tbuckley/cabot-search huggingface dataset:
Abstract P2-05-04: Comparative expression profiling of patient samples and preclinical models of inflammatory breast cancer reveals gene signatures of epithelial plasticity and suppression of TGFb signaling
Authors: SJ Van Laere, M Marsan, PB Vermeulen, P Viens, SH Barsky, M Cristofanilli, LY Dirix, F Bertucci, FM Robertson
Journal: Cancer Research (2013)

Abstract Introduction: Genome-wide expression profiling of samples from patients with and without Inflammatory Breast Cancer (IBC) has revealed novel insights into the biology of IBC. The present study was undertaken to compare these novel insights with data obtained from all available preclinical IBC models including 2 new models that we have recently developed that recapitulate the characteristics of IBC including retention of E-cadherin, formation of tumor emboli and encircling lymphoangiogenesis Materials and Methods: Five replicates of 7 preclinical IBC models (SUM149, SUM190, FC-IBC-01, FC-IBC-02, MDA-IBC-03, KPL-4, and Mary-X) were profiled using Affymetrix HGU133plus2 GeneChips. Using a nearest shrunken centroid algorithm, each expression profile was classified according to an IBC-specific signature identified in patient samples. Available expression profiles were further queried for expression patterns related to Epithelial-to-Mesenchymal Transition (EMT), TGFβ-signaling and IBC-specific patterns of transcription factor activation. Results: Application of our IBC-specific signature (posterior probabilities exceeded 0.50 in at least 4/5 replicates) revealed that out of 7 pre-clinical models of IBC, 3 of these robustly classified as IBC (FC-IBC-01, FC-IBC-02, and KPL-4). All preclinical IBC models were characterized by retention of E-Cadherin expression, absence of ZEB1 expression, attenuated expression of specific components of the TGFβ pathway (TGFβR2, SMAD3, SMAD7, and TGFβ1), and ambiguous activation patterns of several transcription factors involved in regulating cellular plasticity and cell fate decisions (Up in IBC: NR4A2, RARB/RXRA, PTX3, GSC2, and ZEB1; Down in IBC: SOX10, PAX5, and SMAD2). For each of the molecular alterations described above, Z-scores greater than 2 were achieved in at least 4/5 replicates. Conclusions: The observations that we have made using IBC patient tumor samples with regards to EMT, cell plasticity and TGFβ-signaling are corroborated in pre-clinical models of IBC using current analytic approaches, despite the fact that expression patterns of the majority of preclinical models of IBC deviate from the IBC-specific expression patterns observed in patient samples. Our data suggest that despite their highly invasive nature, IBC cancer cells retain an epithelial cell phenotype characterized by E-cadherin expression and loss of ZEB1 which appears to be mediated by, amongst others, attenuated TGFβ-signaling. This study strengthens our hypothesis that cancer cells from IBC exhibit cohesive invasion, and invade as a unit, possibly explaining the presence of florid tumour emboli which is a primary characteristic observed in IBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-05-04.
Results and tissue healing after copper-vapour laser (at 578 nm) treatment of port wine stains and facial telangiectasias
Authors: R.A. NEUMANN, H. LEONHARTSBKRGER, K. BOHLER-SOMMEREGGKR, R. KNOBLER, E.M. KOKOSCHKA, H. HONIGSMANN
Journal: British Journal of Dermatology (1993)

Twenty-four patients with port wine stains (PWS), and 33 patients with facial telangiectasias were treated with a copper-vapour laser (CVL) operating at 578 nm. Good to excellent results were obtained in 52% of PWS and 69% of facial telangiectasias. Enzyme histochemistry revealed vessel-selective damage with energy densities up to 12 J/cm2, but a non-specific coagulation necrosis with higher fluences (> or = 15 J/cm2). With vessel-selective fluences only moderate blanching was obtained in two PWS. All other evaluated patients were treated using non-selective energy densities. Tissue healing was comparable with that after argon laser treatment. The theoretically correct wavelength (578 nm) alone appeared to be no guarantee of vessel-selective damage. The laser employed lacked adequate power (only 1.3 W maximum) to transmit sufficient energy into the tissues in a short exposure time. However, the clinical results confirm the value of the CVL in the treatment of superficial cutaneous angiodysplasias.
Cholinesterase Depression and Its Association with Pesticide Exposure across the Agricultural Season among Latino Farmworkers in North Carolina
Authors: Sara A. Quandt, Haiying Chen, Joseph G. Grzywacz, Quirina M. Vallejos, Leonardo Galvan, Thomas A. Arcury
Journal: Environmental Health Perspectives (2010)

