tbuckley/cabot-search huggingface dataset:
The antifungal mechanism of action of zinc pyrithione
Authors: N.L. Reeder, J. Xu, R.S. Youngquist, J.R. Schwartz, R.C. Rust, C.W. Saunders
Journal: British Journal of Dermatology (2011)

Background Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT. Objectives The objective of this study is to understand the molecular mechanism by which ZPT inhibits fungal growth, the underlying basis for its therapeutic activity. Methods Modern systems biology approaches, such as deletion library screening and microarray analysis, were used in combination with traditional measures of metal content, microbial growth and enzyme assays. Results It was shown that ZPT inhibits fungal growth through increased cellular levels of copper, damaging iron–sulphur clusters of proteins essential for fungal metabolism. Conclusions The molecular basis for the antifungal activity of the commonly used active ZPT has been elucidated, more than 50 years since its introduction, as utilizing a copper toxicity mechanism that targets critical iron–sulphur proteins.
Allergen skin test reactivity in an unselected Danish population
Authors: N.H. Nielsen, U. G. Svendsen, F. Madsen, A. Dirksen
Journal: Allergy (1994)

The aim of this study was to assess the distribution of allergen skin test reactivity in an unselected Danish population. A total of 793 subjects, aged 15–69 years, were invited, and 599 (75.5%) attended. The skin prick test was performed with standardized allergen extracts of high potency. Skin reactivity occurred in 28.4% of the subjects. The frequency of skin reactivity to the specific allergens ranged from 1.5% ( Cladosporium ) to 12.5% ( Dermatophagoides pteronyssinus ), and the frequencies of skin reactivity to the allergen groups (pollen, animal dander, house‐dust mites, and molds) were 17.6%, 8.7%, 14.0%, and 3.2%, respectively. Young women appeared to reflect the average skin reactivity. When compared with young women, skin reactivity to animal dander was more probable in young men (odds ratio (OR) value = 2.6; 95% confidence interval (CI) of odds ratio value = 1.1–6.1). Current smokers were less likely than nonsmokers to be skin‐reactive to pollen (OR = 0.4; 95%, CI = 0.3–0.7). In conclusion, allergen skin test reactivity was common, and was related to sex, age, smoking history, and probably genetic predisposition.
Abstract S1-07: HER2 T cell dependent bispecific antibody (HER2-TDB) for treatment of HER2 positive breast cancer
Authors: Teemu T Junttila, Ji Li, Jennifer Johnston, Maria Hristopoulos, Robyn Clark, Diego Ellerman, Bu-Er Wang, Yijin Li, Mary Mathieu, Guangmin Li, Judy Young, Elizabeth Luis, Gail Lewis Phillips, Eric Stefanich, Cristoph Spiess, Andrew Polson, Bryan Irving, Justin M Scheer, Melissa R Junttila, Mark S Dennis, Robert Kelley, Klara Totpal, Allen Ebens
Journal: Cancer Research (2015)

