tbuckley/cabot-search huggingface dataset:
Does subarachnoid haemorrhage affect the innate immune response?
Authors: Matthijs Kox, Jan Pompe, Astrid Hoedemaekers, Peter Pickkers
Journal: Intensive Care Medicine (2007)

Sir: Immune suppression followinginjury to the central nervous systemis an important clinical issue becauseup to 50% of brain-injury patientsdevelop infection, especially in theﬁrst few days following the insult [1].Recently Naredi et al. [2] tried toestablish the immunomodulatingeffects of the sympathetic nervoussystem following subarachnoidhaemorrhage. The authors foundincreased norepinephrine spilloverfollowing subarachnoidhaemorrhage,indicating sympathetic activation,and elevated levels of circulatingproinﬂammatory cytokines andcomplement such as C3a, interleukin6 and C5b-9. These parameterswere measured to evaluate therelationship between sympatheticnervous system activity and theinﬂammatory response status, but noquantitative correlation between thesetwo systems was found. Followingtissue trauma, as in subarachnoidhaemorrhage, circulating levels ofpro-inﬂammatory cytokines maynot provide a good measure of theinnate immunity because these levelsare mainly the result of the traumaitself [3] and do not reﬂect the innateimmune response to a subsequenttrigger. Therefore the reported riseand subsequent normalisation in thepro-inﬂammatory mediators aftersubarachnoid haemorrhage observedin this study is not surprising.To evaluate the status of theimmune response after subarach-noid haemorrhage or other tissuetraumaexvivostimulationofimmunecells obtained from these patientswith lipopolysaccharide or anotherinﬂammation-provoking compoundwould be more appropriate. More-over, in light of the recently identiﬁed“cholinergic anti-inﬂammatory path-way” future studies into this ﬁeldshould probably consider not onlythe
Radiology in Diagnosis of Coeliac Disease
Authors: W. M. McCrae
Journal: BMJ (1964)

JOURNALx 163 giving the following findings: (1) 66 (71 %) were assessed as recovered or much improved; (2) in 90 % of these 66 cases recovery appeared to have occurred within two years of first attendance; (3) no relation could be demonstrated between outcome and psychiatric in-patient or supportive out-patient treatment; (4) for female patients but not for males a history of previous psychiatric illness was associated with an unfavourable outcome; (5) for patients of both sexes a short duration of illness before the key consultation was related to a favourable outcome; and (6) the frequency with which abnormal personality characteristics were observed at follow-up has prompted the hypothesis that persons with such traits are peculiarly liable to neurosis.
Fel d 1 In The Bed Dust Of Cat Non-Owners Differs Among Ethnicities But Not Neighborhood In Two NYC Cohorts
Authors: K. Panjwani, G.L. Chew, A. Divjan, A.M. Reardon, F.P. Perera, R.L. Miller, M.S. Perzanowski
Journal: Journal of Allergy and Clinical Immunology (2007)
Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2–P2X7 pathway
Authors: Sandra Hubert, Björn Rissiek, Katjana Klages, Jochen Huehn, Tim Sparwasser, Friedrich Haag, Friedrich Koch-Nolte, Olivier Boyer, Michel Seman, Sahil Adriouch
Journal: The Journal of Experimental Medicine (2010)

