tbuckley/cabot-search huggingface dataset:
Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large b-cell lymphoma: a review of the literature
Authors: Carlos A Tirado, Weina Chen, Rolando García, Kelly A Kohlman, Nagesh Rao
Journal: Journal of Hematology & Oncology (2012)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH), as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS). The advent of microarray-based studies (chromosome, RNA, gene expression, etc) has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1) array based CGH; 2) classical CGH; and 3) gene expression profiling studies. The aims of this review were three-fold: (1) to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2) to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3) to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such as Karyotypes and FISH have played a major role in classification schemes of lymphomas, better classification models are clearly needed to further understanding the biology, disease outcome and therapeutic management of DLBCL. In summary, microarray data reviewed here can provide better subtype specific classifications models for DLBCL.
TOTAL LYMPHOID IRRADIATION IN RENAL CADAVERIC TRANSPLANTATION IN DIABETICS
Authors: Mark Waer, Yves Vanrenterghem, Leo Roels, Roger Bouillon, Tony Lerut, Jacques Gruwez, Paul Michielsen, Emmanuel Van Der Schueren, Michel Vandeputte, KianK. Ang
Journal: The Lancet (1985)
Purkinje-Muscle Reentry as a Mechanism of Polymorphic Ventricular Arrhythmias in a 3-Dimensional Model of the Ventricles
Authors: Omer Berenfeld, José Jalife
Journal: Circulation Research (1998)

Abstract —Multiple electrode mapping of the ventricles during complex tachyarrhythmias has revealed focal subendocardial activation whose mechanism remains unexplained. We hypothesized that reentry involving the Purkinje-muscle junctions (PMJs) may be a mechanism for such focal excitations. We have constructed an anatomically appropriate computerized 3-dimensional model of the mammalian ventricles that includes the Purkinje conduction system and 214 PMJs distributed throughout the endocardium. Isochronal maps during normal excitation, as well as during right or left bundle branch block, resembled experimental measurements and compared well with isochronal maps of propagation in the human heart. Activity observed at both sides of a PMJ in the model showed that propagation from Purkinje fibers to muscle was slower than in the opposite direction. Under these realistic and normal conditions, the evolution of reentrant activity involving muscle and the Purkinje network was simulated. The reentry pattern was independent of the initiation site. It evolved with drifting epicardial breakthroughs and transformed on the endocardium from focal activity to figure-of-8 reentry. In addition, the ECG amplitude undulated during the evolution, and decrease in the cycle period, apparent wavelength, and propagation velocity were observed. Finally, the reentry was terminated if the Purkinje system was disconnected from the muscle before it reached a relative steady state. The simulation results suggest the following: (1) Epicardial breakthroughs and endocardial focal activity may originate at the PMJs. (2) The ECG amplitude may decrease as the reentry stabilizes and the excitation wavelength decreases. (3) The Purkinje system may have a double role in the evolution of reentry: first, it is essential to the reentry at the initial stage; second, it may lead to the establishment of intramyocardial reentry, at which time the Purkinje system becomes irrelevant.
Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma
Authors: Keith T. Flaherty, Caroline Robert, Peter Hersey, Paul Nathan, Claus Garbe, Mohammed Milhem, Lev V. Demidov, Jessica C. Hassel, Piotr Rutkowski, Peter Mohr, Reinhard Dummer, Uwe Trefzer, James M.G. Larkin, Jochen Utikal, Brigitte Dreno, Marta Nyakas, Mark R. Middleton, Jürgen C. Becker, Michelle Casey, Laurie J. Sherman, Frank S. Wu, Daniele Ouellet, Anne-Marie Martin, Kiran Patel, Dirk Schadendorf
Journal: New England Journal of Medicine (2012)

Activating mutations in serine–threonine protein kinase B-RAF (BRAF) are found in 50% of patients with advanced melanoma. Selective BRAF-inhibitor therapy improves survival, as compared with chemotherapy, but responses are often short-lived. In previous trials, MEK inhibition appeared to be promising in this population.
Inhibiting signal transducer and activator of transcription-3 increases response to gemcitabine and delays progression of pancreatic cancer
Authors: Kolaparthi Venkatasubbarao, Lindsay Peterson, Shujie Zhao, Ping Hill, Lin Cao, Qing Zhou, Steffan T Nawrocki, James W Freeman
Journal: Molecular Cancer (2013)

