tbuckley/cabot-search huggingface dataset:
Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion Injury
Authors: Jianjun Zhang, Conghui Han, Huijuan Dai, Jianquan Hou, Yang Dong, Xiaolan Cui, Longmei Xu, Ming Zhang, Qiang Xia
Journal: Journal of the American Society of Nephrology (2015)

Natural killer T (NKT) cells are the major early-acting immune cell type and fundamental immune modulators in ischemia-reperfusion injury (IRI). Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2α in T/NKT cells and found that HIF-2α knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. HIF-2α knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1(+) cell depletion or Fas ligand blockade. Compared with wild-type NKT cells, HIF-2α(-/-) NKT cells adoptively transferred to Rag1-knockout mice elicited more severe renal injury, and these mice were not protected by CGS21680, an adenosine A2A receptor agonist. Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT cells and CGS21680-induced cAMP production in thymocytes were HIF-2α-dependent. Hydrogen peroxide-induced Fas ligand expression on thymic wild-type NKT cells was significantly attenuated by CGS21680 treatment, but this effect was lost in HIF-2α(-/-) NKT cells. Finally, CGS21680 and LPS, an inducer of HIF-2α in endothelium, synergistically reduced renal IRI substantially, but this effect was absent in Mx1-Cre-induced global HIF-2α-knockout mice. Taken together, our results reveal a hypoxia/HIF-2α/adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI.
Prospective Study of Oral Contraceptive Use and Risk of Breast Cancer in Women
Authors: I. Romieu, W. C. Willett, G. A. Colditz, M. J. Stampfer, B. Rosner, C. H. Hennekens, F. E. Speizer
Journal: JNCI Journal of the National Cancer Institute (1989)

In 1976, 118,273 female nurses 30–55 years of age with no history of cancer completed a questionnaire regarding possible risk factors. By 1986, after 1,137,415 person-years of follow-up, we had documented 1,799 newly diagnosed cases of breast cancer. Compared with the risk of breast cancer for nonusers of oral contraceptives, the multivariate relative risks were 1.07 (95% confidence interval, 0.97–1.19) for all users, 1.06 (95% confidence interval, 0.96–1.18) for past users, and 1.53 (95% confidence interval, 1.06–2.19) for current users—women who used oral contraceptives up to 2 years before diagnosis of breast cancer. We conclude that overall past use of oral contraceptives is not associated with a substantial increase in the risk of breast cancer. Although we did not find women who used oral contraceptives before the first pregnancy to have an increased risk of breast cancer, the number of women who used oral contraceptives for a long duration in early reproductive life was too small to permit firm conclusions regarding the risk in this subgroup. [J Natl Cancer Inst 81:1313–1321, 1989]
Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer
Authors: G. Sanna, L. Preda, R. Bruschini, M. Cossu Rocca, S. Ferretti, L. Adamoli, E. Verri, L. Franceschelli, A. Goldhirsch, F. Nolè
Journal: Annals of Oncology (2006)
The association of the PTPN22 620W polymorphism with Behcet's disease
Authors: V. Baranathan, M. R Stanford, R. W Vaughan, E. Kondeatis, E. Graham, F. Fortune, W. Madanat, C. Kanawati, M. Ghabra, P. I Murray, G. R Wallace
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> A single nucleotide polymorphism (SNP) of the gene encoding protein tyrosine phosphatase type 22 (PTPN22 620W) has recently been described as a strong common genetic risk factor for human autoimmune disease. We have analysed the association of PTPN22 620W in patients with Behçet's disease (BD). <h3>Methods:</h3> Genomic DNA was obtained from 270 patients with BD from the UK and the Middle East. Normal controls (<i>n</i> = 203) were collected from the same populations. Patients with idiopathic retinal vasculitis from the UK (<i>n</i> = 136) were used as disease controls. PTPN22 620W was detected by SSP–PCR analysis and agarose gel electrophoresis. <h3>Results:</h3> The results showed an inverse correlation between the presence of PTPN22 620W and Behçet's disease in either patient group tested. There was a greatly reduced prevalence in Middle Eastern compared to UK patients and controls. Finally, there was no association with either UK patients with retinal vasculitis compared with UK controls. <h3>Conclusions:</h3> The presence of PTPN22 620W was inversely associated with BD and the distribution of the SNP in the Middle East supports previous findings in the global prevalence.
Variations in the hospital management of self harm in adults in England: observational study
Authors: Olive Bennewith, David Gunnell, Tim Peters, Keith Hawton, Allan House
Journal: BMJ (2004)