CD4+CD25+FoxP3+ regulatory T cells (T reg cells) play a major role in the control of immune responses but the factors controlling their homeostasis and function remain poorly characterized. Nicotinamide adenine dinucleotide (NAD+) released during cell damage or inflammation results in ART2.2–mediated ADP-ribosylation of the cytolytic P2X7 receptor on T cells. We show that T reg cells express the ART2.2 enzyme and high levels of P2X7 and that T reg cells can be depleted by intravenous injection of NAD+. Moreover, lower T reg cell numbers are found in mice deficient for the NAD-hydrolase CD38 than in wild-type, P2X7-deficient, or ART2-deficient mice, indicating a role for extracellular NAD+ in T reg cell homeostasis. Even routine cell preparation leads to release of NAD+ in sufficient quantities to profoundly affect T reg cell viability, phenotype, and function. We demonstrate that T reg cells can be protected from the deleterious effects of NAD+ by an inhibitory ART2.2-specific single domain antibody. Furthermore, selective depletion of T reg cells by systemic administration of NAD+ can be used to promote an antitumor response in several mouse tumor models. Collectively, our data demonstrate that NAD+ influences survival, phenotype, and function of T reg cells and provide proof of principle that acting on the ART2–P2X7 pathway represents a new strategy to manipulate T reg cells in vivo.
Microvascular pressure distribution and responses of pulmonary allografts and cheek pouch arterioles in the hamster to oxygen.
Authors: M J Davis, W L Joyner, J P Gilmore
Journal: Circulation Research (1981)

Despite extensive investigations of the pulmonary circulation using both in vitro and in vitro preparations, few direct microcirculatory studies have been made. Consequently, the mechanisms involved in the response of the pulmonary microvasculature to changes in oxygen tension remain unclear. The present study represents the first direct observation of the responses in pulmonary microvessels to alterations in oxygen tension. Neonatal lung tissue was transplanted into the hamster cheek pouch using a chamber technique. Both tissues were characterized with respect to their microvascular pressure profile and vascular response to hypoxia. The results showed the two tissues to be remarkably different. Small pulmonary and cheek pouch arterioles exhibited opposite responses to changes in oxygen environment; hypoxia elicited a constriction of pulmonary arterioles, but a dilation of cheek pouch arterioles. Pulmonary capillary pressure, although comparable to that measured in the intact lung (13 mm Hg), was substantially lower than cheek pouch capillary pressure, which was within the range of that described for several systemic vascular beds. The microcirculatory effects of oxygen on both tissues were confined to the arteriolar segments. The characteristics of this pulmonary microcirculation are such that it is a unique model for further physiological and pharmacological studies.
Hydrogen sulphide: a bacterial toxin in ulcerative colitis?
Authors: M C Pitcher, J H Cummings
Journal: Gut (1996)

Hydrogen sulphide: a bacterial toxin in ulcerative colitis?The cause of ulcerative colitis (UC) is unknown but it is likely to depend on an interaction between genetic factors, which may determine the immune response or the expres- sion of enzymes that control intracellular metabolism, and environmental factors, such as diet and the nature of the bacterial flora.Ultimately, these factors result in the break- down in the integrity of the colonic epithelial cell barrier and the perpetuation of inflammation.This review focuses on events in the colonic lumen that are largely controlled by environment, including the bacterial conversion of dietary substrates to hydrogen sulphide and the metabolic consequences for the colonic mucosa.
A Risky Business--Identifying Susceptibility Loci for Lung Cancer
Authors: A. F. Gazdar, P. Boffetta
Journal: JNCI Journal of the National Cancer Institute (2010)

The majority of lung cancers are attributable to tobacco usage and other behavioral and environmental risk factors. Tobacco-induced malignancies are fueled by multiple powerful carcinogens and nicotine, a potent addictive agent. Thus, lung cancer is often regarded as being primarily determined by behavioral and environmental factors. However, because only a minority of heavy smokers develops lung cancer, genetic differences in susceptibility to tobacco carcinogens must exist, and lung cancers must arise from complex a Risky Business—identifying Susceptibility loci for lung Cancer
Instantaneous Pressure-Volume Relationships and Their Ratio in the Excised, Supported Canine Left Ventricle
Authors: HIROYUKI SUGA, KIICHI SAGAWA
Journal: Circulation Research (1974)

