tbuckley/cabot-search huggingface dataset:
Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: potential use of hypoallergenic isoforms for immunotherapy.
Authors: F Ferreira, K Hirtenlehner, A Jilek, J Godnik-Cvar, H Breiteneder, R Grimm, K Hoffmann-Sommergruber, O Scheiner, D Kraft, M Breitenbach, H J Rheinberger, C Ebner
Journal: The Journal of Experimental Medicine (1996)

We dissected the T cell activation potency and the immunoglobulin (Ig) E-binding properties (allergenicity) of nine isoforms of Bet v 1 (Bet v 1a-Bet v 1l), the major birch pollen allergen. Immunoblot experiments showed that Bet v 1 isoforms differ in their ability to bind IgE from birch pollen-allergic patients. All patients tested displayed similar IgE-binding patterns toward each particular isoform. Based on these experiments, we grouped Bet v 1 isoforms in three classes: molecules with high IgE-binding activity (isoforms a, e, and j), intermediate IgE-binding (isoforms b, c, and f), and low/no IgE-binding activity (isoforms d, g, and 1). Bet v 1a, a recombinant isoform selected from a cDNA expression library using IgE immunoscreening exhibited the highest IgE-binding activity. Isoforms a, b, d, e, and 1 were chosen as representatives from the three classes for experimentation. The potency of each isoallergen to activate T lymphocytes from birch pollen-allergic patients was assayed using peripheral blood mononuclear cells, allergen-specific T cell lines, and peptide-mapped allergen-specific T cell clones. Among the patients, some displayed a broad range of T cell-recognition patterns for Bet v 1 isoforms whereas others seemed to be restricted to particular isoforms. In spite of this variability, the highest scores for T cell proliferative responses were observed with isoform d (low IgE binder), followed by b, 1, e, and a. In vivo (skin prick) tests showed that the potency of isoforms d and 1 to induce typical urticarial type 1 reactions in Bet v 1-allergic individuals was significantly lower than for isoforms a, b, and e. Taken together, our results indicate that hypoallergenic Bet v 1 isoforms are potent activators of allergen-specific T lymphocytes, and Bet v 1 isoforms with high in vitro IgE-binding activity and in vivo allergenicity can display low T cell antigenicity. Based on these findings, we propose a novel approach for immunotherapy of type I allergies: a treatment with high doses of hypoallergenic isoforms or recombinant variants of atopic allergens. We proceed on the assumption that this measure would modulate the quality of the T helper cell response to allergens in vivo. The therapy form would additionally implicate a reduced risk of anaphylactic side effects.
A British Medical Association Lecture on IMMUNIZATION AGAINST DIPHTHERIA, SCARLET FEVER, AND MEASLES
Authors: S. M. Copeman
Journal: BMJ (1928)

THE outcome of Behriing's researches on diphltheria, result- inig in the introduction of antitoxin, c onstituted a great advance in the treatm-ient of this disease, by affording the possibility of mitigating and even of aborting attack, pr ovided that the antitoxin is employed at a sufficiently early stage.Moreover, if " contacts " are inoculated before any symptoms have developed, incidence of the disease can be prevented.'Unfortunately, however, the passive im- munity thus produeed is of a very fleeting nature, not extending, as a, rule, for a period longer than three weeks or so.
No Effect of High-Dose Vitamin D Supplementation on Glycemic Status or Cardiovascular Risk Factors in Subjects With Prediabetes
Authors: Stina Therese Sollid, Moira Y.S. Hutchinson, Ole M. Fuskevåg, Yngve Figenschau, Ragnar M. Joakimsen, Henrik Schirmer, Inger Njølstad, Johan Svartberg, Elena Kamycheva, Rolf Jorde
Journal: Diabetes Care (2014)

OBJECTIVE In observational studies, low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) randomly assigned to 20,000 IU/week vitamin D3 or placebo. An oral glucose tolerance test was performed at baseline and after 1 year. RESULTS Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups, respectively, and increased by 45.8 nmol/L and 3.4 nmol/L, respectively. With adjustment for baseline concentrations, no differences in measures of glucose metabolism, insulin secretion or sensitivity, blood pressure, or hs-CRP were found after 1 year. There was a slight, but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group, but as there was also a decrease in HDL cholesterol, the change in the total/HDL cholesterol ratio did not differ significantly. Only analyzing subjects with 25(OH)D &amp;lt;50 nmol/L did not change the results. CONCLUSIONS This study shows that vitamin D supplementation does not improve glycemic indices, blood pressure, or lipid status in subjects with IFG and/or IGT.
Clinician Perspectives Regarding the Do-Not-Resuscitate Order
Authors: Amy Sanderson, David Zurakowski, Joanne Wolfe
Journal: JAMA Pediatrics (2013)