Abstract Based on recent clinical success of tumor immunotherapies that block immune suppressive mechanisms to restore T cell function, there is a profound interest in the clinical development of T cell targeted therapies. We have produced a trastuzumab-based HER2 T cell dependent bispecific antibody (HER2-TDB) that conditionally activates T cells resulting in lysis of HER2 expressing cancer cells at low picomolar concentrations. Due to its unique mechanism of action, which is unrelated to HER2 signaling or sensitivity to chemotherapeutic agents, HER2-TDB can eliminate cells refractory to currently approved HER2 therapies. The potent anti-tumor activity of HER2-TDB was demonstrated using four model systems including MMTV-huHER2 and huCD3 transgenic mice. We demonstrate inhibitory effect of PD-L1 expression on the activity of bispecific T cell recruiting antibodies. This resistance mechanism is reversed by anti-PD-L1 treatment and combination of HER2-TDB with anti-PD-L1 immune therapy resulted in enhanced inhibition of tumor growth, increased response rates and durable responses. Significance: This report presents a new immunotherapy for HER2+ breast cancer with an alternative, extremely potent mechanism of action that is effective in cells resistant to current HER2 targeted therapies. Several significant advances are provided to bispecific T cell recruiting antibodies: we characterize a critical resistance mechanism, a potential diagnostic marker, a novel transgenic efficacy model and significantly improve the drug-like properties by using technology based on full length antibodies with natural architecture. Finally we demonstrate the benefit of combining two immune therapies: direct polyclonal recruitment of T cell activity together with inhibiting the T cell suppressive PD-1/PD-L1 signaling results in enhanced and durable long term responses. Citation Format: Teemu T Junttila, Ji Li, Jennifer Johnston, Maria Hristopoulos, Robyn Clark, Diego Ellerman, Bu-Er Wang, Yijin Li, Mary Mathieu, Guangmin Li, Judy Young, Elizabeth Luis, Gail Lewis Phillips, Eric Stefanich, Cristoph Spiess, Andrew Polson, Bryan Irving, Justin M Scheer, Melissa R Junttila, Mark S Dennis, Robert Kelley, Klara Totpal, Allen Ebens. HER2 T cell dependent bispecific antibody (HER2-TDB) for treatment of HER2 positive breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S1-07.
Immunity to Sarcoma 180 and the Induction of Leukemia
Authors: Christiane Dosne de Pasqualini, E. A. D. Holmberg, S. L. Rabasa, A. Pavlovsky
Journal: Cancer Research (1961)

Summary  Sarcoma 180 was 100 per cent fatal in BALB and DBA mice. In the Rockland strain there was a 17 per cent spontaneous expulsion. In these, subsequent implantations, up to 11 times, yielded practically 100 per cent immune animals. Fifteen out of 47 immunized mice (32 per cent) which have died so far, presented a condition consisting of marked hepatosplenomegaly and lymph node enlargement with at times thymus hypertrophy, leukocytosis, and immature cells in the peripheral blood. The histological picture was that of leukemia with massive lymphocytic infiltration of spleen, thymus, liver, lymph nodes, and kidney. Transplants of cellular suspensions of spleen gave rise to a similar condition, serially reproducible. It is concluded that a subcellular agent escaping immunity is present in Sarcoma 180 and is capable of inducing leukemia.
Phase I Study Of LY2784544, a JAK2 Selective Inhibitor, In Patients With Myelofibrosis (MF), Polycythemia Vera (PV), and Essential Thrombocythemia (ET)
Authors: Srdan Verstovsek, Ruben A Mesa, Mohamed E Salama, Jennifer L K Giles, Celine Pitou, Annamaria Hayden Zimmermann, Gregory L Price, Richard A Walgreen, Josef Prchal
Journal: Blood (2013)
Helping Children with Ill or Disabled Parents, by Julia Segal, John Simkins
Authors: A. Sharma
Journal: BMJ (1997)

Julia Segal, John Simkins /Jessica Kingsley Publishers, £14.95, pp 244 /ISBN 1 85302 409 0

Incorporating a wealth of first hand experience, this book sets out what happens to children when their parents are too ill or disabled to parent in the imperfect, guilt ridden way of other parents. Physical as well as mental illness is encompassed in this book-being brought up by parents whose state of mind …
Nuclear translocation of heparanase is involved in cellular differentiation
Authors: Tomoki Yamatsuji, Yoshio Naomoto, Tetsuji Nobuhisa, Takaomi Okawa, Munenori Takaoka, Mehmet Gunduz, Yoko Tabuchi, Toshio Nishikawa, Yasuhiro Shirakawa, Keizou Ohkawa, Dai Kitamoto, Minoru Haisa, Junji Matsuoka, Hiromi Iwagaki, Motowo Nakajima, Noriaki Tanaka
Journal: Cancer Research (2006)

