tbuckley/cabot-search huggingface dataset:
Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis
Authors: M. B. Azad, J. G. Coneys, A. L. Kozyrskyj, C. J. Field, C. D. Ramsey, A. B. Becker, C. Friesen, A. M. Abou-Setta, R. Zarychanski
Journal: BMJ (2013)

<b>Objective</b> To evaluate the association of probiotic supplementation during pregnancy or infancy with childhood asthma and wheeze. <b>Design</b> Systematic review and meta-analysis of randomised controlled trials. <b>Data sources</b> Medline, Embase, and Central (Cochrane Library) databases from inception to August 2013, plus the World Health Organization’s international clinical trials registry platform and relevant conference proceedings for the preceding five years. Included trials and relevant reviews were forward searched in Web of Science. <b>Review methods</b> Two reviewers independently identified randomised controlled trials evaluating probiotics administered to mothers during pregnancy or to infants during the first year of life. The primary outcome was doctor diagnosed asthma; secondary outcomes included wheeze and lower respiratory tract infection. <b>Results</b> We identified 20 eligible trials including 4866 children. Trials were heterogeneous in the type and duration of probiotic supplementation, and duration of follow-up. Only five trials conducted follow-up beyond participants’ age of 6 years (median 24 months), and none were powered to detect asthma as the primary outcome. The overall rate of doctor diagnosed asthma was 10.7%; overall rates of incident wheeze and lower respiratory tract infection were 33.3% and 13.9%, respectively. Among 3257 infants enrolled in nine trials contributing asthma data, the risk ratio of doctor diagnosed asthma in participants randomised to receive probiotics was 0.99 (95% confidence interval 0.81 to 1.21, I<sup>2</sup>=0%). The risk ratio of incident wheeze was 0.97 (0.87 to 1.09, I<sup>2</sup>=0%, 9 trials, 1949 infants). Among 1364 infants enrolled in six trials, the risk ratio of lower respiratory tract infection after probiotic supplementation was 1.26 (0.99 to 1.61, I<sup>2</sup>=0%). We adjudicated most trials to be of high (ten trials) or unclear (nine trials) risk of bias, mainly due to attrition. <b>Conclusions</b> We found no evidence to support a protective association between perinatal use of probiotics and doctor diagnosed asthma or childhood wheeze. Randomised controlled trials to date have not yielded sufficient evidence to recommend probiotics for the primary prevention of these disorders. Extended follow-up of existing trials, along with further clinical and basic research, are needed to accurately define the role of probiotics in the prevention of childhood asthma. <b>Systematic review registration</b> PROSPERO (CRD42013004385).
Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors
Authors: Jaikumar Duraiswamy, Karen M. Kaluza, Gordon J. Freeman, George Coukos
Journal: Cancer Research (2013)

Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression.
Detection by immunoelectron microscopy of immunoglobulin G deposits in skin of immunofiuorescence negative herpes gestationis
Authors: KARL HOLUBAR, KLAUS KONRAD, GEORG STINGL
Journal: British Journal of Dermatology (1977)

Journal Article Detection by immunoelectron microscopy of immunoglobulin G deposits in skin of immunofiuorescence negative herpes gestationis Get access KARL HOLUBAR, KARL HOLUBAR Department of Dermatology (I), University of Vienna, A1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar KLAUS KONRAD, KLAUS KONRAD Department of Dermatology (I), University of Vienna, A1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar GEORG STINGL GEORG STINGL Department of Dermatology (I), University of Vienna, A1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 96, Issue 5, 1 May 1977, Page 569, https://doi.org/10.1111/j.1365-2133.1977.tb07165.x Published: 01 May 1977
Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10–producing suppressive CD4+ T cells
Authors: Dapeng Li, Gabrielle Romain, Anne-Laure Flamar, Dorothée Duluc, Melissa Dullaers, Xiao-Hua Li, Sandra Zurawski, Nathalie Bosquet, Anna Karolina Palucka, Roger Le Grand, Anne O’Garra, Gerard Zurawski, Jacques Banchereau, SangKon Oh
Journal: The Journal of Experimental Medicine (2012)

Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self- and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR.
Markers of Coagulation and Angiogenesis in Cancer-Associated Venous Thromboembolism
Authors: Neil Goldenberg, Susan R. Kahn, Susan Solymoss
Journal: Journal of Clinical Oncology (2003)

Purpose: We sought to determine whether venous thromboembolism in cancer patients is associated with aberrant plasma levels of hemostatic and angiogenic factors. Patients and Methods: Peripheral blood was collected before anticoagulant therapy from cancer patients with acute deep venous thrombosis (DVT; DVT + cancer group, n = 32), those without DVT (cancer control group, n = 36), and patients with acute DVT but no cancer (DVT control group, n = 58). Plasma assays of activation and inhibition of coagulation and fibrinolysis, as well as angiogenesis activation, were then performed. Results: Median levels of thrombin-antithrombin complex, prothrombin fragments 1 + 2, and von Willebrand factor antigen were significantly greater in the DVT + cancer group than in the cancer control and DVT control groups (17.8 ng/mL v 4.6 ng/mL and 9.8 ng/mL, P = .0001 and P = .003, respectively; 3.65 nmol/L v 1.60 nmol/L and 2.71 nmol/L, P &lt; .0001 and P = .011, respectively; and 4.04 U/mL v 2.26 U/mL and 2.06 U/mL, P &lt; .0001, respectively). Median levels of tissue-type plasminogen activator were also significantly higher, while protein C activity was lower in the DVT + cancer group than in the DVT control group (14.6 ng/mL v 9.50 ng/mL, respectively, P = .0005; 0.89 U/mL v 1.11 U/mL, respectively, P = .0008). Conclusion: These data not only support prior observations of coagulation activation in patients with malignancy, but also provide new evidence for enhanced coagulation activation in the setting of acute venous thromboembolism in cancer. Future prospective studies are warranted to determine whether these and other potential markers of hypercoagulability may help to identify cancer patients at highest risk for venous thromboembolism.
Yellow fever and Max Theiler: the only Nobel Prize for a virus vaccine
Authors: Erling Norrby
Journal: The Journal of Experimental Medicine (2007)

In 1951, Max Theiler of the Rockefeller Foundation received the Nobel Prize in Physiology or Medicine for his discovery of an effective vaccine against yellow fever—a discovery first reported in the JEM 70 years ago. This was the first, and so far the only, Nobel Prize given for the development of a virus vaccine. Recently released Nobel archives now reveal how the advances in the yellow fever vaccine field were evaluated more than 50 years ago, and how this led to a prize for Max Theiler.
Erectile dysfunction in systemic sclerosis
Authors: U A Walker, A Tyndall, R Ruszat
Journal: Annals of the Rheumatic Diseases (2009)

Erectile dysfunction (ED) is observed in up to 81% of men with systemic sclerosis (SSc) and therefore should be counselled as a common complaint in this disorder. Whereas ED is frequently associated with atherosclerosis in the general population in which it is also a harbinger of cardiovascular events, ED has a different aetiology in SSc. In SSc the penile blood flow is impaired due to both myointimal proliferation of small arteries and corporal fibrosis. Data on the prevention of ED in SSc are not available. On-demand phosphodiesterase type 5 (PDE-5) inhibitors are not effective in improving erectile function, but fixed daily or alternate day regimens of long acting PDE-5 inhibitors provide a measurable, although often limited, clinical benefit. When intracavernous injections of prostaglandin E1 (alprostadil) are ineffective, the implantation of a penile prosthesis may be considered. Complex treatment options may require the involvement of urology.
Induction of p53 Up-Regulated Modulator of Apoptosis Messenger RNA by Chemotherapeutic Treatment of Locally Advanced Breast Cancer
Authors: Rutger Middelburg, Richard R. de Haas, Henk Dekker, Ron M. Kerkhoven, Paula R. Pohlmann, Adolfo Fuentes-Alburo, Alejandro Mohar, Herbert M. Pinedo, Jan Lankelma
Journal: Clinical Cancer Research (2005)

