tbuckley/cabot-search huggingface dataset:
THE FUNCTIONAL DISSECTION OF AN ANTIGEN MOLECULE: SPECIFICITY OF HUMORAL AND CELLULAR IMMUNE RESPONSES TO GLUCAGON
Authors: George Senyk, E. Brady Williams, Danute E. Nitecki, Joel W. Goodman
Journal: The Journal of Experimental Medicine (1971)

Bovine glucagon, a polypeptide of 29 amino acids, was immunogenic in guinea pigs. The immunologic determinants of glucagon were investigated using isolated tryptic peptides of the hormone. Antibodies from virtually all of more than two dozen animals had specificity primarily for the amino-terminal heptadecapeptide (NM) and showed little or no binding with the carboxy-terminal undeca- and dodecapeptides (C). The smallest synthetic peptide of a series initiated at residue 16 which measurably bound antibody comprised residues 5-16 of glucagon. In cellular immune assays, both NM and C elicited delayed cutaneous reactions and inhibited the migration of peritoneal cells from immune animals. However, only intact glucagon and its C fragment stimulated lymphoid cells to synthesize DNA. While glucagon was somewhat more active than C, the addition of NM to C did not enhance its transforming activity. The smallest synthetic carboxy-terminal peptide with discernible transforming activity comprised residues 19-29 of glucagon. In both native and synthetic C peptide preparations, the undecapeptide was generally more active than the dodecapeptide, although cells from different animals gave different response patterns. The difference between the two is the presence of arginine at the amino-terminus of the peptide chain. Thus, the recognition specificity of populations of antigen-reactive cells from different animals displays a variation which is at least superficially analogous to that of populations of antibody molecules. In limited experiments using NM and C peptides as immunogens, neither gave rise to delayed hypersensitivity or to glucagon-binding circulating antibody, following a regimen which invariably provoked these responses when glucagon itself served as the immunogen. These results indicate that glucagon was cleaved by trypsin along functional lines into two parts, one of which housed the major antigenic determinant and the other of which carried the major immunogenic determinant, and they are highly compatible with a two-cell mechanism of immune induction. An apparent dissociation between the capacity to provoke delayed hypersensitivity reactions and to transform antigen-reactive cells in culture was observed.
A method for the evaluation of the local antiandrogenic action of 5α-reductase inhibitors on human skin
Authors: A. J. M. VERMORKEN, C. M. A. A. GOOS, H. M. J. ROELOFS
Journal: British Journal of Dermatology (1980)

A method has been developed for the first time that allows the evaluation of the effect of therapeutic concentrations of 5 alpha-reductase inhibitors in human skin, without applying radioactivity to the skin. Moreover, the method makes it possible to determine whether inhibition is found only at the application site or also in other parts of the skin.
Chronic sputum production: correlations between clinical features and findings on high resolution computed tomographic scanning of the chest.
Authors: I. E. Smith, E. Jurriaans, S. Diederich, N. Ali, J. M. Shneerson, C. D. Flower
Journal: Thorax (1996)

There are few published data on the correlation between the clinical findings in subjects with chronic sputum production and the appearances on high resolution computed tomographic (HRCT) scans of the chest.HRCT scanning of the chest was performed on 40 subjects with chronic sputum production. Three readers independently reported the scans for the presence or absence of bronchiectasis and the extent of bronchiectasis on the basis of the percentage of involved bronchi in each lobe. Relationships were sought between these findings and the clinical history, physical examination, and laboratory investigations.HRCT scanning showed that 27 subjects had bronchiectasis. Of the clinical features only the continual production of purulent sputum and childhood pertussis were associated with bronchiectasis. There was a positive correlation between the extent of bronchiectasis and dyspnoea, and a negative correlation with forced expiratory volume in one second but not with forced vital capacity.These results indicate that, in subjects with chronic sputum production, only a few clinical features show any correlation with the presence or extent of bronchiectasis as visualised on HRCT scans.
Physiologic responses to the incremental shuttle-walk test in adolescents with idiopathic scoliosis
Authors: Evandro Fornias Sperandio, Anderson Sales Alexandre, Fabíola Pereira Rebouças, Liu Chiao Yi, Patrícia Rios Poletto, Alberto Ofenhejm Gotfryd, Milena Carlos Vidotto, Victor Zuniga Dourado
Journal: European Respiratory Journal (2013)

