tbuckley/cabot-search huggingface dataset:
RELATION BETWEEN EPSTEIN-BARR VIRAL AND CELL MEMBRANE IMMUNOFLUORESCENCE OF BURKITT TUMOR CELLS
Authors: G. Klein, G. Pearson, J. S. Nadkarni, J. J. Nadkarni, E. Klein, G. Henle, W. Henle, P. Clifford
Journal: The Journal of Experimental Medicine (1968)

A comparison was made of the immunofluorescence tests for detection of cell membrane and Epstein-Barr virus antigens in cells from Burkitt tumor biopsies or continuous cultures derived therefrom. On the whole, cell membrane fluorescence in established lines appeared to depend not only upon the presence of EBV but to a considerable degree also upon the extent of the persistent viral infection. There was no constant relationship, however, between the results of the two tests and exceptions to the rule were noted. These observations indicate that different antigens are involved in the two tests. Biopsy cells in general and young cultures may reveal strong MIF activity but few, if any, EBV-positive cells. The reverse, the presence of relatively large numbers of EBV antigen-containing cells in the absence of significant MIF reactions, was also noted on occasion in a few established cultures. The possible interpretations of these findings have been discussed.
Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria
Authors: Katharina Hopp, Andrea G. Cogal, Eric J. Bergstralh, Barbara M. Seide, Julie B. Olson, Alicia M. Meek, John C. Lieske, Dawn S. Milliner, Peter C. Harris
Journal: Journal of the American Society of Nephrology (2015)

Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.
IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells
Authors: Xiaoli Chen, Junke Zheng, Yizhou Zou, Chun Song, Xuemei Hu, Cheng Cheng Zhang
Journal: Journal of Hematology & Oncology (2013)

Abstract Background The role of IGF binding protein 2 (IGFBP2) in cancer development is intriguing. Previously we identified IGFBP2 as an extrinsic factor that supports the activity of hematopoietic stem cells (HSCs). Methods and results Here we investigated the role of IGFBP2 in in human leukemia cells and in the retroviral AML1-ETO9a transplantation acute myeloid leukemia (AML) mouse model. Results IGFBP2 is highly expressed in certain human AML and acute lymphoblastic leukemia (ALL) cells. Inhibition of expression of endogenous IGFBP2 in human leukemia cells led to elevated apoptosis and decreased migration and, consistently, to decreased activation of AKT and other signaling molecules. We also studied the effects of IGFBP2 knockout in the retroviral AML1-ETO9a transplantation AML mouse model. The deletion of IGFBP2 in donor AML cells significantly decreased leukemia development in transplanted mice. Lack of IGFBP2 resulted in upregulation of PTEN expression and downregulation of AKT activation, in the mouse AML cells. The treatment of IGFBP2 deficient AML cells with a PTEN inhibitor restored the wild-type colony forming ability. The deletion of IGFBP2 also led to decreased AML infiltration into peripheral organs and tissues, suggesting that IGFBP2 is required for the migration of AML cells out of bone marrow. Conclusion IGFBP2 is a critical cell-autonomous factor that promotes the survival and migration of acute leukemia cells.
HIV and decontamination procedures.
Authors: E. M. Cooke
Journal: BMJ (1989)

