tbuckley/cabot-search huggingface dataset:
Identifying Cancer Stem Cells in Solid Tumors: Case Not Proven
Authors: Richard P. Hill
Journal: Cancer Research (2006)

Abstract Building on studies of leukemia, a number of recent articles have reported data suggesting that cancer stem cells could be isolated from solid human cancers. Some of these reports have speculated that the isolation of these cells will allow the identification of the specific molecular properties that can be targeted for therapeutic purposes. Although previous work with animal model systems also suggests the presence of stem cells in solid tumors, there remain many uncertainties, both theoretical and technical, about the interpretation of the current results. The case that a small proportion of cells in solid tumors are specific cancer stem cells and that these cells can be successfully identified and isolated has not yet been proven. (Cancer Res 2006; 66(4): 1891-6)
Long term follow‐up after splenectomy performed for immune thrombocytopenic purpura (ITP)
Authors: Joseph Schwartz, Melissa D. Leber, Shmuel Gillis, Austin Giunta, Amiram Eldor, James B. Bussel
Journal: American Journal of Hematology (2003)

Abstract Splenectomy is the only treatment of ITP known to have “curative” effects in a substantial fraction of patients. However, the true long‐term outcome is uncertain and controversial because published series have not adjusted for the duration of follow‐up. This IRB‐approved retrospective study included all patients with ITP who underwent splenectomy between 1988‐1993 at three major medical centers and required a minimum postoperative 5‐year follow‐up. Complete response (CR) was defined as all postsplenectomy platelet counts &gt;150 × 10 9 /L without treatment; partial response (PR) as platelet counts ≥50 × 10 9 /L without treatment; and failure as platelet counts &lt;50 × 10 9 /L or receiving therapy after splenectomy. Seventy‐five patients identified with ITP underwent splenectomy from 1988 to 1993. Three patients died prior to 5‐year follow‐up, and 56 of the 72 patients (78%) were evaluable with follow‐up for five years or longer, median 7.5 years. The immediate postoperative complete remission rate was 77%; 57% of patients have remained in prolonged CR. Thirty‐seven patients (66%) have not required any therapy after splenectomy. Eight patients had platelet counts &gt;150 × 10 9 /L for 4–8.5 years before relapsing; no clear plateau was attained in the remission curve. There was no operative mortality. Ten patients (18%) reported minor postoperative bleeding episodes. No life‐threatening infections, significant heart disease, or pulmonary hypertension developed after splenectomy in the 434 patient‐years of follow‐up. This study helps to define the long‐term results of splenectomy for ITP. Am. J. Hematol. 72:94–98, 2003. © 2003 Wiley‐Liss, Inc.
Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO
Authors: Tiziano M. Scarabelli, Anastasis Stephanou, Evasio Pasini, Gianluca Gitti, Paul Townsend, Kevin Lawrence, Carol Chen-Scarabelli, Louis Saravolatz, David Latchman, Richard Knight, Julius Gardin
Journal: Journal of the American College of Cardiology (2004)
CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration
Authors: Christophe Combadière, Charles Feumi, William Raoul, Nicole Keller, Mathieu Rodéro, Adeline Pézard, Sophie Lavalette, Marianne Houssier, Laurent Jonet, Emilie Picard, Patrice Debré, Mirna Sirinyan, Philippe Deterre, Tania Ferroukhi, Salomon-Yves Cohen, Dominique Chauvaud, Jean-Claude Jeanny, Sylvain Chemtob, Francine Behar-Cohen, Florian Sennlaub
Journal: Journal of Clinical Investigation (2007)

The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.
ICHTHYOSIS HYSTRIX AND NAEVUS VERRUCOSUS
Authors: J. L. BUNCH
Journal: British Journal of Dermatology (1911)

