tbuckley/cabot-search huggingface dataset:
Integrated Microfluidic and Imaging Platform for a Kinase Activity Radioassay to Analyze Minute Patient Cancer Samples
Authors: Cong Fang, Yanju Wang, Nam T. Vu, Wei-Yu Lin, Yao-Te Hsieh, Liudmilla Rubbi, Michael E. Phelps, Markus Müschen, Yong-Mi Kim, Arion F. Chatziioannou, Hsian-Rong Tseng, Thomas G. Graeber
Journal: Cancer Research (2010)

Oncogenic kinase activity and the resulting aberrant growth and survival signaling are a common driving force of cancer. Accordingly, many successful molecularly targeted anticancer therapeutics are directed at inhibiting kinase activity. To assess kinase activity in minute patient samples, we have developed an immunocapture-based in vitro kinase assay on an integrated polydimethylsiloxane microfluidics platform that can reproducibly measure kinase activity from as few as 3,000 cells. For this platform, we adopted the standard radiometric (32)P-ATP-labeled phosphate transfer assay. Implementation on a microfluidic device required us to develop methods for repeated trapping and mixing of solid-phase affinity microbeads. We also developed a solid-state beta-particle camera imbedded directly below the microfluidic device for real-time quantitative detection of the signal from this and other microfluidic radiobioassays. We show that the resulting integrated device can measure ABL kinase activity from BCR-ABL-positive leukemia patient samples. The low sample input requirement of the device creates new potential for direct kinase activity experimentation and diagnostics on patient blood, bone marrow, and needle biopsy samples.
A relative thrombocytosis and elevated mean platelet volume are features of gravitational disease
Authors: M.J.D. GOODFIELD
Journal: British Journal of Dermatology (1986)

Platelet counts were obtained in 60 patients with gravitational ulceration (GU), 60 with gravitational eczema (GE), 56 with endogenous eczema (EE) and 60 normal controls. Mean platelet volume (MPV), a broad index of platelet size, was estimated in the last 40 patients in each group (29 with EE). Causes of a reactive thrombocytosis were excluded. Platelet counts were significantly higher in both gravitational groups than in the EE group or the normal controls (P = 0.001). Ulcer healing produced no significant changes in platelet count, and patients with non-gravitational ulcers had normal platelet counts. MPV was significantly higher in both gravitational groups than in controls after correction for platelet count, by analysis of co-variance (P = 0.01). These differences in platelet parameters in gravitational disease suggest a possible role for platelets in this disease, and platelet inhibiting therapy may be of value at an early stage in the development of the condition.
Care management and mental health.
Authors: G Thornicroft, P Ward, S James
Journal: BMJ (1993)

The community care reforms will produce a new kind of key worker who will organise and budget for packages of care: the care manager. Care management goes live in April 1993 but is still poorly rehearsed and its performance may yet disappoint. This overview sets out the origins of case management, its transformation into care management, and the principles guiding its practice. To spell out how the concept works, plans for care management in Southwark's mental health services are described.
X-RAY EMISSION MICROANALYSIS OF THE DENSITY OF HAIR PROTEINS IN KWASHIORKOR
Authors: R. T. SIMS, T. HALL
Journal: British Journal of Dermatology (1968)

Journal Article X‐RAY EMISSION MICROANALYSIS OF THE DENSITY OF HAIR PROTEINS IN KWASHIORKOR Get access R. T. SIMS, R. T. SIMS Anatomy School (Dr. Sims) and Cavendish Laboratory (Dr. Hall) University of Cambridge Search for other works by this author on: Oxford Academic Google Scholar T. HALL T. HALL Anatomy School (Dr. Sims) and Cavendish Laboratory (Dr. Hall) University of Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 1, 1 January 1968, Pages 35–38, https://doi.org/10.1111/j.1365-2133.1968.tb11903.x Published: 01 January 1968 Article history Accepted: 23 October 1967 Published: 01 January 1968
Acute Onset of Severe Autoimmune Hemolytic Anemia After Treatment With 2‐Chlorodeoxyadenosine for Chronic Lymphocytic Leukemia
Authors: Roger A. Fleischman, David Croy
Journal: American Journal of Hematology (1995)

