tbuckley/cabot-search huggingface dataset:
Influence of Chemoreceptor Stimuli on Genioglossal Response to Negative Pressure in Humans
Authors: STEVEN A. SHEA, TOSHIKI AKAHOSHI, JILL K. EDWARDS, DAVID P. WHITE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Genioglossal muscle (GG) activity is modulated by both chemoreceptive and mechanoreceptive reflexes that help stabilize airway patency. We assessed the effects of blood gas changes, within the range encountered during mild obstructive apnea–arousal cycles, on GG activity and the GG reflex to upper airway negative pressure. Eighteen healthy adults were studied while awake under 5 conditions: (1) baseline (Pet CO2 = 40 mm Hg, SaO2 = 99%); (2) hypercapnia (Pet CO2 = 45 mm Hg); (3) hypocapnia (Pet CO2 = 35 mm Hg, induced via hyperventilation with an iron lung ventilator); (4) hypoxia (SaO2 = 87%); and (5) hypercapnia plus hypoxia (Pet CO2 = 45 mm Hg, SaO2 = 87%). Measurements included airflow, choanal and epiglottic pressures (Pchoa and Pepi), upper airway resistance, phasic and tonic GG EMG, and the GG reflex to negative pressure (Pchoa = − 12.5 cm H2O). Ventilation increased from a baseline of 10.7 up to 22.7 L · min− 1 under conditions of altered blood gases. Peak inspiratory phasic GG EMG increased from 6.5 to 11.1% of maximal contraction but there were no significant changes in either tonic GG EMG (range, 4.3 to 5.8% of maximum) or magnitude of the GG reflex (range, 4.1 to 5.5% of maximum). Among conditions there was a high correlation between upper airway pressures and peak phasic GG EMG (Pchoa, r = 0.97, p < 0.01; Pepi, r = 0.87; p = 0.06). We conclude that in this range of blood gases: (1) the GG reflex to negative pressure is unchanged; (2) slow airway pressure changes throughout inspiration, generated either actively or passively, influence GG EMG activity; and (3) mechanoreceptive control of GG EMG can fully explain all changes in GG activity, suggesting that chemoreceptive inputs to GG are minimal, or are not simply summated with mechanoreceptor inputs.
Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer—a systematic review and meta-analysis
Authors: Charalampos Siristatidis, Theodoros N. Sergentanis, Prodromos Kanavidis, Marialena Trivella, Marianthi Sotiraki, Ioannis Mavromatis, Theodora Psaltopoulou, Alkistis Skalkidou, Eleni Th. Petridou
Journal: Human Reproduction Update (2012)

In response to the ongoing debate on the long-term effects of assisted reproduction technologies, such as IVF, we systematically reviewed and meta-analyzed available evidence on the association between controlled ovarian hyperstimulation for IVF and risk of ovarian, endometrial and cervical cancer. Eligible studies were identified and pooled effect estimates for relative risk (RR) were calculated by cancer type among two reference groups (general population or infertile women), through fixed- or random-effects models as appropriate. Nine cohort studies were synthesized, corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were studied. The synthesis of studies with general population as the reference group pointed to a statistically significant positive association between IVF and increased risk for ovarian (RR = 1.50, 95% confidence interval (CI): 1.17–1.92) and endometrial (RR = 2.04, 95% CI: 1.22–3.43), but not cervical (RR = 0.86, 95% CI: 0.49–1.49) cancers. On the contrary, when infertile women were used as the reference group, no significant associations with ovarian, endometrial or cervical cancer types were noted (RR = 1.26, 95% CI: 0.62–2.55 RR = 0.45, 95% CI: 0.18–1.14 and RR = 5.70, 95% CI: 0.28–117.20, respectively). IVF does not seem to be associated with elevated cervical cancer risk, nor with ovarian or endometrial cancer when the confounding effect of infertility was neutralized in studies allowing such comparisons. Of note, only one study provided follow-up longer than 10 years for the group exposed to IVF. Future cohort studies should preferably use infertile women as the reference group, rely on IVF-registered valid exposure data, adjust for a variety of meaningful confounders and adopt relatively longer follow-up periods before sound conclusions are drawn.
Penicillamine in rheumatoid arthritis.
Authors: W H Lyle
Journal: BMJ (1973)