We have previously shown in the normally ejecting canine left ventricle that E ( t ), the time-varying ratio of instantaneous pressure, P ( t ), to instantaneous volume, V ( t ), is little affected by end-diastolic volume or aortic pressure. The present study on an excised, supported canine heart preparation indicates that the thesis on E ( t ) is also valid for either totally isovolumic or auxobaric beats. Intraventricular volume was measured more accurately than it was in the previous study by a new volumetric system. Regression analysis of the data showed that the instantaneous pressure-volume relationship could be approximated by the equation P ( t ) = E ( t ).[ V ( t ) - V d ], where V d is an empirical constant, over a wide range of intraventricular volume. Similar E ( t ) curves were obtained from both isovolumic and auxobaric beats for a given contractile state. When the contractile state of the preparation was enhanced by a constant-rate infusion (0.2 µg/min) of norepinephrine or isoproterenol into the coronary artery, the peak magnitude of E ( t ) increased 63% from 3.6 mm Hg/ml and the time to peak E ( t ) shortened 10% from 175 msec. We conclude that the present investigation substantiates our earlier study which established a link between E ( t ) and the contractile state of the heart.
Intracellular Bacterial Vectors That Induce CD8+ T Cells with Similar Cytolytic Abilities but Disparate Memory Phenotypes Provide Contrasting Tumor Protection
Authors: Felicity C. Stark, Subash Sad, Lakshmi Krishnan
Journal: Cancer Research (2009)

Induction of a functional CD8(+) T-cell response is the important criterion for cancer vaccines, and it is unclear whether acute or chronic live vectors are better suited for cancer antigen delivery. We have evaluated the tumor protective ability of two recombinant vectors, Listeria monocytogenes (LM) and Salmonella typhimurium (ST), both expressing ovalbumin (OVA). Although both vectors induced a similar OVA-specific CD8(+) T-cell response in the long term, LM-OVA induced mainly central-phenotype (T(CM), CD44(high)CD62L(high)), whereas ST-OVA induced mainly effector-phenotype (T(EM), CD44(high)CD62L(low)) cells. Both vectors induced functional OVA-specific CD8(+) T cells that expressed IFN-gamma and killed targets specifically in vivo. However, only LM-OVA-vaccinated mice were protected against B16-OVA tumors. This correlated to the ability of CD8(+) T cells generated against LM-OVA, but not against ST-OVA, to produce interleukin 2 and exhibit profound homeostatic and antigen-induced proliferation in vivo. Furthermore, adoptive transfer of memory CD8(+) T cells generated against LM-OVA (but not against ST-OVA) into recipient mice resulted in their trafficking to tumor-draining lymph nodes conferring protection. Although cytotoxicity and IFN-gamma production are considered to be the principal functions of memory CD8(+) T cells, the vaccine delivery strategy may also influence memory CD8(+) T-cell quality, and ability to proliferate and traffic to tumors. Thus, for efficacy, cancer vaccines should be selected for their ability to induce self-renewing memory CD8(+) T cells (CD44(high)IL-7Ralpha(high)CD62L(high)) besides their effector functions.
Maternal Lipids Are as Important as Glucose for Fetal Growth
Authors: Smita R. Kulkarni, Kalyanaraman Kumaran, Shobha R. Rao, Suresh D. Chougule, Tukaram M. Deokar, Ankush J. Bhalerao, Vishnu A. Solat, Dattatray S. Bhat, Caroline H.D. Fall, Chittaranjan S. Yajnik
Journal: Diabetes Care (2013)