4614   Heparanase is an endo-β-glucuronidase that specifically cleaves carbohydrate chains of heparan sulfate proteoglycans, which are important components of the extracellular matrix. Heparanase is present in various types of malignant tumors such as stomach, esophagus, bladder, pancreas, liver, prostate, melanoma, breast, and colon cancers. Heparanase expression in tumor cells correlates with the degree of tumor invasiveness and poor prognosis of cancer patients. Recently, we reported that heparanase is located in nucleus as well as in cytoplasm in cancer cells and that nuclear heparanase appears to be related with cancer progression while cytoplasmic heparanase reveals its well known enzymatic function and can be one of key factors to affect fate of cancer patients. At the first, we investigated the role of nuclear heparanase in differentiation by transducing human mammary epithelial cancer cells; MCF-7 with heparanase using a nuclear expression system. We observed that expression of nuclear heparanase allowed the cells to differentiate with the appearance of lipid droplets. To analyze the molecular mechanism of nuclear translocation of heparanase in cellular differentiation, we recruited an in vitro differentiation model of HL-60 cells, a promyelocytic leukemia cell line which differentiates into monocytes and macrophages upon stimulation with TPA or retinoic acid.Using this system, we found that nuclear translocation of heparanase is closely related with cellular differentiation. TPA-induced differentiation of HL-60 cells was inhibited by geldanamycin, which is a specific inhibitor of heat shock protein 90 (HSP90). This data suggest that HSP90 might be a chaperone carrier protein of heparanase which lacks nuclear localization sequence. We further confirmed that only active form of heparanase was detected in nucleus and that nuclear transduction of catalytic negative form of heparanase did not cause differentiation of HL-60 cells, suggesting that nuclear translocation of emzymatically active heparanase is sufficient for induction of differentiation. Our findings emphasized a novel function of heparanase in cancer differentiation and could be potentially useful in the design of therapeutic strategies aimed at the prevention of invasion and metastasis of human cancers by translocation of heparanase from the cytoplasm to the nucleus.
Exhibition: The Painter's Eye
Authors: A. Berger
Journal: BMJ (1999)

At some time, all of us have probably looked at a work of art and said, or at least thought, “I could do that.” But one of the simple beauties of this exhibition is that it presents us with incontrovertible evidence that artists and non-artists are not the same beast. We may be similar in outward appearance, but what goes on in our brains seems to be entirely different. In The Painter's Eye John Tchalenko (the technical side of the partnership) and Humphrey Ocean (the portrait painter) have …
Abstract P300: Cardiovascular Risk Inequality in Subjects with Chronic Kidney Disease by Age, Race and Ethnicity in the United States
Authors: Longjian Liu
Journal: Circulation (2014)

Objectives: Adults with chronic kidney disease (CKD) carry an extraordinarily excess risk for cardiovascular disease (CVD). The present study aimed to test two hypotheses: (1) Non-Hispanic black (NHB) with CKD have significantly higher CVD risk profiles than non-Hispanic white (NHW). (2) This difference significantly contributes to the excess risk of CVD in NHB versus NHW. Methods: A total of 3,939 participants aged 21-74 years old in the baseline Chronic Renal Insufficiency Cohort Study, a multiethnic population-based study supported by the National Institute of Diabetes and Digestive and Kidney Diseases, were analyzed. CKD was classified using estimate glomerular filtration rate. A sum weighted CVDRisk score was developed from multiple CVD risk factors. Differences in CVDRisk score by race/ethnicity were tested using quantile regression (QR), a novel data mining approach to identify distribution of risk factors and outcomes. Results: The prevalence of CVD was 30.7 and 38.2% in NHW and NHB with CKD (p&lt;0.001). The means (SD) of CVDRisk score were 12.6 (5.7) in NHW and 14.6 (6.4) in NHB (p&lt;0.001). QR analysis indicated that NHB had significantly higher CVDRisk score in all quantile (Qs) of CVDRisk score than NHW. This race/ethnicity difference was even worse among younger NHB (aged &lt;65). An estimated 32% of the excess CVD prevalence for NHB versus NHW may be attributable to a higher CVDRisk score in those aged&lt;65 years old. Conclusion: The study highlights an excess and disproportionate distribution of CVD risk factor profile in subjects with CKD for NHB versus NHW. An estimated one third of the excess CVD prevalence in younger NHB with CKD could be explained by their higher CVD risk factor profiles.
Ambulatory quality indicators to prevent infection in sickle cell disease
Authors: Lauren M. Beverung, David Brousseau, Raymond G. Hoffmann, Ke Yan, Julie A. Panepinto
Journal: American Journal of Hematology (2013)

