tbuckley/cabot-search huggingface dataset:
Atypical vascular lesion after radiation therapy for breast cancer.
Authors: Ana Paula Refinetti, Richard Shapiro, Joan Cangiarella, Amber Azniv Guth
Journal: Journal of Clinical Oncology (2012)

184 Background: Atypical vascular lesions (AVLs) are known to occur in the setting of radiation therapy after breast conserving surgery for treatment of breast cancer. Their relationship with potential secondary angiosarcoma has yet not been fully characterized. AVLs typically present as single or multiple pink papules in the skin of the breast. Histologic examination reveals proliferation of dilated vascular channels in the dermis with IHC reactive for CD31, CD34 and D2-40. Management consists of local excision to rule out angiosarcoma. Methods: The pathology records of the NYU Langone Medical Center were queried for patients who were diagnosed with atypical vascular lesions. Results: A total of 3 patients with previous history of breast cancer treated with breast conserving therapy (BCT) and radiation therapy were included in this case series. Two patients were diagnosed with DCIS and one was diagnosed with Invasive ductal carcinoma. The median time between the cancer diagnosis and the development of AVL was 5 years (3-9 years). Presentation was an erythematous skin nodule in two patients and progressive telangectasia in one. Diagnosis was made initially by punch biopsy and it was followed by excisional biopsy in all three cases. Only one patient had residual atypical vascular lesion in the excisional biopsy especimen. Conclusions: AVL is a pathological entity with growing importance over the years due to its questionable progression to angiosarcoma. The improvement in survival of patients diagnosed with breast cancer as well as the widespread use of lumpectomy with breast irradiation for the treatment of the disease have caused an exponential increase in the number of patients seen in daily practice after BCT. Clinicians must implement high surveillance of these patients and have a low threshold for further work up of skin changes in the radiated breast in order to early diagnose these lesions since it is yet unknown which ones will progress to angiosarcoma. There are ongoing studies in the development of immunophenotypical markers such as MYC that will be a useful diagnostic tool to differentiate AVL from its malignant counterpart.
Low Socioeconomic Status, Adverse Gene Expression Profiles, and Clinical Outcomes in Hematopoietic Stem Cell Transplant Recipients
Authors: Jennifer M. Knight, J. Douglas Rizzo, Brent R. Logan, Tao Wang, Jesusa M.G. Arevalo, Jeffrey Ma, Steve W. Cole
Journal: Clinical Cancer Research (2015)

Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biologic mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves upregulation of proinflammatory genes and downregulation of genes involved in type I IFN response and antibody synthesis.We compared pretransplant leukocyte CTRA gene expression between a group of 78 high versus low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes.Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA upregulation compared with matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity, including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival.Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT.
Comparison of tuberculin skin test and in-vitro interferon gamma release tests in diagnosis of tuberculosis in children with household tuberculosis contact
Authors: Hasan Azem Karabacak, Ozge Yilmaz, Ibrahim Tuglu, Fatma Taneli, Suheyla Surucuoglu, Esra Toprak Kanik, Nuri Ozkutuk, Ceyhun Gozukara, Mahmud Mustafa Ozkut, Ahmet Turkeli, Hasan Yuksel
Journal: European Respiratory Journal (2014)