OBJECTIVE To study the relationship between maternal circulating fuels and neonatal size and compare the relative effects of glucose and lipids. RESEARCH DESIGN AND METHODS The Pune Maternal Nutrition Study (1993–1996) investigated the influence of maternal nutrition on fetal growth. We measured maternal body size and glucose and lipid concentrations during pregnancy and examined their relationship with birth size in full-term babies using correlation and regression techniques. RESULTS The mothers (n = 631) were young (mean age 21 years), short (mean height 151.9 cm), and thin (BMI 18.0 kg/m2) but were relatively more adipose (body fat 21.1%). Their diet was mostly vegetarian. Between 18 and 28 weeks’ gestation, fasting glucose concentrations remained stable, whereas total cholesterol and triglyceride concentrations increased and HDL-cholesterol concentrations decreased. The mean birth weight of the offspring was 2666 g. Total cholesterol and triglycerides at both 18 and 28 weeks and plasma glucose only at 28 weeks were associated directly with birth size. One SD higher maternal fasting glucose, cholesterol, and triglyceride concentrations at 28 weeks were associated with 37, 54, and 36 g higher birth weights, respectively (P &amp;lt; 0.05 for all). HDL-cholesterol concentrations were unrelated to newborn measurements. The results were similar if preterm deliveries also were included in the analysis (total n = 700). CONCLUSIONS Our results suggest an influence of maternal lipids on neonatal size in addition to the well-established effect of glucose. Further research should be directed at defining the clinical relevance of these findings.
Characteristics of Epstein-Barr virus activation of human B lymphocytes.
Authors: A G Bird, S Britton, I Ernberg, K Nilsson
Journal: The Journal of Experimental Medicine (1981)

Epstein-Barr virus (EBV) will infect at least every third cell if exposed in vitro to an extensively purified B cell population from human peripheral blood. About 10% of such infected cells will be driven into immunoglobulin synthesis and secretion, as judged by the indirect protein A plaque assay. The appearance of EB nuclear antigen, de novo DNA synthesis, and immunoglobulin secretion are linked phenomena accompanying infection as judged by viral dilution experiments, which yield kinetics of a one-hit order. Induction of immunoglobulin secretion in B cells by EBV requires de novo synthesis of DNA, and consequently, nontransforming EBV (P3HR1) will not induce immunoglobulin secretion and will also specifically block such induction from subsequently added EBV. The termination of immunoglobulin induction by EBV in short-term cultures appears to be T cell dependent.
High prevalence of BRCA1 deletions in BRCAPRO-positive patients with high carrier probability
Authors: S. Veschi, G. Aceto, A.P. Scioletti, V. Gatta, G. Palka, A. Cama, R. Mariani-Costantini, P. Battista, V. Calò, F. Barbera, V. Bazan, A. Russo, L. Stuppia
Journal: Annals of Oncology (2007)
Monocyte Chemotactic Protein-1 Promotes Inflammatory Vascular Repair of Murine Carotid Aneurysms via a Macrophage Inflammatory Protein-1α and Macrophage Inflammatory Protein-2–Dependent Pathway
Authors: Brian L. Hoh, Koji Hosaka, Daniel P. Downes, Kamil W. Nowicki, Cristina E. Fernandez, Christopher D. Batich, Edward W. Scott
Journal: Circulation (2011)

Background— Up to 5% of the population may have a brain aneurysm. If the brain aneurysm ruptures, there is &gt;50% mortality, and more than one third of survivors are dependent. Brain aneurysms detected before rupture can be treated to prevent rupture, or ruptured aneurysms can be treated to prevent rerupture. Endovascular coiling of brain aneurysms is the treatment of choice for some aneurysms; however, up to one quarter of aneurysms may recur. The coiled aneurysms that do not recur are characterized by inflammatory intra-aneurysmal tissue healing; therefore, we studied the biology of this process, specifically the role of monocyte chemotactic protein-1 (MCP-1), a cytokine known for tissue healing. Methods and Results— We created coils with a 50:50 poly- dl -lactic glycolic acid (PLGA) coating that released MCP-1 at 3 different doses (100 μg/mL, 1 mg/mL, and 10 mg/mL) and performed a dose-response study for effect on intra-aneurysmal tissue healing in a murine carotid aneurysm model. We then demonstrated that MCP-1 (100 μg/mL)–releasing coils promote significantly greater aneurysm tissue in-growth than bare platinum or PLGA-only coils. We show that MCP-1 recruits the migration of fibroblasts, macrophages, smooth muscle cells, and endothelial cells in vitro in cell migration assays and in vivo in murine carotid aneurysms. Using gfp + bone marrow-transplant chimeric mice, we demonstrate that the MCP-1–recruited fibroblasts and macrophages are derived from the bone marrow. We demonstrate that this MCP-1–mediated vascular inflammatory repair occurs via a macrophage inflammatory protein (MIP)-1α– and MIP-2–dependent pathway. MCP-1 released from coiled murine aneurysms causes significant upregulation of MIP-1α and MIP-2 expression by cytokine array assay. Blocking MIP-1α and MIP-2 with antagonist antibody causes a significant decrease in MCP-1–mediated intra-aneurysmal tissue healing. Conclusion— Our findings suggest that MCP-1 has a critical role in promoting inflammatory intra-aneurysmal tissue healing in an MIP-1α– and MIP-2–dependent pathway.
HIV-Specific Cd8+ T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function
Authors: Victor Appay, Douglas F. Nixon, Sean M. Donahoe, Geraldine M.A. Gillespie, Tao Dong, Abigail King, Graham S. Ogg, Hans M.L. Spiegel, Christopher Conlon, Celsa A. Spina, Diane V. Havlir, Douglas D. Richman, Anele Waters, Philippa Easterbrook, Andrew J. McMichael, Sarah L. Rowland-Jones
Journal: The Journal of Experimental Medicine (2000)