induction of AIHA despite an ongoing favorable response of the B-cell disease.On the other hand, hemolysis in some patients with pre-existing AIHA has resolved after starting fludarabine [2,4], and in one case 2-CdA [5].Presumably the reduction in neoplastic B cells in these patients was more significant than alterations in T-cell subsets.Since AIHA can occur at any time in the course of CLL, the significance of the association between AIHA and fludarabine has recently been questioned [4].Indeed, in the previously reported cases, hemolysis usually developed after multiple treatment courses given over up to 6-12 months of follow-up, raising the possibility that these cases could have occurred by chance alone [2][3][4].By contrast, in the present case, severe hemolysis began less than 3 weeks after the start of 2-CdA treatment.Indeed, the diagnosis of AIHA coincided with the expected period of maximum drug-induced myeloid and lymphoid toxicity.Despite receiving only one course of 2-CdA, AIHA persisted for 3 months, suggesting that hemolysis was not related to drug binding to the red cell membrane or drug-antibody complexes.We conclude that, similar to previous reports with fludarabine, 2-CdA may be associated with an increased incidence of AIHA in CLL.
Language Ability after Early Detection of Permanent Childhood Hearing Impairment
Authors: Colin R. Kennedy, Donna C. McCann, Michael J. Campbell, Catherine M. Law, Mark Mullee, Stavros Petrou, Peter Watkin, Sarah Worsfold, Ho Ming Yuen, Jim Stevenson
Journal: New England Journal of Medicine (2006)

Children with bilateral permanent hearing impairment often have impaired language and speech abilities. However, the effects of universal newborn screening for permanent bilateral childhood hearing impairment and the effects of confirmation of hearing impairment by nine months of age on subsequent verbal abilities are uncertain.We studied 120 children with bilateral permanent hearing impairment identified from a large birth cohort in southern England, at a mean of 7.9 years of age. Of the 120 children, 61 were born during periods with universal newborn screening and 57 had hearing impairment that was confirmed by nine months of age. The primary outcomes were language as compared with nonverbal ability and speech expressed as z scores (the number of standard deviations by which the score differed from the mean score among 63 age-matched children with normal hearing), adjusted for the severity of the hearing impairment and for maternal education.Confirmation of hearing impairment by nine months of age was associated with higher adjusted mean z scores for language as compared with nonverbal ability (adjusted mean difference for receptive language, 0.82; 95 percent confidence interval, 0.31 to 1.33; and adjusted mean difference for expressive language, 0.70; 95 percent confidence interval, 0.13 to 1.26). Birth during periods with universal newborn screening was also associated with higher adjusted z scores for receptive language as compared with nonverbal ability (adjusted mean difference, 0.60; 95 percent confidence interval, 0.07 to 1.13), although the z scores for expressive language as compared with nonverbal ability were not significantly higher. Speech scores did not differ significantly between those who were exposed to newborn screening or early confirmation and those who were not.Early detection of childhood hearing impairment was associated with higher scores for language but not for speech in midchildhood.
A Cohort Study of People With Diabetes and Their First Foot Ulcer
Authors: Khalida Ismail, Kirsty Winkley, Daniel Stahl, Trudie Chalder, Michael Edmonds
Journal: Diabetes Care (2007)

The aim was to evaluate over 18 months whether depression was associated with mortality in people with their first foot ulcer.A prospective cohort design was used. Adults with their first diabetic foot ulcer were recruited from foot clinics in southeast London, U.K. At baseline, the Schedules for Clinical Assessment in Neuropsychiatry 2.1 was used to define those who met DSM (Diagnostic and Statistical Manual of Mental Disorders)-IV criteria for minor and major depressive disorders. Potential covariates were age, sex, marital status, socioeconomic status, smoking, antidepressant use, A1C, macro- and microvascular complications, and University of Texas classification-based severity and size of ulcer. The main outcome was mortality 18 months later, and A1C was the secondary outcome. The proportion who had an amputation, had recurrence, and whose ulcer had healed was recorded.A total of 253 people with their first diabetic foot ulcer were recruited. The prevalence of minor and major depressive disorder was 8.1% (n = 21) and 24.1% (n = 61), respectively. There were 40 (15.8%) deaths, 36 (15.5%) amputations, and 99 (43.2%) recurrences. In the adjusted Cox regression analysis, minor and major depressive disorders were associated with an approximately threefold hazard risk for mortality compared with no depression (3.23 [95% CI 1.39-7.51] and 2.73 [1.38-5.40], respectively). There was no association between minor and major depression compared with no depression and A1C (P = 0.86 and P = 0.43, respectively).One-third of people with their first diabetic foot ulcer suffer from clinical depression, and this is associated with increased mortality.
Expanded <i>RAS</i>: Refining the Patient Population
Authors: Chloe E. Atreya, Ryan B. Corcoran, Scott Kopetz
Journal: Journal of Clinical Oncology (2015)

