tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: Surfactant protein D is dysregulated in severe asthma
Authors: Rose-Marie Mackay, Christopher Grainge, Laurie Lau, Clair Barber, Howard Clark, Peter Howarth
Journal: European Respiratory Journal (2014)

Aim: To investigate SP-D as a possible biomarker of disease severity in asthma patients  Surfactant protein D (SP-D) is an essential component of the innate immunity within the lung, in enhancing phagocytic removal of viruses, bacteria, allergens and fungi then modulating subsequent inflammation. SP-D also protects with respect to lower airway allergy, regulating cytokine and chemokine profiles during inhalation allergen challenge it enhances removal of apoptotic cells reducing inflammation. SP-D, binds to pollen starch granules enhances their phagocytic uptake and removal from the lungs inhibiting specifically induced mast cell and basophil degranulation. In vivo, SP-D protects against pulmonary hypersensitivity induced by allergens, where SP-D lowers eosinophilia and promotes shifts from a Th2 bias towards a Th1 response. Methods: Matched serum and BAL samples were collected from 10 healthy controls (HC) and 55 asthmatics (26 mild [MA] and 29 severe [SA]) and analysed by SP-D ELISA. Western blots were performed on BAL and serum and compared between the groups. Results: SP-D levels in BAL were significantly lower in SA compared to MA and HC (p
Prevalence of asthma symptoms among Croatian school children is still increasing
Authors: Srdan Banac, Koraljka Manestar, Vojko Rozmanic, Zrinka Korotaj Rozmanic, Ivana Vidovic, Marta Šerer, Nastasja Švraka, Tamara Petric
Journal: European Respiratory Journal (2011)

Bacground: There were disturbing epidemiological data confirming a worldwide increase, including Croatia, in the prevalence of childhood asthma over the last few decades. Recent epidemiological studies shows that this trend seems to be stopped in many countries.

Aim: To estimate the trend of asthma symptoms prevalence among school children in north-west part of Croatia.

Methods: Results of two studies conducted eight years apart, during school years 2001/02 vs. 2009/10, on the same area using the same written and video asthma questionnaires developed by the International Study of Asthma and Allergies in Childhood were compared respectively. The target population comprised two age groups: 6-7years (n=1634 vs. n=1052) and 13-14 years (n=2194 vs. n=1181).

Results: Prevalence of asthma symptoms in the older age group according to written questionnaire (wheezing in last 12 months: 8.4 vs 14.0, p<0.001; wheezing ever: 19.9 vs. 26.1, p<0.001; asthma ever: 5.2 vs. 6.9, p=0.02) showed a rising trend as well as according to video questionnaire (wheezing in last 12 months: 4.6 vs. 6.4, p=0.01; severe wheezing in last 12 months; 2.1 vs. 7.1, p<0.001). There was no significant (NS) change in the prevalence of the same symptoms in the younger age group (wheezing in last 12 months: 9.7 vs. 9.4, p=NS; wheezing ever: 26.2 vs. 26.3, p=NS; asthma ever: 3.9 vs. 5.0, p=NS).

Conclusion: Prevalence of asthma symptoms among older school children in north-west part of Croatia still shows a rising trend. Results obtained in the younger age group of children may suggest that this trend could be stopped in the future.
구연 : 그랜드볼룸 ; B형간염 표면항원 유무가 급성 A형간염의 경과에 미치는 영향 (초)
Authors: 서지영, 서동대, 홍진희, 김선영, 강화미, 전태주, 오태훈, 신원창, 최원충
Journal: Clinical and Molecular Hepatology (2010)
Oral Nutrient Supplementation and Cognitive Function
Authors: Lisa M. Renzi-Hammond, L. Stephen Miller, Billy R. Hammond
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
Predicting Low Accrual in the National Cancer Institute’s Cooperative Group Clinical Trials
Authors: Caroline S. Bennette, Scott D. Ramsey, Cara L. McDermott, Josh J. Carlson, Anirban Basu, David L. Veenstra
Journal: JNCI Journal of the National Cancer Institute (2015)

The extent to which trial-level factors differentially influence accrual to trials has not been comprehensively studied. Our objective was to evaluate the empirical relationship and predictive properties of putative risk factors for low accrual in the National Cancer Institute's (NCI's) Cooperative Group Program, now the National Clinical Trials Network (NCTN).
Occurrence of Nuclear Pockets in Lymphocytes of Normal, Persistent Lymphocytotic and Leukemic Adult Cattle&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A. Weber, J. Andrews, B. Dickinson, V. Larson, R. Hammer, V. Dirks, D. Sorensen, S. Frommes
Journal: JNCI Journal of the National Cancer Institute (1969)

