tbuckley/cabot-search huggingface dataset:
Isolated oculomotor nerve palsy from minor head trauma: Figure 1
Authors: C-C Chen, Y-M Pai, R-F Wang, T-L Wang, C-F Chong
Journal: British Journal of Sports Medicine (2005)

Isolated third cranial nerve palsies in head trauma patients can be the result of direct or indirect damage to the oculomotor nerve. They are usually associated with severe head trauma. We reported a case of isolated oculomotor nerve palsy associated with minor head injury. No initial loss of consciousness was recalled. Computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) of the brain were normal. Previous reports in the literature were reviewed and the possible mechanism of injury was discussed. Head injuries are commonly seen in sports settings. Our case illustrated that even minor head trauma can cause isolated oculomotor nerve palsy in the absence of abnormal brain imaging findings.
A polymorphism in the<i>EAAT2</i>promoter is associated with higher glutamate concentrations and higher frequency of progressing stroke
Authors: Judith Mallolas, Olivia Hurtado, Mar Castellanos, Miguel Blanco, Tomás Sobrino, Joaquín Serena, José Vivancos, José Castillo, Ignacio Lizasoain, María A. Moro, Antoni Dávalos
Journal: The Journal of Experimental Medicine (2006)

It remains unclear why some individuals are susceptible to excitotoxicity after stroke. A possible explanation is impaired glutamate uptake. We have found a highly prevalent polymorphism in the promoter of the glutamate transporter EAAT2 gene that abolishes a putative regulatory site for activator protein–2 (AP-2) and creates a new consensus binding site for the repressor transcription factor GC-binding factor 2 (GCF2). The mutant genotype is associated with increased plasma glutamate concentrations and with a higher frequency of early neurological worsening in human stroke. After transfection into astrocytes, the mutant promoter was not activated by AP-2 and was effectively repressed by GCF2, and its activity in the presence of GCF2 was reduced when compared with the AP-2–cotransfected wild-type promoter. We also show that GCF2 is expressed in ischemic rat brain, suggesting that decreased glutamate uptake occurs in individuals carrying the mutation after stroke. These findings may explain individual susceptibility to excitotoxic damage after stroke as well as the failure of glutamate antagonists in those patients without this polymorphism.
Immunoglobulin Gene Insertions and Deletions in the Affinity Maturation of HIV-1 Broadly Reactive Neutralizing Antibodies
Authors: Thomas B. Kepler, Hua-Xin Liao, S. Munir Alam, Rekha Bhaskarabhatla, Ruijun Zhang, Chandri Yandava, Shelley Stewart, Kara Anasti, Garnett Kelsoe, Robert Parks, Krissey E. Lloyd, Christina Stolarchuk, Jamie Pritchett, Erika Solomon, Emma Friberg, Lynn Morris, Salim S. Abdool Karim, Myron S. Cohen, Emmanuel Walter, M. Anthony Moody, Xueling Wu, Han R. Altae-Tran, Ivelin S. Georgiev, Peter D. Kwong, Scott D. Boyd, Andrew Z. Fire, John R. Mascola, Barton F. Haynes
Journal: Cell Host & Microbe (2014)
Discovery of Mdm2-MdmX E3 Ligase Inhibitors Using a Cell-Based Ubiquitination Assay
Authors: Ariel G. Herman, Miki Hayano, Masha V. Poyurovsky, Kenichi Shimada, Rachid Skouta, Carol Prives, Brent R. Stockwell
Journal: Cancer Discovery (2011)

E3 ubiquitin ligases are of interest as drug targets for their ability to regulate protein stability and function. The oncogene Mdm2 is an attractive E3 ligase to target, as it is the key negative regulator of the tumor suppressor p53, which controls the transcription of genes involved in cell fate. Overexpression of Mdm2 facilitates tumorigenesis by inactivating p53, and through p53-independent oncogenic effects. We developed a high-throughput cellular Mdm2 auto-ubiquitination assay, which we used to discover a class of small-molecule Mdm2 ligase activity inhibitors. These compounds inhibit Mdm2 and p53 ubiquitination in cells, reduce viability of cells with wild-type p53, and synergize with DNA-damaging agents to cause cell death. We determined that these compounds effectively inhibit the E3 ligase activity of the Mdm2-MdmX hetero-complex. This mechanism may be exploitable to create a new class of anti-tumor agents.
Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction?
Authors: A M Lincoff, E J Topol
Journal: Circulation (1993)

