tbuckley/cabot-search huggingface dataset:
Serum CD163 and TARC as Disease Response Biomarkers in Classical Hodgkin Lymphoma
Authors: Kimberley Jones, Frank Vari, Colm Keane, Pauline Crooks, Jamie P. Nourse, Louise A. Seymour, David Gottlieb, David Ritchie, Devinder Gill, Maher K. Gandhi
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin–Reed–Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS cells are sparse within the diseased node, whereas benign CD163+ M2 tissue-associated macrophages (TAM) are prominent. CD163+ cells within the malignant node may be prognostic, but there is no data on serum CD163 (sCD163). The HRS-specific serum protein sTARC shows promise as a disease response biomarker. Tumor-specific and tumor-infiltrating circulating biomarkers have not been compared previously. Experimental Design: We prospectively measured sCD163 and sTARC in 221 samples from 47 patients with Hodgkin lymphoma and 21 healthy participants. Blood was taken at five fixed time-points prior, during, and after first-line therapy. Results were compared with radiological assessment and plasma Epstein-Barr virus DNA (EBV-DNA). Potential sources of circulating CD163 were investigated, along with immunosuppressive properties of CD163. Results: Pretherapy, both sCD163 and sTARC were markedly elevated compared with healthy and complete remission samples. sCD163 better reflected tumor burden during therapy, whereas sTARC had greater value upon completion of therapy. sCD163 correlated with plasma EBV-DNA, and associated with B symptoms, stage, and lymphopenia. Circulating CD163+ monocytes were elevated in patients, indicating that sCD163 are likely derived from circulating and intratumoral cells. Depletion of cHL CD163+ monocytes markedly enhanced T-cell proliferation, implicating monocytes and/or TAMs as potential novel targets for immunotherapeutic manipulation. Conclusion: The combination of circulating tumor-infiltrate (sCD163) and tumor-specific (sTARC) proteins is more informative than either marker alone as disease response biomarkers in early and advanced disease during first-line therapy for cHL. Clin Cancer Res; 19(3); 731–42. ©2012 AACR.
Transcription Factor IRF-1 in Kidney Transplants Mediates Resistance to Graft Necrosis during Rejection
Authors: Marjan Afrouzian, Vido Ramassar, Joan Urmson, Lin-Fu Zhu, Philip F. Halloran
Journal: Journal of the American Society of Nephrology (2002)

In many circumstances kidney transplants remain viable despite extensive inflammation, permitting rejection episodes to be reversed. The mechanisms by which the kidney resists host effector mechanisms are not known. In mouse kidney transplants, resistance requires interferon-gamma (IFN-gamma), which acts on the graft to protect the graft from necrosis during the first days of rejection as well as inducing major histocompatibility complex (MHC) expression. Because some effects of IFN-gamma are mediated by transcription factor IRF-1, the role of IRF-1 in the donor tissue early phases of rejection of mouse kidney allografts was studied. H-2(b) kidneys were transplanted from mice with wild-type IRF-1 genes (WT) or mice with disrupted IRF-1 genes (IRF-1KO) into CBA (H-2(k)) recipients. At day 5 and day 7, IRF-1KO and WT kidneys were functioning despite typical rejection pathology: interstitial infiltration and tubulitis. However, function deteriorated rapidly in rejecting IRF-1KO allografts, associated with widespread epithelial necrosis, peritubular capillary congestion, glomerulitis, and fibrin thrombi in small veins by day 7. At day 21, WT kidneys were viable despite severe tubulitis and arteritis, whereas IRF-1KO kidneys showed massive necrosis of the epithelium despite patent large vessels. Compared with WT kidneys, rejecting IRF-1KO kidneys showed less induction of donor MHC yet had similar mRNA levels of perforin, granzyme B, and Fas ligand and evoked host alloantibody responses. Thus in rejecting kidney transplants, IRF-1 in the graft mediates MHC induction, but it also mediates resistance to necrosis, an effect that could be crucial to permit success in interventions against rejection.
Seasonal distribution of initial diagnosis and clinical recrudescence of eosinophilic esophagitis: a systematic review and meta‐analysis
Authors: A. J. Lucendo, Á. Arias, O. Redondo‐González, J. González‐Cervera
Journal: Allergy (2015)

