tbuckley/cabot-search huggingface dataset:
Abstract 3590: The Bruton tyrosine kinase inhibitor PCI-32765 prevents activation of pro-survival NF-kB pathways in OCI-Ly10 ABC DLBCL cells
Authors: Sriram Balasubramanian, Richard Crowley, Mint Sirisawad, Joseph J. Buggy
Journal: Cancer Research (2011)

Abstract PCI-32765 is a potent and selective small molecule inhibitor of Bruton tyrosine kinase (BTK), a Tec family kinase that is essential to signaling via the B-cell Receptor (BCR) (Honigberg, Proc. Natl Acad. Sci. USA 107:13075, 2010). PCI-32765 is showing encouraging clinical activity in an ongoing Phase I trial (Advani et al., ASCO 2010 meeting, JCO 28: 8012, 2010) in patients with chronic lymphocytic leukemias (CLL), as well as in B-cell Non-Hodgkin's Lymphoma (NHL), including mantle cell, follicular, and diffuse large B-cell lymphomas. Nevertheless, in tissue culture, even at concentrations of PCI-32765 that lead to full occupancy of the active site of Btk, many of the cell lines derived from B cell malignancies do not undergo apoptosis or have significantly reduced growth. This is likely because most established B-cell lines no longer depend on antigen stimulation of the BCR for survival. Recently, Davis et al identified DLBCL cells of the ABC subtype such as OCI-Ly10 that have chronic active BCR signaling and are very sensitive to Btk inhibition by PCI-32765 (Davis et al, Nature 463: 88, 2010). Here we show that PCI-32765 potently and irreversibly inhibits the growth of OCI-Ly10 (EC50 continuous exposure = 10 nM, EC50 1 hour pulse = 50 nM) but not OCI-Ly3 cells, another ABC-DLBCL line in which NF-kB pathway is activated by a mutation in CARD11, which is downstream of BTK. In addition, induction of apoptosis, as shown by caspase activation, Annexin-V flow cytometry and increase in sub-G0 fraction is observed in OCI-Ly10 but not in OCI-Ly3 cells. Both sensitive and resistant cells express Btk at similar levels, and the active site of BTK is fully occupied by the inhibitor in both as shown using a fluorescently-labeled affinity probe. OCI-Ly10 cells are shown to have chronically active BCR signaling to NF-kB which is dose-dependently inhibited by PCI-32765. The activity of PCI-32765 in these lines are further characterized by comparing signal transduction profiles (Lyn, Syk, Btk, PLCγ, ERK, NF-kB), cytokine secretion profiles and mRNA expression profiles, both with and without BCR stimulation, and observed significant differences in these profiles that could lead to clinical biomarkers that identify the most sensitive patient populations to PCI-32765 treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3590. doi:10.1158/1538-7445.AM2011-3590
SERIAL OPTICAL COHERENCE TOMOGRAPHY MORPHOMETRIC ASSESSMENT OF THE NOVEL STANZA™ BIORESORBABLE VASCULAR SCAFFOLD IMPLANTED IN SUPERFICIAL FEMORAL ARTERIES IN A PRE–CLINICAL SHEEP MODEL
Authors: Hiram Bezerra, Daniel Chamie, Tomoaki Kanaya, Yusuke Fujino, Yina Kuang, Wendy Naimark, Maria Palasis, Kentaro Tanaka, Guilherme Attizzani, Marco Costa
Journal: Journal of the American College of Cardiology (2013)
Anaesthesia during Raised Creatine Phosphokinase Activity
Authors: G. Owen, R. J. Kerry
Journal: BMJ (1974)

No adverse effects were observed in a series of patients in whom he levels of creatine phosphokinase (C.P.K.) were known to be raised and who received anaesthetics. The need to exercise caution in the interpretation of screening test results for C.P.K. activity before anaesthesia is stressed.
Abstract 5570: Laminin-5 gamma-2 (LAMC2) is highly expressed in anaplastic thyroid carcinoma and is associated with tumor progression, migration and invasion by modulating signaling of EGFR
Authors: Manoj Garg, Deepika Kanojia, Ryoko Okamoto, Vikas Madan, Wenwen Chien, Abhishek Sampath, Ling-Wen Ding, Meng Xuan, Jonathan W Said, Ngan Doan, Li-Zhen Liu, Henry Yang, Sigal Gery, Gleen D Braunstein, H.Phillip Koeffler
Journal: Cancer Research (2014)