Journal Article ICHTHYOSIS HYSTRIX AND NÆVUS VERRUCOSUS Get access J. L. BUNCH, M.D., D.Sc. J. L. BUNCH, M.D., D.Sc. Physician to the Skin‐Department, Queen's Hospital for Children, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 23, Issue 9, 1 September 1911, Pages 273–276, https://doi.org/10.1111/j.1365-2133.1911.tb16681.x Published: 01 September 1911
Protein-anchoring Strategy for Delivering Acetylcholinesterase to the Neuromuscular Junction
Authors: Mikako Ito, Yumi Suzuki, Takashi Okada, Takayasu Fukudome, Toshiro Yoshimura, Akio Masuda, Shin'ichi Takeda, Eric Krejci, Kinji Ohno
Journal: Molecular Therapy (2012)

Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ). Congenital defects of ColQ cause endplate AChE deficiency and myasthenic syndrome. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq−/− mice recovered motor functions, synaptic transmission, as well as the morphology of the NMJ. ColQ-tailed AChE was specifically anchored to NMJ and its amount was restored to 89% of the wild type. We next characterized the molecular basis of this efficient recovery. We first confirmed that ColQ-tailed AChE can be specifically targeted to NMJ by an in vitro overlay assay in Colq−/− mice muscle sections. We then injected AAV1-COLQ-IRES-EGFP into the left tibialis anterior and detected AChE in noninjected limbs. Furthermore, the in vivo injection of recombinant ColQ-tailed AChE protein complex into the gluteus maximus muscle of Colq−/− mice led to accumulation of AChE in noninjected forelimbs. We demonstrated for the first time in vivo that the ColQ protein contains a tissue-targeting signal that is sufficient for anchoring itself to the NMJ. We propose that the protein-anchoring strategy is potentially applicable to a broad spectrum of diseases affecting extracellular matrix molecules. Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ). Congenital defects of ColQ cause endplate AChE deficiency and myasthenic syndrome. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq−/− mice recovered motor functions, synaptic transmission, as well as the morphology of the NMJ. ColQ-tailed AChE was specifically anchored to NMJ and its amount was restored to 89% of the wild type. We next characterized the molecular basis of this efficient recovery. We first confirmed that ColQ-tailed AChE can be specifically targeted to NMJ by an in vitro overlay assay in Colq−/− mice muscle sections. We then injected AAV1-COLQ-IRES-EGFP into the left tibialis anterior and detected AChE in noninjected limbs. Furthermore, the in vivo injection of recombinant ColQ-tailed AChE protein complex into the gluteus maximus muscle of Colq−/− mice led to accumulation of AChE in noninjected forelimbs. We demonstrated for the first time in vivo that the ColQ protein contains a tissue-targeting signal that is sufficient for anchoring itself to the NMJ. We propose that the protein-anchoring strategy is potentially applicable to a broad spectrum of diseases affecting extracellular matrix molecules.
Refractory iron-deficiency anaemia in a child with portal cavernoma
Authors: S. Pastore, M. Londero, G. Cont, G. Di Leo, A. Ventura
Journal: Gut (2010)

We present the case of a 9-year-old boy affected by portal hypertension due to a portal cavernoma which developed after umbilical vein catheterisation in the neonatal period.

When our patient was 3 years of age splenomegaly developed and investigations revealed portal hypertension. During the following years he developed third degree oesophageal varices, …
Effect of chondroitin sulphate in symptomatic knee osteoarthritis: a multicentre, randomised, double-blind, placebo-controlled study
Authors: B. Mazieres, M. Hucher, M. Zaim, P. Garnero
Journal: Annals of the Rheumatic Diseases (2007)

To evaluate the efficacy and tolerability of chondroitin sulphate (chondroitin sulphate) in knee osteoarthritis.
Prevalence of and Trends in Dyslipidemia and Blood Pressure Among US Children and Adolescents, 1999-2012
Authors: Brian K. Kit, Elena Kuklina, Margaret D. Carroll, Yechiam Ostchega, David S. Freedman, Cynthia L. Ogden
Journal: JAMA Pediatrics (2015)

