tbuckley/cabot-search huggingface dataset:
Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central Nervous System Lymphomas
Authors: Esteban Braggio, Scott Van Wier, Juhi Ojha, Ellen McPhail, Yan W. Asmann, Jan Egan, Jackline Ayres da Silva, David Schiff, M. Beatriz Lopes, Paul A. Decker, Riccardo Valdez, Raoul Tibes, Bruce Eckloff, Thomas E. Witzig, A. Keith Stewart, Rafael Fonseca, Brian Patrick O'Neill
Journal: Clinical Cancer Research (2015)

Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the central nervous system. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain.We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing.Biallelic inactivation of TOX and PRKCD was recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role in PCNSL pathogenesis. In addition, we found a high prevalence of MYD88 mutations (79%) and CDKN2A biallelic loss (60%). Several genes recurrently affected in PCNSL were common with systemic DLBCL, including loss of TNFAIP3, PRDM1, GNA13, TMEM30A, TBL1XR1, B2M, CD58, activating mutations of CD79B, CARD11, and translocations IgH-BCL6. Overall, B-cell receptor/Toll-like receptor/NF-κB pathways were altered in >90% of PNCSL, highlighting its value for targeted therapeutic approaches. Furthermore, integrated analysis showed enrichment of pathways associated with immune response, proliferation, apoptosis, and lymphocyte differentiation.In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas.
Polycystin-1 maturation requires polycystin-2 in a dose-dependent manner
Authors: Vladimir G. Gainullin, Katharina Hopp, Christopher J. Ward, Cynthia J. Hommerding, Peter C. Harris
Journal: Journal of Clinical Investigation (2015)

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited nephropathy responsible for 4%-10% of end-stage renal disease cases. Mutations in the genes encoding polycystin-1 (PC1, PKD1) or polycystin-2 (PC2, PKD2) cause ADPKD, and PKD1 mutations are associated with more severe renal disease. PC1 has been shown to form a complex with PC2, and the severity of PKD1-mediated disease is associated with the level of the mature PC1 glycoform. Here, we demonstrated that PC1 and PC2 first interact in the ER before PC1 cleavage at the GPS/GAIN site and determined that PC2 acts as an essential chaperone for PC1 maturation and surface localization. The chaperone function of PC2 was dependent on the presence of the distal coiled-coil domain and was disrupted by pathogenic missense mutations. In Pkd2-/- mice, complete loss of PC2 prevented PC1 maturation. In Pkd2 heterozygotes, the 50% PC2 reduction resulted in a nonequimolar reduction (20%-25%) of the mature PC1 glycoform. Interbreeding between various Pkd1 and Pkd2 models revealed that animals with reduced levels of functional PC1 and PC2 in the kidney exhibited severe, rapidly progressive disease, illustrating the importance of complexing of these proteins for function. Our results indicate that PC2 regulates PC1 maturation; therefore, mature PC1 levels are a determinant of disease severity in PKD2 as well as PKD1.
Impact of Intravenous Thrombolysis on Short-term Coronary Revascularization Rates
Authors: C D Naylor, S B Jaglal
Journal: JAMA (1990)

Evidence of the potential impact of intravenous thrombolytic therapy on short-term revascularization rates among patients with acute myocardial infarction was sought. Because nonrandomized comparisons with conventional treatment would be subject to various confounders, a meta-analysis of randomized controlled trials was performed. Seven trials were included, applying standard doses of either tissue plasminogen activator or streptokinase without an aggressive revascularization protocol. Follow-up ranged from 14 to 30 days. The revascularization rates among treated patients in all trials were lower than in the conservative arm of the Thrombolysis in Myocardial Infarction Phase II trial, which established the current procedural benchmarks for postthrombolysis management. However, the aggregate volume of bypass surgery and angioplasty in patients treated with tissue plasminogen activator was more than double that of controls (odds ratio, 2.25; 95% confidence interval, 1.31 to 3.94), with a smaller but still significant increase for streptokinase-treated patients (odds ratio, 1.66; 95% confidence interval, 1.08 to 2.59). Combining all trials, the increase in mechanical revascularization was 80% (95% confidence interval, 33% to 144%). Thus, for patterns of practice currently accepted in North America, intravenous thrombolysis for myocardial infarction leads to a significant short-term increase in clinical and angiographic indications for revascularization as compared with conventional treatment. (<i>JAMA</i>. 1990;264:697-702)
Differentiation between traumatic tap and aneurysmal subarachnoid hemorrhage: prospective cohort study
Authors: J. J. Perry, B. Alyahya, M. L. A. Sivilotti, M. J. Bullard, M. Emond, J. Sutherland, A. Worster, C. Hohl, J. S. Lee, M. A. Eisenhauer, M. Pauls, H. Lesiuk, G. A. Wells, I. G. Stiell
Journal: BMJ (2015)