Abstract Context: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy having no effective treatment. Laminin subunit gamma-2 (LAMC2) is an epithelial basement membrane protein involved in cell migration and tumour invasion and might represent an ideal target for the development of novel therapeutic approaches for ATC. Objective: Study the role of LAMC2 in ATC tumorigenesis. Design: LAMC2 expression was evaluated by RT-PCR, western blotting and immunohistochemistry in tumor specimens, adjacent non-cancerous tissues and cell lines. shRNA approach was used to investigate the effect of LAMC2 knockdown on tumorigenesis of ATC. Results: LAMC2 was highly expressed in ATC samples and cell lines compared to normal thyroid tissues. Silencing LAMC2 by shRNA in ATC cells moderately inhibited cell growth in liquid culture and dramatically decreased growth in soft agar and in xenografts growing in immunodeficient mice. Silencing LAMC2 caused cell cycle arrest and significantly suppressed migration, invasion and wound healing of ATC cells. Rescue experiments by overexpressing LAMC2 in LAMC2 knockdown cells, reversed the inhibitory effects as shown by increased cell proliferation and colony formation. Microarray data demonstrated that LAMC2 shRNA significantly altered expression of genes associated with migration, invasion, proliferation and survival. Immunoprecipitation and co-localization experiments showed that LAMC2 bound to EGFR in ATC cells. Silencing LAMC2 partially blocked EGF-mediated activation of EGFR and its downstream pathway. Interestingly, cetuximab (EGFR blocking antibody) or EGFR siRNA additively enhanced the anti-proliferative activity of the LAMC2 knockdown ATC cells compared to control cells. Conclusions: To our knowledge, this is the first report investigating the effect of LAMC2 on cell growth, cell cycle, migration, invasion and EGFR signaling in ATC cells, suggesting that LAMC2 may be a potential therapeutic target for treatment of ATC. Citation Format: Manoj Garg, Deepika Kanojia, Ryoko Okamoto, Vikas Madan, Wenwen Chien, Abhishek Sampath, Ling-Wen Ding, Meng Xuan, Jonathan W Said, Ngan Doan, Li-Zhen Liu, Henry Yang, Sigal Gery, Gleen D Braunstein, H.Phillip Koeffler. Laminin-5 gamma-2 (LAMC2) is highly expressed in anaplastic thyroid carcinoma and is associated with tumor progression, migration and invasion by modulating signaling of EGFR. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5570. doi:10.1158/1538-7445.AM2014-5570
Left ventricular diastolic Doppler characteristics in beta-thalassemia major.
Authors: D T Kremastinos, D P Tsiapras, G A Tsetsos, E I Rentoukas, H P Vretou, P K Toutouzas
Journal: Circulation (1993)

BACKGROUND Diastolic left ventricular function expressed by diastolic Doppler characteristics of the left ventricle has never been properly investigated. METHODS AND RESULTS Left ventricular inflow and pulmonary vein flow patterns were assessed by Doppler echocardiography in 88 beta-thalassemia major patients with normal left ventricular systolic function; 34 were young (age, 15.1 +/- 3.2 years) and 54 were adults (age, 25.1 +/- 3.6 years). The findings were compared with those obtained from 22 young (age, 13.8 +/- 2.4 years) and 24 adult (age, 25.3 +/- 4.1 years) normal individuals. In both groups of patients, peak flow velocities in early (E) and late (A) diastole were higher than in the control subjects (young E: P &lt; .01; adult E: P &lt; .001; young A: P &lt; .05; adult A: P &lt; .05), whereas no difference was found in the E/A ratio, deceleration time, or isovolumic relaxation time. Pulmonary vein systolic (S) and diastolic (D) velocities were also higher in beta-thalassemia major patients compared with the control subjects (young S: P &lt; .05; adult S: P &lt; .05; young D: P &lt; .05; adult D: P &lt; .05). Restrictive left ventricular abnormalities were only found in 7 patients who were among the oldest beta-thalassemia major population of the adult group (P &lt; .01) with highly elevated mean serum ferritin. In comparison to the remaining adult patients, interventricular septum and left ventricular posterior wall thickness were increased (P &lt; .01 and P &lt; .01, respectively). The left atrium and right ventricle were dilated (P &lt; .05 and P &lt; .01, respectively). CONCLUSIONS Doppler diastolic indexes in beta-thalassemia major patients with normal left ventricular systolic function are similar to those seen in conditions with an increased preload, probably because of chronic anemia. Only severe iron loading and deposition in the myocardium leads to the restrictive abnormalities of left ventricular filling.
Comparison of inflammatory events in skin sites with and without cutaneous late-phase reactions after prominent immediate IgE-mediated responses
Authors: Burton Zweiman, Anne R. Moskovitz, Carolyn von Allmen
Journal: Journal of Allergy and Clinical Immunology (1998)