Abstract Background Among the solid tumors, human pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis. Gemcitabine is the standard first line of therapy for pancreatic cancer but has limited efficacy due to inherent or rapid development of resistance and combining EGFR inhibitors with this regimen results in only a modest clinical benefit. The goal of this study was to identify molecular targets that are activated during gemcitabine therapy alone or in combination with an EGFR inhibitor. Methods PDAC cell lines were used to determine molecular changes and rates of growth after treatment with gemcitabine or an EGFR inhibitor, AG1478, by Western blot analysis and MTT assays respectively. Flow cytometric analysis was performed to study the cell cycle progression and rate of apoptosis after gemcitabine treatment. ShRNA was used to knockdown STAT3. An in vivo orthotopic animal model was used to evaluate STAT3 as a target. Immunohistochemical analysis was performed to analyze Ki67 and STAT3 expression in tumors. Results Treatment with gemcitabine increased the levels of EGFR Tyr1068 and ERK phosphorylation in the PDAC cell lines tested. The constitutive STAT3 Tyr705 phosphorylation observed in PDAC cell lines was not altered by treatment with gemcitabine. Treatment of cells with gemcitabine or AG1478 resulted in differential rate of growth inhibition. AG1478 efficiently blocked the phosphorylation of EGFR Tyr1068 and inhibited the phosphorylation of down-stream effectors AKT and ERKs, while STAT3 Tyr705 phosphorylation remained unchanged. Combining these two agents neither induced synergistic growth suppression nor inhibited STAT3 Tyr705 phosphorylation, thus prompting further studies to assess whether targeting STAT3 improves the response to gemcitabine or AG1478. Indeed, knockdown of STAT3 increased sensitivity to gemcitabine by inducing pro-apoptotic signals and by increasing G1 cell cycle arrest. However, knockdown of STAT3 did not enhance the growth inhibitory potential of AG1478. In vivo orthotopic animal model results show that knockdown of STAT3 caused a significant reduction in tumor burden and delayed tumor progression with increased response to gemcitabine associated with a decrease in the Ki-67 positive cells. Conclusions This study suggests that STAT3 should be considered an important molecular target for therapy of PDAC for enhancing the response to gemcitabine.
Cancer Control and Functional Outcomes of Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Systematic Review of the Literature
Authors: Daher C. Chade, James Eastham, Markus Graefen, Jim C. Hu, R. Jeffrey Karnes, Laurence Klotz, Francesco Montorsi, Hendrik van Poppel, Peter T. Scardino, Shahrokh F. Shariat
Journal: European Urology (2012)
Normal sweat secretion rate in patients with alopecia areata
Authors: D.DE BERKER, J.L REES
Journal: British Journal of Dermatology (1995)

We have examined sweat secretion rates in 22 patients with alopecia areata, and 22 age- and sex matched controls. Mean sweat rate on the forearm in patients with alopecia areata was 20 mg/cm2 per h (95% confidence limits 15–25 mg/cm2 per h), and in controls was 24.1 mg/cm2 per h (95% confidence limits 19.1–29.1 mg/cm2 per h). Sweat secretion was higher in males than females in both the disease and control groups (27.8 mg/cm2 per h [95% confidence limits 21.3–34.3 mg/cm2 per h], compared with 18.08 mg/cm2 per h [95% confidence limits 14.63-21.6 mg/cm2]; P > 0.01). Our results confirm the previously reported sex difference in sweat secretion rate, and demonstrate that there is no statistically significant difference between patients with alopecia areata and controls. We discuss our results in the light of a previous report claiming that patients with alopecia areata have reduced rates of cholinergic-induced sweating.
Amyloidogenesis. One serum amyloid A isotype is selectively removed from the circulation.
Authors: R L Meek, J S Hoffman, E P Benditt
Journal: The Journal of Experimental Medicine (1986)