While data exist regarding the frequency and timing of the do-not-resuscitate (DNR) order in children, little is known about clinician attitudes and behaviors regarding this order.To identify clinician attitudes regarding the meaning, implication, and timing of the DNR order for pediatric patients.Physicians and nurses from practice settings where advance care planning typically takes place were surveyed regarding their attitudes and behaviors about DNR orders.In total, 107 physicians and 159 nurses responded to the survey (N = 266). There was substantial variability in the interpretation of the DNR order. Most clinicians (66.9%) believe that a DNR order indicates limitation of resuscitative measures only on cardiopulmonary arrest. In reality, however, more than 85% believe that care changes beyond response to cardiopulmonary arrest, varying from increased attention to comfort to less clinician attentiveness. In addition, most clinicians reported that resuscitation status discussions take place later in the illness course than is ideal.Clinicians use the DNR order not only as a guide for therapeutic decisions during a cardiopulmonary arrest but also as a surrogate for broader treatment directives. Most clinicians believe that DNR discussions should take place earlier than they actually do. Interventions aimed at improving clinician knowledge and skills in advance care discussions as well as the development of orders that address overall goals of care may improve care for children with serious illness.
Interpretations of three sputum smear examinations at the first diagnosis in our hospital's tuberculosis patients
Authors: Kanako Kobayashi, Shuichi Yano, Toshikazu Ikeda
Journal: European Respiratory Journal (2012)

Purpose: Toman et al. (1979) suggested that three serial sputum smear examinations were recommended as a standard method for tuberculosis (TB) diagnosis. However, this was based on direct smear methods with Ziehl-Nielsen staining. Thus, we investigated if three sputum examinations were necessary for our hospital using homogenization/digestion, concentration, and fluorochrome staining.

Methods: We evaluated TB patients admitted to our hospital between April 1, 2005 and December 31, 2009. A retrospective study was used to assess each test's positivity Specimens were evaluated using Gaffky's number and sputum properties by Miller and Jones classification. Sputum was transported promptly, and N-acetyl-L-cysteine (NALC)-2% NaOH was added. After sputum underwent homogenization/digestion and decontamination, a specimen was immediately spun down in a refrigerated centrifuge. Fluorochrome staining of smears was used.

Results: Of 268 patients who met the screening criteria, 204 were positive on their first sputum smear (76.1%). Nineteen patients whose first sputum smear was negative became positive with the second test (7.1%). Eight patients whose first and second tests were negative became positive with the third test (3.0%). After excluding strongly positive smear patients, 134 among 198 patients were positive on their first sputum smear (67.7%). With an M1 or M2 sputum property, 114 among 168 patients were positive on their first sputum smear (67.9%). In contrast, with P1-P3, 81 among 89 patients were positive on the first sputum smear (91.0%).

Conclusion: TB patients with weakly positive smears or with a not purulent sputum property should undergo three sputum smear tests.
Lung cancer * 4: Chemotherapy for non-small cell lung cancer: the end of the beginning
Authors: M Cullen
Journal: Thorax (2003)

The development of chemotherapy for NSCLC over the last 20 years is reviewed, particularly with regard to its palliative effects. New “fourth generation” agents designed to inhibit specific biological pathways thought to be crucial to tumour growth give cause for optimism in the future treatment of NSCLC.
Polygenic Risk and the Developmental Progression to Heavy, Persistent Smoking and Nicotine Dependence
Authors: Daniel W. Belsky, Terrie E. Moffitt, Timothy B. Baker, Andrea K. Biddle, James P. Evans, HonaLee Harrington, Renate Houts, Madeline Meier, Karen Sugden, Benjamin Williams, Richie Poulton, Avshalom Caspi
Journal: JAMA Psychiatry (2013)

Genome-wide hypothesis-free discovery methods have identified loci that are associated with heavy smoking in adulthood. Research is needed to understand developmental processes that link newly discovered genetic risks with adult heavy smoking.To test how genetic risks discovered in genome-wide association studies of adult smoking influence the developmental progression of smoking behavior from initiation through conversion to daily smoking, progression to heavy smoking, nicotine dependence, and struggles with cessation.A 38-year, prospective, longitudinal study of a representative birth cohort.The Dunedin Multidisciplinary Health and Development Study of New Zealand.The study included 1037 male and female participants.We assessed genetic risk with a multilocus genetic risk score. The genetic risk score was composed of single-nucleotide polymorphisms identified in 3 meta-analyses of genome-wide association studies of smoking quantity phenotypes.Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerström Test of Nicotine Dependence), and cessation difficulties were evaluated at 8 assessments spanning the ages of 11 to 38 years.Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that 2 adolescent developmental phenotypes-early conversion to daily smoking and rapid progression to heavy smoking-mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history.Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers.
Some Account of the Operations Practised in the Nineteenth Century for the Relief of Tension of the Eyeball, Glaucoma, etc
Authors: J. V. Solomon
Journal: BMJ (1864)