Variability in organisation and provision of services for patients with self harm was striking.There was twofold variation across hospitals in levels of psychosocial assessment, fourfold variation in the proportion of Details of the sampling process, a table, and the audit form are on bmj.
Effect of a platelet activating factor antagonist, WEB 2086, on allergen induced asthmatic responses.
Authors: A Freitag, R M Watson, G Matsos, C Eastwood, P M O'Byrne
Journal: Thorax (1993)

BACKGROUND--Platelet activating factor (PAF) has been implicated in the pathogenesis of airway hyperresponsiveness in asthma. The purpose of this study was to evaluate the effects of a selective PAF antagonist (WEB 2086), given in doses known to antagonise the effects of inhaled PAF in human subjects, on allergen induced early and late asthmatic responses and on airway hyperresponsiveness. METHODS--Eight atopic, mildly asthmatic subjects were studied during a screening period and two treatment periods. During the screening period subjects inhaled an allergen to which they were known to be sensitised and the response was measured as the fall in the forced expired volume in one second (FEV1) to show the presence of early (0-1 h) and late (3-7 h) asthmatic responses. On another day the subjects inhaled allergen diluent. During the treatment periods subjects inhaled allergen after one week9s pretreatment with WEB 2086 (100 mg three times a day) or placebo administered in a randomised, double blind, crossover fashion. Histamine airway responsiveness was measured 24 hours before and 24 hours after allergen and the results were expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). RESULTS--The maximal early asthmatic response after allergen with placebo treatment was 18.4% (SE 4.4%) and with WEB 2086 18.9% (4.4%). The maximal late response with placebo treatment was 21.7% (5.3%) and with WEB 2086 21.2% (3.0%). The log difference (before and after allergen) in histamine PC20 was 0.35 (0.06) after placebo treatment and 0.30 (0.1) after WEB 2086. CONCLUSIONS--These results indicate that one week of treatment with an orally administered PAF antagonist (WEB 2086) does not attenuate allergen induced early or late responses or airway hyperresponsiveness.
Paneth cell marker CD24 in NOD2 knockout organoids and in inflammatory bowel disease (IBD)
Authors: Johan Van Limbergen, Kaoru Geddes, Paul Henderson, Richard K Russell, Hazel E Drummond, Jack Satsangi, Anne M Griffiths, Dana J Philpott, David C Wilson
Journal: Gut (2013)

We read with great interest the article by Shanahan et al 1 describing the roles of environmental conditions, notably co-housing with wild type (WT) littermates, and mouse genetic background in nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)-dependent production of anti-microbial peptides in the mouse intestine. These authors demonstrate that expression, translation and anti-microbial activity of α-defensins are independent of NOD2.1 Robertson et al 2 recently confirmed that housing conditions rather than NOD2 status influenced intestinal microbiota composition. Shanahan et al address the question whether an increase in the number of Paneth cells could compensate for a NOD2-dependent reduction in the level of defensin production in Paneth cells. Using a combination of hematoxylin and eosin staining (to assess crypt numbers), immunohistochemistry (using anti-lyzozyme staining) and flow cytometry (sorting for expression of lyzozyme and lack of expression of CD45—a haematopoietic cell marker) of the entire ilea of WT and NOD2-deficient mice showed NOD2 status did not influence Paneth cell numbers.1

