiac and cerebrovascular disease, . . .
At a Children’s Hospital
Authors: Hyun Kim
Journal: JAMA (2016)

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
Human Fetomaternal Passage of Erythrocytes
Authors: W. P. Crecer, M. R. Steele
Journal: New England Journal of Medicine (1957)

IN 1941 Levine et al.1 proposed an etiology for erythroblastosis fetalis that required the entrance of fetal red blood cells into the maternal circulation. This requirement then led to the question of whether fetal erythrocytes enter the maternal circulation only in the disease, erythroblastosis fetalis, or do so also in many normal pregnancies. Levine considered the latter view more likely and suggested that the low incidence of erythroblastosis fetalis in relation to the frequency of the combination of Rh-negative mother and Rh-positive fetus was due to low antibody-forming ability on the part of many mothers.2 Others have held that fetomaternal . . .
Outpatient bone marrow harvesting without general anesthesia.
Authors: E G de Vries, D T Sleijfer, N H Mulder
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.9.1367 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2671291 Outpatient bone marrow harvesting without general anesthesia. E G de VriesxE G de VriesSearch for articles by this author , D T SleijferxD T SleijferSearch for articles by this author , N H MulderxN H MulderSearch for articles by this author https://doi.org/10.1200/JCO.1989.7.9.1367 PDF "Outpatient bone marrow harvesting without general anesthesia.." Journal of Clinical Oncology, 7(9), pp. 1367–1368© 1989 by American Society of Clinical Oncology