The use of peptide–human histocompatibility leukocyte antigen (HLA) class I tetrameric complexes to identify antigen-specific CD8+ T cells has provided a major development in our understanding of their role in controlling viral infections. However, questions remain about the exact function of these cells, particularly in HIV infection. Virus-specific cytotoxic T lymphocytes exert much of their activity by secreting soluble factors such as cytokines and chemokines. We describe here a method that combines the use of tetramers and intracellular staining to examine the functional heterogeneity of antigen-specific CD8+ T cells ex vivo. After stimulation by specific peptide antigen, secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1β, and perforin is analyzed by FACS® within the tetramer-positive population in peripheral blood. Using this method, we have assessed the functional phenotype of HIV-specific CD8+ T cells compared with cytomegalovirus (CMV)-specific CD8+ T cells in HIV chronic infection. We show that the majority of circulating CD8+ T cells specific for CMV and HIV antigens are functionally active with regards to the secretion of antiviral cytokines in response to antigen, although a subset of tetramer-staining cells was identified that secretes IFN-γ and MIP-1β but not TNF-α. However, a striking finding is that HIV-specific CD8+ T cells express significantly lower levels of perforin than CMV-specific CD8+ T cells. This lack of perforin is linked with persistent CD27 expression on HIV-specific cells, suggesting impaired maturation, and specific lysis ex vivo is lower for HIV-specific compared with CMV-specific cells from the same donor. Thus, HIV-specific CD8+ T cells are impaired in cytolytic activity.
Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-α
Authors: S.S. Legha, S. Ring, A. Bedikian, C. Plager, O. Eton, A.C. Buzaid, N. Papadopoulos
Journal: Annals of Oncology (1996)
Simple and Accurate Electrocardiographic Criteria to Differentiate Takotsubo Cardiomyopathy From Anterior Acute Myocardial Infarction
Authors: Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Satoshi Morita, Jun Okuda, Noriaki Iwahashi, Kengo Tsukahara, Tatsuya Nakachi, Masayoshi Kiyokuni, Toshiyuki Ishikawa, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2010)
Positive impact of selective outpatient management of high-risk acute myelogenous leukemia on the incidence of septicemia
Authors: T.Y. Halim, K.W. Song, M.J. Barnett, D.L. Forrest, D.E. Hogge, S.H. Nantel, T.J. Nevill, J.D. Shepherd, C.A. Smith, H.J. Sutherland, C.L. Toze, J.C. Lavoie
Journal: Annals of Oncology (2007)
Distinct Clinical Features of Paraganglioma Syndromes Associated With &lt;EMPH TYPE="ITAL"&gt;SDHB&lt;/EMPH&gt; and &lt;EMPH TYPE="ITAL"&gt;SDHD&lt;/EMPH&gt; Gene Mutations
Authors: Hartmut P. H. Neumann
Journal: JAMA (2004)