CD24, a heavily glycosylated protein marker of intestinal crypt stem cells and Paneth cells, is upregulated in inflammatory bowel disease (IBD).3 ,4 Sato et al 3 demonstrated that the combination of CD24hi and …
LYME DISEASE:A Review of Aspects of Its Immunology and Immunopathogenesis
Authors: Leonard H. Sigal
Journal: Annual Review of Immunology (1997)

▪ Abstract Lyme disease, caused by Borrelia burgdorferi, causes a multisystem inflammatory ailment, although the precise means of tissue damage are not well understood. It is clear that the organism is present at the site of inflammation in many organs and that many of the features of the illness are relieved by antibiotic therapy. A complex interaction between spirochete and immune systems of a number of mammalian hosts, in human disease and animal models, has been described. It is clear that T cells and macrophages are intimately associated with the pathogenesis of arthritis and that immune mechanisms are involved in other aspects of disease. Inflammation directed at persistence of Borrelial antigens is a plausible explanation for persisting arthritis. Autoimmunity based on molecular mimicry may play a role in the pathogenesis of Lyme disease. Humoral immunity plays a protective role, prompting interest in vaccine development. Significant variation in certain of the outer surface proteins suggests that multiple proteins, peptides, or chimeric vaccines may be needed to provide a sufficiently broad humoral protective response.
Delayed-enhanced magnetic resonance imaging detects myocardial fibrosis in patients with chronic aortic valve disease
Authors: Marcelo Nigri, Carlos E. Rochitte, Flavio Tarasoutchi, JoséR. Parga, Luiz F. Ávila, Roney O. Sampaio, Guilherme S. Spina, Luiz F. Cardoso, JoséF. Ramires, Max Grinberg
Journal: Journal of the American College of Cardiology (2003)
Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD).
Authors: H I Harinck, S E Papapoulos, H J Blanksma, A J Moolenaar, P Vermeij, O L Bijvoet
Journal: BMJ (1987)

Early and late responses to treatment with either oral (600 mg/day) or intravenous (20 mg/day) (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (aminohydroxypropylidene bisphosphonate; APD) were studied in 142 patients with Paget9s disease of bone who had not previously been treated with bisphosphonate. The efficacy of three therapeutic regimens was compared: (a) oral aminohydroxypropylidene bisphosphonate given continuously until six months after the serum alkaline phosphatase activity had returned to normal (long term); (b) oral aminohydroxypropylidene bisphosphonate given until urinary hydroxyproline excretion had returned to normal (short term); (c) intravenous aminohydroxypropylidene bisphosphonate for 10 days. With either oral or intravenous treatment the decrease in urinary hydroxyproline excretion was rapid and always preceded the fall in serum alkaline phosphatase activity. Normal urinary hydroxyproline excretion is essential for return of the serum alkaline phosphatase activity to normal. Complete biochemical remission, defined as return of the serum alkaline phosphatase activity to normal, was obtained in 129 patients (91%). The median duration of remission as assessed by actuarial analysis was 2.7 years. This study found no difference in the long term among the three modes of treatment, suggesting that for most patients with Paget9s disease a short course of intravenous aminohydroxypropylidene bisphosphonate will produce longlasting, complete remission without need for maintenance treatment.
Therapeutics to block autoantibody initiation and propagation in systemic lupus erythematosus and rheumatoid arthritis
Authors: Jolien Suurmond, Yong Rui Zou, Sun Jung Kim, Betty Diamond
Journal: Science Translational Medicine (2015)