IMPORTANCE Recent national data suggest there were improvements in serum lipid concentrations among US children and adolescents between 1988 and 2010 but an increase in or stable blood pressure (BP) during a similar period.OBJECTIVE To describe the prevalence of and trends in dyslipidemia and adverse BP among US children and adolescents.DESIGN The National Health and Nutrition Examination Survey, a cross-sectional survey.SETTING Noninstitutionalized US population.PARTICIPANTS Children and adolescents aged 8 to 17 years with measured lipid concentrations (n = 1482) and BP (n = 1665).MAIN OUTCOMES AND MEASURES Adverse concentrations of total cholesterol (TC) (Ն200 mg/dL), high-density lipoprotein cholesterol (HDL-C) (<40 mg/dL), and non-HDL-C (Ն145 mg/dL) (to convert TC, HDL-C, and non-HDL-C to millimoles per liter, multiply by 0.0259) and high or borderline BP were examined.Definitions of BP were informed by the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents.Analyses of linear trends in dyslipidemias and BP were conducted overall and separately by sex across 7 periods (1999-2000, 2001
SERUM-DEPENDENT PHAGOCYTOSIS OF PARAFFIN OIL EMULSIFIED WITH BACTERIAL LIPOPOLYSACCHARIDE
Authors: Thomas P. Stossel, Chester A. Alper, Fred S. Rosen
Journal: The Journal of Experimental Medicine (1973)

Paraffin oil containing oil red O and emulsified with lipopolysaccharide obtained from Escherichia coli was ingested rapidly by guinea pig polymorphonuclear leukocytes or human peripheral blood granulocytes and monocytes after opsonization by fresh homologous serum. The initial rate of engulfment of the particles was spectrophotometrically assayed by determination of cell-associated oil red O and reflected the opsonic activity of the serum. This activity was resistant to dialysis but labile to heat, hydrazine, and zymosan, required divalent cations, and was maximal in the presence of Ca(++) and Mg(++). It was associated with the fixation of [(125)I]C3 to the lipopolysaccharide particles. Genetically C3-deficient serum had no opsonic activity, and this activity was restored by the addition of purified C3. Normal and C4-deficient guinea pig serum and normal, C2-, and C4-deficient human sera were equally effective in opsonizing lipopolysaccharide particles and lipopolysaccharide particles sensitized with heat-inactivated lipopolysaccharide immune serum. Cord serum deficient in glycine-rich beta-glycoprotein (GBG) (properdin factor B) had diminished opsonic activity which was improved by addition of purified GBG. Thus, C3 fixation to lipopolysaccharide particles occurs by means of the properdin system, and the opsonization and ingestion of lipopolysaccharide particles constitutes a quantitative functional assay of this pathway.
Validity of enzyme-linked immunosorbent assays of cross-linked fibrin degradation products as a measure of clot lysis.
Authors: P R Eisenberg, A S Jaffe, D C Stump, D Collen, E G Bovill
Journal: Circulation (1990)

Concentrations of cross-linked fibrin degradation products (XL-FDPs) in plasma, measured by enzyme-linked immunosorbent assays (ELISAs) based on monoclonal antibodies (MAbs) raised against fragment D-dimer of cross-linked fibrin, increase when patients are given fibrinolytic agents. Whether XL-FDPs derive from circulating cross-linked fibrin polymers in plasma, compared with clot-associated fibrin, has been questioned because increases in XL-FDP are measured by some assays after fibrinolysis in vitro in the absence of clot. We characterized the source of XL-FDP immunoreactivity in plasma of patients with acute myocardial infarction and ischemic heart disease and the response to plasminogen activation in vitro induced by pharmacological concentrations of tissue-type plasminogen activator (t-PA) and streptokinase. XL-FDPs were measured with two different ELISA. One, "pan-specific tag ELISA," was based on a capture MAb specific for XL-FDP and a tag MAb that recognizes an epitope exposed in the fragment D region of both fibrin and fibrinogen, whereas the other, "fibrin-specific tag ELISA," was based on a capture and tag MAbs both specific for fibrin. After plasminogen activation was induced in vitro in plasma from patients with myocardial infarction, increased concentrations of XL-FDP were measured by the pan-specific tag ELISA; however, concentrations measured with the fibrin-specific tag ELISA were not increased. To determine the mechanism for this discrepancy, plasma was subjected to immunoadsorption with a MAb specific for fragment D-dimer before and after in vitro activation of the fibrinolytic system and immunoblotting with a fragment D-dimer-specific MAb and with the pan-specific MAb. Increased concentrations of fragment D-dimer, as well as fibrinogen fragment D at high concentrations, were recognized by the specific MAb. Non-cross-linked fragments were also shown by immunoblotting with the pan-specific MAb to coprecipitate with cross-linked fibrin fragments. This suggested the increased concentrations of XL-FDP measured by the pan-specific tag ELISA after in vitro activation of the fibrinolytic system were due to detection of non-cross-linked fibrinogen fragments. However, fibrin fragment D-dimer concentrations were found to increase in plasma of 15 patients given t-PA for acute myocardial infarction. We conclude fragment D-dimer in plasma of patients during thrombolysis does not originate from circulating soluble cross-linked fibrin but rather is a marker of solid-phase fibrin dissolution, which may be quantitated with assays based on capture and tag antibodies that do not detect fibrinogen or its degradation products.
Hemoglobin A1c as a Predictor of Incident Diabetes
Authors: Peiyao Cheng, Britta Neugaard, Philip Foulis, Paul R. Conlin
Journal: Diabetes Care (2011)