Exercise limitation has been described in patients with adolescent idiopathic scoliosis (AIS). However, whether the walking performance is impaired in these patients should be elucidated. We aimed to evaluate physiologic responses to the incremental shuttle-walk test (ISWT) in patients with AIS. Twenty-nine patients with AIS and 20 healthy adolescents aged 10-18 years performed two ISWT. During the second test, oxygen uptake (VO 2 ), CO 2  production (VCO 2 ), ventilation (VE) and heart rate (HR) were continuously monitored. We assessed the following rates of changes during the ISWT: ΔVO 2 /Δwalking-velocity, ΔHR/ΔVO 2 , ΔVE/ΔVCO 2 , and linearized Δtidal-volume (VT)/ΔlnVE. Forced expiratory volume in 1s (FEV 1 ) and forced vital capacity (FVC) were also assessed. Patients with AIS showed significant lower values of incremental shuttle-walk distance (ISWD: 498 ± 144 vs. 604 ± 85 m), peak VO 2  [median (interquartile range), 25 (21-27) vs. 28 (24-33) mL/min/kg], peak VE (43 ± 16 vs. 52 ± 14 L/min) as well as lower FEV 1  [2.77 (2.48 to 3.17) vs. 3.33 (3.16 to 3.81) L] and FVC (2.51 ± 0.68 vs. 2.94 ± 0.66 L). Patients also presented significant shalower slope of ΔVT/ΔlnVE (0.32 ± 12 vs. 0.45 ± 16), i.e., worse breathing pattern during exercise. In patients, peak VO 2  correlated significantly with ISWD (r = 0.80), FVC (r = 0.78), FEV 1  (r = 0.73) and ΔVT/ΔlnVE (r = 0.58). We conclude that patients with AIS present significant walking limitation due to impaired pulmonary function and breathing pattern during exercise. This impairment may partialy explain the reluctance of patients with AIS to perform exercises. Thus, walking-based aerobic exercises should be encouraged in these patients.
Rate of Tension Development in Cardiac Muscle Varies With Level of Activator Calcium
Authors: Matthew R. Wolff, Kerry S. McDonald, Richard L. Moss
Journal: Circulation Research (1995)

In skeletal muscle, the rate of transition from weakly bound to force-generating crossbridge states increases as calcium concentration is increased. To examine possible calcium sensitivity of this transition in cardiac muscle, we determined the kinetics of isometric tension development during steady activation in detergent-permeabilized rat ventricular trabeculae (n = 7) over a range of calcium concentrations. Force-generating crossbridges in activated trabeculae were disrupted by a brief, rapid release and restretch equivalent to 20% muscle length (15 degrees C), which resulted in a subsequent phase of tension redevelopment that was well fit by a monoexponential function (rate constant, ktr). Sarcomere length was monitored by laser diffraction and held constant during tension redevelopment by an iterative adaptive feedback control system. The ktr increased from 3.6 +/- 0.8 s-1 at the lowest calcium concentration studied (pCa 5.9) to 9.5 +/- 1.3 s-1 during maximal activation (pCa 4.5). The relationship between relative ktr and relative tension was approximately linear over a wide range of [Ca2+] (r2 = .94). This result differs quantitatively from results in skeletal muscle, in which ktr is sensitive to [Ca2+] primarily at higher activation levels. This observation is also inconsistent with a recent suggestion that the rate of force development in living myocardium is independent of the activation level. Our results in skinned myocardium can be explained by a model in which calcium is a graded regulator of both the extent and rate of binding of force-generating crossbridges to the thin filament.
Iron deficiency anaemia--how far to investigate?
Authors: R Sahay, B B Scott
Journal: Gut (1993)

Since 1980 investigations, by this group, of patients with iron deficiency anaemia and no obvious cause, have been limited to upper gastrointestinal endoscopy, with small bowel biopsy, and barium enema. This study attempted to follow up 93 consecutive patients whose anaemia remained obscure after these investigations to determine the outcome and assess the safety of this limited approach. In 1991/92 questionnaires were sent to the general practitioners. Eighty three completed questionnaires were received. Ten patients had died all unrelated to the iron deficiency anaemia. The mean follow up of the 73 living patients was six years (range 4-12). Sixty five (89%) had a normal haemoglobin concentration and only 15 were still taking oral iron. Possible causes for the anaemia were found in 17-non-steroidal anti-inflammatory drug use in 10, menstruation in two, gastrectomy in three, poor nutrition in two. No other cause emerged. It is concluded that this limited investigative approach is safe.
Magnesium Supplementation Combined with N-Acetylcysteine Protects against Postischemic Acute Renal Failure
Authors: Magali de Araujo, Lucia Andrade, Terezila M. Coimbra, Adilson C. Rodrigues, Antonio Carlos Seguro
Journal: Journal of the American Society of Nephrology (2005)