with but a single fold and this, it is sug- gested, is acceptable pending the general adoption of A5 size papers.It also in- corporates a useful gusset of about 6 mm to allow for expansion and would give a most useful increase in writing area as regards continuation cards.The large scale use by the Services would suggest possibilities of economies in its production for the N.H.S. and in filing systems.-Iam, etc.,
Islet-Specific T-Cell Responses and Proinflammatory Monocytes Define Subtypes of Autoantibody-Negative Ketosis-Prone Diabetes
Authors: Barbara M. Brooks-Worrell, Dinakar Iyer, Ivonne Coraza, Christiane S. Hampe, Ramaswami Nalini, Kerem Ozer, Radhika Narla, Jerry P. Palmer, Ashok Balasubramanyam
Journal: Diabetes Care (2013)

OBJECTIVE Ketosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis (DKA) in patients lacking typical features of type 1 diabetes. A validated classification scheme for KPD includes two autoantibody-negative (“A−”) phenotypic forms: “A−β−” (lean, early onset, lacking β-cell functional reserve) and “A−β+” (obese, late onset, with substantial β-cell functional reserve after the index episode of DKA). Recent longitudinal analysis of a large KPD cohort revealed that the A−β+ phenotype includes two distinct subtypes distinguished by the index DKA episode having a defined precipitant (“provoked,” with progressive β-cell function loss over time) or no precipitant (“unprovoked,” with sustained β-cell functional reserve). These three A− KPD subtypes are characterized by absence of humoral islet autoimmune markers, but a role for cellular islet autoimmunity is unknown. RESEARCH DESIGN AND METHODS Islet-specific T-cell responses and the percentage of proinflammatory (CD14+CD16+) blood monocytes were measured in A−β− (n = 7), provoked A−β+ (n = 15), and unprovoked A−β+ (n = 13) KPD patients. Genotyping was performed for type 1 diabetes–associated HLA class II alleles. RESULTS Provoked A−β+ and A−β− KPD patients manifested stronger islet-specific T-cell responses (P &amp;lt; 0.03) and higher percentages of proinflammatory CD14+CD16+ monocytes (P &amp;lt; 0.01) than unprovoked A−β+ KPD patients. A significant relationship between type 1 diabetes HLA class II protective alleles and negative T-cell responses was observed. CONCLUSIONS Provoked A−β+ KPD and A−β− KPD are associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations. In contrast, unprovoked A−β+ KPD lacks both humoral and cellular islet autoimmunity.
Cardiopulmonary Responses to Exercise in Women with Sickle Cell Anemia
Authors: Leigh A. Callahan, Kristy F. Woods, George A. Mensah, Leigh T. Ramsey, Paule Barbeau, Bernard Gutin
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Multiple factors contribute to exercise intolerance in patients with sickle cell anemia, but little information exists regarding the safety of maximal cardiopulmonary exercise testing (CPET) or the mechanisms of exercise limitation in these patients. The purpose of the present study was to examine these issues. Seventeen adult women with sickle cell anemia underwent symptom-limited maximal CPET using cycle ergometry and ramp protocols; blood gases and lactate concentrations were measured every 2 minutes. All patients completed CPET without complications. No patient demonstrated a mechanical ventilatory limitation to exercise or had evidence of myocardial ischemia. However, we observed three pathophysiologic patterns of response to exercise in these patients. Eleven patients had low peak V·O2, low anaerobic threshold (AT), gas exchange abnormalities, and high ventilatory reserve; this pattern is consistent with exercise limitation due to pulmonary vascular disease in this patient subgroup. Three patients had low peak V·O2, low AT, no gas exchange abnormalities, and a high heart rate reserve, a pattern consistent with peripheral vascular disease and/or a myopathy. The remaining three patients had low peak V·O2, low AT, no gas exchange abnormalities, and a low heart rate reserve; this pattern of exercise limitation is best explained by anemia.
Phosphodiesterase 4 inhibition of 2-integrin adhesion caused by leukotriene B4 and TNF- in human neutrophils
Authors: A. Y. Meliton, N. M. Muñoz, A. Lambertino, E. Boetticher, J. Learoyd, X. Zhu, A. R. Leff
Journal: European Respiratory Journal (2006)

