tbuckley/cabot-search huggingface dataset:
Effect of histocompatibility factors on pulmonary retention of indium‐111‐labeled granulocytes
Authors: Janice P. Dutcher, Charles Riggs, Jeremiah J. Fox, Gerald S. Johnston, Dottie Norris, Peter H. Wiernik, Charles A. Schiffer
Journal: American Journal of Hematology (1990)

Abstract Granulocyte transfusions are associated with a number of side effects including febrile transfusion reactions and occasionally pulmonary infiltrates. There is evidence that the presence of preformed antibodies may be a cause of these complications. In this study, allogeneic 111 lndium‐labeled granulocytes were used to evaluate the pulmonary retention of radioactivity in alloimmunized and non‐alloimmunized patients in an attempt to assess antibody effect on granulocyte migration. After injection of labeled allogeneic granulocytes into neutropenic patients, the ratios of lung to heart activity were calculated for the first 30 min of scanning. There was significantly greater retention of radioactivity from cells in the lungs of patients who were alloimmunized, having both lymphocytotoxic (anti‐HLA) and leukoagglutinating antibodies, compared to the activity in the lungs of non‐alloimmunized patients ( P &lt; 0.001) or of patients receiving autologous granulocytes ( P &lt; 0.001). This study demonstrates that labeled, mismatched granulocytes may be retained in the lungs for a significantly longer time in patients with preformed antibodies. This implies that transfusion of large numbers of such mismatched granulocytes, i. e., granulocyte transfusions, may also be retained in the lungs of alloimmunized patients, which could lead to pulmonary compromise. Therefore, granulocyte transfusions from random donors should not be given to alloimmunized patients.
Routine Use of Bilateral Skeletonized Internal Thoracic Artery Grafting
Authors: D. Pevni, G. Uretzky, A. Mohr, R. Braunstein, A. Kramer, Y. Paz, I. Shapira, R. Mohr
Journal: Circulation (2008)

Skeletonized harvesting of the internal thoracic artery (ITA) decreases the severity of sternal devascularization, thus reducing the risk of postoperative sternal complications in patients undergoing bilateral ITA grafting.Between 1996 and 2001, 1515 consecutive patients underwent skeletonized bilateral ITA grafting. Of the 1179 male and 336 female patients, 641 (42.3%) were >70 years of age, and 519 (34.2%) had diabetes mellitus. Operative mortality was 2.8%. Early postoperative morbidity included sternal infection (1.6%), cerebrovascular accident (3%), and perioperative myocardial infarction (1%). Multiple regression analysis showed chronic obstructive pulmonary disease (odds ratio, 11.3; 95% confidence interval [CI], 4.45 to 28.55), repeat operation (odds ratio, 12.7; 95% CI, 3.25 to 49.56), and diabetes mellitus (non-insulin dependent: odds ratio, 4.64; 95% CI, 1.85 to 11.59; insulin dependent: odds ratio, 6.9; 95% CI, 1.35 to 35.27) to be associated with increased risk of sternal infection. Follow-up (between 5 and 12 years) revealed 305 late deaths. Kaplan-Meier 10-year survival rates for patients <65, 65 to 74, and >75 years of age were 87%, 75%, and 52%, respectively. Cox regression analysis revealed increased overall mortality (early and late) in patients with peripheral vascular disease (hazard ratio [HR], 1.8; 95% CI, 1.39 to 2.33), patients >75 years of age (HR, 7.23; 95% CI, 4.16 to 12.55), those undergoing repeat operations (HR, 2.22; 95% CI, 1.27 to 3.89), patients with preoperative congestive heart failure (HR, 1.64; 95% CI, 1.29 to 3.75), and those with chronic renal failure (HR, 1.52; 95% CI, 1.11 to 2.01). Operations performed without cardiopulmonary bypass were associated with better postoperative survival (HR, 0.66; 95% CI, 0.49 to 0.87).Bilateral ITA grafting is associated with low morbidity and good long-term results. Use of skeletonized bilateral ITA is appropriate for the elderly and most patients with diabetes; however, it is not recommended for repeat operations or for patients with chronic obstructive pulmonary disease.
Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy
Authors: A.L. Bane, T.J. Whelan, G.R. Pond, S. Parpia, G. Gohla, A.W. Fyles, J.-P. Pignol, K.I. Pritchard, S. Chambers, M.N. Levine
Journal: Annals of Oncology (2014)