Most current therapies for the autoimmune diseases systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), as well as many of the drugs in the therapeutic pipeline, reduce the autoimmune inflammatory process but lead to a general immunosuppression. The goal of the next generation of therapies should be to reduce autoimmunity while at the same time better maintain immunocompetence. We propose three approaches for accomplishing this goal: (i) modulate antigen presentation to the adaptive immune system, (ii) alter B cell selection in the germinal center, and (iii) use decoy antigens to prevent the formation of proinflammatory immune complexes. These approaches are based on recent advances in the field: We now appreciate the role of dendritic cell function in autoimmune disease and the importance of citrullinated proteins as neoantigens in RA. There is also new recognition that most pathogenic autoantibodies are produced by B cells that have matured within the germinal center and that immune complexes in both diseases contain ligands for Toll-like receptors. We propose that treatments that target these newly revealed aspects of RA and SLE will decrease systemic inflammation with less immunocompromise.
Melanoma in xeroderma pigmentosum type C children: Overrepresentation of desmoplastic type?
Authors: Stéphanie Leclerc-Mercier, Christine Bodemer, Benoit Michel, Nadem Soufir, Eva Bourdon-Lanoy, Annonciade Frassatti-Biaggi, Philippe Delanoe, Sylvie Fraitag, Smail Hadj-Rabia
Journal: Journal of the American Academy of Dermatology (2015)
Exercise during pregnancy. A narrative review asking: what do we know?
Authors: Ruben Barakat, María Perales, Nuria Garatachea, Jonatan R Ruiz, Alejandro Lucia
Journal: British Journal of Sports Medicine (2015)

Although there is no consensus as to whether exercise is beneficial during pregnancy, most studies report it poses no risk to either the mother or the fetus, and many suggest it to be beneficial to both. This review, which examines the evidence available, also reveals the many differences in study design followed, the type of exercise undertaken and the variables measured, which make it difficult to compare results. Advances in our understanding of the effects of exercise during pregnancy might best be made by undertaking randomised clinical trials with standardised protocols. However, most of the studies examining the relationship between exercise and pregnancy report no complications on maternal or fetal well-being. This is also in line with recent review studies advising that the pregnant population without obstetric contraindications should be encouraged to exercise during pregnancy. Therefore, the results of the present review stimulate those responsible for the healthcare of the pregnant woman to recommend moderate exercise throughout pregnancy without risk to maternal and fetal health.
Test-Retest Reliability of a Functional MRI Working Memory Paradigm in Normal and Schizophrenic Subjects
Authors: Dara S. Manoach, Elkan F. Halpern, Todd S. Kramer, Yuchiao Chang, Donald C. Goff, Scott L. Rauch, David N. Kennedy, Randy L. Gollub
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Repeated functional magnetic resonance imaging (fMRI) studies of schizophrenic subjects may identify brain activity changes in response to interventions. To interpret the findings, however, it is crucial to know the test-retest reliability of the measures used. METHOD: The authors scanned seven normal subjects and seven schizophrenic subjects on two occasions during performance of a working memory task. They quantified the reliability of task performance and brain activation. RESULTS: In both groups, task performance was reliable, and all a priori regions were activated in group-averaged test and retest data. In individual schizophrenic subjects, however, indices of cognitive activation were not reliable across sessions. Normal subjects showed reasonable reliability of activation. CONCLUSIONS: Even given reliable task performance, stable clinical status, and a stable pattern of group-averaged activation, individual subjects showed unreliable brain activation. This suggests that repeated fMRI studies of schizophrenia should control for sources of variation, both artifactual and intrinsic.
Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma
Authors: P. Lepesant, M. Crinquette, S. Alkeraye, X. Mirabel, V. Dziwniel, B. Cribier, L. Mortier
Journal: British Journal of Dermatology (2015)

Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.
Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells
Authors: Hélène Bour-Jordan, Benoît L. Salomon, Heather L. Thompson, Gregory L. Szot, Matthew R. Bernhard, Jeffrey A. Bluestone
Journal: Journal of Clinical Investigation (2004)