Farmworkers can be exposed to a wide variety of pesticides. Assessing cholinesterase activity over time can be used to monitor exposure to organophosphorus and carbamate pesticides.The goal of this study was to document patterns and variation in cholinesterase levels across the agricultural season (May-August) among field-workers, and to explore the association of cholinesterase depression with pesticide exposure across the agricultural season.Dried blood samples collected from 231 migrant farmworkers sampled from camps in eastern North Carolina up to four times across a summer agricultural season were analyzed for cholinesterase activity, and urine samples were analyzed for metabolites of organophosphorus and carbamate pesticides. Reductions of >or= 15% from an individual's highest value were identified and considered evidence of meaningful cholinesterase activity depression.The average cholinesterase activity levels were lowest in June, with significantly higher mean values in July and August. When adjusted for age, sex, minutes waited to shower, and days worked in the fields, the number of organophosphorus and carbamate pesticides detected in urine predicted reductions in cholinesterase activity.These data demonstrate that workers are experiencing pesticide exposure. Greater enforcement of existing safety regulations or strengthening of these regulations may be warranted. This study demonstrates that serial measurements of cholinesterase activity across an agricultural season can detect exposure to pesticides among field-workers.
Comparison of serum 25-OH vitamin D concentrations in rheumatoid arthritis and osteoarthrosis.
Authors: H A Bird, M Peacock, J H Storer, V Wright
Journal: BMJ (1980)

time had been stable in the therapeutic range (two to three times control) taking 6 mg warfarin daily.He discontinued his carbamazepine, and when seen four weeks later his prothrombin time was five times control.He subsequently required 4 mg warfarin daily to maintain his prothrombin time at two to three times control.Some months later he started taking carbamaze- pine 300 mg daily again.The prothrombin time was measured weekly and his warfarin dose adjusted as necessary.His serum y-glutamyl-transferase (y-GT) concentration was also measured weekly.His warfarin requirements increased from 3-5 mg daily to 5 5 mg daily over a period of five weeks and his serum y-GT rose from 11 U/I to 27 U/l during the same period.The effects of carbamazepine on warfarin dose and y-GT are shown in the figure.
Variability of area measurements obtained with different intravascular ultrasound catheter systems: impact on clinical trials and a method for accurate calibration
Authors: Paul Schoenhagen, Timothy D. Crowe, William A. Magyar, Shelly Sapp, Jennifer Popovich, Geoffrey D. Vince, Steven E. Nissen, Murat E. Tuzcu
Journal: Journal of the American College of Cardiology (2002)
Letter: Serum thyrotrophin and lipid levels in summer and winter.
Authors: H Hedstrand, L Wide
Journal: BMJ (1973)

bined with oestrogen.'6Phenothiazines have been shown to increase plasma prolactin'5 and might possibly be associated with an in- creased incidence of breast cancer.16Male patients with gynaecomastia, except when associated with drugs like phenothiazines, do not have raised prolactin levels,"3 so that this hormone may not be necessary for breast growth (normal or abnormal) in humans.In summary, we agree that breast cancer response to hormones is a most complex subject.However, we suggest that the theory of different clones within one tumour or its metastases adequately explains variable re- sponses to endocrine manipulation.-Weare, etc.,
Immunoglobulin kappa light chain variable region gene complex organization and immunoglobulin genes encoding anti-DNA autoantibodies in lupus mice.
Authors: R Kofler, R Strohal, R S Balderas, M E Johnson, D J Noonan, M A Duchosal, F J Dixon, A N Theofilopoulos
Journal: Journal of Clinical Investigation (1988)