To determine whether tumor grade, molecular subtype and hypoxia predict response to hypofractionated versus standard radiotherapy (RT) following breast-conserving surgery (BCS) for node-negative breast cancer in a randomized controlled trial (RCT).Formalin-fixed paraffin-embedded (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology review and assessment of tumor grade using the Nottingham grading system was carried out. Tumors were classified by molecular subtype as luminal A, luminal B, HER2 enriched, basal-like or unclassified using a six-biomarker panel; ER, PR, HER-2, Ki67, CK5/6 and EGFR. Tumors were also classified as hypoxic based on the expression of HIF1α, CAIX or GLUT-1. The primary end point was local recurrence (LR).Median follow-up was 12 years. In the multivariable Cox model, molecular subtype was the only factor predictive of LR, the 10-year cumulative incidence was 4.5% for luminal A and basal-like, 7.9% for luminal B and 16.9% for HER-2 enriched tumors (P < 0.01). Tumor grade, molecular subtype or hypoxia did not predict response to hypofractionation.In women enrolled in the HWBI trial following BCS tumor molecular subtype predicted LR. However tumor grade, molecular subtype and hypoxia did not predict response to hypofractionation suggesting that patients with node-negative breast tumors of all grades and molecular subtypes may be safely treated with hypofractionated RT regimens.
High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation
Authors: Annalisa Chiocchetti, Manuela Indelicato, Thea Bensi, Riccardo Mesturini, Mara Giordano, Selina Sametti, Luca Castelli, Flavia Bottarel, Maria Clorinda Mazzarino, Letizia Garbarini, Francesca Giacopelli, Guido Valesini, Claudio Santoro, Irma Dianzani, Ugo Ramenghi, Umberto Dianzani
Journal: Blood (2003)
Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies
Authors: Inka Albrecht, Cecilia Wick, Åsa Hallgren, Anna Tjärnlund, Kanneboyina Nagaraju, Felipe Andrade, Kathryn Thompson, William Coley, Aditi Phadke, Lina-Marcela Diaz-Gallo, Matteo Bottai, Inger Nennesmo, Karine Chemin, Jessica Herrath, Karin Johansson, Anders Wikberg, A. Jimmy Ytterberg, Roman A. Zubarev, Olof Danielsson, Olga Krystufkova, Jiri Vencovsky, Nils Landegren, Marie Wahren-Herlenius, Leonid Padyukov, Olle Kämpe, Ingrid E. Lundberg
Journal: Journal of Clinical Investigation (2015)

Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1–negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.
Mucocutaneous Lymph Node Syndrome (Kawasaki Disease) in Adults
Authors: E. Dale Everett
Journal: JAMA (1979)

Mucocutaneous lymph node syndrome has been reported to occur only in children. Three adults aged 16 to 27 years had findings compatible with this illness. Patients with fever, polymorphous skin eruption, congested conjunctiva, reddened palms and soles, red lips and oral mucous membrane, and soft-tissue swelling of the peripheral extremities and who experience membranous desquamation of fingers and toes should be suspected of having mucocutaneous lymph node syndrome. No laboratory test is currently available for confirmation of the diagnosis.
Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.
Authors: R D Pullan, G A Thomas, M Rhodes, R G Newcombe, G T Williams, A Allen, J Rhodes
Journal: Gut (1994)