The era of precision medicine has changed the treatment paradigm for some cancers, but for others, the term precision is a stretch. New targets and therapies have broadened choices for patients with lung cancer or melanoma; however, in colorectal cancer (CRC), for example, the evolution of biomarkers has been primarily to inform whom not to treat rather than to identify the patients who will benefit from treatment. The refinements in CRC have been limiting rather than expansive; by broadening the definition of RAS mutations, fewer patients have multiple targeted options.
Akt Determines Replicative Senescence and Oxidative or Oncogenic Premature Senescence and Sensitizes Cells to Oxidative Apoptosis
Authors: Veronique Nogueira, Youngkyu Park, Chia-Chen Chen, Pei-Zhang Xu, Mei-Ling Chen, Ivana Tonic, Terry Unterman, Nissim Hay
Journal: Cancer Cell (2008)
Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart
Authors: Manuel D. Cerqueira, Neil J. Weissman, Vasken Dilsizian, Alice K. Jacobs, Sanjiv Kaul, Warren K. Laskey, Dudley J. Pennell, John A. Rumberger, Thomas Ryan, Mario S. Verani
Journal: Circulation (2002)

Nuclear cardiology, echocardiography, cardiovascular magnetic resonance (CMR), cardiac computed tomography (CT), positron emission computed tomography (PET), and coronary angiography are imaging modalities that have been used to measure myocardial perfusion, left ventricular function, and coronary anatomy for clinical management and research. Although there are technical differences between these modalities, all of them image the myocardium and the adjacent cavity. However, the orientation of the heart, angle selection for cardiac planes, number of segments, slice display and thickness, nomenclature for segments, and assignment of segments to coronary arterial territories have evolved independently within each field. This evolution has been based on the inherent strengths and weaknesses of the technique and the practical clinical application of these modalities as they are used for patient management. This independent evolution has resulted in a lack of standardization and has made accurate intra- and cross-modality comparisons for clinical patient management and research very difficult, if not, at times, impossible.

Attempts to standardize these options for all cardiac imaging modalities should be based on the sound principles that have evolved from cardiac anatomy and clinical needs.1–3⇓⇓ Selection of standardized methods must be based on the following criteria:





An earlier special report from the American Heart Association, American College of Cardiology, and Society of Nuclear Medicine4 defined standards for plane selection and display orientation for serial …
Extracellular Engagement of α6 Integrin Inhibited Urokinase-Type Plasminogen Activator–Mediated Cleavage and Delayed Human Prostate Bone Metastasis
Authors: Michael O. Ports, Ray B. Nagle, Gerald D. Pond, Anne E. Cress
Journal: Cancer Research (2009)

Expression of alpha(6) integrin, a laminin receptor, on tumor cell surfaces is associated with reduced patient survival and increased metastasis in a variety of tumors. In prostate cancer, tumor extracapsular escape occurs in part via laminin-coated nerves and vascular dissemination, resulting in clinically significant bone metastases. We previously identified a novel form of alpha(6) integrin, called alpha(6)p, generated by urokinase-type plasminogen activator-dependent cleavage of the laminin-binding domain from the tumor cell surface. Cleavage increased laminin-dependent migration. Currently, we used the known conformation sensitivity of integrin function to determine if engagement of the extracellular domain inhibited integrin cleavage and the extravasation step of metastasis. We show that alpha(6) integrin was present on prostate carcinoma escaping the gland via nerves. Both endogenous and inducible levels of alpha(6)p were inhibited by engaging the extracellular domain of alpha(6) with monoclonal antibody J8H. J8H inhibited tumor cell invasion through Matrigel. A severe combined immunodeficient mouse model of extravasation and bone metastasis produced detectable, progressive osteolytic lesions within 3 weeks of intracardiac injections. Injection of tumor cells, pretreated with J8H, delayed the appearance of metastases. Validation of the alpha(6) cleavage effect on extravasation was confirmed through a genetic approach using tumor cells transfected with uncleavable alpha(6) integrin. Uncleavable alpha(6) integrin significantly delayed the onset and progression of osseous metastases out to six weeks post-injection. The results suggest that alpha(6) integrin cleavage permits extravasation of human prostate cancer cells from circulation to bone and can be manipulated to prevent metastasis.
Expression and Subcellular Distribution of Novel Glomerulus-Associated Proteins Dendrin, Ehd3, Sh2d4a, Plekhh2, and 2310066E14Rik
Authors: Jaakko Patrakka, Zhijie Xiao, Masatoshi Nukui, Minoru Takemoto, Liqun He, Asmundur Oddsson, Ljubica Perisic, Anne Kaukinen, Cristina Al-Khalili Szigyarto, Mathias Uhlén, Hannu Jalanko, Christer Betsholtz, Karl Tryggvason
Journal: Journal of the American Society of Nephrology (2007)