Magnesium is a potent vasodilator whose effects have not been evaluated in renal ischemia. The antioxidant properties of N-acetylcysteine (NAC) partially protect animals from ischemic/reperfusion injury. This study was designed to evaluate magnesium supplementation, alone or combined with NAC, on ischemic acute renal failure. Rats were maintained on normal diets, supplemented or not with MgCl(2).6H(2)O (1% in drinking water) for 23 d, and some rats received NAC (440 mg/kg body wt) on days 20 to 23. On day 21, ischemia was induced by clamping both renal arteries for 30 min. Five groups were studied: Normal, ischemia, ischemia+magnesium, ischemia+NAC, and ischemia+magnesium+NAC. GFR (inulin clearance), renal blood flow (RBF), FEH(2)O, and FENa were determined. Serum magnesium was decreased in ischemia-only rats. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. However, NAC completely restored the tubular damage induced by ischemia/reperfusion. Semiquantitative immunoblotting showed that NAC prevented the decreased expression of Na-K-2Cl co-transporter and aquaporin 2 after renal ischemia/reperfusion. Untreated rats with acute renal failure demonstrated markedly decreased endothelial nitric oxide synthase expression. Significantly, treatment with NAC, magnesium, or both completely inhibited downregulation of endothelial nitric oxide synthase. The tubular necrosis scores were lower in rats that were treated with NAC alone or with the magnesium-NAC combination. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. The NAC protected tubules from ischemia, decreased infiltrating macrophages/lymphocytes, and had a mild protective effect on GFR. In ischemic/reperfusion injury, renal function benefits more from the magnesium-NAC combination than from magnesium alone.
Deoxycholic acid influences cholesterol solubilization and microcrystal nucleation time in gallbladder bile
Authors: S. Hyder Hussaini, Stephen P. Pereira, Gerard M. Murphy, R. Hermon Dowling
Journal: Hepatology (1995)

Little is known about the effects of biliary deoxycholic acid on the partitioning of biliary cholesterol between vesicles and micelles and on the rate of nucleation of cholesterol microcrystals, key steps in gallstone formation. Therefore, 43 samples of fresh gallbladder bile were obtained from a heterogeneous group of patients with and without stones. Univariate and multivariate analyses were then applied to determine the inter-relationships between biliary cholesterol saturation, total lipid concentration, and bile acid species and (1) the distribution of biliary cholesterol between vesicles and micelles and (2) the cholesterol microcrystal nucleation time. The percentage of deoxycholic acid in bile was shown to be linearly related to the cholesterol saturation index (r = .54; P < .001), the vesicular cholesterol:phospholipid molar ratio (r = .53; P < .001), and the molar concentration of cholesterol in the vesicles (r = .59; P < .001). The mean proportion of biliary deoxycholic acid conjugates was also greater in patients with rapid nucleation times (23.4 +/- SEM 1.1%) than in those with slow nucleation times (17.3 +/- 1.9%; P < .05). As total bile lipid concentration increased, the proportion of total biliary cholesterol in vesicles decreased (r = .53; P < .001), whereas the molar concentration of vesicular cholesterol increased (r = .42, P < .01). The cholesterol saturation indices, total bile lipid concentration, and proportion of biliary deoxycholate were independent determinants of the molar concentration of cholesterol in vesicles. We conclude that relative increases in the percentage of deoxycholic acid and in bile lipid concentration, favor the partitioning of cholesterol into vesicles. In turn, this leads to an increase in the vesicular cholesterol:phospholipid molar ratio and thus to a decrease in the cholesterol microcrystal nucleation time.
Relationship Between Chest Compression Rates and Outcomes From Cardiac Arrest
Authors: Ahamed H. Idris, Danielle Guffey, Tom P. Aufderheide, Siobhan Brown, Laurie J. Morrison, Patrick Nichols, Judy Powell, Mohamud Daya, Blair L. Bigham, Dianne L. Atkins, Robert Berg, Dan Davis, Ian Stiell, George Sopko, Graham Nichol
Journal: Circulation (2012)

Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions per minute. Animal and human studies have reported that blood flow is greatest with chest compression rates near 120/min, but few have reported rates used during out-of-hospital (OOH) cardiopulmonary resuscitation or the relationship between rate and outcome. The purpose of this study was to describe chest compression rates used by emergency medical services providers to resuscitate patients with OOH cardiac arrest and to determine the relationship between chest compression rate and outcome.
The draft genome of a socially polymorphic halictid bee, Lasioglossum albipes
Authors: Sarah D Kocher, Cai Li, Wei Yang, Hao Tan, Soojin V Yi, Xingyu Yang, Hopi E Hoekstra, Guojie Zhang, Naomi E Pierce, Douglas W Yu
Journal: Genome biology (2013)

Taxa that harbor natural phenotypic variation are ideal for ecological genomic approaches aimed at understanding how the interplay between genetic and environmental factors can lead to the evolution of complex traits. Lasioglossum albipes is a polymorphic halictid bee that expresses variation in social behavior among populations, and common-garden experiments have suggested that this variation is likely to have a genetic component. We present the L. albipes genome assembly to characterize the genetic and ecological factors associated with the evolution of social behavior. The de novo assembly is comparable to other published social insect genomes, with an N50 scaffold length of 602 kb. Gene families unique to L. albipes are associated with integrin-mediated signaling and DNA-binding domains, and several appear to be expanded in this species, including the glutathione-s-transferases and the inositol monophosphatases. L. albipes has an intact DNA methylation system, and in silico analyses suggest that methylation occurs primarily in exons. Comparisons to other insect genomes indicate that genes associated with metabolism and nucleotide binding undergo accelerated evolution in the halictid lineage. Whole-genome resequencing data from one solitary and one social L. albipes female identify six genes that appear to be rapidly diverging between social forms, including a putative odorant receptor and a cuticular protein. L. albipes represents a novel genetic model system for understanding the evolution of social behavior. It represents the first published genome sequence of a primitively social insect, thereby facilitating comparative genomic studies across the Hymenoptera as a whole.
Prolactin mediates psychological stress-induced dysfunction of regulatory T cells to facilitate intestinal inflammation
Authors: Wei Wu, Mingming Sun, Huan-Ping Zhang, Tengfei Chen, Ruijin Wu, Changqin Liu, Gui Yang, Xiao-Rui Geng, Bai-Sui Feng, Zhigang Liu, Zhanju Liu, Ping-Chang Yang
Journal: Gut (2014)

<h3>Objective</h3> The dysfunction of immune regulation plays a critical role in the pathogenesis of a number of chronic inflammatory disorders, such as IBD. A close relationship between psychological stress and intestinal inflammation has been noted; the underlying mechanism remains elusive. This study aims to elucidate a pathological pathway between psychological stress and the dysfunction of regulatory T cells (Treg), and its effect on facilitating intestinal inflammation. <h3>Design</h3> A restraint stress model was employed to induce psychological stress in mice. The functions of Tregs were determined by assessing the immune suppressor effects in the intestine. A mouse model of intestinal inflammation was established using a low dose of trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) together with the challenge of chronic stress. <h3>Results</h3> After treating mice with restraint stress, the suppressor function of intestinal Treg was compromised, although the frequency of Treg was not changed in the intestine. Further observation revealed that stress induced Tregs in the intestine to differentiate into foxhead box P3<sup>+</sup> interleukin (IL)-17<sup>+</sup> tumour necrosis factor (TNF)-α<sup>+</sup> T cells. We also observed that exposure to stress-derived prolactin induced dendritic cells (DC) to produce IL-6 and IL-23 in vitro and in vivo, which played a critical role in altering Treg9s phenotypes. Treating mice with chronic stress facilitated the initiation of intestinal inflammation by a low dose of TNBS or DSS, which was abolished by pretreatment with an inhibitor of prolactin, the cabergoline. <h3>Conclusions</h3> Psychological stress-derived prolactin alters DC and Treg9s properties to contribute to intestinal inflammation.
Epithelial Human Leukocyte Antigen-DR Expression Predicts Reduced Recurrence Rates and Prolonged Survival in Rectal Cancer Patients
Authors: Elza C. de Bruin, Cornelis J.H. van de Velde, J. Han J.M. van Krieken, Corrie A.M. Marijnen, Jan Paul Medema
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The development of local and distant recurrences is a major problem in the treatment of rectal cancer patients. In this study, we investigated whether epithelial human leukocyte antigen-DR (HLA-DR) expression allowed discrimination between high and low tumor recurrence rates, and analyzed the mechanism behind its expression. Experimental Design: The role of IFNγ in HLA-DR expression was studied in rectal cancer cell lines and tumors by promoter-specific analyses of class II transactivator (CIITA). The predictive value of epithelial HLA-DR expression was investigated by immunohistochemical evaluation of 1,016 rectal tumors, obtained from a large prospective trial. Associations with recurrences and survival were determined by univariate and multivariate log-rank testing. Results: HLA-DR was induced by IFNγ in rectal cancer cell lines. Activity of the IFNγ-inducible pIV-CIITA promoter correlated with epithelial HLA-DR expression in rectal tumors. Patients with HLA-DR–positive tumors developed less frequent local and distant recurrences [1.6% versus 9.1% (P = 0.0015) and 15.3% versus 29.9% (P &amp;lt; 0.0001), respectively, after 5 years of follow-up] and had better survival (78.6% versus 61.3%; P &amp;lt; 0.0001) than patients with HLA-DR–negative tumors. Epithelial HLA-DR was more often found in lower tumor-node-metastasis (TNM) stages. Next to TNM and circumferential resection margin, HLA-DR expression was independently associated with lower distant recurrence rates and prolonged survival. Conclusions: Epithelial HLA-DR expression can be used as a marker to discriminate patients with high or low risk of developing recurrences. The possible involvement of IFNγ, the relationship with lower TNM stages, and the independent effect on recurrence development together suggest that the host immune response plays an important role in controlling tumor cells.
Effective posttransplant antitumor immunity is associated with TLR-stimulating nucleic acid–immunoglobulin complexes in humans
Authors: Yun Lin, Li Zhang, Ann X. Cai, Mark Lee, Wandi Zhang, Donna Neuberg, Christine M. Canning, Robert J. Soiffer, Edwin P. Alyea, Jerome Ritz, Nir Hacohen, Terry K. Means, Catherine J. Wu
Journal: Journal of Clinical Investigation (2011)