Thrombolytic therapy significantly improves the natural history of acute myocardial infarction, but recent data suggest that current reperfusion strategies have yet to realize the maximum potential for reduction of mortality and salvage of ventricular function. Coronary patency rates as high as 85% assessed by angiography 90 minutes after initiation of treatment greatly overestimate the efficacy of thrombolytic regimens, as this conventional angiographic "snapshot" view does not satisfactorily reflect the dynamic processes of coronary artery recanalization and reocclusion or the adequacy of myocardial perfusion. In fact, only the unusual patient appears to achieve optimal reperfusion for acute myocardial infarction, with a substantial deterioration of benefit in many patients due to insufficiently early or rapid recanalization, incomplete patency with TIMI grade 2 flow or critical residual coronary stenoses, absence of myocardial tissue reflow despite epicardial artery patency, intermittent coronary patency, subsequent reocclusion, or reperfusion injury. Recently developed techniques to critically assess the quality of reperfusion, coupled with the introduction of novel pharmacological agents and an improved understanding of the roles and mechanisms of existing thrombolytic and adjunctive drugs, have provided the opportunity to overcome many of the present limitations of reperfusion therapy. Emerging strategies to achieve optimal reperfusion are directed at enhancement of the velocity and quality of thrombolysis, amelioration of the adverse effects of reperfusion, and use of alternative pathways to myocardial salvage.
Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma--a Pediatric Brain Tumor Consortium study
Authors: S. Gururangan, J. Fangusaro, T. Young Poussaint, A. Onar-Thomas, R. J. Gilbertson, S. Vajapeyam, A. Gajjar, S. Goldman, H. S. Friedman, R. J. Packer, J. M. Boyett, L. E. Kun
Journal: Neuro-Oncology (2012)

A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in cases of pediatric recurrent ependymoma (EPN) to estimate sustained objective response rate and progression-free survival (PFS). Eligible patients received 2 doses of single-agent BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion-weighted and T1 dynamic contrast enhanced permeability imaging and tumor immunohistochemistry for vascular endothelial growth factor (VEGF)–A and –B, hypoxia inducible factor–2α, VEGF receptor (R)–2, and carbonic anhydrase (CA)–9. Thirteen evaluable patients received a median of 3 courses (range, 2–12) of BVZ + CPT-11. No sustained response was observed in any patient. Median time to progression in 10 patients was 2.2 months (range, 1.9–6.3). Two patients had stable disease for 10 months and 12 months, respectively. Six-month PFS was 25.7% (SE = 11.1%). Grades I–III toxicities related to BVZ treatment included fatigue in 4 patients, systemic hypertension in 2, epistaxis in 1, headache in 1, and avascular necrosis of bone in 1. Although there was a decrease in the mean diffusion ratio following 2 doses of BVZ, it did not correlate with PFS. BVZ + CPT-11 was well tolerated but had minimal efficacy in cases of recurrent EPN.
Yes Sir, no Sir, not much difference Sir
Authors: M. Clarke, L. Clarke, T. Clarke
Journal: Journal of the Royal Society of Medicine (2007)

To assess whether making the sender's knighthood explicit in a series of letters would have any detectable effect on the response.A random sequence was generated by flipping a coin to determine whether a letter would have 'Sir Iain Chalmers' or 'Iain Chalmers' typed under the signature. This sequence was prepared independently of the preparation of an alphabetic list of the intended recipients and was then used to determine which letter would be sent. The allocation could not be influenced by prior knowledge of the recipient. Two batches of letters were sent.Medical royal colleges and associated faculties, and postgraduate medical and dental schools in the UK.Presidents and deans of medical royal colleges and deans of postgraduate medical and dental schools in the UK.Rates of response and the mean number of days between the posting of the original letter and the date on the response.No differences between the groups were detected in the response rates: 91% and 90% for 'Sir Iain Chalmers' and 'Iain Chalmers' (relative rate for response of 1.01, 95%CI 0.83-1.23, P = 0.92), or in the mean number of days to response ('Sir': 32 days; 'no Sir': 33 days).This finding is consistent with a systematic review of responses to postal surveys, in which the effect of the status of the signatory was investigated. Combining our result with the two trials that are most comparable to our study, in which letters from professors were compared with letters from students, gives a relative response rate of 1.00 (95% CI 0.91-1.10, P = 0.99). There is, therefore, no evidence from the existing randomized experiments that the status of the signatory has any impact on the likelihood or promptness of response-even if the status was conferred by the British monarch.
Can patient centered outcomes research improve healthcare?
Authors: Thomas W Concannon
Journal: BMJ (2015)