The association between seasonality and diagnosis and/or recrudescence of eosinophilic esophagitis (EoE) remains unclear, with some studies demonstrating a higher diagnostic rate in those months with a higher aeroallergen load while others rule out this association.We performed a systematic search of the MEDLINE, EMBASE, and SCOPUS databases for studies on the seasonality of the initial diagnosis or recrudescence (i.e., food bolus impaction) of EoE. Summary estimates, including 95% confidence intervals, were calculated for seasonal variation in diagnosis or incidence of food bolus impaction. A random-effects meta-regression model was made using aggregate-level data to compare seasonality in EoE diagnosis and recrudescence. Publication bias risks were assessed by means of funnel plot analysis.Of 1078 references found, data were finally collected from 18 studies which included a total of 16,846 EoE patients. Of all new cases of EoE diagnosed per year, 27.1% were diagnosed in spring and 21.5% in winter. No overall statistical differences in the annual seasonal distribution of newly diagnosed EoE cases were observed in the random-effects meta-regression model (P = 0.132). Similarly, a homogenous distribution of episodes of EoE recrudescence throughout the year was noted, with no significant differences between seasons (P = 0.699). No significant publication bias was found.This systematic review found no significant variations in the seasonal distribution of either the diagnosis or clinical recrudescence of EoE throughout the year.
Circulating plasmablasts/plasmacells as a source of anticitrullinated protein antibodies in patients with rheumatoid arthritis
Authors: Priscilla F Kerkman, Yoann Rombouts, Ellen I H van der Voort, Leendert A Trouw, Tom W J Huizinga, René EM Toes, Hans U Scherer
Journal: Annals of the Rheumatic Diseases (2013)

Objective To study the characteristics and phenotype of anticitrullinated protein antibody (ACPA)-specific B cells in peripheral blood of patients with rheumatoid arthritis (RA). Methods Peripheral blood B cells from ACPA-positive patients with RA were cultured with or without stimulating factors. Following culture, supernatants were assessed for the presence of ACPA-IgG and non-specific total IgG by ELISA. Results Following stimulation, ACPA were detectable in up to 100% of culture wells. Of interest, ACPA were also produced spontaneously by unstimulated peripheral blood mononuclear cells. In both cases, the average ACPA titre per culture well correlated with ACPA serum titres. No ACPA production was detectable in B cell cultures from ACPA-negative patients with RA or healthy controls. Importantly, FACS-sorting experiments located spontaneous ACPA production to the CD20 negative B cell population corresponding to circulating plasmablasts/cells. Conclusions ACPA-specific peripheral blood B cells are not confined to the CD20 positive memory pool, as circulating plasmablasts/cells spontaneously producing ACPA are also readily detectable. The latter points to an ongoing B cell immune response against citrullinated proteins and contrasts conventional immune responses against, for example, vaccines, where antigen-specific plasmablasts appear in peripheral blood only shortly after vaccination. These circulating, ACPA-specific plasmablasts/cells might represent targets for novel therapeutic interventions.
Multicentric, Randomized, Controlled Trial to Evaluate Blood Glucose Control by the Model Predictive Control Algorithm Versus Routine Glucose Management Protocols in Intensive Care Unit Patients
Authors: Johannes Plank, Jan Blaha, Jeremy Cordingley, Malgorzata E. Wilinska, Ludovic J. Chassin, Cliff Morgan, Stephen Squire, Martin Haluzik, Jaromir Kremen, Stepan Svacina, Wolfgang Toller, Andreas Plasnik, Martin Ellmerer, Roman Hovorka, Thomas R. Pieber
Journal: Diabetes Care (2006)