Objectives To describe the findings in cerebrospinal fluid from patients with acute headache that could distinguish subarachnoid hemorrhage from the effects of a traumatic lumbar puncture. Design A substudy of a prospective multicenter cohort study. Setting 12 Canadian academic emergency departments, from November 2000 to December 2009. Participants Alert patients aged over 15 with an acute non-traumatic headache who underwent lumbar puncture to rule out subarachnoid hemorrhage. Main outcome measure Aneurysmal subarachnoid hemorrhage requiring intervention or resulting in death. Results Of the 1739 patients enrolled, 641 (36.9%) had abnormal results on cerebrospinal fluid analysis with >1×106/L red blood cells in the final tube of cerebrospinal fluid and/or xanthochromia in one or more tubes. There were 15 (0.9%) patients with aneurysmal subarachnoid hemorrhage based on abnormal results of a lumbar puncture. The presence of fewer than 2000×106/L red blood cells in addition to no xanthochromia excluded the diagnosis of aneurysmal subarachnoid hemorrhage, with a sensitivity of 100% (95% confidence interval 74.7% to 100%) and specificity of 91.2% (88.6% to 93.3%). Conclusion No xanthochromia and red blood cell count <2000×106/L reasonably excludes the diagnosis of aneurysmal subarachnoid hemorrhage. Most patients with acute headache who meet this cut off will need no further investigations and aneurysmal subarachnoid hemorrhage can be excluded as a cause of their headache.
Optimization and clinical validation of a pathogen detection microarray
Authors: Christopher W Wong, Charlie Lee Wah Heng, Leong Wan Yee, Shirlena WL Soh, Cissy B Kartasasmita, Eric AF Simoes, Martin L Hibberd, Wing-Kin Sung, Lance D Miller
Journal: Genome biology (2007)

Abstract DNA microarrays used as 'genomic sensors' have great potential in clinical diagnostics. Biases inherent in random PCR-amplification, cross-hybridization effects, and inadequate microarray analysis, however, limit detection sensitivity and specificity. Here, we have studied the relationships between viral amplification efficiency, hybridization signal, and target-probe annealing specificity using a customized microarray platform. Novel features of this platform include the development of a robust algorithm that accurately predicts PCR bias during DNA amplification and can be used to improve PCR primer design, as well as a powerful statistical concept for inferring pathogen identity from probe recognition signatures. Compared to real-time PCR, the microarray platform identified pathogens with 94% accuracy (76% sensitivity and 100% specificity) in a panel of 36 patient specimens. Our findings show that microarrays can be used for the robust and accurate diagnosis of pathogens, and further substantiate the use of microarray technology in clinical diagnostics.
B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue
Authors: H S Carlsen
Journal: Gut (2002)

<b>Background and aims:</b> In mice, the B lymphocyte chemoattractant (BLC) CXC chemokine ligand 13 (CXCL13) is sufficient to induce a series of events leading to the formation of organised lymphoid tissue. Its receptor, CXCR5, is required for normal development of secondary lymphoid tissue. However, the human counterpart, B cell attracting chemokine 1 (BCA-1) has only been detected in the stomach and appendix and not in other parts of normal or diseased gut. Hence to elucidate the potential role of this chemokine and its receptor in human gut associated lymphoid tissue (GALT), we analysed their expression in normal intestine and ulcerative colitis (UC). <b>Methods:</b> Frozen sections of surgical specimens were studied by multicolour immunofluorescence staining, in situ mRNA hybridisation, and reverse transcription-polymerase chain reaction. <b>Results:</b> BCA-1 mRNA was detected in all normal colonic and UC specimens. BCA-1 was produced and accumulated in relation to peripheral dendritic elements of lymphoid follicles in Peyer9s patches and normal colon, as well as in irregular lymphoid aggregates in UC lesions. BCA-1 was partially associated with the traditional follicular dendritic cell phenotype but also with extracellular fibrils in GALT structures. CXCR5 protein was expressed by mantle zone B cells and appeared at a high level on scattered germinal centre T cells. <b>Conclusions:</b> BCA-1 and CXCR5 are expressed in normal GALT structures as well as in irregular lymphoid aggregates in UC. This strongly suggests that BCA-1 plays an important role not only in the formation of normal GALT but also in the generation of aberrant lymphoid tissue in inflammatory bowel disease.
Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit
Authors: Charles G. Lo, Ying Xu, Richard L. Proia, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2005)