Introduction:  The aim of this study was to compare nonspecific and specific tuberculosis (TB) antigen IL-18 and IL-27 response of peripheral mononuclear cells in BCG vaccinated children who do and do not develop latent TB after household contact with an adult TB case.   Methods:  We enrolled 40 children aged 12-60 months who had in-house family member with proven TB to this cross sectional study. We recorded all children9s age and gender and tuberculin skin test (TST) result. Blood samples were taken for peripheral blood mononuclear cell culture (PBMC) and QuantiFERON TB test. IL-18 and IL-27 levels were measured in the PBMC supernatant without stimulation and after stimulation with ESAT-6 + CFP-10.   Results:  Among these children 13 were TST (+) and 27 were TST (-). Quantiferon testing revealed that all 27 TST(-) children were also quantiferon (-) while seven of the TST (+) were quantiferon (+). IL-18 and IL-27 levels in unstimulated PBMC supernatants from TDT (-) Quantiferon (-), TDT (+) Quantiferon (-) and TDT (+) Quantiferon (+) groups were not significantly different (p = 0.956 and p = 0694). Levels of IL-18 and IL-27 in PBMC supernatant after ESAT6+CFP-10 stimulation were significantly different among these three groups (p=0.003 ve p=0.022).   Conclusion:  Low L-18 and IL-27 response of peripheral blood mononuclear cells levels may play a role in development of TB infection in BCG vaccinated children with household TB contact and this might indicate a specific immune deviation. Moreover, PBMC IL-27 response carries a potential to be used as a diagnostic tool for confirmation of infection in TST (+) BCG vaccinated children.
Nasal NO measurement in preschool children: Feasibility and validation of a novel tidal breathing technique
Authors: Andreas Jung, Christian Geidel, Irmela Heinrichs, Alexander Moeller, Guenter Menz, Roger Lauener
Journal: European Respiratory Journal (2011)

Background:  Screening for primary ciliary dyskinesia (PCD) in preschool children by measurement of nasal nitrite oxide (nNO) is difficult due to a lack of standardization and reference values. This study aimed to compare a conventional nNO measurement technique with a tidal breathing technique through a straw.   Methods:  nNO was assessed by the Niox Flex system in children and adults with chronic rhino-sinusitis (CRS), confirmed PCD and in healthy controls. Measurements consisted of 2 tests with subjects holding their breath (BH), followed by 2 tests with tidal breathing through a straw (TB).   Results:  88 subjects were recruited. 71 (81%) or 77 (88%) subjects performed either a valid BH or a valid TB test, respectively. In the preschool age group (n=22), 19 subjects (86%) had a valid TB test with only 10 individuals (45%) performing a valid BH test. A high correlation between TB and BD values were observed (r 2 =0.954, p 2 =0.341, p   Conclusion:  Nasal NO measurement by TB with a straw is a feasible and valid method in all age groups. Results correlate well with nNO levels measured by conventional techniques. Almost all preschool children were able to perform a valid TB test. A larger study is on the way to determine reference values in preschool children using the established TB method with a straw.
Phase I trial and pharmacokinetic study of all-trans-retinoic acid administered on an intermittent schedule in combination with interferon-alpha2a in pediatric patients with refractory cancer.
Authors: P C Adamson, G Reaman, J Z Finklestein, J Feusner, S L Berg, S M Blaney, M O'Brien, R F Murphy, F M Balis
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the maximum-tolerated dose (MTD) of all-trans-retinoic acid (ATRA) administered on an intermittent oral schedule with interferon-alpha2a (IFN-alpha2a) in children with refractory cancer, and whether the marked reduction in plasma ATRA concentrations observed with chronic daily oral dosing could be circumvented with an intermittent dosing schedule. PATIENTS AND METHODS Thirty-three children with refractory cancer (stratified by age, &lt; or = 12 and &gt; 12 years) were treated with ATRA 3 consecutive days per week and IFN-alpha2a 3 x 10(6) U/m2 5 consecutive days per week, both repeated weekly. The starting dose of ATRA was 60 mg/m2/d divided into three doses, with planned escalations to 90 and 120 mg/m2/d. Because severe headaches have been noted to occur on the initial day of ATRA administration, only two of three doses of ATRA were administered on day 1 of each week. RESULTS Pseudotumor cerebri or dose-limiting headache was observed in two of five patients older than 12 years treated at the 120-mg/m2/d dose level and in one of six &lt; or = 12 years at the 90-mg/m2/d level. Other non-dose-limiting toxicities of ATRA included reversible elevations in hepatic transaminases and triglycerides, dry skin, cheilitis, and nausea/vomiting. One child with recurrent neuroblastoma had an objective response of 6 months' duration, and one with recurrent Wilms' tumor had histologic maturation of multiple tumors. This intermittent schedule allowed for exposure to relatively high plasma concentrations of ATRA on a repetitive basis. Following 30-mg/m2 doses, the ATRA area under the concentration-time curve (AUC) decreased from 96 +/- 14 micromol/L/min on day 1 to 26 +/- 24 micromol/L/min by day 3 of drug administration, but on day 1 of the fourth consecutive week of therapy, the AUC averaged 110 +/- 16 micromol/L/min. The recommended pediatric phase II dose of ATRA administered on this schedule is 90 mg/m2/d. CONCLUSION An intermittent schedule of ATRA administration appears to circumvent the low plasma drug exposure that is a result of the sustained upregulation of metabolism when this drug is administered on a chronic daily schedule. Based on the results of this trial, a phase II trial of ATRA/IFN-alpha2a in neuroblastoma and Wilms' tumor using this schedule is in progress.
Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid of a patient with ANCA negative Wegener's granulomatosis
Authors: H Mukae, N Matsumoto, J Ashitani, H Mashimoto, J Kadota, M Nakazato, S Kohno, S Matsukura
Journal: European Respiratory Journal (1996)