tenderness of the scalp (for example, when brushing hair), general malaise, and exquisite pain on palpation over the temporal artery.If temporal arteritis is suspected and especially if the erythrocyte sedimentation rate is increased prednisolone 60 mg or intravenous steroids, or both, should be given immediately as delay may result in blindness.Metabolic causes of headache are rare, but the morning headache ofsleep apnoea is becoming increasingly recognised.Daytime sleeping and disturbed sleep with snoring in the presence of obesity and respiratory disease suggest sleep apnoea.The diagnosis requires nocturnal monitoring of the blood gas tensions, and treatment is directed at the underlying cause.Cranial neuralgias, nerve trunk pain, and the pain of deafferentiation may be distinguished from other headaches by the distribution of pain along specific cranial nerves.Other signs of cranial nerve disease -for example, optic neuritis and the Tolosa-Hunt syndrome (granulomatous angiitis causing painful ophthalmoplegia) -may be found.Neuralgias need not be accompanied by signs-for example, trigeminal and glossopharyngeal neuralgia.Abnormal signs should always be investigated.Trigeminal neuralgia, a relapsing and remitting disorder, is best treated for as long as possible with drugs, carbamazepine being the best.'Its dose may be increased to the maximum tolerated and in resistant cases phenytoin added.Surgery may be needed, and in this case radio frequency rhizotomy is probably the best treatment.
Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosing spondylitis after treatment with infliximab
Authors: S Visvanathan, C Wagner, J C Marini, D Baker, T Gathany, J Han, D van der Heijde, J Braun
Journal: Annals of the Rheumatic Diseases (2007)

Objective: To evaluate the relationship between biomarker levels and disease activity and the spinal inflammation detected by magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS). Methods: Patients with AS were randomly assigned in a 3:8 ratio to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, 12 and 18. Sera were collected for biomarker analysis at weeks 0, 2 and 24 and were analysed for levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores and pre- and post-gadolinium T1 and short τ inversion recovery MRIs were collected at baseline and week 24. Results: Significantly greater reductions in IL-6, VEGF and CRP were observed at weeks 2 and 24 in the infliximab group compared with the placebo group (all p&lt;0.001). Baseline IL-6 levels &gt;7.38 pg/ml and CRP levels &gt;1.5 mg/dl were associated with increased rates of clinical response after 24 weeks. Multiple regression analyses showed that reductions from baseline to week 2 in IL-6, but not CRP or VEGF, were significantly associated with reductions in MRI activity and BASDAI scores from baseline to week 24 in the infliximab group (p&lt;0.001). Conclusions: Significant reductions in IL-6, VEGF and CRP were observed with infliximab compared with placebo. High levels of baseline IL-6 and CRP were associated with clinical response after infliximab treatment. Early reductions in IL-6 were significantly associated with improvements in disease activity and the spinal inflammation detected by MRI.
The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease
Authors: Jonathan H Fox, Teal Connor, Vanita Chopra, Kate Dorsey, Jibrin A Kama, Dorothee Bleckmann, Claudia Betschart, Daniel Hoyer, Stefan Frentzel, Marian DiFiglia, Paolo Paganetti, Steven M Hersch
Journal: Molecular Neurodegeneration (2010)

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD). In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD.Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels.Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.
Gender difference in jumping and landing among 15-18-year old icelandic national youth soccer players
Authors: H Magnúsdóttir, T Sveinsson, Á Árnason
Journal: British Journal of Sports Medicine (2011)

Background After puberty female athletes are in 2–7 times higher risk of tearing the anterior cruciate ligament as compared to males. Objective To compare following factors between 15 and 18 years boys and girls participating in soccer: 1) Vertical jump height. 2) Jump- and landing technique in drop jump. 3) EMG activity around the knee during jumping and landing. Design Observational, cross-sectional study. Setting National youth soccer teams in Iceland. Participants 20 boys and 17 girls, 15–18 years, from three soccer teams and also participating in Icelandic national youth soccer teams were invited to participate. Of these, 10 boys and 10 girls accepted participation and showed up for testing. Main outcome measurement (1) Jump height in counter movement jumps. (2) Degree of knee valgus during drop jumps. (3) EMG onset latency for five different muscles in each thigh during drop jumps. Results Boys jumped significantly higher than girls in countermovement jump (30.3±2.6 cm vs 22.6±3.8 cm, p&lt;0.001). In the drop jump, girls had significantly increased knee valgus compared to boys in three of five test points: when toes touch the floor (165.1±4.0° vs 168.7±4.1°, p=0.05), at 25% of the height from lowest position (163.3±6.4° vs 169.2±9.0°, p=0.013) and at toe off, when jumping up again (162.5±4.2° vs 167.2±4.4°, p=0.01). No difference was found for the lowest position or for 25% of the height from the lowest position to toe off. No gender difference was found for onset latencies of the leg muscles, except for right biceps femoris, where girls activated this muscle earlier before landing than boys (−0.31±0.39 vs −0.12±0.13, p&lt;0.001). Conclusion Boys jumped higher than girls. Girls had more knee valgus during landing, at 25% from the lowest position on the way down and, during toe off. No gender differences were found for muscle onset latencies except for one thigh muscle.
Protecting ischemic hearts by modulation of SR calcium handling
Authors: M TANNO, T MIURA
Journal: Cardiovascular Research (2007)