Sphingosine-1-phosphate receptor 1 (S1P1) was recently shown to be required for lymphocyte egress from lymphoid organs. Here we have examined the relationship between S1P1 abundance on the cell and egress efficiency. Using an integrin neutralization approach to separate the processes of entry and exit, we show that pertussis toxin treatment reduces lymphocyte egress from lymph nodes. Retrovirally mediated S1P1 overexpression is sufficient to reduce B cell accumulation in the splenic white pulp and to promote egress of activated T cells from lymph nodes, whereas S1P1+/−cells have reduced lymph node exit efficiency. Furthermore, lymphocyte S1P1 is down-regulated in the blood, up-regulated in lymphoid organs, and down-regulated again in the lymph. We propose that cyclical ligand-induced modulation of S1P1 on circulating lymphocytes contributes to establishing their lymphoid organ transit time.
Autoantibodies to inner ear and endothelial antigens in Cogan's syndrome
Authors: Claudio Lunardi, Caterina Bason, Massimo Leandri, Riccardo Navone, Maurizio Lestani, Enrico Millo, Umberto Benatti, Michele Cilli, Ruggero Beri, Roberto Corrocher, Antonio Puccetti
Journal: The Lancet (2002)
Association between sibship size and allergic diseases in the Glasgow Alumni Study
Authors: S Kinra
Journal: Thorax (2005)

<b>Background:</b> Recent epidemiological studies consistently report an inverse association between sibship size and allergic disease, but evidence from individuals born before the 1980s is inconsistent. As information on relative permanence of this finding may offer clues to its biological explanation, the association between sibship size and allergic disease in individuals born between 1918 and 1952 was investigated. <b>Methods:</b> Cross sectional surveys conducted by the Student Health Service at the University of Glasgow (1948–68) provided data on 14 140 men and women aged 16–30 years at the time of examination. The main outcome measures studied were self-reported asthma, eczema-urticaria, and hay fever. <b>Results:</b> A total of 1677 individuals (11.9%) provided a positive history of at least one of the three allergic diseases: 457 (3.2%) asthma, 594 (4.2%) eczema-urticaria, and 885 (6.3%) hay fever. Compared with those without siblings (reference odds ratio = 1), the odds ratios (95% confidence intervals) for having any allergic disease among those with one, two or three siblings were 0.86 (0.75 to 0.99), 0.80 (0.69 to 0.93), and 0.70 (0.60 to 0.83), respectively (p<sub>trend</sub>&lt;0.001). Increasing birth order and low socioeconomic position in childhood were associated with a lower risk of allergy. Adjustment for birth order, year of birth, age, sex, socioeconomic position in childhood, and family history of allergy did not materially alter the results. <b>Conclusions:</b> There is a robust inverse association between sibship size and allergic disease even among people born in the first half of the 20th century. These results favour relatively time-independent explanations for this phenomenon (such as the hygiene hypothesis or parity related changes in the intrauterine environment) over new environmental exposures.
Balancing the risk of injury to gymnasts: how effective are the counter measures?
Authors: R M Daly, S L Bass, C F Finch
Journal: British Journal of Sports Medicine (2001)