Phosphodiesterase (PDE)4 inhibition attenuates neutrophilic inflammation in chronic obstructive pulmonary disease. The objective of the present study was to examine the efficacy and mechanism by which PDE4 inhibition blocks adhesion of beta(2)-integrin to an endothelial counterligand. Neutrophils (polymorphonuclear leukocytes (PMNs)) were isolated from humans receiving no medication. Adhesion was analysed by myeloperoxidase activity. The effects of cilomilast+/-salmeterol on the following were determined: 1) surface CD11b expression; 2) adhesion; 3) intracellular cyclic adenosine monophosphate (cAMP) concentration; and 4) extracellular signal-regulated kinase (ERK)-1/2-mediated group IVA-phospholipase A(2) (gIVA-PLA(2)) phosphorylation caused by leukotriene (LT)B(4) or tumour necrosis factor (TNF)-alpha activation. Either cilomilast or rolipram+/-salmeterol caused concentration-related blockade of LTB(4)-induced adhesion to counterligand, but had no effect on TNF-alpha-activated PMNs. A comparable increase in intracellular cAMP concentration for PMNs activated with LTB(4) and TNF-alpha was caused by 1 muM cilomilast and 0.1 microM salmeterol. Upregulation of surface CD11b expression and ERK-1/2 phosphorylation were blocked by cilomilast or rolipram+/-salmeterol for PMNs activated by LTB(4), but not for cells stimulated by TNF-alpha. Cilomilast+/-salmeterol also blocked gIVA-PLA(2) phosphorylation caused by LTB(4) but not TNF-alpha. In conclusion, the current study demonstrates that both leukotriene B(4) and tumour necrosis factor-alpha upregulate cyclic adenosine monophosphate. However, cyclic adenosine monophosphate does not block beta(2)-integrin adhesion caused by tumour necrosis factor-alpha. It was concluded that tumour necrosis factor-alpha prevents inhibition of extracellular signal-regulated kinase-1/2-mediated group IVA-phospholipase A(2) activation, which is essential for beta(2)-integrin adhesion in polymorphonuclear leukocytes.
Medical Decision Making in Antipsychotic Drug Choice for Schizophrenia
Authors: Johannes Hamann, Bernadette Langer, Stefan Leucht, Raymonde Busch, Werner Kissling
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The influence of patient and physician variables on antipsychotic drug choice for patients with schizophrenia was assessed. METHOD: Interviews with 100 psychiatrists on drug choice for 200 patients suffering from schizophrenia were conducted. Data were analyzed by using multiple logistic regression. RESULTS: Older physicians were up to five times more likely to prescribe first-generation antipsychotics. Patient variables did not influence treatment decisions significantly. CONCLUSIONS: There is an urgent need for more research on clinical decision making and quality management.
Surfactant Proteins A and D Suppress Alveolar Macrophage Phagocytosis via Interaction with SIRPα
Authors: William J. Janssen, Kathleen A. McPhillips, Matthew G. Dickinson, Derek J. Linderman, Konosuke Morimoto, Yi Qun Xiao, Kelly M. Oldham, R. William Vandivier, Peter M. Henson, Shyra J. Gardai
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Efficient removal of apoptotic cells is essential for the resolution of acute pulmonary inflammation. Alveolar macrophages ingest apoptotic cells less avidly than other professional phagocytes at rest but overcome this defect during acute inflammation. Surfactant protein (SP)-A and SP-D are potent modulators of macrophage function and may suppress clearance of apoptotic cells through activation of the transmembrane receptor signal inhibitory regulatory protein α (SIRPα).Objectives: To investigate whether binding of SP-A and SP-D to SIRPα on alveolar macrophages suppresses apoptotic cell clearance.Methods: Phagocytosis of apoptotic cells was assessed using macrophages pretreated with SP-A, SP-D, or the collectin-like molecule C1q. Binding of SP-A and SP-D to SIRPα was confirmed in vitro using blocking antibodies and fibroblasts transfected with active and mutant SIRPα. The effects of downstream molecules SHP-1 and RhoA on phagocytosis were studied using SHP-1–deficient mice, sodium stibogluconate, and a Rho kinase inhibitor. Lipopolysaccharide was given to chimeric mice to study the effects of SP-A and SP-D binding on inflammatory macrophages.Measurements and Main Results: Preincubation of macrophages with SP-A or SP-D suppressed apoptotic cell clearance. Surfactant suppression of macrophage phagocytosis was reversed by blocking SIRPα and inhibiting downstream molecules SHP-1 and RhoA. Macrophages from inflamed lungs ingested apoptotic cells more efficiently than resting alveolar macrophages. Recruited mononuclear phagocytes with low levels of SP-A and SP-D mediated this effect.Conclusions: SP-A and SP-D tonically inhibit alveolar macrophage phagocytosis by binding SIRPα. During acute pulmonary inflammation, defects in apoptotic cell clearance are overcome by recruited mononuclear phagocytes.
Comparative Performance of ATRIA, CHADS2, and CHA2DS2-VASc Risk Scores Predicting Stroke in Patients With Atrial Fibrillation
Authors: Hendrika A. van den Ham, Olaf H. Klungel, Daniel E. Singer, Hubert G.M. Leufkens, Tjeerd P. van Staa
Journal: Journal of the American College of Cardiology (2015)
Targeted Delivery of Tumor Antigens to Activated Dendritic Cells via CD11c Molecules Induces Potent Antitumor Immunity in Mice
Authors: Huafeng Wei, Suhui Wang, Dapeng Zhang, Sheng Hou, Weizhu Qian, Bohua Li, Huaizu Guo, Geng Kou, Jinqiu He, Hao Wang, Yajun Guo
Journal: Clinical Cancer Research (2009)