Germline mutations of the genes encoding succinate dehydrogenase subunits B (SDHB) and D (SDHD) predispose to paraganglioma syndromes type 4 (PGL-4) and type 1 (PGL-1), respectively. In both syndromes, pheochromocytomas as well as head and neck paragangliomas occur; however, details for individual risks and other clinical characteristics are unknown.To determine the differences in clinical features in carriers of SDHB mutations and SDHD mutations.Population-based genetic screening for SDHB and SDHD germline mutations in 417 unrelated patients with adrenal or extra-adrenal abdominal or thoracic pheochromocytomas (n = 334) or head and neck paragangliomas (n = 83), but without syndromic features, from 2 registries based in Germany and central Poland, conducted from April 1, 2000, until May 15, 2004.Demographic and clinical findings with respect to gene mutation in SDHB vs SDHD compared with nonmutation carriers.A total of 49 (12%) of 417 registrants carried SDHB or SDHD mutations. In addition, 28 SDHB and 23 SDHD mutation carriers were newly detected among relatives of these carriers. Comparison of 53 SDHB and 47 SDHD total mutation carriers showed similar ages at diagnosis but differences in penetrance and of tumor manifestations. Head and neck paragangliomas (10/32 vs 27/34, respectively, P<.001) and multifocal (9/32 vs 25/34, respectively, P<.001) tumors were more frequent in carriers of SDHD mutations. In contrast, SDHB mutation carriers have an increased frequency of malignant disease (11/32 vs 0/34, P<.001). Renal cell cancer was observed in 2 SDHB mutation carriers and papillary thyroid cancer in 1 SDHB mutation carrier and 1 SDHD mutation carrier.In contrast with SDHD mutation carriers (PGL-1) who have more frequent multifocal paragangliomas, SDHB mutation carriers (PGL-4) are more likely to develop malignant disease and possibly extraparaganglial neoplasias, including renal cell and thyroid carcinomas. Appropriate and timely clinical screening is recommended in all patients with PGL-1 and PGL-4.
Formoterol Turbuhaler as reliever medication in patients with acute asthma
Authors: A. R. Rubinfeld, R. Scicchitano, A. Hunt, P. J. Thompson, A. Van Nooten, O. Selroos
Journal: European Respiratory Journal (2006)

The aim of this study was to compare the efficacy and safety of formoterol <i>versus</i> salbutamol as reliever medication in patients presenting at an emergency dept with acute asthma. A randomised, double-blind, double-dummy, parallel group study was performed in four Australian emergency treatment centres. The study included a total of 78 adult patients (mean baseline forced expiratory volume in one second (FEV<sub>1</sub>) 1.83 L; 59% predicted) with acute asthma. Based on the expected dose equivalence of formoterol Turbuhaler® 4.5 µg (delivered dose) and salbutamol pressurised metered-dose inhaler 200 µg (metered dose), patients received a total of formoterol Turbuhaler® 36 µg (delivered) or salbutamol pressurised metered-dose inhaler with spacer 1,600 µg (metered), divided into two equal doses at 0 and 30 min. FEV<sub>1</sub>, peak expiratory flow and systemic β<sub>2</sub>-agonist effects were monitored for 4 h. The primary variable was FEV<sub>1</sub> % pred at 45 min. At 45 min, mean increases in FEV<sub>1</sub> expressed in % pred were 6.6% and 9.3%, respectively, with a small adjusted mean difference in favour of salbutamol (3.0%, 95% confidence interval −2.0–8.0). Transient increases in systemic β<sub>2</sub>-agonist effects occurred predominantly with salbutamol, although no significant treatment differences were observed. Eight patients discontinued due to adverse events. In this study of patients presenting at emergency depts with acute asthma, formoterol Turbuhaler® 36 µg was well tolerated and, as rescue therapy, had an efficacy that was not different from that of salbutamol pressurised metered-dose inhaler with spacer 1,600 µg in the number of patients studied.