Several studies have suggested that HbA(1c) levels may predict incident diabetes. With new recommendations for use of HbA(1c) in diagnosing diabetes, many patients with HbA(1c) results below the diagnostic threshold will be identified. Clinicians will need to categorize risk for a subsequent diabetic diagnosis in such patients. The objective of this study was to determine the ability of HbA(1c) to predict the incidence of a diabetic diagnosis.We performed a historical cohort study using electronic medical record data from two Department of Veterans Affairs Medical Centers. Patients (n = 12,589) were identified with a baseline HbA(1c) <6.5% between January 2000 and December 2001 and without a diagnosis of diabetes. Patients (12,375) had at least one subsequent follow-up visit. These patients were tracked for 8 years for a subsequent diagnosis of diabetes.During an average follow-up of 4.4 years, 3,329 (26.9%) developed diabetes. HbA(1c) ≥ 5.0% carried a significant risk for developing diabetes during follow-up. When compared with the reference group (HbA(1c) <4.5%), HbA(1c) increments of 0.5% between 5.0 and 6.4% had adjusted odds ratios of 1.70 (5.0-5.4%), 4.87 (5.5-5.9%), and 16.06 (6.0-6.4%) (P < 0.0001). Estimates of hazard ratios similarly showed significant increases for HbA(1c) ≥ 5.0%. A risk model for incident diabetes within 5 years was developed and validated using HbA(1c), age, BMI, and systolic blood pressure.The incidence of diabetes progressively and significantly increased among patients with an HbA(1c) ≥ 5.0%, with substantially expanded risk for those with HbA(1c) 6.0-6.4%.
DNA Sequence Variation in the Mitochondrial Control Region of Subterranean Mole Rats, Spalax ehrenbergi Superspecies, in Israel
Authors: A. Reyes
Journal: Molecular Biology and Evolution (2003)

The complete mitochondrial control region was sequenced for 60 individuals representing different populations for each of the four species of the subterranean mole rat Spalax ehrenbergi superspecies in Israel: Spalax galili (2n = 52), S. golani (2n = 54), S. carmeli (2n = 58), and S. judaei (2n = 60). The control region of all species and populations is very similar both in length (979 to 983 bp) and in base composition. As in agreement with previous surveys on mitochondrial control regions on mammals, the mole rat control region can be divided into a central domain and two flanking domains, ETAS (extended termination associated sequences) and CSB (conserved sequence blocks). Along with the common conserved blocks found in these domains (ETAS1, ETAS2, CSB1, CSB2, and CSB3), we have also detected in all individuals an ETAS1-like and a CSB1-like element, both in the ETAS domain. The most conserved region was the central domain, followed by the CSB and ETAS domains, showing important differences in the four species analyzed. Phylogenetic analysis supported the existence of two clades. One clade contained individuals belonging to Spalax galili (2n = 52) and S. golani (2n = 54), separated in two different branches depending on the species. The other clade contained individuals belonging to S. carmeli (2n = 58) and S. judaei (2n = 60) mixed together, suggesting a more recent event of speciation. Within species we have observed a southward trend of increasing variability. These results have been explained as a consequence of the adaptation of the species to ecological factors such as aridity and temperature stresses.
Abnormal Parietal Cortex Activation During Working Memory in Schizophrenia: Verbal Phonological Coding Disturbances Versus Domain-General Executive Dysfunction
Authors: M Deanna, John G. Csernansky
Journal: American Journal of Psychiatry (2007)