The glomerular capillary tuft is a highly specialized microcapillary that is dedicated to function as a sophisticated molecular sieve. The glomerulus filter has a unique molecular composition, and several essential glomerular proteins are expressed in the kidney exclusively by glomerular podocytes. A catalog of >300 glomerulus-upregulated transcripts that were identified using expressed sequence tag profiling and microarray analysis was published recently. This study characterized the expression profile of five glomerulus-upregulated transcripts/proteins (ehd3, dendrin, sh2d4a, plekhh2, and 2310066E14Rik) in detail. The expression pattern of these novel glomerular transcripts in various mouse tissues was studied using reverse transcriptase-PCR, Northern blotting, and in situ hybridization. For studying the distribution of corresponding proteins, polyclonal antibodies were raised against the gene products, and Western blotting, immunofluorescence, and immunoelectron microscopic analyses were performed. Remarkably, it was discovered that all five transcripts/proteins were expressed in the kidney exclusively by glomerular cells. Ehd3 was expressed only by glomerular endothelial cells. Importantly, ehd3 is the first gene ever shown to be expressed exclusively by glomerular endothelial cells and not by other endothelial cells in the kidney. Dendrin, sh2d4a, plekhh2, and 2310066E14Rik, however, were transcribed solely by podocytes. With the use of polyclonal antibodies, dendrin, sh2d4a, and plekhh2 proteins were localized to the slit diaphragm and the foot process, whereas 2310066E14Rik protein was localized to the podocyte major processes and cell body. This study provides fresh insights into glomerular biology and uncovers new possibilities to explore the role of these novel proteins in the glomerular physiology and pathology.
Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial
Authors: M Ladetto, S Vallet, F Benedetti, U Vitolo, M Martelli, V Callea, C Patti, P Coser, A Perrotti, M Sorio, C Boccomini, A Pulsoni, C Stelitano, R Scimè, M Boccadoro, R Rosato, F De Marco, M Zanni, P Corradini, C Tarella
Journal: Leukemia (2006)
A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis
Authors: L. Padyukov, M. Seielstad, R. T. H. Ong, B. Ding, J. Ronnelid, M. Seddighzadeh, L. Alfredsson, L. Klareskog
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Rheumatoid arthritis (RA) can be divided into two major subsets based on the presence or absence of antibodies to citrullinated peptide antigens (ACPA). Until now, data from genome-wide association studies (GWAS) have only been published from ACPA-positive subsets of RA or from studies that have not separated the two subsets. The aim of the current study is to provide and compare GWAS data for both subsets. <h3>Methods</h3> and results GWAS using the Illumina 300K chip was performed for 774 ACPA-negative patients with RA, 1147 ACPA-positive patients with RA and 1079 controls from the Swedish population-based case–control study EIRA. Imputation was performed which allowed comparisons using 1 723 056 single nucleotide polymorphisms (SNPs). No SNP achieved genome-wide significance (2.9 × 10<sup>–8</sup>) in the comparison between ACPA-negative RA and controls. A case–case association study was then performed between ACPA-negative and ACPA-positive RA groups. The major difference in this analysis was in the HLA region where 768 HLA SNPs passed the threshold for genome-wide significance whereas additional contrasting SNPs did not reach genome-wide significance. However, one SNP close to the <i>RPS12P4</i> locus in chromosome 2 reached a p value of 2 × 10<sup>6</sup> and this locus can thus be considered as a tentative candidate locus for ACPA-negative RA. <h3>Conclusions</h3> ACPA-positive and ACPA-negative RA display significant risk allele frequency differences which are mainly confined to the HLA region. The data provide further support for distinct genetic aetiologies of RA subsets and emphasise the need to consider them separately in genetic as well as functional studies of this disease.
Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation
Authors: Erin R. Mehlhop-Williams, Michael J. Bevan
Journal: The Journal of Experimental Medicine (2014)