Abstract Purpose: In biopsies of patients with locally advanced breast cancer, we investigated the in vivo changes of the gene expression pattern induced by chemotherapy to find genes that are potentially responsible for the efficacy of the drug. Experimental Design: Early cellular responses to chemotherapy-induced damage, both in vivo and in vitro, were investigated by analyzing chemotherapy-induced changes in gene expression profiles. Core biopsies were taken from nine patients with locally advanced breast cancer, before and at 6 hours after initiation of doxorubicin-based chemotherapy. Both samples were cohybridized on the same microarray containing 18,000 cDNA spots. Results: The analysis revealed marked differences in gene expression profile between treated and untreated samples. The gene which was most frequently found to be differentially expressed was p53 up-regulated modulator of apoptosis (PUMA). This gene was up-regulated in eight of nine patients with an average factor of 1.80 (range, 1.36-2.73). In vitro MCF-7 breast cancer cells exposed to clinically achievable doxorubicin concentrations for 6 hours revealed marked induction of PUMA mRNA, as well. Conclusions: This is the first report describing PUMA mRNA to be up-regulated as a response to chemotherapy in patients. Because PUMA is a known member of the family of BH3-only proapoptotic proteins, this finding suggests PUMA's potential importance for the response to anticancer drugs.
Association of Amino Acid Sequence in the Pkr–Eif2 Phosphorylation Homology Domain and Response to Interferon Therapy
Authors: Kazuaki Chayama, Fumitaka Suzuki, Akihito Tsubota, Masahiro Kobayashi, Yasuji Arase, Satoshi Saitoh, Yoshiyuki Suzuki, Naoya Murashima, Kenji Ikeda, Norihiko Takahashi, Moritoshi Kinoshita, Hiromitsu Kumada
Journal: Hepatology (2000)