The deposits of fibrils found in amyloidosis of the A type are derived from only one of the three serum amyloid A (SAA) gene products, namely SAA2. In order to explore the mechanism of SAA isotype-specific amyloid protein AA deposition, the molecular kinetics of the serum amyloid proteins were examined in CBA mice during casein induction of amyloidosis. The presence of SAA mRNA in spleen was searched for; hepatic SAA1 and SAA2 mRNA levels, rates of specific protein synthesis and secretion by hepatocytes, and serum levels were measured during a 20-d period of amyloid induction. We observed the following: small amounts of amyloid substance appeared in the spleen by day 5 and increased steadily over the ensuing 15 d to occupy nearly 30% of splenic volume by day 20. No SAA mRNA was detected in spleen at any time during induction of amyloid formation. Total serum SAA levels peaked 1 d after we began casein treatment, and thereafter declined. This decline was accounted for entirely by a dramatic fall in SAA2, while SAA1 levels remained nearly constant throughout. The ratios of hepatic SAA2:SAA1 mRNA, as determined by in vitro translation, remained constant during the 20-d period, as did amounts of SAA1 and SAA2 synthesized and secreted by freshly isolated hepatocytes. These data indicate that the deposition of amyloid A protein derived from SAA2 is not due to local SAA production in spleen, nor excessive SAA2 production compared with SAA1, but involves the selective and accelerated removal of SAA2 from the circulating pool of both SAA1 and SAA2.
Deposition and clearance of 2 μ particles in the tracheobronchial tree of normal subjects—smokers and nonsmokers
Authors: Ruy V. Lourenço, Mary F. Klimek, Claudia J. Borowski
Journal: Journal of Clinical Investigation (1971)

Deposition and clearance of inhaled particles of iron oxide labeled with (198)Au were studied in 19 normal subjects (10 nonsmokers and 9 smokers). For this purpose, monodisperse aerosols of particles with a 2 mu diameter were produced in a spinning disc atomizer. Thoracic counts and images with a scintillation camera were begun immediately after inhalation of the aerosol and continued for 6 hr. In all subjects, smokers and nonsmokers, the deposition of the particles was uniform throughout both lung fields, with approximately half of the particles deposited in the ciliated airways (tracheobronchial deposition) and half in the nonciliated airways (alveolar deposition). Tracheobronchial clearance in nonsmokers occurred immediately after inhalation, first at a fast rate for particles deposited in the largest and most central airways, and then at a slower rate for particles from the smaller and more peripheral airways. Photoscintigrams showed that the particles cleared steadily with no retention in any area. The general pattern of clearance may be likened to a model of multiple conveyor belts with speed increasing from the peripheral to the central airways in such a way as to prevent "particle jams" at airway confluence points. In smokers, tracheobronchial clearance was delayed for periods of 1-4 hr after inhalation. Furthermore, in contrast with the findings in nonsmokers, significant clearance was still occurring in many of the smokers in the 5th and 6th hr after inhalation. Also, photoscintigrams showed an abnormal accumulation of particles in the large airways several hours after inhalation of the aerosol.
Mechanisms of resveratrol-induced platelet apoptosis
Authors: K. H. Lin, G. Hsiao, C. M. Shih, D. S. Chou, J. R. Sheu
Journal: Cardiovascular Research (2009)