CD11c is an antigen receptor predominantly expressed on dendritic cells (DC), to which antigen targeting has been shown to induce robust antigen-specific immune responses. To facilitate targeted delivery of tumor antigens to DCs, we generated fusion proteins consisting of the extracellular domain of human HER or its rat homologue neu, fused to the single-chain fragment variable specific for CD11c (scFv(CD11c)-HER2/neu).Induction of cellular and humoral immune responses and antitumoral activity of the fusion proteins admixed with DC-activating CpG oligonucleotides (scFv(CD11c)-HER2/neu(CpG)) were tested in transplantable HER2/neu-expressing murine tumor models and in transgenic BALB-neuT mice developing spontaneous neu-driven mammary carcinomas.Vaccination of BALB/c mice with scFv(CD11c)-HER2(CpG) protected mice from subsequent challenge with HER2-positive, but not HER2-negative, murine breast tumor cells, accompanied by induction of strong HER2-specific T-cell and antibody responses. In a therapeutic setting, injection of scFv(CD11c)-HER2(CpG) caused rejection of established HER2-positive tumors. Importantly, antitumoral activity of such a fusion protein vaccine could be reproduced in immunotolerant BALB-neuT mice, where scFv(CD11c)-neu(CpG) vaccination significantly protected against a subsequent challenge with neu-expressing murine breast tumor cells and markedly delayed the onset of spontaneous mammary carcinomas.CD11c-targeted protein vaccines for in vivo delivery of tumor antigens to DCs induce potent immune responses and antitumoral activities and provide a rationale for further development of this approach for cancer immunotherapy.
Hyperglycaemia as a predictor of outcome during non-invasive ventilation in decompensated COPD
Authors: B Chakrabarti, R M Angus, S Agarwal, S Lane, P M A Calverley
Journal: Thorax (2009)

Hyperglycaemia predicts a poor outcome in Intensive Care Unit (ICU) patients. Whether this is true for respiratory failure necessitating non-invasive ventilation (NIV) is not known.To determine whether hyperglycaemia within 24 h of admission independently predicts outcome of NIV during acute decompensated ventilatory failure complicating chronic obstructive pulmonary disease (COPD) exacerbations.Patients with COPD presenting with acute hypercapnic respiratory failure at University Hospital Aintree between June 2006 and September 2007 and receiving NIV within 24 h of admission were studied prospectively. Random blood glucose levels were measured before NIV administration.88 patients (mean baseline pH 7.25, PaCO(2) 10.20 kPa, and PaO(2) 8.19 kPa) met the inclusion criteria, with NIV normalising arterial pH off therapy in 79 (90%). After multivariate logistic regression, the following predicted outcome: baseline respiratory rate (OR 0.91; 95% CI 0.84 to 0.99), random glucose > or = 7 mmol/l (OR 0.07; 95% CI 0.007 to 0.63) and admission APACHE II (Acute Physiology and Chronic Health Evaluation II) score (OR 0.75; 95% CI 0.62 to 0.90). The combination of baseline respiratory rate (RR) <30 breaths/min and random glucose <7 mmol/l increased prediction of NIV success to 97%, whilst use of all three factors was 100% predictive.In acute decompensated ventilatory failure complicating COPD, hyperglycaemia upon presentation was associated with a poor outcome. Baseline RR and hyperglycaemia are as good at predicting clinical outcomes as the APACHE II score. Combining these variables increases predictive accuracy, providing a simple method of early risk stratification.
Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis
Authors: J O Lindsay
Journal: Gut (2003)