The goal of this study was to determine whether the regions of the prefrontal and parietal cortices showing abnormal activation among individuals with schizophrenia during working memory tasks are associated with either 1) phonological coding processes that may be specific to verbal tasks (i.e., ventral prefrontal and parietal cortices) or 2) domain-general executive processes engaged by verbal and nonverbal tasks (i.e., dorsal prefrontal and parietal cortices).The participants were 57 medicated individuals with schizophrenia and 120 healthy subjects. Functional magnetic resonance imaging was used to scan all participants during performance of verbal and nonverbal 2-back working memory tasks.In the healthy subjects there was similar bilateral dorsal prefrontal and inferior parietal cortex activation for both the verbal and nonverbal working memory tasks, but greater left ventral prefrontal and parietal cortex activation during verbal compared to nonverbal working memory. Individuals with schizophrenia showed bilateral deficits in dorsal frontal and parietal activation during both verbal and nonverbal working memory tasks. They also demonstrated the typical pattern of greater activity for verbal, as compared to nonverbal, working memory in ventral prefrontal and parietal regions, although they showed less verbal superiority in a left ventral prefrontal region.These results support the hypothesis that working memory deficits in individuals with schizophrenia reflect deficits in activation of brain regions associated with the central executive components of working memory rather than domain-specific storage buffers.
Implementation and adoption of nationwide electronic health records in secondary care in England: qualitative analysis of interim results from a prospective national evaluation
Authors: A. Robertson, K. Cresswell, A. Takian, D. Petrakaki, S. Crowe, T. Cornford, N. Barber, A. Avery, B. Fernando, A. Jacklin, R. Prescott, E. Klecun, J. Paton, V. Lichtner, C. Quinn, M. Ali, Z. Morrison, Y. Jani, J. Waring, K. Marsden, A. Sheikh
Journal: BMJ (2010)

To describe and evaluate the implementation and adoption of detailed electronic health records in secondary care in England and thereby provide early feedback for the ongoing local and national rollout of the NHS Care Records Service.A mixed methods, longitudinal, multisite, socio-technical case study.Five NHS acute hospital and mental health trusts that have been the focus of early implementation efforts and at which interim data collection and analysis are complete. Data sources and analysis Dataset for the evaluation consists of semi-structured interviews, documents and field notes, observations, and quantitative data. Qualitative data were analysed thematically with a socio-technical coding matrix, combined with additional themes that emerged from the data. Main results Hospital electronic health record applications are being developed and implemented far more slowly than was originally envisioned; the top-down, standardised approach has needed to evolve to admit more variation and greater local choice, which hospital trusts want in order to support local activity. Despite considerable delays and frustrations, support for electronic health records remains strong, including from NHS clinicians. Political and financial factors are now perceived to threaten nationwide implementation of electronic health records. Interviewees identified a range of consequences of long term, centrally negotiated contracts to deliver the NHS Care Records Service in secondary care, particularly as NHS trusts themselves are not party to these contracts. These include convoluted communication channels between different stakeholders, unrealistic deployment timelines, delays, and applications that could not quickly respond to changing national and local NHS priorities. Our data suggest support for a "middle-out" approach to implementing hospital electronic health records, combining government direction with increased local autonomy, and for restricting detailed electronic health record sharing to local health communities.Experiences from the early implementation sites, which have received considerable attention, financial investment and support, indicate that delivering improved healthcare through nationwide electronic health records will be a long, complex, and iterative process requiring flexibility and local adaptability both with respect to the systems and the implementation strategy. The more tailored, responsive approach that is emerging is becoming better aligned with NHS organisations' perceived needs and is, if pursued, likely to deliver clinically useful electronic health record systems.