We believe it can; now we should put it to the test

The Patient-Centered Outcomes Research Trust Fund (PCORTF) was established in 2009 to support research that is funded, designed, carried out, and put into practice within a culture of patient centeredness.1 A legislatively mandated review in 2017 of the “adequacy and use of funding” will be used to determine whether PCORTF funding levels should be continued or adjusted after its authorization runs out in autumn 2019. As 2017 approaches, researchers ought to begin taking stock of our work in patient centered outcomes research: how well are we are doing and what might we do better?

In the linked paper (doi:10.1136/bmj.h3786), Xian and colleagues present a solid example of how to refocus research on questions, outcomes, and approaches that could help patients and clinicians to make better healthcare decisions. The team studied prescribing of warfarin for patients with ischemic stroke who were discharged from hospital between 2009 and 2011 with persistent or paroxysmal atrial fibrillation or flutter.2 This study was funded by the Patient-Centered Outcomes Research Institute (PCORI) in 2013.

This team’s preliminary work with patients resulted in prioritization …
THE CELLULAR TRANSFORMATION OF INJECTED COLLOIDAL IRON COMPLEXES INTO FERRITIN AND HEMOSIDERIN IN EXPERIMENTAL ANIMALS
Authors: Goetz W. Richter
Journal: The Journal of Experimental Medicine (1959)

As revealed by electron microscopy and electron diffraction, the physical state of ferric hydroxide micelles contained in iron-dextran, saccharated iron oxide, and hydrous ferric oxide ("ferric hydroxide") differs notably from the state of the ferric hydroxide in ferritin or hemosiderin. By virtue of this difference one can trace the intracellular transformation of colloidal iron, administered parenterally, into ferritin and hemosiderin. One hour after intraperitoneal injection of iron-dextran or saccharated iron oxide into mice, characteristic deposits were present in splenic macrophages, in sinusoidal endothelial cells of spleen and liver, and in vascular endothelial cells of various renal capillaries. Four hours after injection, small numbers of ferritin molecules were identifiable about intracellular aggregates of injected iron compounds; and by the 6th day, ferritin was abundant in close proximity to deposits of injected iron compounds. The latter were frequently situated in cytoplasmic vesicles delimited by single membranes. These vesicles were most frequently found in tissue obtained during the first 6 days after injection; and in certain of the vesicles ferritin molecules surrounded closely packed aggregates of injected material. Much unchanged ferric hydroxide was still present in macrophages and vascular endothelial cells 3 to 4 weeks after injection. While electron microscopy left no doubt about the identity of injected ferric hydroxide on the one hand, and of ferritin or hemosiderin on the other, histochemical tests for iron failed in this respect. Precipitation of ferric hydroxide (hydrous ferric oxide) from stabilized colloidal dispersions of iron-dextran was brought about in vitro by incubation with minced mouse tissue (e.g. liver), but not by incubation with mouse serum or blood. Subcutaneous injections of hydrous gel of ferric oxide into mice initially produced localized extracellular precipitates. Most of the material was still extracellular 16 days after injection, though part of it was phagocytized by macrophages near the site of injection; but apparently none reached the spleen in unaltered form. Five days after injection and thereafter, much ferritin was present in macrophages about the site of injection and in the spleen. The findings show that iron preparations widely used in therapy can be identified within cells, and that their intracellular disposition and fate can be followed at the molecular level. Considered in the light of previous work, they indicate that the characteristic structure of the ferric hydroxide micelles in molecules of ferritin is specific, and develops during the union of apoferritin with ferric hydroxide. Apparently this union does not depend upon specific cell components.
Monoclonal antibodies defining functional sites on the toxin superantigen staphylococcal enterotoxin B.
Authors: A R Hamad, A Herman, P Marrack, J W Kappler
Journal: The Journal of Experimental Medicine (1994)