<b>Introduction:</b> Interleukin 10 knockout (IL-10−/−) mice spontaneously develop a Th1 T cell mediated colitis with many similarities to Crohn’s disease. Daily injections of IL-10 are unable to induce remission in mice with established disease. In contrast, we have shown previously that intravenous administration of adenoviral vectors encoding IL-10 (AdvmuIL-10) induces hepatic IL-10 release and leads to long term disease suppression with profound systemic immunoregulatory changes. <b>Aims:</b> To determine whether rectal delivery of AdvmuIL-10 induces localised colonic IL-10 expression without systemic immune suppression, and assess its therapeutic efficacy in IL-10−/− mice with established colitis. <b>Results:</b> A single rectal infusion of 5×10<sup>8</sup> PFU AdvmuIL-10 to 10 week IL-10−/− mice resulted in a median level of 27.3 pg/mg IL-10 in colonic homogenates harvested one week later. IL-10−/− mice with established colitis treated with an enema of 5×10<sup>8</sup> PFU AdvmuIL-10 entered clinical and histological remission whereas empty cassette adenovirus (Adv0) or phosphate buffered saline (PBS) treated mice developed progressive disease. After four weeks, the histological score of AdvmuIL-10 treated mice (4.4 (1.5)) was significantly lower than that of Adv0 (11.1 (1.1); p&lt;0.001) and PBS (10.9 (1.0); p&lt;0.01) treated controls. In addition, the stool concentration of IL-1β over the four week experiment was significantly higher in mice treated with saline or Adv0 than in those treated with AdvmuIL-10 (p&lt;0.01). <b>Conclusion:</b> Local AdvmuIL-10 therapy reverses colitis in IL-10−/− mice without the systemic effects seen after intravenous administration. Gene therapy strategies using adenoviral vectors encoding immunoregulatory cytokines may prove to be a potent approach to the treatment of chronic inflammatory diseases such as Crohn’s disease.
A double‐blind comparison between a new multi‐dose powder inhaler (Turbuhaler®) and metered dose inhaler in children with asthma
Authors: C. HULTQUIST, H. AHLSTRÖM, N.‐I. M. KJELLMAN, L.‐Å. MALMQVIST, E. SVENONIUS, S. MELIN
Journal: Allergy (1989)

Turbuhaler® is a ready‐loaded multiple dose inhaler which does not require co‐ordination between release of dose and inhalation. 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler (MDI). The trial consisted of two parts. In the first part of the study, which made use of a double‐blind cross‐over design, the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI. In the second part, which was open, all patients were treated with Turbuhaler for 2 weeks. At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference. There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI. A majority of the patients thought Turbuhaler had the best effect and was easy to use.
Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug
Authors: Alan G. Ramsay, Amy J. Johnson, Abigail M. Lee, Güllü Gorgün, Rifca Le Dieu, William Blum, John C. Byrd, John G. Gribben
Journal: Journal of Clinical Investigation (2008)

Cancer is associated with immune deficiency, but the biologic basis of this is poorly defined. Here we demonstrate that impaired actin polymerization results in CD4+ and CD8+ T cells from patients with chronic lymphocytic leukemia (CLL) exhibiting defective immunological synapse formation with APCs. Although this synapse dysfunction was in part a result of the CLL cells having poor APC function, defective actin polymerization was also identified in T cells from patients with CLL. We further demonstrate that, following contact with CLL cells, defects in immune synapse formation were induced in healthy allogeneic T cells. This required direct contact and was inhibited by blocking adhesion molecules on CLL B cells. In T cells from patients with CLL and in T cells from healthy individuals that had been in contact with CLL cells, recruitment of key regulatory proteins to the immune synapse was inhibited. Treatment of autologous T cells and CLL cells with the immunomodulating drug lenalidomide resulted in improved synapse formation. These results define what we believe to be a novel immune dysfunction in T cells from patients with CLL that has implications for both autologous and allogeneic immunotherapy approaches and identifies repair of immune synapse defects as an essential step in improving cancer immunotherapy approaches.