We report a case of Wegener's granulomatosis (WG), with neutrophil accumulation in bronchoalveolar lavage fluid (BALF). Peripheral blood neutrophilia was present but the anti-neutrophil cytoplasmic antibody (ANCA) was negative. The serum and BALF levels of neutrophil-related cytokines, including interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF) and IL-1 beta, were increased, particularly in BALF. Plasma and BALF levels of neutrophil elastase and defensins, which are released by neutrophils and are potentially toxic to cells, were also elevated. Our findings suggest that neutrophils and neutrophil-related cytokines may play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody negative as well as anti-neutrophil cytoplasmic antibody positive Wegener's granulomatosis.
Identification of a cis-regulatory element which may drive Runx1 expression in hematopoietic stem cells
Authors: Cherry Ee Lin Ng, Motomi Osato, Giselle Nah, Namiko Yamashita, Hao Jin, Zilong Wen, Yoshiaki Ito
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C6 

RUNX1 is essential for definitive hematopoeisis and is frequently mutated in human leukemias. In addition, RUNX1 haploinsufficiency causes familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). However the precise transcriptional regulation of Runx1 remains largely unknown due to the extremely large size of the mammalian Runx gene loci which spans approximately 1.0Mb in human RUNX genes. We first took a comparative genomics approach and identified 93 conserved non-coding sequences (CNSs). In addition, we utilised retroviral integration sites (RISs) information obtained from Retrovirus Tagged Cancer Gene Database (RTCGD), assuming that regions of non-coding DNA flanked by RISs mark “open” regions which are likely accessible to transcription factors and RISs may be good indicators of nearby cis-regulatory regions. Using this novel approach we highlighted 10 CNSs. These CNSs were individually fused with EGFP and injected into one-cell stage zebrafish embryos to assess their in vivo ability to drive GFP during different developmental stages which corresponds to endogenous Runx1 expression. We identified a mouse CNS (mCNS-20) which drives GFP expression in the intermediate cell mass (ICM) region. Interestingly, GFP expression was also observed in some circulating hematopoietic cells. We hypothesise that these cells are likely to be haematopoietic stem cells (HSCs) since they appear to have arisen from the ICM region which in turn undergoes morphogenesis to form the dorsal aorta where HSCs emerge from. Quantitative chromatin-immunoprecipitation (qChIP) has also been carried out using antibodies against modified histones which mark either open or close regions of chromatin. We verified that in cells expressing Runx1 , mCNS-20 region is associated with histone modifications which mark “open” chromatin. In contrast, in cells which do not express Runx1, mCNS-20 region is not “open”. Further analysis using mCNS20-GFP transgenic mice is in progress.
Laryngeal movements during mechanical insufflation-exsufflation
Authors: Tiina Andersen, Astrid Sandnes, Ove Fondenes, Thomas Halvorsen, John-Helge Heimdal, Magnus Hilland, Tom Karlsen, Thor-Andre Ellingsen, Ola Røksund
Journal: European Respiratory Journal (2011)