To minimise injury risk and maximise gymnastics performance, coaches, parents, and health professionals working with young gymnasts need to understand and practise safe gymnastics.To (a) identify the various injury counter measures specific to gymnastics, (b) critically review the literature describing each injury prevention measure, and (c) assess, using available risk factor and injury data, the weight of evidence to support each of these counter measures. Specific recommendations for further research and implementation strategies to prevent injury and improve safety are also given.The relevant literature was identified through the use of Medline (1966 to May 1998) and SPORT Discus (1975 to May 1998) searches, hand searching of journals and reference lists, and discussions with key Australian gymnastics organisations.The key gymnastics injury counter measures identified in this review include coaching (physical preparation, education, spotting, and performance technique), equipment, and the health support system (medical screening, treatment, and rehabilitation). Categorisation of the type of evidence for the effectiveness of each of these counter measures in preventing injury showed that most of it is based on informal opinion/anecdotal evidence, uncontrolled data based studies, and several prospective epidemiological studies. There is no evidence from formally controlled trials or specific evaluation studies of counter measures for gymnastics.Although gymnastics is a sport associated with young participants and frequent high volume, high impact training, there is a paucity of information on injury risk factors and the effectiveness of injury practices. Further controlled trials are needed to examine the extent to which injury prevention counter measures can prevent or reduce the occurrence of injury and re-injury. Particular attention should be devoted to improving training facilities, the design and testing of apparatus and personal equipment used by gymnasts, and coaching and the role of spotting in preventing injury.
Rheumatoid and psoriatic knee synovitis: clinical, grey scale, and power Doppler ultrasound assessment of the response to etanercept
Authors: U Fiocco
Journal: Annals of the Rheumatic Diseases (2004)

To determine the effect of tumour necrosis factor alpha (TNFalpha) blockade with etanercept in refractory knee joint synovitis (KJS) in rheumatoid and psoriatic arthritis, by local and systemic disease activity assessment and combined grey scale and power Doppler ultrasonographic monitoring.27 knees affected by rheumatoid KJS (n = 12) and psoriatic KJS (n = 8) were assessed before receiving treatment and at 3 and 12 months' follow up. Time dependent clinical changes in disease activity were monitored by C reactive protein, erythrocyte sedimentation rate (ESR), global health status (GHS), and Ritchie (RAI) and knee joint articular (KJAI) indices; synovial changes were monitored by ultrasonographic and power Doppler indices for grey scale synovial thickening and for distinct intrasynovial vessel power Doppler flow configurations (fluid/synovium interface (F/SI-PD) and pannus/cartilage interface (P/CI-PD)). Interobserver and intraobserver variability of grey scale and power Doppler ultrasonographic was evaluated. Response to treatment was assessed by analysis of variance for repeated measures on clinical and ultrasonographic variables.Rapid (3 months) reduction in F/SI-PD flow (p<0.001), parallel to reductions of C reactive protein (p<0.05), ESR (p<0.001), KJAI (p<0.002), RAI, and GHS (p<0.001), was sustained at 12 months when it was accompanied by reduction in both synovial thickening and P/CI-PD flow (p<0.001). No differences (ANOVA) were noted at baseline or at 12 months in clinical and ultrasonographic variables between either the rheumatoid or the psoriatic KJS groups.Grey scale and power Doppler ultrasonography are reliable measures of long term change in rheumatoid and psoriatic KJS disease activity in response to anti-TNFalpha treatment with etanercept.
ACTIVATION OF PROFIBRINOLYSIN BY ANTIGEN-ANTIBODY REACTION AND BY ANAPHYLACTOID AGENTS; ITS RELATION TO COMPLEMENT
Authors: Georges Ungar, Evelyn Damgaard, Fred P. Hummel
Journal: The Journal of Experimental Medicine (1953)

The activation of profibrinolysin in sensitized guinea pig serum when mixed in vitro with the homologous antigen was confirmed with a more accurate and more reliable method than the one previously used. A study was made of some of the conditions required for obtaining maximum activation. Profibrinolysin activation was also induced in normal guinea pig serum by addition of certain "anaphylactoid" agents such as peptone, tween 20, morphine, octylamine, octadecylamine, and 48/80. The specific antigen and the anaphylactoid agents produce activation only when added to whole, fresh, unheated serum. Profibrinolysin activation by these agents, as opposed to activation by streptokinase, seems to require the intervention of a kinase system (serofibrinokinase) inactivated by fractionation of serum and by heating to 56 degrees C. Whenever serum was submitted to treatments which caused fractionation, fixation or inhibition of complement, serofibrinokinase was also inactivated. Under the conditions investigated the behavior of this kinase was indistinguishable from that of complement.
An oncologist-based model of cancer genetic counselling for hereditary breast and ovarian cancer
Authors: A. Contegiacomo, M. Pensabene, I. Capuano, L. Tauchmanova, M. Federico, D. Turchetti, L. Cortesi, P. Marchetti, E. Ricevuto, G. Cianci, S. Venuta, V. Barbieri, V. Silingardi
Journal: Annals of Oncology (2004)
Staphylococcal infection of a left ventricular aneurysm.
Authors: I R Starkey, D K Kaplan, J A Thorpe
Journal: Thorax (1986)