We have investigated the genetic origin of autoantibody production in several strains of mice that spontaneously develop a systemic lupus erythematosus-like disease. Restriction fragment length polymorphism analyses of gene loci encoding kappa light chain variable regions (Igk-V) demonstrated, as shown previously for the Ig heavy chain locus, that autoantibody production and disease occur in different Igk-V haplotypes. Moreover, autoimmune mice with known genetic derivation inherited their Igk-V loci essentially unaltered from their nonautoimmune ancestors. New Zealand black lupus mice, with unknown genetic derivation, had a possibly recombinant Igk-V haplotype, composed of V kappa loci that were primarily indistinguishable from those of nonautoimmune strains from either of the two potential donor haplotypes. The heavy and light chain gene segments (variable, diversity, joining) encoding anti-DNA antibodies were diverse and often closely related, or even identical, to those found in antibodies to foreign antigens in normal mice. Only 1 of 11 sequenced variable region genes could not be assigned to existing variable region gene families; however, corresponding germline genes were present in the genome of normal mice as well. These data argue against abnormalities in the genes and mechanisms generating antibody diversity in lupus mice and suggest a remarkable genetic and structural diversity in the generation of anti-DNA binding sites.
External aortic root support for Marfan syndrome
Authors: Adil Polat, Ebru Bal Polat, Vedat Erentug
Journal: Journal of the Royal Society of Medicine (2010)

We have read the interesting article by Pepper and colleagues1 about their experience on the external support of the aortic root in Marfan syndrome. This is a good contribution to the expanding literature about Marfan syndrome; however, there are few facts that should be clarified.

First of all, 66 patients have been removed from the analysis for the comparison of the groups due to previous operations or re-operations. Why? Re-operation in the Marfan patients is an important fact that should be kept in mind in planning the operation. As we have reported before,2 about 20% of our patients had ≥1 re-operations due to dilatations in the other segments of the aorta or mitral valve problems. Second, the follow-up data of the 20 patients are unclear. There is a figure of aortic dimensions but the time of the last postoperative examination from the time of the operation is unclear. In our report of the long-term results of the aortic root operations, Marfan syndrome was found to be associated with decreased long-term survival.3 Third, as the authors have stated, the aneurysm does not necessarily precedes aortic dissection in Marfan patients. That is why; the operation indication is lower than that of the normal population.4 In order to take advantage of refraining from the use of anticoagulation, is it wise to take the risk of an aortic dissection in this segment? We have used similar external support for an abdominal aneurysm in one of our patients in a re-operation2 in order to decrease the operation risk. However, a young population like this mandates a more definitive treatment in our point of view.

We would like to thank the authors for their study and would like to hear their contributions to the discussion.
Abstract A48: Novel dual mode fluorine MRI, NIR fluorescent probe for noninvasive detection of tumor-associated inflammation.
Authors: Anthony Balducci, Yi Wen, Yang Zhang, Brooke M. Helfer, Kevin Hitchens, Wilson Meng, Jelena Janjic, Amy Wesa
Journal: Cancer Research (2013)

Abstract Tumor-associated macrophage are active in both tumor progression and remission processes, affecting prognosis depending on the nature of their involvement. Imaging macrophage recruitment and persistence to gauge tumor from normal host tissue is an area of great interest. Herein we propose the use of a novel dual mode fluorine magnetic resonance imaging (MRI), near infrared (NIR) fluorescent probe for the non-invasive detection of tumor associated inflammation. The use of this technique allows for rapid optical assessment of tumor associated macrophage as well as the specificity and detailed resolution provided by pairing 19F and conventional 1H MRI. Upon administration of the 19F/NIR reagent, tumors were visible at 6h. Both the liver and spleen were also visible due to clearance through the reticuloendothelial system. Use of the dual mode reagent was also compatible with MRI visualization, where detection of inflammation was in the periphery of, and not integral to, the tumor itself, information that could not be detected by optical means. Upon resection of the tumor, liver, spleen and other regions of interest fluorescence detection within the organs/tissue correlated with fluorine content and agreed with macrophage infiltrates and regions of reagent clearance. Flow cytometric analysis of whole blood show the preferential labeling of the macrophage population and immunofluorescent analysis of labeled macrophage further confirms cellular labeling. Dual functioning contrast agents enable both quick monitoring and sensitive quantification when evaluating the tumor microenvironment and potential changes in macrophage infiltrates as a result of therapeutic intervention. Citation Format: Anthony Balducci, Yi Wen, Yang Zhang, Brooke M. Helfer, Kevin Hitchens, Wilson Meng, Jelena Janjic, Amy Wesa. Novel dual mode fluorine MRI, NIR fluorescent probe for noninvasive detection of tumor-associated inflammation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A48.
Changes in peripheral venous compliance after myocardial infarction
Authors: B. F. ROBINSON, J. COLLIER, CH. NACHEV
Journal: Cardiovascular Research (1972)