The occurrence of nuclear pockets in leukocytes was studied in four groups of dairy cattle. These were animals with 1) normal hemograms from leukemia-free herds, 2) normal hemograms from multiple-case leukemia herds, 3) persistent lymphocytosis from multiple-case leukemia herds, and 4) clinical leukemia. These nuclear pockets generally resembled those in man and other species, but were limited to lymphocytes. Statistical evaluation of the frequency of occurrence of nuclear pockets in the lymphocytes of these four groups showed that: 1) Lymphocytic and leukemic animals had six times as many lymphocytes with nuclear pockets as animals with normal hemograms. Differences were significant both in mean frequency of lymphocytes with nuclear pockets (39.9 vs. 6.8/thousand) and in their distribution. 2) The difference in mean frequency of nuclear pockets in animals with normal hemograms from leukemia-free herds was not significant as compared to normal hemogram animals from multiple-case leukemia herds. However, the latter group had a significantly higher variance. 3) Lymphocytotic and leukemic animals belong to one common population in terms of mean frequency and variance of occurrence of lymphocytes with nuclear pockets.
A gene expression algorithm for the prediction of platinum sensitivity in ovarian cancer.
Authors: J. S. Ferriss, Y. Kim, D. Theodorescu, L. R. Duska, J. Lee
Journal: Journal of Clinical Oncology (2010)

5021 Background: Despite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy. In vitro models predicting chemosensitivity rely on cellular phenotypes and are hampered by the extrapolation of data from culture to clinic. Gene expression models can predict therapeutic responses without these constraints. We tested our gene based co-expression extrapolation (COXEN) algorithm on a cohort of 65 ovarian cancer patients to assess its clinical utility. Methods: COXEN is an in silico algorithm that predicts chemosensitivity of tumors based on genomic expression signatures and has been reported previously. In brief, NCI- 60 cell lines were used to identify candidate drug sensitivity biomarkers for carboplatin and paclitaxel. Candidate biomarkers were then narrowed by examining concordant expression patterns between cell lines and a historical set of ovarian cancer patients. Biomarkers were further triaged by examining expression patterns of frozen and formalin-fixed paraffin embedded (FFPE) tissue samples. Models were refined using an independent cohort from which the final prediction models were obtained. To evaluate the clinical utility of COXEN in ovarian cancer, we performed genome-wide profiling on FFPE samples of 65 patients obtained prior to adjuvant chemotherapy. We then retrospectively applied COXEN to this cohort to evaluate the predictive success. Results: COXEN correctly stratified platinum sensitive and resistant patients (p = 0.019) with sensitivity = 93%, specificity = 33%, PPV = 65%, and NPV = 78%. Paclitaxel response was also significantly stratified (p = 0.033) with sensitivity = 96%, specificity = 26%, PPV = 61%, and NPV = 86%. Models for platinum-taxane combination demonstrated a significant survival difference between the predicted responders and nonresponders with median survival of 12.9 months vs. 8.1 months (p = 0.045). Conclusions: COXEN successfully predicted platinum resistance and reliably discriminated taxane response in this retrospective cohort. Prediction of platinum response is clinically relevant and, if reliable, could alter primary management of ovarian cancer. Prospective evaluation of the COXEN model is underway. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Key Genomics Key Genomics
First results of long-term rituximab maintenance treatment in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03
Authors: C. J. Taverna, S. Bassi, F. Hitz, W. Mingrone, T. Pabst, L. Cevreska, A. del Giglio, D. A. Vorobiof, M. Simcock, M. Ghielmini
Journal: Journal of Clinical Oncology (2009)