Background: A number of inflammatory events have been detected in skin chambers overlying sites of developing late-phase reactions (LPR) to pollen antigens in sensitive subjects. However, the pathogenic significance of such events is still unclear. Objective: We sought to compare inflammatory responses and cytokine levels in skin chambers that overlie sites of antigen challenge in individuals with and individuals without LPRs after immediate wheal responses of similar intensity. Results: Early histamine releases at antigen sites were similar in eight subjects with LPR (+/+ group) and eight subjects without LPR (+/– group). However, histamine releases during hours 2 through 5 of antigen challenge were significantly greater in the +/+ subjects than in the +/– subjects. Total exuding leukocytes; percent eosinophils; and levels of eosinophil cationic protein, lactoferrin, and IL-8 were significantly greater at antigen versus buffer control challenge sites in both the +/+ and +/– groups, with no significant differences between the groups. IL-1 and IL-6 levels were not greater at antigen sites than at buffer sites. Conclusions: The only significantly greater antigen-induced response detected in +/+ subjects than in +/– subjects was in later histamine release, which is possibly a marker of other inflammatory responses because histamine itself does not induce LPRs. Other inflammatory events assessed may be somewhat greater in +/+ subjects, but not significantly so. (J Allergy Clin Immunol 1998;101:110-5.)
Performance on the NBME Part I examination
Authors: J. L. Uva
Journal: JAMA (1995)

ABSTRACT To the Editor. —In a recent issue of JAMA, Dr Dawson and colleagues1 investigated the performance of men and women from various racial and ethnic backgrounds on the NBME Part I examination. Many factors contributing to the differences in performances were discussed. However, one possible vital confounder unfortunately was never mentioned: undiagnosed adult learning disabilities.Undiagnosed adult learning disabilities could pose serious undermining of the validity of the examination, especially for the medical students who failed the examination. Recently, there has been an increase in the diagnosis of adults with learning disabilities such as dyslexia, dyscalcula, and attention-deficit hyperactivity disorder. A stimulating hypothesis is that bright, undiagnosed learning-disabled medical students are unable to compensate for their learning disability on standardized examinations. As a result, these previously academically successful students do poorly on the Scholastic Aptitude Test, the Medical College Admission Test (MCAT), and the NBME. In these scenarios, an
Diagnosis of Insulin Secreting Tumour by Retrograde Pancreatography
Authors: J. Papp, L. Korányi, J. Bielawski
Journal: Endoscopy (1976)

The case of a 26-year-old male with insulinoma is presented. An insulin secreting tumour was indicated by laboratory data. The tumour was accurately localized by endoscopic retrograde pancreatography, as verified by subsequent surgery.
Tropomodulin3-null mice are embryonic lethal with anemia due to impaired erythroid terminal differentiation in the fetal liver
Authors: Zhenhua Sui, Roberta B. Nowak, Andrea Bacconi, Nancy E. Kim, Hui Liu, Jie Li, Amittha Wickrema, Xiu-li An, Velia M. Fowler
Journal: Blood (2013)
Oxford Textbook of Sports Medicine
Authors: Peter J. Dorsen
Journal: JAMA (1995)

The 748-page Oxford Textbook of Sports Medicine is dedicated to  as one contribution to a healthy lifestyle. An international group of sports medicine talent, under editors Harries, Williams, Stanish, and Micheli, accomplishes this goal  a multidisciplinary approach, because those who look after the injured are professionally obliged to offer advice on how injuries can be treated and avoided.  Although the 80 distinguished contributors produce a concise reference work in the broad spectrum of sports medicine, there is plenty within this very British tome to assist the smalltown high school team doctor as well as the exercise specialist or physiologist.  Sir Roger Bannister, the world's first sub-four-minute miler and a practicing physician himself, notes, with some 25% of the population, including children and students, now regularly taking part in sport, the problem of treatment of injuries can no longer be regarded as a 'Cinderella' area of medicine.  In Man
Emergency pre-hospital management of patients admitted with acute asthma
Authors: A J Simpson
Journal: Thorax (2000)