Changes in the compliance of a superficial hand vein have been studied in patients suffering from myocardial infarction. Venoconstriction was a constant finding during the first day after infarction, and the response appeared to be mediated by the sympathetic nervous system. A number of possible initiating factors have been investigated but did not appear to be important in determining the response; the main cause remains to be identified.
Acyclovir Prevents Reactivation of Herpes Simplex Labialis in Skiers
Authors: Spotswood L. Spruance
Journal: JAMA (1988)

To determine the effectiveness of an antiviral to prevent herpes labialis during a brief, high-risk circumstance, 147 persons with a history of sun-induced recurrences were treated prophylactically with oral acyclovir or matching placebo and were observed during their ski holidays. Five (7%) of 75 acyclovir-treated subjects developed lesions compared with 19 (26%) of 72 persons in the placebo group.
Leukopenia Secondary to Sulfadiazine Silver
Authors: Gilles L. Fraser
Journal: JAMA (1979)

SULFADIAZINE silver 1% cream has been available in the United States since 1973 for the topical treatment of burns. This bactericidal agent acts on the cell membranes and cell walls of a variety of Gram-positive and Gram-negative bacteria as well as on yeast. Its relative freedom from appreciable side effects such as electrolyte and acid-base disturbances, staining, and pain on application has contributed to its popularity. Rash (which responds to antihistamine therapy), fever, tachycardia, and leukocytosis occur infrequently. More serious in nature is the possibility that the hematologic side effects of the sulfonamides in general could be expected with sufficient systemic absorption of sulfadiazine silver. Leukopenia associated with sulfadiazine silver is one hematologic reaction that has only recently been recognized. It is a relatively common occurrence with an incidence of 3% to 5%.<sup>1,2</sup>The scarceness of information in the literature describing this possible drug-induced reaction prompted our report. <h3>Report</h3>
Different Potencies of Angiotensin Receptor Blockers at Suppressing Adrenal β-Arrestin1–Dependent Post-Myocardial Infarction Hyperaldosteronism
Authors: Anastasios Lymperopoulos, Emmanuel Sturchler, Ashley Bathgate-Siryk, Samalia Dabul, Dilayda Garcia, Karlee Walklett, Giuseppe Rengo, Patricia McDonald, Walter J. Koch
Journal: Journal of the American College of Cardiology (2014)
Chronic complications in patients with slowly progressing autoimmune type 1 diabetes (LADA).
Authors: B Isomaa, P Almgren, M Henricsson, M R Taskinen, T Tuomi, L Groop, L Sarelin
Journal: Diabetes Care (1999)

To study the prevalence of chronic diabetic complications in patients with the slowly progressing autoimmune form of type 1 diabetes, also referred to as latent autoimmune diabetes in adults (LADA).We evaluated factors associated with chronic diabetic complications in 59 patients with GAD antibodies (GADAs) and age at onset of diabetes >35 years and in 59 GADA-negative type 2 diabetic patients. The prevalence of chronic complications was further compared with the prevalence in 111 type 1 diabetic patients.The LADA patients had lower BMI (P = 0.04), waist-to-hip ratio (P = 0.02 for men and P = 0.03 for women), and fasting C-peptide concentrations (P<0.001) higher HDL2 concentrations (P = 0.04), and less hypertension (58 vs. 75%, P = 0.05) than the type 2 diabetic patients. These differences were even more marked in patients with short disease duration. The prevalence of retinopathy (51 vs. 56%), neuropathy (29 vs. 27%), and microalbuminuria (27 vs. 29%) did not differ between the groups. The type 1 diabetic patients had lower prevalence of neuropathy (13%, P = 0.02) and higher prevalence of retinopathy (76%, P = 0.002) compared with the other groups. Neither the prevalence of coronary heart disease (CHD) (56 vs. 58%) nor cardiovascular mortality (7.4 vs. 12.4%, P = 0.2) significantly differed between the LADA and type 2 diabetic patients. In a multiple logistic regression analysis, glycemic control was associated with CHD (P = 0.02) in the LADA group but not in the type 2 diabetic group.Glycemic control is a stronger risk factor for cardiovascular disease in LADA patients than in patients with type 2 diabetes. This could be related to the lower prevalence of the metabolic syndrome seen in the former.
Persistent measles infection in malnourished children.
Authors: J Dossetor, H C Whittle, B M Greenwood
Journal: BMJ (1977)