Four monoclonal antibodies (mAbs) were produced binding to four nonoverlapping epitopes on the superantigen staphylococcal enterotoxin B (SEB). The mAbs were tested for their ability to detect SEB bound to major histocompatibility complex (MHC) class II, to inhibit SEB binding to MHC class II, to inhibit SEB stimulation of T cell hybridomas, to bind to various nonfunctional mutants of SEB, and to capture and present SEB and its mutants to T cells in the absence of MHC class II. We concluded that two mAbs, B344 and B327, bound to epitopes not required for superantigen function, one mAb, 2B33, blocked an MHC interaction site on SEB, and the fourth mAb, B87, blocked the T cell recognition site on SEB. Moreover, two mAbs (B344 and 2B33) were capable of presenting SEB, although much less efficiently than APC, to CD4- but not CD4+ T cell hybridomas. The results confirm the functional domains on SEB originally defined by mutation and show that MHC class II is not always an essential component of the superantigen ligand.
Deletion of the NH2-terminal residue converts monocyte chemotactic protein 1 from an activator of basophil mediator release to an eosinophil chemoattractant.
Authors: M Weber, M Uguccioni, M Baggiolini, I Clark-Lewis, C A Dahinden
Journal: The Journal of Experimental Medicine (1996)

Chemotactic cytokines of the CC subfamily (CC chemokines) are considered as major mediators of allergic inflammation owing their actions on basophil and eosinophil leukocytes. The monocyte chemotactic protein (MCP) 1 is a potent inducer of mediator release from basophils but is inactive on eosinophils. To obtain information on the structural determinants of the activities of MCP-1, we have synthesized several NH2-terminally truncated analogues and tested their effects on basophils and eosinophils. Through deletion of the NH2-terminal residue, MCP-1(2-76) was obtained, which was a potent activator of eosinophils, as assessed by chemotaxis, cytosolic free Ca2+ changes, actin polymerization, and that induction of the respiratory burst. In contrast, the activity of MCP-1(2-76) on basophil leukocytes was dramatically decreased (50-fold) compared with that of full-length MCP-1. Deletion of the next residue led to total loss of activity on eosinophil and basophil leukocytes. Analogues with three or four residue deletions, MCP-1(4-76) and MCP-1(5-76), were again active on both cells, whereas all further truncation analogues, MCP-1(6-76) through MCP-1(10-76), were inactive. Thus, a minimal structural modification can change receptor and target cell selectivity of MCP-1. Our observations indicate that the recognition sites of CC chemokine receptors on eosinophils and basophils are similar, although they discriminate between MCP-1 and MCP-1(2-76) and suggest NH2-terminal processing as a potential mechanism for the regulation of CC chemokine activities.
Mybl2 expression is under genetic control and contributes to determine a hepatocellular carcinoma susceptible phenotype
Authors: Maddalena Frau, Sara Ladu, Diego F. Calvisi, Maria M. Simile, Piero Bonelli, Lucia Daino, Maria L. Tomasi, Maria A. Seddaiu, Francesco Feo, Rosa M. Pascale
Journal: Journal of Hepatology (2010)
Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B
Authors: De‐Ke Jiang, Xiao‐Pin Ma, Hongjie Yu, Guangwen Cao, Dong‐Lin Ding, Haitao Chen, Hui‐Xing Huang, Yu‐Zhen Gao, Xiao‐Pan Wu, Xi‐Dai Long, Hongxing Zhang, Youjie Zhang, Yong Gao, Tao‐Yang Chen, Wei‐Hua Ren, Pengyin Zhang, Zhuqing Shi, Wei Jiang, Bo Wan, Hexige Saiyin, Jianhua Yin, Yuan‐Feng Zhou, Yun Zhai, Pei‐Xin Lu, Hongwei Zhang, Xiaoli Gu, Aihua Tan, Jin‐Bing Wang, Xian‐Bo Zuo, Liang‐Dan Sun, Jun O. Liu, Qing Yi, Zengnan Mo, Gangqiao Zhou, Ying Liu, Jielin Sun, Yin Yao Shugart, S. Lilly Zheng, Xue‐Jun Zhang, Jianfeng Xu, Long Yu
Journal: Hepatology (2015)

Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome‐wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two‐stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [ CFB ], P meta =1.28 × 10 −34 ; and rs422951 [T320A] in NOTCH4 , P meta = 5.33 × 10 −16 ); one synonymous variant (rs378352 in HLA‐DOA corresponding to HLA‐DOA *010101, P meta = 1.04 × 10 −23 ); and one noncoding variant (rs2853953 near HLA‐C , P meta = 5.06 × 10 −20 ). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40 , P meta = 2.95 × 10 −15 ). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA‐C , rs1419881 at TCF19 , rs652888 at EHMT2 , rs2856718 at HLA‐DQB1 , rs7453920 at HLA‐DQB2 , rs3077 at HLA‐DPA1 , and rs9277535 at HLA‐DPA2 , which are all located in the HLA region, 9.84 × 10 −71 ≤ P meta ≤ 9.92 × 10 −7 ). Conclusion : Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease. (H epatology 2015;62:118‐128)
(28) Multiple leiomyomata
Authors: E.A. Bingham
Journal: British Journal of Dermatology (1984)

Journal Article (28) Multiple leiomyomata Get access E.A. Bingham E.A. Bingham Massereene Hospital, Antrim Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Pages 72–73, https://doi.org/10.1111/j.1365-2133.1984.tb05298.x Published: 01 July 1984
EXTRACELLULAR THIOLS AND THIOL/DISULFIDE REDOX IN METABOLISM
Authors: Siobhan E. Moriarty-Craige, Dean P. Jones
Journal: Annual Review of Nutrition (2004)

Many proteins present on cell surfaces and located in extracellular fluids contain cysteine and methionine residues that are subject to oxidation. These proteins, which include transporters, receptors, and enzymes, respond to variations in the extracellular thiol/disulfide redox environment. Changes in activity of these proteins can alter the ability of organs to function normally and influence processes such as nutritional absorption, secretory function, neurotransmission, and susceptibility to toxicants. In addition, extracellular redox can regulate tissue homeostasis through effects on cell proliferation, differentiation, apoptosis, and immune function. Consequently, extracellular redox can have important influences on health status and disease states and thus could be a target for nutritional interventions.
Attitudes Toward Diabetes Affect Maintenance of Drug-Free Remission in Patients With Newly Diagnosed Type 2 Diabetes After Short-Term Continuous Subcutaneous Insulin Infusion Treatment
Authors: Ailing Chen, Zhimin Huang, Xuesi Wan, Wanping Deng, Jiyan Wu, Licheng Li, Qiuling Cai, Haipeng Xiao, Yanbing Li
Journal: Diabetes Care (2012)

OBJECTIVE Short-term intensive insulin treatment in patients with newly diagnosed type 2 diabetes can improve β-cell function and insulin sensitivity, which results in long-term remission without need for further antidiabetes medication. Patient attitudes toward their disease were assessed using the Diabetes Care Profile (DCP) tool to evaluate the potential impact on maintaining long-term remission. RESEARCH DESIGN AND METHODS Newly diagnosed patients with type 2 diabetes were recruited and treated with continuous subcutaneous insulin infusion (CSII) for 2–3 weeks. They were also invited to participate in diabetes self-management intervention during hospitalization and complete a DCP questionnaire on attitudes toward diabetes at baseline and 3, 6, and 12 months after suspension of CSII. RESULTS Near normoglycemia was achieved by 118 patients after short-term CSII, with 65 remaining in drug-free remission for &amp;gt;1 year. They had significantly better glycemic control and greater restoration of acute insulin response after CSII as well as higher educational attainment compared with patients experiencing relapse. They also achieved higher scores in positive attitude, (belief in) importance of care, care ability, self-care adherence, and less negative attitude. Differences between the two groups became greater over time. Cox proportional hazards model analysis indicated that greater self-care adherence (hazard ratio 0.184, P &amp;lt; 0.001) and homeostasis model assessment of insulin resistance before treatment (0.854, P = 0.053) were independent predictors for long-term remission, whereas elevated 2-h postprandial plasma glucose after CSII (1.156, P = 0.015) was a risk factor for relapse. CONCLUSIONS Attitudes toward diabetes affect long-term drug-free remission in newly diagnosed patients with type 2 diabetes after short-term CSII.