The purpose of this study was to identify rates of adherence for three outpatient quality indicators noted by Wang et al. (Pediatrics 2011;128:484–493): (1) influenza vaccine, (2) pneumococcal immunizations, and (3)penicillin prophylaxis in patients with sickle cell disease (SCD) in a Medicaid sample. These variables were chosen based on Wang and colleagues' suggestion that these variables are important for the assessment of the quality of care of children with SCD. We hypothesized that the overall rate of adherence would be poor with adults having worse rates of adherence than children. We conducted a retrospective cohort study using the Wisconsin State Medicaid database over a 5-year period to assess the preventative medication adherence of individuals with SCD. Preventative medication variables in this study included influenza vaccination,pneumococcal immunizations (PCV7, PPV23), and penicillin prophylaxis. As predicted, the 2003–2007 Wisconsin State Medicaid database showed patients with SCD had low adherence in terms of recommended influenza vaccinations (21.58% adherent), PPV23 pneumococcal immunizations (43.47% adherent), and penicillin prophylaxis (18.18% adherent). Pneumococcal immunizations for PCV7 were higher than expected (77.27%adherent). Although children tended to adhere to recommended preventative medications more than adults,overall adherence was low. Although we cannot explain why adherence is low, it is likely due to multiple factors at the patient- and provider-level. We encourage patients and providers to create a partnership to meet adherence recommendations, and we describe our strategies for increasing adherence.
Evidence of Incomplete Left Ventricular Relaxation in the Dog
Authors: Myron L. Weisfeldt, James W. Frederiksen, Frank C. P. Yin, James L. Weiss
Journal: Journal of Clinical Investigation (1978)

Although it has been proposed that incomplete relaxation explains certain increases in left ventricular end diastolic pressure relative to volume, there has been no clear demonstration that incomplete relaxation occurs in the intact working ventricle. To identify incomplete relaxation, left ventricular pressure-dimension relationships were studied in 10 canine right heart bypass preparations during ventricular pacing. The fully relaxed, exponential diastolic pressure-dimension line for each ventricle was first determined from pressure and dimension values at the end of prolonged diastoles after interruption of pacing. For 167 beats during pacing under widely varying hemodynamic conditions, diastolic pressure-dimension values encountered this line defining the fully relaxed state during the filling period indicating that relaxation was complete before end diastole. The time constant for isovolumic exponential pressure fall (T) was determined for all beats. For this exponential function, if no diastolic filling occurred, 97% of pressure fall would be complete by 3.5 T after maximal negative dP/dt. For the 167 beats the fully relaxed pressure-dimension line was always encountered before 3.5 T. With very rapid pacing rates (170-200 beats/min) and(or) with pharmacologic prolongation of relaxation, incomplete relaxation occurred as evidenced by the fact that the line defining the fully relaxed state was never reached during diastole (n = 15). This evidence of incomplete relaxation occurred only when the subsequent beat began before 3.5 T but did not always occur under these conditions. Thus, an increase in end diastolic pressure relative to diastolic volume may result from incomplete relaxation under conditions of sufficiently rapid heart rate or sufficiently prolonged ventricular relaxation. Incomplete relaxation does not occur when the next beat begins more than 3.5 T after maximum negative dP/dt.
Lung Cancer DSA: A platform for discovery of biomarkers in lung cancer
Authors: Kevni Ellison, Austin Tanney
Journal: Clinical Cancer Research (2008)

A10   Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide with poor differential diagnosis of the disease and with low response rates to standard chemotherapy treatment. It is therefore a subject of extensive research focused on identification of reliable genomics biomarkers to aid in accurate classification of the disease, predicting its progression and patients’ response to both available therapies and those in development. Powerful genomics tools used in this research are however lacking disease focus and thus are likely to miss potentially vital information contained in patients’ tissue samples.  Through a combination of large-scale in-house sequencing, gene expression profiling and public sequence and gene expression data mining we have characterised the transcriptome of NSC lung cancer and used this information to create a unique disease focused microarray - Lung Cancer DSA™ research tool. Built on the Affymetrix GeneChip® platform the tool allows for interrogation of ~60,000 transcripts relevant to Lung Cancer, tens of thousands of which are unavailable on leading commercial microarrays. Presented here are the array design process and the results of experiments carried out to demonstrate the array’s utility for use in biomarker discovery projects with using NSCLC and normal samples.
Scientists Take Aim at Angiogenesis to Treat Degenerative Eye Diseases
Authors: Tracy Hampton
Journal: JAMA (2004)