OBJECTIVE—To evaluate a fully automated algorithm for the establishment of tight glycemic control in critically ill patients and to compare the results with different routine glucose management protocols of three intensive care units (ICUs) across Europe (Graz, Prague, and London). RESEARCH DESIGN AND METHODS—Sixty patients undergoing cardiac surgery (age 67 ± 9 years, BMI 27.7 ± 4.9 kg/m2, 17 women) with postsurgery blood glucose levels &amp;gt;120 mg/dl (6.7 mmol/l) were investigated in three different ICUs (20 per center). Patients were randomized to either blood glucose management (target range 80–110 mg/dl [4.4–6.1 mmol/l]) by the fully automated model predictive control (MPC) algorithm (n = 30, 10 per center) or implemented routine glucose management protocols (n = 30, 10 per center). In all patients, arterial glucose was measured hourly to describe the glucose profile until the end of the ICU stay but for a maximum period of 48 h. RESULTS—Compared with routine protocols, MPC treatment resulted in a significantly higher percentage of time within the target glycemic range (% median [min–max]: 52 [17–92] vs. 19 [0–71]) over 0–24 h (P &amp;lt; 0.01). Improved glycemic control with MPC treatment was confirmed in patients remaining in the ICU for 48 h (0–24 h: 50 [17–71] vs. 21 [4–67], P &amp;lt; 0.05, and 24–48 h: 65 [38–96] vs. 25 [8–79], P &amp;lt; 0.05, for MPC [n = 16] vs. routine protocol [n = 13], respectively). Two hypoglycemic events (&amp;lt;54 mg/dl [3.0 mmol/l]) were observed with routine protocol treatment. No hypoglycemic event occurred with MPC. CONCLUSIONS—The data suggest that the MPC algorithm is safe and effective in controlling glycemia in critically ill postsurgery patients.
Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain high intragastric pH in patients with peptic ulcer bleeding: a prospective randomised controlled study.
Authors: J Labenz, U Peitz, C Leusing, B Tillenburg, A L Blum, G Borsch
Journal: Gut (1997)

BACKGROUND: In healthy subjects, continuous infusions of high dose ranitidine and omeprazole produce high intragastric pH values. AIM: To test the hypothesis that both drugs also maintain high intragastric pH values in patients with bleeding ulcers. PATIENTS AND METHODS: In two parallel studies, 20 patients with bleeding duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was continuously recorded with a glass electrode placed 5 cm below the cardia. RESULTS: Both drugs rapidly raised the intragastric pH above 6. During the second 12 hour period, however, the percentage of time spent below a pH of 6 was 0.15% with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with ranitidine (p = 0.002). CONCLUSIONS: Primed infusions of omeprazole after a bolus produced consistently high intragastric pH values in patients with bleeding peptic ulcers, whereas primed infusions with ranitidine were less effective during the second half of a 24 hour treatment course. This loss of effectiveness may be due to tolerance.
Transplantation of Cryopreserved Teeth: A Systematic Review
Authors: Thanaphum Osathanon
Journal: International Journal of Oral Science (2010)

The aim of this article was to examine the research articles regarding biological and mechanical properties of cryopreserved teeth for potential use in tooth transplantation. A systematic review of literatures was performed by Pubmed searching with assigned key words from January 1, 1990 to June 8, 2009. All articles were examined for inclusion criteria. Secondary search was conducted by hand-search through references of included articles from primary search. A total of 24 articles were obtained from both primary and secondary search and used as fundamental articles in this review. Periodontal ligament tissues of cryopreserved teeth were able to maintain their biological properties resulted in a satisfactory healing of periodontium. Dental pulp tissues, however, may be compromised by limitation of permeability of cryopreservative agent into pulp cavity. Therefore, an endodontic treatment of transplanted cryopreserved teeth was recommended. Cryopreserved teeth had comparable mechanical properties to those of normal teeth. Importantly, the success of cryopreserved tooth transplantation treatment in orthodontic patients was reported. The cryopreserved teeth for tooth banking have a potential clinical application for treatment of missing teeth. Case selection, however, is critical for treatment success. More studies and data regarding masticatory function and periodontal healing of transplanted cryopreserved teeth are needed.
Intercostal Neuralgia of Pregnancy
Authors: A. Bernard Pleet
Journal: JAMA (1980)