See article by Zhou et al.  [4]  (pages 487–497) in this issue. 

The sarcoplasmic reticulum (SR) plays a crucial role in excitation-contraction coupling by regulating the concentration and distribution of intracellular Ca2+. The functions of the SR are known to be compromised by ischemia/reperfusion, but whether SR dysfunction contributes to Ca2+ overload and injury in cardiomyocytes during ischemia/reperfusion has been controversial for a decade. Studies using isolated cardiomyocytes subjected to simulated ischemia/reperfusion generally support the role of the SR in Ca2+ overload at the time of “reperfusion” [1]. However, findings in earlier studies, which examined the effects of ischemia on the SR Ca2+ uptake and Ca2+ release using isolated SR preparations from whole hearts, are contradictory. A study by Chen et al. [2] assessed the Ca2+ concentration in the SR by 19F-NMR in isolated beating hearts and showed that it was well maintained during a 25-min period of ischemia, while the cytosolic Ca2+ level was significantly increased after the onset of ischemia. Furthermore, calculation of the free energy for Ca2+-ATPase and for ATP hydrolysis suggests that the … 

* Corresponding author. Tel.: +81 11 611 2111 ex2721; fax: +81 11 644 7958. tannom{at}sapmed.ac.jp
Amyotrophic Lateral Sclerosis Risk for Spinocerebellar Ataxia Type 2<i>ATXN2</i>CAG Repeat Alleles
Authors: Annalese G. Neuenschwander, Khanh K. Thai, Karla P. Figueroa, Stefan M. Pulst
Journal: JAMA Neurology (2014)

Repeats of CAG in the ataxin 2 gene (ATXN2) in the long-normal range (sometimes referred to as intermediate) have been identified as modifiers of amyotrophic lateral sclerosis (ALS) risk. Prior studies have used thresholding considering various cutoffs for ATXN2 repeat length.To calculate association between ATXN2 CAG repeat alleles and increased risk of ALS across multiple ethnic groups.The MEDLINE database was searched for studies published by December 29, 2013, reporting ATXN2 CAG repeat length in patients with ALS and controls.Studies were included if they reported original data on relative risks or odds ratios (ORs) from ALS and control populations for individual ATXN2 alleles. Review articles that reported no new data were not included in the analysis.Analysis of allele distribution was performed to ensure that all studies followed identical allele sizing. The ORs, 95% confidence intervals, and population attributable risk percentages were calculated according to standard procedures.Occurrence of ALS associated with ATXN2 repeat alleles, expressed as ORs.Nine studies were analyzed, including 7505 controls and 6151 sporadic ALS cases. The ALS and control cohorts were recruited from different geographical and ethnic regions including the United States, French Canada/Canada, Belgium and the Netherlands, Germany, Italy, mainland China, Turkey, and Flanders-Belgium. The ATXN2 CAG repeat lengths ranged from 13 to 39 in patients with ALS and from 13 to 34 in controls. The ORs were less than 1.00 for alleles with 25 to 28 repeats. The OR was 1.55 for 30 repeats, but this elevation was not statistically significant (95% CI, 0.88-2.73). The ORs were 2.70 (95% CI, 1.47-4.93) for 31 CAG repeats, 11.09 (95% CI, 4.16-29.57) for 32 repeats, and 5.76 (95% CI, 1.79-18.57) for 33 repeats.In contrast to prior studies with smaller numbers, risk for ALS associated with long-normal alleles is complex. Alleles with 27 and 28 repeats lower ALS risk slightly. The risk for ALS increases beginning with 29 repeats and reaches a maximum at 32 and 33 repeats. Of note, alleles with repeats of these lengths are known to be predisposed to meiotic expansion to full-penetrance mutant alleles. In patients with ALS, alleles with 31 to 33 repeats may have undergone preferential expansion in motor neurons during mitosis or DNA repair. Our meta-analysis provides a framework for counseling individuals with long-normal ATXN2 repeats.
Multiplatform genome-wide identification and modeling of functional human estrogen receptor binding sites.
Authors: Vinsensius B Vega, Chin-Yo Lin, Koon Siew Lai, Say Li Kong, Min Xie, Xiaodi Su, Huey Fang Teh, Jane S Thomsen, Ai Li Yeo, Wing Kin Sung, Guillaume Bourque, Edison T Liu
Journal: Genome biology (2006)