8534 Background: Rituximab maintenance has been shown to be effective in patients with follicular lymphoma. The optimal duration of maintenance remains unknown. Methods: We prospectively registered 270 patients with untreated, chemotherapy resistant or relapsed follicular lymphoma. All patients received rituximab induction consisting of 4 weekly doses (375 mg/m 2 ). Responding patients (PR and CR) were randomized to a short maintenance consisting of four doses of rituximab (375 mg/m 2 ) every two months (arm A) or prolonged maintenance consisting of rituximab every two months for a maximum of five years or until progression or unacceptable toxicity (arm B). Primary endpoint was event-free survival. Here we present the safety analysis. Results: From October 2004 to November 2007 165 patients were randomized, 82 in arm A and 83 in arm B. The median follow up is 22.7 months. A total of 442 hematological and non-hematological adverse events were observed, 27 of grade 3 and 6 of grade 4. Five subsequent cancers and 9 grade 3 and 4 infections were reported. Grade 3 and 4 neutropenia occurred in 5 patients, decreased levels of IgG were observed in 19 patients. Four grade 3 infections occurred after 2 years of maintenance. In arm B, maintenance was stopped due to unacceptable toxicity (fever) in 1 patient after 18 months and due to subsequent breast cancer in 1 patient after 20 months. One patient died 4 months after randomization because of ileus and consecutive peritonitis; considered to be unrelated to therapy. Twenty-nine patients are on maintenance for two or more years of which 6 patients are on for three or more years. In this analysis, median duration of the prolonged maintenance is 23.7 months. Conclusions: Rituximab maintenance beyond two years is feasible. We do not have evidence for increased toxicity after 2 years of maintenance. However, close follow up of patients under prolonged rituximab maintenance is necessary. The trial has been closed for accrual but there are still patients on treatment. [Table: see text]
Pembrolizumab (Pembro; Mk-3475) for Advanced Melanoma (Mel): Randomized Comparison of Two Dosing Schedules
Authors: C. Robert, A.M. Joshua, J.S. Weber, A. Ribas, F.S. Hodi, R.F. Kefford, A. Daud, J.D. Wolchok, W-J. Hwu, T.C. Gangadhar, A. Patnaik, P. Hersey, R. Dronca, H. Zarour, Y. Ge, J.A. Lindia, M. Giannotti, S. Ebbinghaus, S.P. Kang, O. Hamid
Journal: Annals of Oncology (2014)
Abstract 18811: Plasma Renin Activity Test Versus US Joint National Committee Guidelines for Selecting Initial Antihypertensive Drug
Authors: Michael H Alderman, John H Laragh, Jean E Sealey, Hillel W Cohen
Journal: Circulation (2012)

Background: US National Guidelines promote initiating treatment for nearly all hypertensive patients with a natriuretic drug. We now report a double-blind, randomized controlled trial to compare that with a Plasma Renin Activity (PRA) test guided therapeutic approach. Methods: Hypertensive participants (n=164) consented to (i) replacement of antihypertensive drugs with placebo for at least 4 weeks and then (ii) a 5 month double blind study to compare BP control and BP change achieved by initial monotherapy: Experimental = guided by PRA (n=82) v. Control = hydrochlorothiazide (HCTZ) (n=82). Results: Eligible subjects were 45% males with a mean±SD age 60±9, entry BP 152±10/86±10mmHg,and median (IQR) PRA 0.7 (0.2, 1.4)ng/mL/hr. Experimental subjects were given a diuretic if PRA &lt;0.65 (n=32?), or olmesartan if PRA ≥0.65 ng/mL/hr (n=50?). At 4 months, 72% of both Experimental and Control groups achieved BP &lt;140/90mmHg, (132±15/76±11 v. 134±14/79±9mmHg,p=.39/.18 respectively). As expected, in subjects with PRA&lt;0.65ng/mL/hr BP decline was similar in Experimental and Control groups. By contrast, in 91 patients with PRA ≥ .65ng/mL/hr, after adjusting for entry BP Experimental subjects (n=50) had a significantly greater mean±SE fall in systolic BP [_-4.9±2.4mmHg (p=.04)] and a borderline significantly greater fall when not adjusted (_-4.5±2.3mmHg, p=.06). Conclusions: Effectiveness of PRA guided therapy is identical to US National Guidelines for patients with PRA &lt; 0.65 ng/mL/hr. However, it significantly improved BP treatment in patients with PRA ≥ 0.65ng/ml/hr. Moreover, in this clinical trial of moderately hypertensive patients, initial monotherapy lowered BP to &lt;140/90 mmHg in nearly 3/4 of subjects. These results suggest that routine PRA determination can improve both the effectiveness and efficiency of hypertension treatment.
Changes in phosphorylation and dephosphorylation status of cytoskeleton and their regulator proteins in CD34+ stem cells after G-CSF stimulation and in AML
Authors: H. Lannert, M. Lenze, T. Able, B. J. Park, A. Lenze, S. Meissner, V. Eckstein, A. D. Ho, S. Leicht, T. Franz
Journal: Journal of Clinical Oncology (2009)