Donor lymphocyte infusion (DLI), whereby donor mononuclear cells are infused into patients, is one of the few effective immunotherapeutic strategies that generate long-lasting tumor remissions. We previously demonstrated that chronic myelogenous leukemia (CML) patients treated with DLI develop high-titer plasma antibodies specific for CML-associated antigens, the majority of which have been reported to bind nucleic acids These observations led us to predict that circulating antibody-antigen complexes in DLI-responsive patients carry nucleic acids that can engage innate immune sensors. Consistent with this, we report here that post-DLI plasma from 5 CML patients that responded to DLI treatment induced massive upregulation of MIP-1α, IP-10, and IFN-α in normal blood mononuclear cells. Importantly, this was not observed with plasma obtained before DLI and from DLI nonresponders and imatinib-treated patients. This endogenous immunostimulatory activity required nucleic acid and protein for its adjuvant effect and activated antigen-presenting cells through the RNA and DNA sensors TLR8 and TLR9. Presence of the immunoglobulin Fc receptor CD32 enhanced cellular responses, suggesting that immunoglobulins associate with this activity. Finally, a TLR-induced expression signature was detectable in post-DLI but not pre-DLI blood, consistent with an active circulating TLR8/9-stimulating factor. We have therefore demonstrated that effective tumor immunity correlates with the presence of endogenous nucleic acid–immunoglobulin complexes in patient plasma, thus providing a putative mechanism for the induction of potent antigen-specific immunity against malignant cells.
Effect of cigarette smoking on the humoral immune response in pigeon fanciers
Authors: T. Carrillo, F. Rodriguez de Castro, M. Cuevas, F. Diaz, P. Cabrera
Journal: Allergy (1991)

Tobacco smoking is associated with increased prevalence of various diseases. In this study, we have used an indirect enzyme-linked immunosorbent assay (ELISA) to investigate the specific IgG response to pigeon serum and its relationship to tobacco smoking. In a large group of pigeon fanciers the development of pigeon breeder's disease and some of the clinical features were also investigated. We found a sensitization rate of 31.9%, a lower degree than that found by other authors, in spite of using a less specific antigen. We also found that fanciers who are current cigarette smokers had significantly lower levels of IgG antibody to pigeon serum (P less than 0.001). Finally, 11.9% of the population had chronic bronchitis as their only manifestation of possible pigeon-related disease. 19.6% of the sensitized fanciers had chronic bronchitis, were non-smokers and had no other risk factor for developing chronic bronchitis.