Left ventricular aneurysm formation is a common complication of myocardial infarction. Depending on the definition used, the incidence in survivors of acute myocardial infarction is between 4% and 40%, with mural thrombi present in about half of all aneurysms. Infection of these thrombi at times of bacteraemia might be expected to occur quite commonly but has been described only occasionally. We present such a case and review previously reported cases.
AZD1152, a Selective Inhibitor of Aurora B Kinase, Inhibits Human Tumor Xenograft Growth by Inducing Apoptosis
Authors: Robert W. Wilkinson, Rajesh Odedra, Simon P. Heaton, Stephen R. Wedge, Nicholas J. Keen, Claire Crafter, John R. Foster, Madeleine C. Brady, Alison Bigley, Elaine Brown, Kate F. Byth, Nigel C. Barrass, Kirsten E. Mundt, Kevin M. Foote, Nicola M. Heron, Frederic H. Jung, Andrew A. Mortlock, F. Thomas Boyle, Stephen Green
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In the current study, we examined the in vivo effects of AZD1152, a novel and specific inhibitor of Aurora kinase activity (with selectivity for Aurora B). Experimental Design: The pharmacodynamic effects and efficacy of AZD1152 were determined in a panel of human tumor xenograft models. AZD1152 was dosed via several parenteral (s.c. osmotic mini-pump, i.p., and i.v.) routes. Results: AZD1152 potently inhibited the growth of human colon, lung, and hematologic tumor xenografts (mean tumor growth inhibition range, 55% to ≥100%; P &amp;lt; 0.05) in immunodeficient mice. Detailed pharmacodynamic analysis in colorectal SW620 tumor-bearing athymic rats treated i.v. with AZD1152 revealed a temporal sequence of phenotypic events in tumors: transient suppression of histone H3 phosphorylation followed by accumulation of 4N DNA in cells (2.4-fold higher compared with controls) and then an increased proportion of polyploid cells (&amp;gt;4N DNA, 2.3-fold higher compared with controls). Histologic analysis showed aberrant cell division that was concurrent with an increase in apoptosis in AZD1152-treated tumors. Bone marrow analyses revealed transient myelosuppression with the drug that was fully reversible following cessation of AZD1152 treatment. Conclusions: These data suggest that selective targeting of Aurora B kinase may be a promising therapeutic approach for the treatment of a range of malignancies. In addition to the suppression of histone H3 phosphorylation, determination of tumor cell polyploidy and apoptosis may be useful biomarkers for this class of therapeutic agent. AZD1152 is currently in phase I trials.
The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans
Authors: Tyl H. Taylor, Susan A. Gitlin, Jennifer L. Patrick, Jack L. Crain, J. Michael Wilson, Darren K. Griffin
Journal: Human Reproduction Update (2014)

Chromosomal mosaicism, the presence of two or more distinct cell lines, is prevalent throughout human pre- and post-implantation development and can lead to genetic abnormalities, miscarriages, stillbirths or live births. Due to the prevalence and significance of mosaicism in the human species, it is important to understand the origins, mechanisms and incidence of mosaicism throughout development.Literature searches were conducted utilizing Pubmed, with emphasis on human pre- and post-implantation mosaicism.Mosaicism persists in two separate forms: general and confined. General mosaicism is routine during human embryonic growth as detected by preimplantation genetic screening at either the cleavage or blastocyst stage, leading to mosaicism within both the placenta and fetus proper. Confined mosaicism has been reported in the brain, gonads and placenta, amongst other places. Mosaicism is derived from a variety of mechanisms including chromosome non-disjunction, anaphase lagging or endoreplication. Anaphase lagging has been implicated as the main process by which mosaicism arises in the preimplantation embryo. Furthermore, mosaicism can be caused by any one of numerous factors from paternal, maternal or exogenous factors such as culture media or possibly controlled ovarian hyperstimulation during in vitro fertilization (IVF). Mosaicism has been reported in as high as 70 and 90% of cleavage- and blastocyst-stage embryos derived from IVF, respectively.The clinical consequences of mosaicism depend on which chromosome is involved, and when and where an error occurs. Mitotic rescue of a meiotic error or a very early mitotic error will typically lead to general mosaicism while a mitotic error at a specific cell lineage point typically leads to confined mosaicism. The clinical consequences of mosaicism are dependent on numerous aspects, with the consequences being unique for each event.