e22067 Background: The cytoskeleton is a cellular ‘scaffolding‘ or ‘skeleton‘ contained within the cytoplasm. It is a dynamic structure that maintains cell shape, enables cellular motion. ADF/cofilin is a family of actin-binding proteins which disassembles actin filaments. LIMK2 is phosphorylated and activated by ROCK, a downstream effector of Rho, and phosphorylates cofilin, inhibiting its actin-depolymerizing activity. Profilin binds to actin. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. Cdk1 phosphorylates beta tubulin. In mitotic cells, phosphorylated tubulin is excluded from microtubules, being present in the soluble tubulin fraction. Stathmin/Op18 is a cytosolic phosphoprotein which regulates the dynamics of microtubules. The process of tumor proliferation and metastasis is characterized by high rates of mitosis and migration into distant tissues. In this study we investigated the expression of cytoskeleton proteins in native hematopoietic CD34+ stem cells from BM in comparison to mobilized peripheral blood stem cells (mPBSCs) from G-CSF stimulated donors as well as CD34+ cells from AML. Methods: An Auto-MACS (Miltenyi) and FACS Vantage SE cell sorter (Becton Dickinson) was used to process high enriched (&gt;99%) CD34+ cells fractions from MNCs. Proteomics was performed with the Proteome Works System (BioRad). Protein identification was carried out by Q-TOF and ion trap mass spectrometer analyses. Phosphoproteins were detected with ProQ-Diamond stain and specific antibodies. Results: The comparative proteome analyses show that 1. actin, tubulin, vimentin are overexpressed and phosphorylated, 2. cofilin and profilin are unphosphorylated, and 3. Stathmin is overexpressed in G-CSF mobilized hematopoietic stem cells and in AML in his active ‘dephosphorylated‘ form. Conclusions: Highly enriched hematopoietic CD34+ cells are a prerequisite for the qualitative and quantitative phospho/proteome analyses. Our results show, that mobilized stem cells “in vivo” and AML cells increase cytoskeleton proteins expression and cause a complex phosphorylation status, which may explain the regulation of migration and metastasis. No significant financial relationships to disclose.
Effects of Cirrhosis on Short-term and Long-term Survival of Patients With Hepatitis B–related Hepatocellular Carcinoma
Authors: Vincent L. Chen, An K. Le, Nathan G. Kim, Lily H. Kim, Nghia H. Nguyen, Pauline P. Nguyen, Changqing Zhao, Mindie H. Nguyen
Journal: Clinical Gastroenterology and Hepatology (2016)
Protective role of silibinin on matrix metalloproteinase-2 and activator protein-1 on LoVo cells
Authors: C. Lin, Y. Chen
Journal: Journal of Clinical Oncology (2009)

e15136 Background: Silibinin, a flavonoid and the major active component of milk thistle, has been as a safe diet supplement for several decades. It has been proved with anti-hepatotoxic properties and pleiotropic anticancer capabilities. Current study aimed to investigate the role of silibinin as potential therapeutic target of colon cancer through antiangiogenesis and its related molecular mechanisms with matrix metalloproteinase- 2 (MMP-2) and activator protein-1 (AP-1). Colon cancer cell line, LoVo cells, treated with a major prognostic factor, interleukin-6 (IL-6), was studied. Methods and Results: By western blot analysis, silibinin suppressed MMP- 2 protein expression in time- and concentration-dependent manners. Furthermore, the inhibitors of JNK/AP-1 binding activity abolished the expression of MMP-2 in IL-6-stimulated LoVo cells, but not PI3K pathways. We also demonstrated that silibinin inhibited IL-6- stimulated LoVo cell migration and further tumor angiogenesis, which similar to the effects from addition with AP-1 inhibitor. By EMSA, the binding activity of AP-1 in LoVo cells was also decreased with silibinin treatment. In addition, the imaging of confocal microscopy revealed that AP-1 presentation was attenuated on IL-6-stimulated LoVo cells plus silibinin treatment. Conclusions: Taken together, these data indicated that silibinin inhibits angiogenesis through the suppression of MMP-2 expression and AP-1 binding activity in colon cancer cells. It suggests a novel anti-metastatic application of silibinin in colon cancer chemoprevention. No significant financial relationships to disclose.
Antitumor Immunity in the Shope Papilloma-Carcinoma Complex. IV. Search for a Transmissible Factor Increasing the Frequency of Tumor Regression&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. A. Evans, John J. Thomsen
Journal: JNCI Journal of the National Cancer Institute (1969)