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
Measurement of exhaled nitric oxide in children, 2001: E. Baraldi and J.C. de Jongste on behalf of the Task Force
Authors: E. Baraldi, J.C. de Jongste, B. Gaston, K. Alving, P.J. Barnes, H. Bisgaard, A. Bush, C. Gaultier, H. Grasemann, J.F. Hunt, N. Kissoon, G.L. Piacentini, F. Ratjen, P. Silkoff, S. Stick
Journal: European Respiratory Journal (2002)

Measurement of fractional exhaled nitric oxide in exhaled air is an exciting innovative technique that gives new insights in to the pathophysiology of lung disease and asthma in particular, with many potential clinical applications. Careful standardisation of measurement techniques will facilitate the use of this new measurement in paediatric respiratory medicine: this Task Force was set up for this purpose. Methodologies, for use in all age groups, are already available and there are abundant questions relating to interpretation and application of fractional exhaled nitric oxide waiting to be addressed. Noninvasiveness and instantaneous results potentially make it a suitable monitoring instrument for use in children. Exhaled nitric oxide measurement has definitely found its way into clinical research in paediatric respiratory medicine. Evidence for clinically-useful applications is accumulating, and the merits of this new technique must now be demonstrated in larger studies, using standardised methodology in an appropriate setting.
Needs to be within framework of decision making based on decision analysis
Authors: J. Dowie
Journal: BMJ (1996)

within the new journal can be divined.There is no reference to the second hand methodology, just the quoting of subjectively attractive and unqualified conclusions, fourth hand.Those who are concerned with validity will examine raw data and access much more exten- sive databases by standard methods on the Inter- net on a more comprehensive scale at only second hand level.Those who are not concerned with validity will find a ready substitute for
Abstract 12598: Impact of Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease on Systemic Inflammation and Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Mahmoud S Al Rifai, Michael J Blaha, Roger S Blumenthal, Michael G Silverman, Khurram Nasir, Matthew J Budoff, Ron Blankstein
Journal: Circulation (2014)

Introduction: We sought to characterize the association of three adiposity-related risk factors - obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) - with the outcomes of increased inflammation and subclinical atherosclerosis. Methods: We conducted a cross-sectional analysis of 3976 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with adequate CT imaging to diagnose NAFLD. For the study exposures, obesity was defined as BMI ≥30 kg/m 2 , metabolic syndrome by ATP III criteria, and NAFLD using non-contrast cardiac CT and a liver/spleen attenuation ratio (L/S) 0. In order to assess for a possible gradient-response, adjusted logistic regression was used to examine the association of a stepwise increase in the number of three adiposity-related risk factors with increased inflammation and subclinical atherosclerosis. Additional models were conducted stratifying by gender or ethnicity. Results: Mean age of participants was 63 years, 45% were male, 37% were white, 10% Chinese, 30% African American, and 23% Hispanic. NAFLD was associated with an odds ratio for high hs-CRP and CAC&gt;0 of 1.54 (1.27-1.87) and 1.41 (1.15-1.73), respectively, adjusting for obesity, metabolic syndrome and traditional risk factors. There was a positive interaction between female gender and NAFLD in the association with high hs-CRP (p=0.01). There was no interaction by race. Importantly, with increasing number of adiposity-related risk factors, the odds ratios of high hs-CRP and CAC&gt;0 increased in a graded fashion, suggesting a collective association (Figure). Conclusion: There is an association between three adiposity-related risk factors - obesity, metabolic syndrome, and NAFLD - with both increased inflammation and subclinical coronary atherosclerosis.