The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse results from a breakdown in tolerance to pancreatic islet antigens. CD28-B7 and CD40 ligand-CD40 (CD40L-CD40) costimulatory pathways affect the development of disease and are promising therapeutic targets. Indeed, it was shown previously that diabetes fails to develop in NOD-B7-2-/- and NOD-CD40L-/- mice. In this study, we examined the relative role of these 2 costimulatory pathways in the balance of autoimmunity versus regulation in NOD mice. We demonstrate that initiation but not effector function of autoreactive T cells was defective in NOD-B7-2-/- mice. Moreover, the residual proliferation of the autoreactive cells was effectively controlled by CD28-dependent CD4+CD25+ regulatory T cells (Treg's), as depletion of Treg's partially restored proliferation of autoreactive T cells and resulted in diabetes in an adoptive-transfer model. Similarly, disruption of the CD28-B7 pathway and subsequent Treg deletion restored autoimmunity in NOD-CD40L-/- mice. These results demonstrate that development of diabetes is dependent on a balance of pathogenic and regulatory T cells that is controlled by costimulatory signals. Thus, elimination of Treg's results in diabetes even in the absence of costimulation, which suggests a need for alternative strategies for immunotherapeutic approaches.
Chronic activation of the prostaglandin receptor EP4 promotes hyaluronan-mediated neointimal formation in the ductus arteriosus
Authors: Utako Yokoyama, Susumu Minamisawa, Hong Quan, Shibnath Ghatak, Toru Akaike, Eri Segi-Nishida, Shiho Iwasaki, Mari Iwamoto, Suniti Misra, Kouichi Tamura, Hideaki Hori, Shumpei Yokota, Bryan P. Toole, Yukihiko Sugimoto, Yoshihiro Ishikawa
Journal: Journal of Clinical Investigation (2006)

PGE, a potent vasodilator, plays a primary role in maintaining the patency of the ductus arteriosus (DA). Genetic disruption of the PGE-specific receptor EP4, however, paradoxically results in fatal patent DA (PDA) in mice. Here we demonstrate that EP4-mediated signals promote DA closure by hyaluronic acid–mediated (HA-mediated) intimal cushion formation (ICF). Chronic EP4 stimulation by ONO-AE1-329, a selective EP4 agonist, significantly enhanced migration and HA production in rat DA smooth muscle cells. When HA production was inhibited, EP4-mediated migration was negated. Activation of EP4, adenylyl cyclase, and PKA all increased HA production and the level of HA synthase 2 (HAS2) transcripts. In immature rat DA explants, ICF was promoted by EP4/PKA stimuli. Furthermore, adenovirus-mediated Has2 gene transfer was sufficient to induce ICF in EP4-disrupted DA explants in which the intimal cushion had not formed. Accordingly, signals through EP4 have 2 essential roles in DA development, namely, vascular dilation and ICF. The latter would lead to luminal narrowing, helping adhesive occlusion and permanent closure of the vascular lumen. Our results imply that HA induction serves as an alternative therapeutic strategy for the treatment of PDA to the current one, i.e., inhibition of PGE signaling by cyclooxygenase inhibitors, which might delay PGE-mediated ICF in immature infants.
Antistreptococcus Serum in Septic Absorption
Authors: G. S. Macgregor
Journal: BMJ (1897)

CASE Ix.Eczema.-Hospitalpatient: While under treatment for tinea barb., developed a papular and erythematous eczema of flexor surface of both upper arms.Worse on the right.and involving bend of elbow.CASE X. Eczema.-Hospitalpatient: While under treatment for a bulla of right forefinger, the cause of which it was impossible to ascertain, developed an attack of eczema of the left arm and left side of face.CASE XI.Vesicutlar Eruption -Private patient: A lady showed me a small "blister" on the right ring-finger, for which a mild boracic oint- ment was ordered.In a few days she developed a large vesicular erup- tion on both hands, attended with malaise, headIache, and gastro-intestinal catarrh.CASE XTI.Erythema Mfultijorme.-Hospitalpatient: A girl, aged I2, six or seven weeks before coming under observation, had pediculi capitis and "sores" on the, scalp.On January 4th "blisters" first formed round the mouth and nostrils, became purulent and confluent, and now presented the appearance of an ordinary impetiginous eruption.On January ixith a multiform erythenma, very extensive and well marked.appeared on both arms; at the same time a bullous erythema appeared on the face and front of neck.