A wide variation has been observed in the frequency of spontaneous regressions of papillomas on rabbits subjected to a standard inoculum of Shope papilloma virus. From the pattern of these regressions in different groups of rabbits, we suspected that regression frequency might be increased by a transmissible agent or agents occurring commonly in rabbitry-reared animals. In experiments designed to test this hypothesis, fresh, pooled blood, nasal washings, and fecal suspensions were transferred from rabbits, with early complete tumor regression and a high incidence of regression, to normal San Juan rabbits, captured in the wild or reared from wild animals held in isolation. Such rabbits typically show a low regression frequency. Shope papilloma virus was inoculated onto pretreated animals and suitable controls approximately 1 month later. The resulting papillomas on pretreated animals were smaller and regression frequency was increased as compared with controls. San Juan rabbits born and reared in a commercial rabbitry in close association with New Zealand White rabbits likewise developed smaller tumors and exhibited a higher regression frequency than control San Juan rabbits kept in isolation. The evidence supports the concept that some component of the indigenous microbial or viral flora of at least some rabbitry-reared rabbits inhibits the growth of tumors and increases the frequency of regressions of Shope papillomas.
Induction of tumor cell death by anti-GD2 monoclonal antibodies (MoAb): Requirement of antibody Fc and a long residence time (slow k<i><sub>off</sub></i>)
Authors: H. XU, J. Hu, N. V. Cheung
Journal: Journal of Clinical Oncology (2007)

13507 Background: Anti-GD2 MoAbs have shown clinical activities against neuroblastoma (NB) and other neuroectodermal tumors. Besides complement mediated (CMC) and antibody-dependent cell mediated cytotoxicities (ADCC), they can directly induce cell death. However, MoAb and their genetic constructs differ substantially in death-inducing efficiency. Although multivalent binding is important for these functions, the roles of association on rate (k on ), dissociation off rate (k off ), valency and Fc have not been carefully defined. Methods: We tested a panel of purified anti-GD2 MoAbs, MoAb fragment, and single chain variable fragment (scFv) fusion protein. The kinetics of in vitro binding was measured by surface plasmon resonance (SPR) using BIACORE 2000. NB cell lines (LAN1, NMB7, BE(2)C, SKNER, SKNJD and SKNLP) were treated with MoAb in vitro, their survivals were studied by the chromogenic assay and IC 50 derived using Sigmaplot. Results: The most efficient cell kill against NB was 3F8 (mIgG 3 ) with an average IC 50 of 4.7 ug/ml. In contrast, IC 50 was &gt;30 ug/ml for 14.G2a (mIgG 2a ), ME361 (mIgG 2a ) and S220–51 (mIgG 3 ). It was &gt;100 ug/ml for 3F8 class-switch variant 3G6 (mIgM), 3F8-F(ab’) 2 (fragment), and 5F11scFv-streptavidin (tetramer). By SPR, the apparent affinity K d (equilibrium dissociation constant) of 3F8 [1.1x10 -8 M] was higher than that of 3F8-F(ab’) 2 [3.3x10 -8 M], 14.G2a [9.0x10 - 8 M], ME361 [4.6x10 -7 M], and S220–51 [4.6x10 -6 M], but lower than that of decameric IgM 3G6 [6.5x10 - 9 M] and tetrameric 5F11scFv-streptavidin [2.6x10 -9 M]. The affinity advantage of 3F8 over other bivalent MoAbs was primarily due to its slower k off [3.0x10 -4 sec -1 ] when compared to other MoAbs [1.1x10 - 3 -7.3x10 -2 sec -1 ]. Conclusions: Different structural forms of anti-GD2 MoAb have distinct efficiency in inducing NB cell death as well as binding affinity to GD2. Since these properties can affect CMC and ADCC, they may in turn influence the clinical efficacy of immunotherapy. Our findings suggest the importance of an intact IgG 3 molecule (the presence of Fc), as well as a long residence time (slow k off ). No significant financial relationships to disclose.