The thickness of adherent mucus gel on the surface of colonic mucosa was measured in surgically resected specimens from 46 'control' patients most of whom had carcinoma of the colon; 12 were from right colon, 17 left colon, and 21 from rectum. In addition specimens were examined from 17 patients with ulcerative colitis and 15 patients with Crohn's disease. In controls a continuous layer of mucus was readily seen on specially prepared sections viewed by phase contrast illumination. Mean values for right and left colon and rectum were 107 (48), 134 (68), and 155 (54) microns respectively with a significant difference between right colon and rectum (p = 0.015). Values in ulcerative colitis showed greater variation and in those areas with acute inflammation mucosa was denuded of the mucus layer. In contrast, values for Crohn's disease were normal or greater than normal in thickness--right colon 190 (83) microns compared with 107 48 microns, p = 0.0093. A series of validation experiments are described for the method used to measure mucus thickness. The possible role of mucus in the pathogenesis of inflammatory bowel disease is discussed.
An analogue device for the measurement of cardiovascular variables
Authors: H. PULS, G. ELZINGA
Journal: Cardiovascular Research (1978)

An analogue device is described which is designed to analyse repetitive signals. It measures peak amplitudes, time to peak values, areas, and values at a preset time. The results can be displayed or recorded on a beat-to-beat basis, or an average can be taken over up to 31 consecutive beats.
Recycling and target binding capacity of human natural killer cells.
Authors: M Ullberg, M Jondal
Journal: The Journal of Experimental Medicine (1981)

By combining a newly established single-cell cytotoxicity assay in agarose (16) with estimations of the maximum natural killer (NK) potential (Vmax) by 51Cr release that percentage of target-binding cells (TBC), the fraction of active killers among TBC, the kinetics of single-cell cytotoxicity, and the recycling of effector cells was studied. Using nylon wool-passed peripheral lymphocytes, approximately 10% of the cells will bind to NK- susceptible target cell lines. Most of these have receptors for IgG. Some 50% will go on to kill T cell targets and some 20% to kill the standard target cell K-562. As the individual NK cell is shown to have the capacity to recycle, i.e., to kill more than one target cell in the 3-h test period, and as recycling seems to vary between individuals, there is no consistent correlation between the number of TBC and 51Cr-release values. It seems as if the single-cell cytotoxicity assay, as presently performed in agarose, is a valuable complement to Vmax determinations by 51Cr-release to study the different steps involved in the cytolytic process: recognition, enzyme activation, and effector cell recycling. The discrimination between these steps will probably be necessary to define mechanisms influencing NK cells in different disease states as well as in learning more about the normal function and regulation of the human NK system.
AlkB Homologue 2–Mediated Repair of Ethenoadenine Lesions in Mammalian DNA
Authors: Jeanette Ringvoll, Marivi N. Moen, Line M. Nordstrand, Lisiane B. Meira, Bo Pang, Anders Bekkelund, Peter C. Dedon, Svein Bjelland, Leona D. Samson, Pål Ø. Falnes, Arne Klungland
Journal: Cancer Research (2008)

Abstract Endogenous formation of the mutagenic DNA adduct 1,N6-ethenoadenine (εA) originates from lipid peroxidation. Elevated levels of εA in cancer-prone tissues suggest a role for this adduct in the development of some cancers. The base excision repair pathway has been considered the principal repair system for εA lesions until recently, when it was shown that the Escherichia coli AlkB dioxygenase could directly reverse the damage. We report here kinetic analysis of the recombinant human AlkB homologue 2 (hABH2), which is able to repair εA lesions in DNA. Furthermore, cation exchange chromatography of nuclear extracts from wild-type and mABH2−/− mice indicates that mABH2 is the principal dioxygenase for εA repair in vivo. This is further substantiated by experiments showing that hABH2, but not hABH3, is able to complement the E. coli alkB mutant with respect to its defective repair of etheno adducts. We conclude that ABH2 is active in the direct reversal of εA lesions, and that ABH2, together with the alkyl-N-adenine-DNA glycosylase, which is the most effective enzyme for the repair of εA, comprise the cellular defense against εA lesions. [Cancer Res 2008;68(11):4142–9]
Prognostic Factors for Survival in Adult Patients With Recurrent Glioma Enrolled Onto the New Approaches to Brain Tumor Therapy CNS Consortium Phase I and II Clinical Trials
Authors: Kathryn A. Carson, Stuart A. Grossman, Joy D. Fisher, Edward G. Shaw
Journal: Journal of Clinical Oncology (2007)