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are well known predictive factors of poor response to interferon (IFN) therapy. In addition, a sparsity of amino acid substitutions in the interferon sensitivity determining region (ISDR) is also predictive of a poor response to IFN in patients with genotype 1b, although this issue is still controversial. Recently, a 12 amino acid domain in the E2 protein of HCV (PKR-eIF2 alpha phosphorylation homology domain [PePHD]) has been reported to bind with and block the virus replication inhibition ability of PKR, suggesting that the interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of IFN. To clarify the significance of amino-acid sequences in this domain in predicting the effect of IFN therapy, we analyzed 82 patients with genotype 1b. Eleven patients (13.4%) responded to treatment whereas the remaining 71 patients (86.6%) were nonresponders. Multivariate analysis showed that only HCV load and amino-acid substitutions in the ISDR were predictive of sustained response to IFN. Amino-acid substitutions in the PePHD were detected in only eight of 82 patients (9.8%), and did not correlate with the therapeutic effect of IFN. However, amino-acid-sequence analyses of quasispecies before and after 1 week of IFN therapy showed elimination of clones with substitutions in this domain. Our results suggest that amino-acid sequences of the PePHD domain may be related to viral resistance to IFN but do not predict the outcome of IFN therapy as amino-acid substitutions in this domain are rare.
Randomised controlled trial of exercise for low back pain: clinical outcomes, costs, and preferences
Authors: J. K. Moffett, D. Torgerson, S. Bell-Syer, D. Jackson, H. Llewlyn-Phillips, A. Farrin, J. Barber
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To evaluate effectiveness of an exercise programme in a community setting for patients with low back pain to encourage a return to normal activities. <b>Design:</b> Randomised controlled trial of progressive exercise programme compared with usual primary care management. Patients9 preferences for type of management were elicited independently of randomisation. <b>Participants:</b> 187 patients aged 18-60 years with mechanical low back pain of 4 weeks to 6 months9 duration. <b>Interventions:</b> Exercise classes led by a physiotherapist that included strengthening exercises for all main muscle groups, stretching exercises, relaxation session, and brief education on back care. A cognitive-behavioural approach was used. <b>Main outcome measures:</b> Assessments of debilitating effects of back pain before and after intervention and at 6 months and 1 year later. Measures included Roland disability questionnaire, Aberdeen back pain scale, pain diaries, and use of healthcare services. <b>Results:</b> At 6 weeks after randomisation, the intervention group improved marginally more than the control group on the disability questionnaire and reported less distressing pain. At 6 months and 1 year, the intervention group showed significantly greater improvement in the disability questionnaire score (mean difference in changes 1.35, 95% confidence interval 0.13 to 2.57). At 1 year, the intervention group also showed significantly greater improvement in the Aberdeen back pain scale (4.44, 1.01 to 7.87) and reported only 378 days off work compared with 607 in the control group. The intervention group used fewer healthcare resources. Outcome was not influenced by patients9 preferences. <b>Conclusions:</b> The exercise class was more clinically effective than traditional general practitioner management, regardless of patient preference, and was cost effective. <h3>Key messages</h3> Patients with back pain need to return to normal activities as soon as possible but are often afraid that movement or activity may be harmful An exercise programme led by a physiotherapist in the community and based on cognitive-behavioural principles helped patients to cope better with their pain and function better even one year later Patients9 preferences for type of management did not affect outcome Patients in the intervention group tended to use fewer healthcare resources and took fewer days off work This type of exercise programme should be more widely available
Phosphorus Binders and Survival on Hemodialysis
Authors: Tamara Isakova, Orlando M. Gutie[Combining Acute Accent]rrez, Yuchiao Chang, Anand Shah, Hector Tamez, Kelsey Smith, Ravi Thadhani, Myles Wolf
Journal: Journal of the American Society of Nephrology (2008)

Although hyperphosphatemia is a risk factor for mortality, there are limited data on whether therapy with phosphorus binders affects survival. We analyzed a prospective cohort study of 10,044 incident hemodialysis patients using Cox proportional hazards analyses to compare 1-yr all-cause mortality among patients who were or were not treated with phosphorus binders. We performed intention-to-treat analyses to compare patients who began treatment with phosphorus binders during the first 90 d after initiating hemodialysis (n = 3555) with those who remained untreated during that period (n = 5055). We also performed as-treated analyses that modeled phosphorus binder treatment as a time-dependent exposure. We compared survival in a subcohort of treated (n = 3186) and untreated (n = 3186) patients matched by their baseline serum phosphate levels and propensity score of receiving phosphorus binders during the first 90 d. One-year mortality was 191 deaths/1000 patient-years at risk. Treatment with phosphorus binders was independently associated with decreased mortality compared with no treatment in the intention-to-treat, as-treated, and matched analyses. The results were independent of baseline and follow-up serum phosphate levels and persisted in analyses that excluded deaths during the first 90 d of hemodialysis. In summary, treatment with phosphorus binders is independently associated with improved survival among incident hemodialysis patients. Although confirmatory studies are needed in the dialysis setting, future placebo-controlled, randomized trials of phosphorus binders might focus on predialysis patients with chronic kidney disease and normal serum phosphate levels.
Plexiform lesions with giant cells.
Authors: D Heath, P Smith
Journal: Thorax (1982)