Little is known about the management of acute asthma prior to hospital admission. Pre-hospital treatment of patients referred to hospital with acute asthma was therefore studied in 150 patients divided into three groups: those in the Edinburgh Emergency Asthma Admission Service (EEAAS) who can contact an ambulance and present directly to respiratory services when symptoms arise (n = 38), those under continuing supervision at a hospital respiratory outpatient clinic (n = 54), and those managed solely in primary care (n = 58).Standardised admission forms detailing aspects of pre-hospital management, case records, GP referral letters, and ambulance patient transport forms were analysed.In each group airflow obstruction had improved upon arrival at hospital, the effect being most marked in patients transported by ambulance (p<0. 001) and in those receiving nebulised beta(2) agonists prior to admission (p<0.005). However, 25% of patients arrived without having nebulised beta(2) agonists and 37% without having glucocorticoids. EEAAS patients were least likely to receive nebulised beta(2) agonists before arrival at hospital (p<0.05). This observation was attributable to a tendency for these patients to travel to hospital by car rather than by ambulance.There is an important shortfall in administration of bronchodilators and glucocorticoids for acute asthma before arrival at hospital. Ambulances equipped with nebulised bronchodilators provide the optimal mode of transport to hospital for patients with acute asthma. In Edinburgh ambulances are not being used by a significant proportion of the population with asthma, possibly because of the mistaken belief that personal transport arrangements reduce journey time to hospital.
Identification of the 37-kd rat liver protein that forms an acetaldehyde adductin vivo as ?4-3-ketosteroid 5?-reductase
Authors: Y Zhu, M J Fillenwarth, D Crabb, L Lumeng, R C Lin
Journal: Hepatology (1996)

Acetaldehyde, the first product of alcohol metabolism, is highly reactive. Several proteins have been shown to be covalently modified by acetaldehyde in vivo . We have previously reported the detection of a cytosolic 37-kd protein-acetaldehyde adduct (-AA) in the liver of alcohol-fed rats. The liver extract from an alcohol-fed rat was subjected to 2-dimensional (2D) sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), transferred to polyvinylidene difluoride (PVDF) membrane, and the 37-kd protein-AA spot was digested with trypsin and sequenced for amino acids. Degenerate oligonucleotides corresponding to a peptide sequence of the protein-AA were used as the probe to screen a λ gt11 rat liver complementary DNA (cDNA) library. A clone that extended to a potential ATG start codon was identified. The open reading frame was 978 nucleotides long, encoding 326 amino acid residues. The sequence matched that of rat liver Δ 4 -3-ketosteroid 5β-reductase. The cloned cDNA was expressed in Escherichia coli using pGEX-KG as the vector. The expressed protein was found to be of correct molecular weight. It reacted with an antibody that recognized the unmodified liver 37-kd protein by Western blotting. Peptide profiles of tryptic- digested recombinant protein and the purified rat liver 37-kd protein were similar and yielded the same peptide sequence. Δ 4-3-ketosteroid 5β-reductase catalyzes the reduction of key intermediates during bile acid biosynthesis. Whether modification of the 5β-reductase by acetaldehyde affects the enzyme activity and bile acid synthesis remains to be studied.
Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14
Authors: P. St George-Hyslop, J. Haines, E. Rogaev, M. Mortilla, G. Vaula, M. Pericak-Vance, J-F Foncin, M. Montesi, A. Bruni, S. Sorbi, I. Rainero, L. Pinessi, D. Pollen, R. Polinsky, L. Nee, J. Kennedy, F. Macciardi, E. Rogaeva, Y. Liang, N. Alexandrova, W. Lukiw, K. Schlumpf, R. Tanzi, T. Tsuda, L. Farrer, J-M Cantu, R. Duara, L. Amaducci, L. Bergamini, J. Gusella, A. Roses, D. Crapper McLachlan
Journal: Nature Genetics (1992)
Methotrexate Therapy for Psoriasis
Authors: Alan Menter
Journal: JAMA (1988)

To the Editor.—  In the June 24 issue ofTHE JOURNAL, two cases of pancytopenia related to low-dose methotrexate therapy for psoriasis were reported.1The opening paragraph of this report has the following sentence: With the exception of the need for periodic biopsy of the liver and the avoidance of alcohol,1it is a simple, easily complied-with regimen for often disabling disease. This is misleading and a major oversimplification of the care needed, both by physician and patient, in using this potentially dangerous drug. In reviewing the two patients' case reports, we were struck by the fact that neither should have continued or possibly even been given methotrexate therapy. The first patient continued to have ... mild thrombocytopenia in temporal relation to methotrexate therapy on several occasions, suggesting a possibly idiosyncratic response to methotrexate. The second patient's medical history was ... notable for alcoholic liver disease.  As discussed in the
The Baltic states: building on 20 years of health reforms
Authors: E. van Ginneken, J. Habicht, L. Murauskiene, D. Behmane, P. Mladovsky
Journal: BMJ (2012)