PREGNANCY has long been associated with a number of well-defined neuralgias and peripheral neuropathies such as meralgia paraesthetica, sciatica, and the carpal tunnel syndrome.<sup>1</sup>We wish to call attention to a less common neuralgic complication of the gravid state. <h3>Report of a Case</h3> A 31-year-old woman was referred to the neurology service in the seventh month of her second pregnancy for evaluation of abdominal pain. Three years previously, in the eighth month of her first pregnancy, she experienced painful dysesthesias in the right hypochondrium, which promptly abated in the immediate postpartum period, leaving her with a small hypesthetic zone just to the right of the xyphoid process. In the sixth month of her second pregnancy, dysesthesias recurred in the right hypochondrium and lumbar area, involving thoracic dermatomal levels T-7 through T-11. Her medical history suggested the presence of an ill-defined autoimmune disease: four years previously she had thyrotoxicosis treated
Early diagnostic Achilles tendinopathy in patients with psoriasis and arthralgia
Authors: R Sokolik, B Nowak, M Ponikowska, P Wiland
Journal: Annals of the Rheumatic Diseases (2010)

Psoriatic arthritis belongs to a group of spondyloarthropaties that are characterised by, among other things, enthesopathy. The most typical enthesitis is heel pain related to inflammation of the Achilles tendon or the plantar fascia insertion. Musculoskeletal ultrasonography is a useful tool for evaluating joint and soft tissue pathology and it can be used to visualise enthesopathy.1,2,3 …
Inhalation experiments with extracts of Aspergillus fumigatus on patients with allergic aspergillosis and aspergilloma
Authors: E. A. M. Stevens, C. Hilvering, N. G. M. Orie
Journal: Thorax (1970)

A description is given of the reaction to inhalation of Aspergillus extract by seven patients with aspergillosis, including five with aspergillomas. The nature of, and possible causes for, such reactions are discussed on the basis of their resemblance to the symptomatology of the vegetable dust syndromes. The findings may contribute to a better understanding of the pathogenesis of fever in aspergillosis.
Direct effect of beta-adrenergic stimulation on renin release by the rat kidney slice in vitro.
Authors: M H Weinberger, W Aoi, D P Henry
Journal: Circulation Research (1975)

Controversy exists regarding the mechanism by which catecholamines stimulate renin secretion in vivo. A sensitive rat kidney slice system was utilized to study the direct effects of adrenergic agonists and antagonists on renin release in vitro. Catecholamines were protected from degradation by the addition of ascorbic acid to the incubation medium. Significant dose-related stimulation of renin release was observed with epinephrine and norepinephrine in concentrations from 1.5 times 10(-9) to 1.5 times 10(-7)M and with isoproterenol in concentrations from 2 times 10(-9) to 2 times 10(-7)M. No significant stimulation was seen with 10(-10)M concentrations of the three agents. Methoxamine (10(-6)M) stimulated renin release significantly (P less than 0.01). The stimulation observed with epinephrine, norepinephrine, or isoproterenol was blocked by d,l- and l-propranolol (2 times 10(-4)M) but not by d-ropranolol (2 times 10(-4)M) or phentolamine (9 times 10(-4)M). Methoxamine-induced stimulation was abolished by d,l-propranolol but not by phentolamine. These data that the in vitro kidney slice system is responsive to physiological concentrations of catecholamines when they are protected from degradation. The results further demonstrate a direct stimulatory role for beta-adrenergic agents on renin release and suggest that alpha-adrenergic effects seen in vivo are mediated indirectly by hemodynamic, vascular, or functional changes in the kidney.
Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate
Authors: M.N. Fornier, A.D. Seidman, M.K. Schwartz, F. Ghani, R. Thiel, L. Norton, C. Hudis
Journal: Annals of Oncology (2005)
Progranulin modulates zebrafish motoneuron development in vivoand rescues truncation defects associated with knockdown of Survival motor neuron 1
Authors: Babykumari P Chitramuthu, David C Baranowski, Denis G Kay, Andrew Bateman, Hugh Pj Bennett
Journal: Molecular Neurodegeneration (2010)