Introduction:  Mechanical insufflation-exsufflation (MI-E) is the most effective approach to increase peak cough flow in patients with neuromuscular diseases, thereby potentially augmenting airway clearance. Co-ordinated movements of the glottis are probably crucial for effect, but laryngeal response patterns to MI-E have not been studied.   Aims:  Visualize laryngeal response patterns to MI-E in healthy subjects.   Methods:  Ten healthy volunteers (21-26 years) were examined with video recorded flexibel transnasal fiberoptic laryngoscopy during MI-E (Cough Assist®, Respironics, USA) according to a standardized protocol at pressures of ±20 to 50 cmH 2 O. Participants were instructed to inhale during insufflation and to cough or actively exhale during exsufflation. Laryngeal patency and movements during MI-E was assessed from video recordings according to a pre-set scheme.   Results:  In all subjects and regardless of the applied pressure and instructions, the vocal cords abducted during insufflation and exsufflation. Coordinated glottic closure and opening on instruction to cough was found in 10/10. At exsufflation pressures of -40 to -50 cmH 2 O, hypopharyngeal obstruction was observed in 6/10. Cough presented as sequential glottic closures in the majority. Retroflex movement of the epiglottis, partially occluding the laryngeal entrance, was observed in three subjects during insufflation, irrespective of pressures.   Conclusion:  The laryngeal response patterns to MI-E in healthy subjects was as described for spontaneous cough. Negative pressures may cause temporary hypopharyngeal obstruction, and retroflex movement of the epiglottis may obstruct airflow. The examination was well tolerated and may be considered for use in patients.
A general account of selection: Biology, immunology, and behavior
Authors: David L. Hull, Rodney E. Langman, Sigrid S. Glenn
Journal: Behavioral and Brain Sciences (2001)

Authors frequently refer to gene-based selection in biological evolution, the reaction of the immune system to antigens, and operant learning as exemplifying selection processes in the same sense of this term. However, as obvious as this claim may seem on the surface, setting out an account of "selection" that is general enough to incorporate all three of these processes without becoming so general as to be vacuous is far from easy. In this target article, we set out such a general account of selection to see how well it accommodates these very different sorts of selection. The three fundamental elements of this account are replication, variation, and environmental interaction. For selection to occur, these three processes must be related in a very specific way. In particular, replication must alternate with environmental interaction so that any changes that occur in replication are passed on differentially because of environmental interaction. One of the main differences among the three sorts of selection that we investigate concerns the role of organisms. In traditional biological evolution, organisms play a central role with respect to environmental interaction. Although environmental interaction can occur at other levels of the organizational hierarchy, organisms are the primary focus of environmental interaction. In the functioning of the immune system, organisms function as containers. The interactions that result in selection of antibodies during a lifetime are between entities (antibodies and antigens) contained within the organism. Resulting changes in the immune system of one organism are not passed on to later organisms. Nor are changes in operant behavior resulting from behavioral selection passed on to later organisms. But operant behavior is not contained in the organism because most of the interactions that lead to differential replication include parts of the world outside the organism. Changes in the organism's nervous system are the effects of those interactions. The role of genes also varies in these three systems. Biological evolution is gene-based (i.e., genes are the primary replicators). Genes play very different roles in operant behavior and the immune system. However, in all three systems, iteration is central. All three selection processes are also incredibly wasteful and inefficient. They can generate complexity and novelty primarily because they are so wasteful and inefficient.
Proton Magnetic Resonance Spectroscopic Imaging in Children With Recurrent Primary Brain Tumors
Authors: Katherine E. Warren, Joseph A. Frank, Jeanette L. Black, Rene S. Hill, Josef H. Duyn, Alberta A. Aikin, Bobbi K. Lewis, Peter C. Adamson, Frank M. Balis
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Proton magnetic resonance spectroscopic imaging ( 1 H-MRSI) is a noninvasive technique for spatial characterization of biochemical markers in tissues. We measured the relative tumor concentrations of these biochemical markers in children with recurrent brain tumors and evaluated their potential prognostic significance. PATIENTS AND METHODS: 1 H-MRSI was performed on 27 children with recurrent primary brain tumors referred to our institution for investigational drug trials. Diagnoses included high-grade glioma (n = 10), brainstem glioma (n = 7), medulloblastoma/peripheral neuroectodermal tumor (n = 6), ependymoma (n = 3), and pineal germinoma (n = 1). 1 H-MRSI was performed on 1.5-T magnetic resonance imagers before treatment. The concentrations of choline (Cho) and N-acetyl-aspartate (NAA) in the tumor and normal brain were quantified using a multislice multivoxel method, and the maximum Cho:NAA ratio was determined for each patient’s tumor. RESULTS: The maximum Cho:NAA ratio ranged from 1.1 to 13.2 (median, 4.5); the Cho:NAA ratio in areas of normal-appearing brain tissue was less than 1.0. The maximum Cho:NAA ratio for each histologic subtype varied considerably; approximately equal numbers of patients within each tumor type had maximum Cho:NAA ratios above and below the median. Patients with a maximum Cho:NAA ratio greater than 4.5 had a median survival of 22 weeks, and all 13 patients died by 63 weeks. Patients with a Cho:NAA ratio less than or equal to 4.5 had a projected survival of more than 50% at 63 weeks. The difference was statistically significant (P = .0067, log-rank test). CONCLUSION: The maximum tumor Cho:NAA ratio seems to be predictive of outcome in children with recurrent primary brain tumors and should be evaluated as a prognostic indicator in newly diagnosed childhood brain tumors.
Are New Oral Anticoagulants Ready for Use in Patients With Cancer?
Authors: Paul C. Hendrie, David A. Garcia
Journal: Journal of the National Comprehensive Cancer Network (2013)