Transcription factor binding sites (TFBS) impart specificity to cellular transcriptional responses and have largely been defined by consensus motifs derived from a handful of validated sites. The low specificity of the computational predictions of TFBSs has been attributed to ubiquity of the motifs and the relaxed sequence requirements for binding. We posited that the inadequacy is due to limited input of empirically verified sites, and demonstrated a multiplatform approach to constructing a robust model.Using the TFBS for the estrogen receptor (ER)alpha (estrogen response element [ERE]) as a model system, we extracted EREs from multiple molecular and genomic platforms whose binding to ERalpha has been experimentally confirmed or rejected. In silico analyses revealed significant sequence information flanking the standard binding consensus, discriminating ERE-like sequences that bind ERalpha from those that are nonbinders. We extended the ERE consensus by three bases, bearing a terminal G at the third position 3' and an initiator C at the third position 5', which were further validated using surface plasmon resonance spectroscopy. Our functional human ERE prediction algorithm (h-ERE) outperformed existing predictive algorithms and produced fewer than 5% false negatives upon experimental validation.Building upon a larger experimentally validated ERE set, the h-ERE algorithm is able to demarcate better the universe of ERE-like sequences that are potential ER binders. Only 14% of the predicted optimal binding sites were utilized under the experimental conditions employed, pointing to other selective criteria not related to EREs. Other factors, in addition to primary nucleotide sequence, will ultimately determine binding site selection.
No Clinically Significant Association between CFH and ARMS2 Genotypes and Response to Nutritional Supplements
Authors: Emily Y. Chew, Michael L. Klein, Traci E. Clemons, Elvira Agrón, Rinki Ratnapriya, Albert O. Edwards, Lars G. Fritsche, Anand Swaroop, Gonçalo R. Abecasis
Journal: Ophthalmology (2014)
Additional Genetic High-Risk Features Such As 11q Deletion, 17p Deletion, and <i>V3-21</i> Usage Characterize Discordance of ZAP-70 and <i>VH</i> Mutation Status in Chronic Lymphocytic Leukemia
Authors: Alexander Kröber, Johannes Bloehdorn, Sebastian Hafner, Andreas Bühler, Till Seiler, Dirk Kienle, Dirk Winkler, Markus Bangerter, Richard F. Schlenk, Axel Benner, Peter Lichter, Hartmut Döhner, Stephan Stilgenbauer
Journal: Journal of Clinical Oncology (2006)