Apoptotic events have recently been found to occur in platelets, which are anuclear. Resveratrol is present in red wine and has various biological activities, including inhibition of platelet aggregation. Although considerable evidence is available as to the induction of tumour cell apoptosis by resveratrol, resveratrol's effects on platelet apoptosis have not yet been investigated. In the present study, we demonstrate that resveratrol also markedly stimulates apoptosis in washed human platelets. Resveratrol (5–25 µM) completely inhibited platelet aggregation stimulated by collagen. Furthermore, resveratrol time- and concentration-dependently stimulated dissipation of the mitochondrial membrane potential (ΔΨm), activation of caspases-9, -3, and -8, gelsolin and actin cleavage, Bid cleavage into truncated Bid, Bax translocation, cytochrome c release, and phosphatidylserine exposure but not P-selectin expression in washed human platelets. The presence of z-IETD-fmk, a caspase-8 inhibitor, markedly reversed tBid formation and caspase activation and partially reversed the dissipation of platelet ΔΨm stimulated by resveratrol. In addition, resveratrol also directly evoked dissipation of ΔΨm and release of cytochrome c from isolated mitochondria. Furthermore, resveratrol shortened platelet survival or enhanced platelet clearance in an in vivo study. This study demonstrates for the first time that resveratrol simultaneously inhibits platelet aggregation and stimulates platelet apoptosis. Stimulation of platelet apoptosis by resveratrol may represent the increased therapeutic potential for patients suffering from thrombotic conditions or thrombocytosis to promote platelet destruction and thus prevent pathological clotting. Furthermore, this study also provides a novel conception that rigorous surveillance of platelet numbers may be important during resveratrol treatment in the clinic.
Rheumatoid arthritis, corticosteroid therapy and hip fracture.
Authors: C Cooper, C Coupland, M Mitchell
Journal: Annals of the Rheumatic Diseases (1995)

To identify the risk of hip fracture in patients with rheumatoid arthritis and those taking corticosteroids.In a population based case-control study, we compared 300 consecutive patients with hip fracture aged 50 years and over from a defined district and 600 age and sex matched community controls.The risk of hip fracture was increased in patients with rheumatoid arthritis (odds ratio (OR) 2.1; 95% confidence interval (CI) 1.0 to 4.7) and those receiving corticosteroids (OR 2.7; 95% CI 1.2 to 5.8). The risk attributable to rheumatoid arthritis was markedly reduced by adjusting for functional impairment, while that for steroid use remained after adjusting for body mass index, smoking, alcohol, and functional status.Hip fracture risk is approximately doubled amongst patients with rheumatoid arthritis and among those taking steroids. These risk increases are, to some extent, independent of each other. In rheumatoid arthritis, the risk was most closely associated with functional impairment, whereas steroid use did not appear to be confounded by this variable.
The gold rush 1925-35.
Authors: R Y Keers
Journal: Thorax (1980)

Although from the time of Koch onwards there had been desultory experiments with a variety of gold preparations in the management of pulmonary tuberculosis, gold as a recognised and accepted treatment did not emerge until 1925. In that year Holger Mollgaard of Copenhagen introduced sanocrysin, a double thiosulphate of gold and sodium, with which he had conducted an extensive series of animal experiments. The results of these were considered to justify its use in clinical practice and two physicians, Secher and Faber, undeterred by its toxicity, reported enthusiastically in its favour. Other Danish physicians followed but, alarmed by violent reactions, modified the dosage, an example followed by British workers. Encouraging results continued to be reported although each series contained a significant proportion of failures, and toxicity remained high. The first properly planned and fully controlled clinical trial took place in the United States and produced a report which was wholly adverse and which sounded the death knell of gold therapy throughout America. Until 1934-35 gold was used extensively in Europe but thereafter there was a sudden and largely universal cessation of interest and within a few years gold, introduced with such éclat and carrying so many high hopes, had vanished from the therapy of tuberculosis even though, at that point, no better alternative was available.
Vasoconstriction of stenotic coronary arteries during dynamic exercise in patients with classic angina pectoris: reversibility by nitroglycerin.
Authors: J E Gage, O M Hess, T Murakami, M Ritter, J Grimm, H P Krayenbuehl
Journal: Circulation (1986)