serious and at times of fatal mischief.They have been the cause of infantile convulsions and conse- quent death; and surely in a diseased condition they may naturally be expected to interfere with the health of the adult, who is arrived at that period of life at which he is more at the mercy of their mis- chievous tendeincies, though in his case the evil may proceed in a subtler form, and with a slower pace.
Structural and Functional Properties of Deep Abdominal Subcutaneous Adipose Tissue Explain Its Association With Insulin Resistance and Cardiovascular Risk in Men
Authors: Kyriakoula Marinou, Leanne Hodson, Senthil K. Vasan, Barbara A. Fielding, Rajarshi Banerjee, Kerstin Brismar, Michael Koutsilieris, Anne Clark, Matt J. Neville, Fredrik Karpe
Journal: Diabetes Care (2013)

Fat distribution is an important variable explaining metabolic heterogeneity of obesity. Abdominal subcutaneous adipose tissue (SAT) is divided by the Scarpa's fascia into a deep subcutaneous adipose tissue (dSAT) and a superficial subcutaneous adipose tissue (sSAT) layer. This study sought to characterize functional differences between the two SAT layers to explore their relative contribution to metabolic traits and cardiovascular risk (CVR) profile.We recruited 371 Caucasians consecutively from a local random, population-based screening project in Oxford and 25 Asian Indians from the local community. The depth of the SAT layers was determined by ultrasound (US), and adipose tissue (AT) biopsies were performed under US guidance in a subgroup of 43 Caucasians. Visceral adipose tissue (VAT) mass was quantified by dual-energy X-ray absorptiometry scan.Male adiposity in both ethnic groups was characterized by a disproportionate expansion of dSAT, which was strongly correlated with VAT mass. dSAT depth was a strong predictor of global insulin resistance (IR; homeostatic model assessment of IR), liver-specific IR (insulin-like growth factor binding protein-1), and Framingham risk score independently of other measures of adiposity in men. Moreover, dSAT had higher expression of proinflammatory, lipogenic, and lipolytic genes and contained higher proportions of saturated fatty acids. There was increased proportion of small adipocytes in dSAT.SAT is heterogeneous; dSAT expands disproportionally more than sSAT with increasing obesity in Caucasian males (confirmed also in Asian Indians). Its expansion is related to increased CVR independent of other adiposity measures, and it has biological properties suggestive of higher metabolic activity contributing to global IR.
Calcium-responsive transactivator (CREST) protein shares a set of structural and functional traits with other proteins associated with amyotrophic lateral sclerosis
Authors: Michail S Kukharsky, Annamaria Quintiero, Taisei Matsumoto, Koji Matsukawa, Haiyan An, Tadafumi Hashimoto, Takeshi Iwatsubo, Vladimir L Buchman, Tatyana A Shelkovnikova
Journal: Molecular Neurodegeneration (2015)

Mutations in calcium-responsive transactivator (CREST) encoding gene have been recently linked to ALS. Similar to several proteins implicated in ALS, CREST contains a prion-like domain and was reported to be a component of paraspeckles.We demonstrate that CREST is prone to aggregation and co-aggregates with FUS but not with other two ALS-linked proteins, TDP-43 and TAF15, in cultured cells. Aggregation of CREST affects paraspeckle integrity, probably by trapping other paraspeckle proteins within aggregates. Like several other ALS-associated proteins, CREST is recruited to induced stress granules. Neither of the CREST mutations described in ALS alters its subcellular localization, stress granule recruitment or detergent solubility; however Q388stop mutation results in elevated steady-state levels and more frequent nuclear aggregation of the protein. Both wild-type protein and its mutants negatively affect neurite network complexity of unstimulated cultured neurons when overexpressed, with Q388stop mutation being the most deleterious. When overexpressed in the fly eye, wild-type CREST or its mutants lead to severe retinal degeneration without obvious differences between the variants.Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity. A change in CREST levels in neurons which might occur under pathological conditions would have a profound negative effect on neuronal homeostasis.
Factors Influencing Collateral Blood Flow to the Dog's Lung
Authors: PETER F. SALISBURY, PETER WEIL, DAVID STATE
Journal: Circulation Research (1957)