Theplexiform lesion isoneofthemoststriking histological lesions associated withpulmonary hypertension. Itisthediagnostic feature ofplexogenic pulmonary arteriopathy, thedesignation given byaworking party oftheWorldHealth Organisation1 tothat formofhypertensive pulmonary vascular disease whichmaycomplicate pre- andpost-tricuspid congenital cardiac shunts, primary pulmonary hypertension, andrarecasesof cirrhosis oftheliver andportal veinthrombosis.2 This lesion hasbeenstudied intensively andbothitshistological andultrastructural features arefamiliar tomorbid anatomists. Recently wesawahistopathological variant withgiant cells whichwassounusual astomerit report. Pulmonary vascular pathology Thelungtissue studied wasobtained atnecropsy froma womanof26years, withan aortopulmonary septal defect complicated bypulmonary hypertension, whohad undergone cardiac catheterisation. Themuscular pulmonaryarteries (100to1000,uminexternal diameter) showedmedialhypertrophy andconcentric-laminar intimal proliferation oftheonion-skin variety. There weremanyplexiform lesions composed ofdilated, sac-like branches ofpulmonary arteries inwhichhaddeveloped aplexus ofthin-walled vessels separated bysepta containing plumpcells withrounded nuclei. Insomeofthe plexiform lesions, presumed tobeolder, thesepta were thicker andfibrous. Theparent vessels showedpatchy fibrinoid necrosis whichisknowntobethebasis for thedevelopment ofplexiform lesions.3 Someoftheelastic pulmonary arteries showedcalcification anddisruption oftheir elastic laminae withsmall mineralised deposits intheintima andadventitia. Thehistology oftheplexiformlesions was unusual for, scattered amongthe anticipated cells forming theproliferation, there were large foreign bodygiant cells withmultiple nuclei (fig 1). Manyofthemhadengulfed small fragments whichwere paleblueinsections stained withhaematoxylin andeosin. Thesefragments proved tobebrightly refractile inpolarisedlight (fig 2).Fortuitous sections revealed thatthe intracellular foreign bodies werederived fromlong fibres, upto66,uminlength, withacentral linear split. Discussion
Long-term correction of bilirubin UDPglucuronyltransferase deficiency in rats by in utero lentiviral gene transfer
Authors: Jurgen Seppen, Roos van der Rijt, Norbert Looije, Niek P van Til, Wouter H Lamers, Ronald P.J Oude Elferink
Journal: Molecular Therapy (2003)

Bilirubin is glucuronidated by bilirubin UDP-glucuronyltransferase (UGT1A1) before biliary excretion. Because bilirubin is toxic, patients with Crigler-Najjar type I (CN), who have no UGT1A1 activity, suffer severe brain damage early in childhood. The Gunn rat is the model for CN type 1. Gunn rat fetuses were injected with 10(7) transducing units of UGT1A1 lentiviral vector at the end of the third trimester on embryonic day 19. Serum bilirubin of injected Gunn rats was lowered by 45% compared to untreated controls. This decrease was highly significant (P < 10(6)) and was sustained for more than a year. In treated Gunn rats, bilirubin glucuronides were present in bile and UGT1A1 protein was detected in tissue. Liver, intestine, stomach, pancreas, and other organs were transduced and mostly contained 1% or less vector copies per genome. Tissue distribution was variable among experimental animals but high transduction levels were seen in pancreas and intestine in most animals. Immunohistochemistry of these organs revealed transduction of pancreatic acinar cells and intestinal epithelium. Injection of a lentiviral UGT1A1 vector into third-trimester Gunn rat fetuses corrects the metabolic deficiency and mediates a reduction of serum bilirubin levels that would be therapeutic in humans.
THE RELATION OF HYDROSTATIC PRESSURE TO THE GRADIENT OF CAPILLARY PERMEABILITY
Authors: Philip D. McMaster, Stephen Hudack, Peyton Rous
Journal: The Journal of Experimental Medicine (1932)

The gradient of permeability along the capillaries of voluntary muscle and the capillaries and venules of skin exists independently of the hydrostatic conditions, though influenced by them. Its presence cannot be explained by a graded tonic contraction of the capillaries. The evidence,-like that of previous papers,-points to local differences in the barrier offered by the wall of these vessels as responsible for the gradient.