Purpose Prognostic factor analyses have proven useful in predicting outcome in patients with newly diagnosed malignant glioma. Similar analyses in patients with recurrent glioma could affect the design and conduct of clinical trials substantially. Patients and Methods Between 1995 and 2002, 333 adults with recurrent gliomas were enrolled onto 10 phase I or II trials of systemic or local therapy. The studies had similar inclusion criteria and were conducted within the New Approaches to Brain Tumor Therapy CNS Consortium. Ninety-three percent of the patients have died. Cox proportional hazards (PH) regression and recursive partitioning analysis (RPA) were performed to identify prognostic factors. Results Factors associated with an increased risk of death were increased age, lower Karnofsky performance score (KPS), initial and on-study histologies of glioblastoma multiforme (GBM), corticosteroid use, shorter time from original diagnosis to recurrence, and tumor outside frontal lobe. The final PH model included initial histology of GBM (relative risk [RR] = 2.01), 10-year increase in age (RR = 1.23), KPS less than 80 (RR = 1.54), and corticosteroid use (RR = 1.49). RPA resulted in seven classes. Median survival time was poorest in non-GBM patients with KPS less than 80 or GBM patients, age ≥ 50 years, corticosteroid use (4.4 months; 95% CI, 3.6 to 5.4 months); median survival was best in patients with initial histology other than GBM with KPS ≥ 80 and tumor confined to the frontal lobe (25.7 months; 95% CI, 18.7 to 52.5), and was 7.0 months (95% CI, 6.2 to 8.0 months) for all patients. Conclusion Initial histology, age, KPS, and corticosteroid use are prognostic for survival in recurrent glioma patients. To allow comparisons across phase II trials, enrollment criteria may need to be restricted.
Favorable impact of the interleukin-4 receptor allelic variant I75 on the survival of diffuse large B-cell lymphoma patients demonstrated in a large prospective clinical trial
Authors: N Schoof, F von Bonin, S Zeynalova, M Ziepert, W Jung, M Loeffler, M Pfreundschuh, L Trümper, D Kube
Journal: Annals of Oncology (2009)
Cell mediated immunity to corn starch in starch-induced granulomatous peritonitis.
Authors: R L Goodacre, R L Clancy, R A Davidson, J E Mullens
Journal: Gut (1976)

Two patients with histologically diagnosed starch induced granulomatous peritonitis (SGP) have been shown to have cell mediated immunity to corn starch using the techniques of macrophage migration inhibition and lymphocyte DNA synthesis. Control groups of normal subjects, patients with uncomplicated laparotomy, and patients with Crohn's disease were negative in both tests. Lymphocytes from two patients with band adhesions, one of whom had biopsy evidence of a granulomatous reaction to starch, were sensitized to starch. Cell mediated immunity to starch may contribute to the pathogenesis of SGP, and some band adhesions may be a chronic low grade manifestation of this disorder.
Plasma Insulin and C-Peptide Levels During Continuous Subcutaneous Insulin Infusion
Authors: Gerard Slama, Kim Nguyen Phuoc Buu, Georges Tchobroutsky, Anne Delage, Nelly Desplanque
Journal: Diabetes Care (1979)

A study was performed to estimate the absorption kinetics of insulin infused subcutaneously. Four insulin-dependent diabetic subjects had their insulin pumped through a subcutaneously implanted fine polyethylene catheter at a constant rate of 5.0 +/- 0.3 ml/h but at two different insulin concentrations: 218 mU/ml between meals, and 2400 mU/ml at the start of breakfast, lunch, and dinner (lasting 20, 30, and 30 min, respectively). The amount (40 U/day) and distribution of insulin delivered was identical in the four patients in order to facilitate comparison between the subjects. No attempt was made to normalize their blood glucose during the study period. A study of the kinetics of insulin absorption was made by assaying plasma insulin levels; lack of plasma anti-insulin antibodies was verified; plasma C-peptide levels were measured and were far below values observed in the fed state in nondiabetic patients. The mean maximum insulin level reached after switching from low to high concentration insulin was observed 87 +/- 2 min after breakfast, 117 +/- 22 min after lunch, and 125 +/- 20 min after dinner. Differences observed are not significant. These values are similar to those observed after subcutaneous injection of 40 U/ml Regular insulin as a single bolus. After switching from high to low concentration, plasma insulin levels did not return to their basal values before the third or fourth hour. Subcutaneous insulin infusion could be a safe and easy way of insulin administration in an open-loop system; however, this method does not seem to be suitable for a closed-loop system.
No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial
Authors: H Haibel, H C Brandt, I H Song, A Brandt, J Listing, M Rudwaleit, J Sieper
Journal: Annals of the Rheumatic Diseases (2006)