Progranulin (PGRN) encoded by the GRN gene, is a secreted glycoprotein growth factor that has been implicated in many physiological and pathophysiological processes. PGRN haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to progressive neuronal atrophy in the form of frontotemporal lobar degeneration (FTLD). This form of the disease is associated with neuronal inclusions that bear the ubiquitinated TAR DNA Binding Protein-43 (TDP-43) molecular signature (FTLD-U). The neurotrophic properties of PGRN in vitro have recently been reported but the role of PGRN in neurons is not well understood. Here we document the neuronal expression and functions of PGRN in spinal cord motoneuron (MN) maturation and branching in vivo using zebrafish, a well established model of vertebrate embryonic development.Whole-mount in situ hybridization and immunohistochemical analyses of zebrafish embryos revealed that zfPGRN-A is expressed within the peripheral and central nervous systems including the caudal primary (CaP) MNs within the spinal cord. Knockdown of zfPGRN-A mRNA translation mediated by antisense morpholino oligonucleotides disrupted normal CaP MN development resulting in both truncated MNs and inappropriate early branching. Ectopic over-expression of zfPGRN-A mRNA resulted in increased MN branching and rescued the truncation defects brought about by knockdown of zfPGRN-A expression. The ability of PGRN to interact with established MN developmental pathways was tested. PGRN over-expression was found to reverse the truncation defect resulting from knockdown of Survival of motor neuron 1 (smn1). This is involved in small ribonucleoprotein biogenesis RNA processing, mutations of which cause Spinal Muscular Atrophy (SMA) in humans. It did not reverse the MN defects caused by interfering with the neuronal guidance pathway by knockdown of expression of NRP-1, a semaphorin co-receptor.Expression of PGRN within MNs and the observed phenotypes resulting from mRNA knockdown and over-expression are consistent with a role in the regulation of spinal cord MN development and branching. This study presents the first in vivo demonstration of the neurotrophic properties of PGRN and suggests possible future therapeutic applications in the treatment of neurodegenerative diseases.
Variations among gamma-globulins at the antigenic site revealed by pepsin digestion.
Authors: R C Williams, T G Lawrence
Journal: Journal of Clinical Investigation (1966)

The pepsin site, an antigenic determinant of human y-globulin uncovered by proteolytic digestion of IgG 1 by pepsin, has previously been described and characterized by Osterland, Harboe, and Kunkel (3).By using anti-Rh antibodies digested with pepsin at pH 4.1, it was found that 20% of normal sera and 57% of sera from patients with rheumatoid arthritis contained anti-y-globulin factors, primarily 7 S, which agglutinated cells coated with pepsin-digested human incomplete antibody.Of particular interest was the finding that these agglutination reactions could not be inhibited by whole y-globulin, but only by pepsin or papain digests of human y-globulin performed at pH 4.1.Under these conditions a 5 S pepsin fragment re- lated to Fab-fragment remained, whereas Fc-fragment was digested to dialyzable peptides.Fab
Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B–null mice
Authors: Young Hun Choi, Sunhee Park, Steven Hockman, Emilia Zmuda-Trzebiatowska, Fredrik Svennelid, Martin Haluzik, Oksana Gavrilova, Faiyaz Ahmad, Laurent Pepin, Maria Napolitano, Masato Taira, Frank Sundler, Lena Stenson Holst, Eva Degerman, Vincent C. Manganiello
Journal: Journal of Clinical Investigation (2006)

Cyclic nucleotide phosphodiesterase 3B (PDE3B) has been suggested to be critical for mediating insulin/IGF-1 inhibition of cAMP signaling in adipocytes, liver, and pancreatic beta cells. In Pde3b-KO adipocytes we found decreased adipocyte size, unchanged insulin-stimulated phosphorylation of protein kinase B and activation of glucose uptake, enhanced catecholamine-stimulated lipolysis and insulin-stimulated lipogenesis, and blocked insulin inhibition of catecholamine-stimulated lipolysis. Glucose, alone or in combination with glucagon-like peptide-1, increased insulin secretion more in isolated pancreatic KO islets, although islet size and morphology and immunoreactive insulin and glucagon levels were unchanged. The beta(3)-adrenergic agonist CL 316,243 (CL) increased lipolysis and serum insulin more in KO mice, but blood glucose reduction was less in CL-treated KO mice. Insulin resistance was observed in KO mice, with liver an important site of alterations in insulin-sensitive glucose production. In KO mice, liver triglyceride and cAMP contents were increased, and the liver content and phosphorylation states of several insulin signaling, gluconeogenic, and inflammation- and stress-related components were altered. Thus, PDE3B may be important in regulating certain cAMP signaling pathways, including lipolysis, insulin-induced antilipolysis, and cAMP-mediated insulin secretion. Altered expression and/or regulation of PDE3B may contribute to metabolic dysregulation, including systemic insulin resistance.