Thirty malnourished and 25 well-nourished children were studied six to 31 days after the onset of a measles rash. Evidence of the virus was found in 40% of the malnourished children but in none of the well-nourished controls. Giant cells were found in the nasal secretions of five out of 17 malnourished children and measles antigen was detected in the lymphocytes of eight out of 28. The malnourished children showed depressed cell-mediated immunity to measles and candida antigens and a low response to meningococcal vaccine. Fifteen died from intercurrent infections. Malnutrition was thought to have depressed the immune response in these children, resulting in a severe and prolonged attack of measles. This, in turn, led to further damage to the immune system and more severe malnutrition. Thus these children were made susceptible to intercurrent infection.
The majority of liver transplant recipients with normal liver enzymetests (LET) exhibit long term liver graft lesions
Authors: M. Bismuth, G.P. Pageaux, C. Duvoux, V. Costes, E.S. Zafrani, J.M. Fabre, P. Blanc, D. Cherqui, J. Domergue, D. Dhumeaux, D. Larrey
Journal: Journal of Hepatology (2000)
On Managing Adolescents
Authors: A. H. Chapman
Journal: JAMA (1960)

During adolescence the individual must move from a position of dependence on the family home toward emotional, social, and economic independence. It is also the period of sexual maturation, with the need for sound, acceptable channeling of sexual urges. The physician is often consulted about the problems and adjustments of adolescents and their parents, and for this he needs some simple rules and valid advice to offer these patients. A set of rules is outlined, emphasizing that the adjustments of adolescence require flexibility by both parents and adolescents as the parents gradually relinquish authority and control to the adolescent who progressively assumes them. Seven guide rules to facilitate this transition are given and the major pitfalls of adolescence are discussed.
β <sub>2</sub> - and β <sub>3</sub> -Adrenergic Receptor Polymorphisms Are Related to the Onset of Weight Gain and Blood Pressure Elevation Over 5 Years
Authors: Kazuko Masuo, Tomohiro Katsuya, Yuxiao Fu, Hiromi Rakugi, Toshio Ogihara, Michael L. Tuck
Journal: Circulation (2005)

The genes responsible for obesity are candidate genes for obesity-related diseases, such as hypertension. Functional polymorphisms in the beta2- and beta3-adrenergic receptors have been reported to be associated with hypertension and obesity.To longitudinally clarify the relevance to alterations in beta-adrenergic receptor polymorphisms related to weight gain, blood pressure (BP) elevation, and sympathetic nerve activity as measured by plasma norepinephrine level, we studied 160 young, nonobese, normotensive men. Changes in body weight, BP, plasma norepinephrine levels, and beta2-adrenergic (Arg16Gly, Gln27Glu) and beta3-adrenergic (Trp64Arg) receptor polymorphisms were measured periodically over a 5-year period. Weight gain and BP elevation were defined as > or =10% increases from entry levels over 5 years in body mass index or mean BP. The presence of the Gly16 allele of Arg16Gly was associated with a higher frequency of weight gain and BP elevation over the 5-year period. The subjects carrying the Glu27 allele of Gln27Glu and the Trp64 allele of Trp64Arg had a higher frequency of BP elevation. Significantly higher levels of plasma norepinephrine at entry and at year 5 were observed in the subjects with the Gly16 allele of Arg16Gly and the Glu27 allele of Gln27Glu compared with those without the Gly16 or the Glu27 alleles.These results demonstrate that the Gly16 allele is related to greater weight gain and BP elevation. Additionally, Glu27 and Trp64 alleles are linked to BP elevation. The subjects carrying the beta2-polymorphisms linked to weight gain and BP elevation also have higher plasma norepinephrine levels that are present at entry before weight gain and BP elevation. These findings suggest that beta2-adrenergic receptor polymorphisms in association with a heightened sympathetic nerve activity could predict the future onset of obesity and hypertension, as shown in the 5-year longitudinal study.