A hallmark of immunological memory is the ability of previously primed T cells to undergo rapid recall responses upon antigen reencounter. Classic work has suggested that memory T cells proliferate in response to lower doses of antigen than naive T cells and with reduced requirements for co-stimulation. In contrast to this premise, we observed that naive but not memory T cells proliferate in vivo in response to limited antigen presentation. To reconcile these observations, we tested the antigen threshold requirement for cell cycle entry in naive and central memory CD8+ T cells. Although both naive and memory T cells detect low dose antigen, only naive T cells activate cell cycle effectors. Direct comparison of TCR signaling on a single cell basis indicated that central memory T cells do not activate Zap70, induce cMyc expression, or degrade p27 in response to antigen levels that activate these functions in naive T cells. The reduced sensitivity of memory T cells may result from both decreased surface TCR expression and increased expression of protein tyrosine phosphatases as compared with naive T cells. Our data describe a novel aspect of memory T cell antigen threshold sensitivity that may critically regulate recall expansion.
Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma
Authors: S. Rao, D. Watkins, D. Cunningham, D. Dunlop, P. Johnson, P. Selby, B.W. Hancock, C. Fegan, D. Culligan, S. Schey, T.C.M. Morris, T. Lissitchkov, J.W. Oliver, J.T. Holmlund
Journal: Annals of Oncology (2004)
Functional Phosphodiesterase 11A Mutations May Modify the Risk of Familial and Bilateral Testicular Germ Cell Tumors
Authors: Anelia Horvath, Larissa Korde, Mark H. Greene, Rossella Libe, Paulo Osorio, Fabio Rueda Faucz, Marie Laure Raffin-Sanson, Kit Man Tsang, Limor Drori-Herishanu, Yianna Patronas, Elaine F. Remmers, Maria Eleni Nikita, Jason Moran, Joseph Greene, Maria Nesterova, Maria Merino, Jerome Bertherat, Constantine A. Stratakis
Journal: Cancer Research (2009)

Abstract Inactivating germline mutations in phosphodiesterase 11A (PDE11A) have been implicated in adrenal tumor susceptibility. PDE11A is highly expressed in endocrine steroidogenic tissues, especially the testis, and mice with inactivated Pde11a exhibit male infertility, a known testicular germ cell tumor (TGCT) risk factor. We sequenced the PDE11A gene-coding region in 95 patients with TGCT from 64 unrelated kindreds. We identified 8 nonsynonymous substitutions in 20 patients from 15 families: four (R52T, F258Y, G291R, and V820M) were newly recognized, three (R804H, R867G, and M878V) were functional variants previously implicated in adrenal tumor predisposition, and one (Y727C) was a known polymorphism. We compared the frequency of these variants in our patients to unrelated controls that had been screened and found negative for any endocrine diseases: only the two previously reported variants, R804H and R867G, known to be frequent in general population, were detected in these controls. The frequency of all PDE11A-gene variants (combined) was significantly higher among patients with TGCT (P = 0.0002), present in 19% of the families of our cohort. Most variants were detected in the general population, but functional studies showed that all these mutations reduced PDE activity, and that PDE11A protein expression was decreased (or absent) in TGCT samples from carriers. This is the first demonstration of the involvement of a PDE gene in TGCT, although the cyclic AMP signaling pathway has been investigated extensively in reproductive organ function and their diseases. In conclusion, we report that PDE11A-inactivating sequence variants may modify the risk of familial and bilateral TGCT. [Cancer Res 2009;69(13):5301–6]
AN UNUSUAL ERUPTION IN CONGENITAL SYPHILIS ("THE RETICULAR SYPHILIDE")
Authors: C. RASCH
Journal: British Journal of Dermatology (1929)

Journal Article AN UNUSUAL ERUPTION IN CONGENITAL SYPHILIS (“THE RETICULAR SYPHILIDE”) Get access C. RASCH C. RASCH Dermatological Clinic of the University of Copenhagen–Director, C. Rasch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 41, Issue 4, 1 April 1929, Pages 155–157, https://doi.org/10.1111/j.1365-2133.1929.tb09328.x Published: 01 April 1929
Sensitization to Mouse Allergen and Asthma Morbidity in a Population of Boston Women
Authors: W. Phipatanakul, A.A. Litonjua, T.A.E. Platts-Mills, L. Naccara, J.C. Celedon, H. Abdulkerim, S.T. Weiss, D.R. Gold
Journal: Journal of Allergy and Clinical Immunology (2007)