The collateral circulation of the lung, i.e., that part of the bronchial flow which drains into the pulmonary veins, was studied by a heart-lung arrangement in which the lesser and systemic circuits of dogs could be perfused separately. In this preparation the collateral supply amounted to 0.5 to 1 per cent of the total arterial flow under approximately normal conditions. The changes in this collateral flow under a variety of experimental conditions were studied. These included variable systemic, venous and pulmonar pressures, lung collapse, air embolism, and actions of CO 2 and serotonin.
Dietary Supplementation with Silymarin Inhibits 3,2′-Dimethyl-4-Aminobiphenyl–Induced Prostate Carcinogenesis in Male F344 Rats
Authors: Hiroyuki Kohno, Rikako Suzuki, Shigeyuki Sugie, Hiroyuki Tsuda, Takuji Tanaka
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Silymarin has been shown to be a potent anticarcinogenic agent. Here, we investigated the modifying effects of dietary feeding with a naturally occurring polyphenolic antioxidant flavonoid silymarin on 3,2′-dimethyl-4-aminobiphenyl (DMAB)–induced prostatic carcinogenesis in male F344 rats. Experimental Design: Male F344 rats were given s.c. injections of DMAB (25 mg/kg body weight) every other week for 20 weeks. They also received the experimental diet containing 100 or 500 ppm silymarin for 40 weeks, starting 1 week after the last dosing of DMAB. All of the rats were sacrificed 60 weeks after the start of the experiment. Histopathology and immunohistochemistry for proliferative cell nuclear antigen, cyclin D1, and apoptotic indices were done in the prostatic lesions, including invasive adenocarcinomas, intraepithelial neoplasms, and nonlesional glands. Results: Dietary feeding with 500 ppm silymarin significantly inhibited the incidence of prostatic adenocarcinoma when compared with the DMAB-alone group (17.6% versus 50.0%, P &amp;lt; 0.05). The proliferative cell nuclear antigen– and cyclin D1–positive indices in adenocarcinomas, prostatic intraepithelial neoplasm, and nonlesional glands in rats treated with DMAB and silymarin were slightly lower than that of the DMAB-alone group. Also, dietary administration of silymarin increased apoptotic index in prostatic adenocarcinoma by measuring immunohistochemically positive nuclei for ssDNA. Conclusions: Our results indicate that silymarin exerts chemopreventive ability against chemically induced prostatic carcinogenesis through apoptosis induction and modification of cell proliferation.
Something old, something new: Changing views on the cellular mechanisms of heart failure
Authors: Karin R. Sipido, David Eisner
Journal: Cardiovascular Research (2005)

See article by Fauconnier et al.  [84]  (pages 204–212) in this issue. 

Despite improvements in therapy, mortality in heart failure (HF) remains high, and there is a need for alternative and additional approaches [1,2]. The possibility of replacement and/or supporting the failing heart with new cardiomyocytes from stem cells, implanted or recruited locally, is one of the exciting possibilities under investigation [3]. Other approaches aim at improving the function of the failing myocytes. Although the temporal and causal relationship between the development of chronic HF and myocyte dysfunction remains unclear [4], there is little doubt that at the time of advanced HF, the isolated myocytes have reduced contractility, in particular under normal physiological stress, i.e. at physiological heart rates and in the response to adrenergic stimulation. The first trials with chronic inotropic therapy, however, had a very poor outcome, and the idea was abandoned for quite a long time [5]. However, new ideas to improve contractility of the myocytes are growing from recent insights into the cellular mechanisms underlying the contractile dysfunction and the link to signals for remodeling. In this editorial, we will briefly review the background of excitation–contraction coupling and changes in heart failure against which these views developed and discuss some future perspectives.

The process of excitation–contraction coupling has been reviewed extensively and is schematically illustrated in Fig. 1 [6,7]. Central in the link between membrane depolarization and contraction is the transient elevation of [Ca2+]i, or [Ca2+]i transient.



Fig. 1 
Schematic of excitation–contraction coupling. During the action potential, Ca2+ enters the cell through voltage-activated Ca2+ channels, with a small additional amount entering through the Na/Ca exchanger, NCX, depending on the [Na+]i. This Ca2+ acts as trigger to activate the Ca … 



*Corresponding author. Tel.: +32 16 347153; fax: +32 16 345844. Email address: Karin.Sipido{at}med.kuleuven.be
Lack of effect of topical spironolactone on sebum excretion
Authors: Shernaz Walton, W.J. Cunliffe, P. Lookingbill, K. Keczkes
Journal: British Journal of Dermatology (1986)

Journal Article Lack of effect of topical spironolactone on sebum excretion Get access Shernaz Walton, Shernaz Walton Department of Dermatology, The General Infirmary, Leeds LS1 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar W.J. Cunliffe, W.J. Cunliffe Department of Dermatology, The General Infirmary, Leeds LS1 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. Lookingbill, P. Lookingbill Milton S. Hershey Medical Centre, Pennsylvania State University, Hershey, Pennsylvania 17033, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar K. Keczkes K. Keczkes Hull Royal Infirmary, Hull, HU 2JZ, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 114, Issue 2, 1 February 1986, Pages 261–264, https://doi.org/10.1111/j.1365-2133.1986.tb02807.x Published: 01 February 1986