To examine the potential therapeutic effect of methotrexate 20 mg given weekly as subcutaneous injections to 20 patients with ankylosing spondylitis refractory to non-steroidal antirheumatic drugs.20 patients with ankylosing spondylitis, a mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 5.6 (range 4-9.3) and predominantly axial manifestations were treated with weekly 15 mg methotrexate subcutaneously for 4 weeks, which was then increased to 20 mg subcutaneously for the next 12 weeks. Clinical outcome assessments included, among others, BASDAI score physical function, spinal mobility, patients' and physicians' global assessment (visual analogue scale), peripheral joint assessment, quality of life (Short Form 36) and C reactive protein. The primary end point of the study was a 20% improvement on the ASsessments in Ankylosing Spondylitis (ASAS 20) scale.Using an intention-to-treat analysis, ASAS 20 was achieved in only 25% of patients. An ASAS 40 response was achieved in 10% of patients, and no patient reached an ASAS 70 response or the ASAS criteria for partial remission. For the mean BASDAI score, no change was observed between baseline and week 16 (baseline 5.6 v week 16, 5.6). No improvement was observed in any of the clinical parameters or C reactive protein, except a small but non-significant decrease in the number of swollen joints.In this open study, methotrexate did not show any benefit for axial manifestations in patients with active ankylosing spondylitis beyond the expected placebo response.
Prediction of Breast Tumor Progression by Integrity of Free Circulating DNA in Serum
Authors: Naoyuki Umetani, Armando E. Giuliano, Suzanne H. Hiramatsu, Farin Amersi, Taku Nakagawa, Silvana Martino, Dave S.B. Hoon
Journal: Journal of Clinical Oncology (2006)

Purpose Cell-free DNA circulating in serum is a candidate molecular biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic cells, DNA released from dead cancer cells varies in size. Serum DNA integrity, the ratio of longer fragments to total DNA, may be clinically useful for detecting breast cancer progression. Patients and Methods Serum samples from 51 healthy females and 83 females with primary breast cancers (eight American Joint Committee on Cancer stage 0, 24 stage I, 27 stage II, 21 stage III, and three stage IV) were assessed preoperatively. Serum DNA integrity was assessed by fragment length-dependent quantitative real-time polymerase chain reaction of ALU DNA repeats. Results Mean serum DNA integrity was significantly higher in patients with stage II, III, and IV breast cancers than in healthy females (P = .005, P &lt; .0001, and P = .002, respectively). The receiver operating characteristic (ROC) curve for discriminating patients with stage II or more advanced breast cancers from healthy females had an area under the curve (AUC) of 0.79 (95% CI, 0.70 to 0.86). Mean serum DNA integrity was positively correlated to size of invasive cancers (r = 0.48; P &lt; .0001) and significantly higher in the presence of lymphovascular invasion (LVI; 0.25 ± 0.02 v 0.17 ± 0.02; P &lt; .0001) or lymph node (LN) metastasis (0.27 ± 0.02 v 0.14 ± 0.02; P &lt; .0001). The ROC curve for discriminating LN metastasis had an AUC of 0.81 (95% CI, 0.72 to 0.89). Serum DNA integrity and LVI were significant for predicting LN metastasis in a multivariate analysis (P = .0002 and P &lt; .0001, respectively). Conclusion Integrity of serum circulating DNA is a promising molecular biomarker for detecting breast cancer tumor progression and regional LN metastases.