The Baltic States are recovering from a crisis as deep as Greece’s. Van Ginneken and colleagues suggest that the crisis has provided an opportunity to improve efficiency and equity, although concerns about financial sustainability and the impact on public health remain
14 Development of an animal model for autoimmune hepatitis: breaking of self-tolerance in the CYP2D6 humanized mouse by viral infection
Authors: U CHRISTEN, A RHODE, E JOHNSON, M MANNS, M VONHERRATH
Journal: Hepatology (2003)

Vaccines aiming to activate cytotoxic T cells require cross-presentation of exogenous antigen by antigen-presenting cells (APCs). We recently developed a synthetic nanoparticle vaccine platform that targets lymph node-resident dendritic cells (DCs), capable of mounting an immune response to conjugated antigen. Here, we explore routes of processing and the efficiency of MHC I cross-presentation of OVA peptides conjugated using both reducible and non-reducible linkages, exploring the hypothesis that reduction-sensitive conjugation will lead to better antigen cross-presentation. Both clathrin and macropinocytic pathways were implicated in nanoparticle uptake by colocalization and inhibitor studies. Cross-presentation by DCs was demonstrated by direct antibody staining and in vitro stimulation of CD8+ T cells from OT-I mice and was indeed most efficient with the reduction-sensitive conjugation. Similarly, we observed IFN-γ production by CD4+ T cells from OT-II mice. Finally, immunization with the OVA peptide-bearing nanoparticles resulted in in vivo proliferation and IFN-γ production by adoptively transferred CD8+ OT-I T cells and was also most efficient with reduction-sensitive linking of the peptide antigen. These results demonstrate the relevance of the poly(propylene sulfide) nanoparticle vaccine platform and antigen conjugation scheme for activating both cytotoxic and helper T cell responses.
Apparent haematuria: an early sign in polymyositis
Authors: R. Lim, J. L W Parker
Journal: BMJ (1988)

Myoglobin, the protein containing haem, is released from striated muscle in conditions causing rhabdomyolysis.The myoglobinuria which may follow may be recognisable as dark urine and causes a Apparent haematuriain a flu-lik positive reaction on reagent strip testing for blood.We report three sign of polymyositis in the subcl cases in which this phenomenon featured prominently in the earlier diagnosis and treatment presentation of dermatomyositis, a subset of polymyositis with characteristic skin lesions. Case 1Three months before admission a 20 year old man noticed reddening of his knuckles followed a month later by difficulty in climbing stairs.He attended his general practitioner a month afterwards when he thought he was passing blood in his urine.Reagent strip testing gave a positive result.He remained under observation until he developed generalised aches and pains, headache, malaise, and progressive symmetrical limb weakness four weeks later, when viral illness was diagnosed.Mild dysphagia and a rash ensued, leading to his admission.Examination showed erythematous plaques on knuckles, elbows, and knees and a diffuse erythematous rash on his face and trunk.Muscle tenderness was present but not wasting.Proximal muscles were weaker than distal.Peak expiratory flow rate was 550 1/min.Urine testing with Multistix yielded 4+ blood and 2+ protein.Microscopy of fresh urine showed 3+ granular casts but no erythrocytes; culturing showed no pathogens.Myoglobin, however, was detected.Plasma urea and electrolyte values were normal.Antinuclear factor was present at a titre of 1/1280 but DNA binding was normal.Taken together with the classical clinical picture, a serum creatine phosphokinase activity of 38 680 IU/l (normal <200) was considered to confirm the diagnosis of dermatomyositis.Chemotherapy consisted of prednisolone 120 mg/day plus azathioprine 150 mg/day, boosted by three days of intravenous methylprednisolone 1 g/day and a further three days of intravenous cyclophosphamide 150 mg daily when his cough weakened considerably and his peak expiratory flow rate dropped to 200 1/min with pronounced fatigability.Improvement was marginal but enough to avert the need for assisted ventilation.Five months after admission and despite prednisolone 90 mg plus azathioprine 150 mg daily he was still having difficulty going up and down stairs and sitting up unaided.His serum creatine phosphokinase activitv was 525 IU/I. Case 2A 55 year old man presented with a history of maculopapular rash for four months; pain, stiffness, and swelling of knees and shoulders for two months; myalgia and weakness for one month; and dark brown, frothy urine for three weeks.There was periorbital oedema, periungual erythema, and an erythematous rash on the trunk and upper arms, which were wasted.Muscle power was graded 3/5 proximally and 4/5 distally in the arms and 2/5 proximally and 3/5 distally in the legs.He could barely lift his head or sit