Immunoglobulin heavy chain variable-region (VH) gene mutation status and zeta-associated protein 70 (ZAP-70) expression are correlated in chronic lymphocytic leukemia (CLL), but their concordance is variable. The goal of this study was to elucidate additional factors potentially characterizing their discordance.We evaluated ZAP-70 expression by flow cytometry, VH status by DNA sequencing, and genomic aberrations by fluorescence in situ hybridization in 148 CLL patients. The parameters were analyzed for their associations and their individual prognostic impact.ZAP-70 expression and VH mutation status were strongly associated in CLL without additional genetic high-risk-features as defined by the absence of 11q or 17p deletion and V3-21 usage (concordance 84%). In contrast, the proportion of discordant cases was significantly higher (39%), if such additional genetic high-risk features were present. Discordant cases with V3-21 usage were almost exclusively ZAP-70 positive and VH mutated (89%), whereas all but one of the discordant cases with high-risk aberrations were ZAP-70 negative and VH unmutated (92%). By multivariate regression analysis, two models were developed, which both include high-risk genomic aberrations and, alternatively, VH mutation status and V3-21 usage or ZAP-70 expression as independent outcome predictors.There were characteristic modes of discordance between ZAP-70 and VH mutation status depending on the presence or absence of additional genetic high-risk features such as 11q and 17p deletion or V3-21 usage. Although the biologic background for these findings is yet to be determined, these data have biologic and clinical implications regarding ZAP-70 as a pathogenic factor and outcome predictor, respectively.
(28) Variegate porphyria
Authors: D.M. Williamson
Journal: British Journal of Dermatology (1987)

Journal Article (28) Variegate porphyria Get access D.M. Williamson D.M. Williamson Pontefract General Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue s32, 1 June 1987, Pages 77–78, https://doi.org/10.1111/j.1365-2133.1987.tb12068.x Published: 01 June 1987
Hypoxia-Induced Autophagy Promotes Tumor Cell Survival and Adaptation to Antiangiogenic Treatment in Glioblastoma
Authors: Yu-Long Hu, Michael DeLay, Arman Jahangiri, Annette M. Molinaro, Samuel D. Rose, W. Shawn Carbonell, Manish K. Aghi
Journal: Cancer Research (2012)

Antiangiogenic therapy leads to devascularization that limits tumor growth. However, the benefits of angiogenesis inhibitors are typically transient and resistance often develops. In this study, we explored the hypothesis that hypoxia caused by antiangiogenic therapy induces tumor cell autophagy as a cytoprotective adaptive response, thereby promoting treatment resistance. Hypoxia-induced autophagy was dependent on signaling through the hypoxia-inducible factor-1α (HIF-1α)/AMPK pathway, and treatment of hypoxic cells with autophagy inhibitors caused a shift from autophagic to apoptotic cell death in vitro. In glioblastomas, clinically resistant to the VEGF-neutralizing antibody bevacizumab, increased regions of hypoxia and higher levels of autophagy-mediating BNIP3 were found when compared with pretreatment specimens from the same patients. When treated with bevacizumab alone, human glioblastoma xenografts showed increased BNIP3 expression and hypoxia-associated growth, which could be prevented by addition of the autophagy inhibitor chloroquine. In vivo targeting of the essential autophagy gene ATG7 also disrupted tumor growth when combined with bevacizumab treatment. Together, our findings elucidate a novel mechanism of resistance to antiangiogenic therapy in which hypoxia-mediated autophagy promotes tumor cell survival. One strong implication of our findings is that autophagy inhibitors may help prevent resistance to antiangiogenic therapy used in the clinic.
RGS2 is an important target gene of Flt3-ITD mutations in AML and functions in myeloid differentiation and leukemic transformation
Authors: Joachim Schwäble, Chunaram Choudhary, Christian Thiede, Lara Tickenbrock, Bülent Sargin, Claudia Steur, Maike Rehage, Annika Rudat, Christian Brandts, Wolfgang E. Berdel, Carsten Müller-Tidow, Hubert Serve
Journal: Blood (2004)