To study the vasomotility of normal and diseased coronary arteries during dynamic exercise, symptom-limited supine bicycle exercise during cardiac catheterization was performed by 18 patients with classic angina pectoris. The cardiovascular response was assessed by hemodynamic measurements and computer-assisted determination of normal and stenotic coronary artery luminal areas from biplane coronary angiograms made before, during, and after exercise. After baseline measurements were recorded, 12 patients (group 1) performed bicycle exercise for 3.4 min (mean), reaching a maximum workload of 81 W (mean); at the end of exercise they received 1.6 mg sublingual nitroglycerin. After measurements at rest in six other patients (group 2), 0.1 mg intracoronary nitroglycerin was given, followed by exercise (3.8 min, 96 W; NS) and sublingual nitroglycerin as in group 1. During exercise in group 1, luminal area of the coronary stenosis decreased to 71% of resting levels (p less than .001), while area of the normal coronary artery increased to 123% of control (p less than .001). After sublingual nitroglycerin at the end of exercise, area of the normal vessel further increased to 140% of control (p less than .001), while luminal area of the stenosis dilated to 112% of resting levels (p less than .001 vs exercise, NS vs rest). Pretreatment with intracoronary nitroglycerin increased both normal (121%; p less than .05) and stenotic (122%; p less than .05) luminal areas, while preventing the previously observed narrowing of stenosis during exercise (114%; NS). Exercise resulted in a similar heart rate-systolic pressure product and caused angina pectoris in two-thirds of the patients in each group. However, patients pretreated with intracoronary nitroglycerin (group 2) had a lower mean pulmonary arterial pressure during maximum exercise (35 mm Hg) than those patients (group 1) not receiving pretreatment (47 mm Hg; p less than .001). Group 2 patients reached a percentage of their predicted work capacity (65%) that was about the same as that during previous upright bicycle exercise (71%; NS), while group 1 patients had a significantly lower work capacity (51% of predicted) than that before catheterization (82%; p less than .001). Hence, narrowing of coronary artery stenosis during dynamic exercise is attributable to active vasoconstriction due to its reversibility by preexercise intracoronary nitroglycerin. Patients who did not experience narrowing of stenosis during exercise (group 2) had less evidence of myocardial ischemia (lower mean pulmonary arterial pressure) and maintained their work capacity.(ABSTRACT TRUNCATED AT 400 WORDS)
Neo-aortic root dilation and valve regurgitation up to 21 years after staged reconstruction for hypoplastic left heart syndrome
Authors: Meryl S Cohen, Bradley S Marino, Doff B McElhinney, Daniëlle Robbers-Visser, Wendy van der Woerd, J.William Gaynor, Thomas L Spray, Gil Wernovsky
Journal: Journal of the American College of Cardiology (2003)
Tie2 Expression and Phosphorylation in Angiogenic and Quiescent Adult Tissues
Authors: Adrianne L. Wong, Zishan A. Haroon, Sabine Werner, Mark W. Dewhirst, Charles S. Greenberg, Kevin G. Peters
Journal: Circulation Research (1997)

Abstract Angiogenesis, the process of new vessels sprouting from the existing vasculature, is a critical process during early development. However, angiogenesis rarely occurs in the adult, except in response to cyclic hormonal stimulation in the ovary and uterus, in response to injury, and in response to pathological conditions such as tumorigenesis and diabetes mellitus. Tie2 (also known as Tek) is a novel endothelium-specific receptor tyrosine kinase, which has been demonstrated to be essential for the development of the embryonic vasculature; Tie2 knockout mice die by embryonic day 10.5 with specific defects in the formation of microvessels. Tie2 is downregulated later in embryogenesis, and its function in the adult has been relatively unexplored. To gain insight into the potential functions of Tie2 in the adult vasculature, Tie2 expression was examined in adult tissues undergoing angiogenesis and in quiescent tissues. Tie2 expression was localized by immunohistochemistry to the endothelium of neovessels in rat tissues undergoing angiogenesis during hormonally stimulated follicular maturation and uterine development and in healing skin wounds. Immunoprecipitation and RNase protection assay demonstrated upregulation of Tie2 protein and mRNA in rat and mouse skin wounds, respectively. Moreover, Tie2 immunoprecipitated from skin wounds was tyrosine-phosphorylated, indicating active downstream signaling. Surprisingly, Tie2 was also expressed in the entire spectrum of the quiescent vasculature (arteries, veins, and capillaries) in a wide range of adult tissues, and Tie2 immunoprecipitated from quiescent adult tissues was also tyrosine-phosphorylated. Together, these results suggest a dual function for Tie2 in adult tissues involving both angiogenesis and vascular maintenance.