Patients with cancer have long been an important and enigmatic part of basic science and clinical research in thromboembolic disease. The reciprocal deleterious effects on outcomes of a cancer diagnosis on patients with thrombosis and a thrombotic event on patients with cancer have been observed and documented for more than a century. Patients with cancer continue to be one of the more difficult populations to manage using the available unfractionated and low-molecular-weight heparins and the oral vitamin K antagonists. High rates of failure and bleeding complications have made researchers and practitioners alike seek newer more effective anticoagulation agents. The novel oral direct thrombin and activated factor Xa inhibitors have been shown in large clinical trials to be safe and efficacious in many prophylaxis and treatment settings. However, practitioners who treat patients with cancer should be cautious using these agents until more studies are specifically performed in this thrombophilic patient population.
Diagnosis of occupational asthma from serial plots of PEF; first year results of open access to the Oasys internet database
Authors: Cedd B.S.G. Burge, P. Sherwood Burge, Jessica Harvey, Richard Barraclough, Jennifer Hoyle, Trine Thilsing, Christophe Paris
Journal: European Respiratory Journal (2011)

Occupational asthma requires validation. The most accessible first stage is diagnostic confirmation from serial measurements of PEF or FEV1, supported by all evidence-based reviews. Reliance on these diagnostic methods is limited by interpreter disagreement and record quality. The Oasys diagnostic aid overcomes both of these problems by applying evidence-based data quality and interpreter-independent diagnoses. In April 2010 we made Oasys freely available via the internet. Uploaded records are anonymous but their country of origin can often be identified from the email address. We compare the results of uploaded records for the first 9 months of open access, with records entered in 2010 from our centre, where Oasys has been in use for many years. 349 records have been entered from our centre and 321 records uploaded from centres outside our own; sources including Denmark (32), other UK (165), Korea (5), Italy (5), Taiwan (5) and Unknown (99).  The table shows that other centres using Oasys are able to achieve similar quality and diagnostic confirmation to our own and is suitable for more widespread use. It is freely available via www.occupationalasthma.com/occupational_asthma_pageview.aspx?id=4443.