tbuckley/cabot-search huggingface dataset:
Contribution of Virus-specific CD8+ Cytotoxic T Cells to Virus Clearance or Pathologic Manifestations of Influenza Virus Infection in a T Cell Receptor Transgenic Mouse Model
Authors: Demetrius Moskophidis, Dimitris Kioussis
Journal: The Journal of Experimental Medicine (1998)

The ability of influenza virus to evade immune surveillance by neutralizing antibodies (Abs) directed against its variable surface antigens provides a challenge to the development of effective vaccines. CD8+ cytotoxic T lymphocytes (CTLs) restricted by class I major histocompatibility complex molecules are important in establishing immunity to influenza virus because they recognize internal viral proteins which are conserved between multiple viral strains. In contrast, protective Abs are strain-specific. However, the precise role of effector CD8+ CTLs in protection from influenza virus infection, critical for understanding disease pathogenesis, has not been well defined. In transgenic mice with a very high frequency of antiinfluenza CTL precursors, but without protective Abs, CD8+ CTLs conferred protection against low dose viral challenge, but exacerbated viral pathology and caused mortality at high viral dose. The data suggest a dual role for CD8+ CTLs against influenza, which may present a challenge to the development of effective CTL vaccines. Effector mechanisms used by CD8+ CTLs in orchestrating clearance of virus and recovery from experimental influenza infection, or potentiation of lethal pathology, are discussed.
Self-Rated Health and Health Care Use Among Women With Histories of Gestational Diabetes Mellitus
Authors: Catherine Kim, Anjel Vahratian
Journal: Diabetes Care (2009)

OBJECTIVE To examine self-rated health and health care utilization among women with a history of gestational diabetes mellitus (hGDM). RESEARCH DESIGN AND METHODS This study was a cross-sectional analysis of the 2006 National Health Interview Survey of parous women with (n = 370) and without (n = 6,695) hGDM. RESULTS Women with hGDM reported fair or poor health status and ≥10 office visits in the past year more frequently than women without hGDM. The higher prevalence of obesity in hGDM women accounted for their poorer self-rated health after adjustment for other demographic factors. Whereas the association between hGDM and more frequent office visits was reduced after adjustment for demographic factors including health insurance, hGDM was still associated with a lower odds of contact with a mental health professional. CONCLUSIONS Because of obesity, women with hGDM have poorer self-rated health than women without hGDM. Contact with mental health providers was reduced compared with women without hGDM.
Severity of T cell subset dysregulation influences the probability of achieving drug-induced remission in early arthritis
Authors: R Cuthbert, R Parmar, J Nam, E Villeneuve, D Corscadden, K Henshaw, P Emery, F Ponchel
Journal: Annals of the Rheumatic Diseases (2010)

BackgroundThe authors reported that immunological parameters can predict the response to treatment in early rheumatoid arthritis independently of the treatment received as well as relapse in patients who achieved clinical remission.Normal naive CD4 T cell frequency predicted the ability of patients to achieve remission after 12 months of therapy.In contrast, regulatory T cell (Treg) frequency was not associated with remission but the frequency of Tregs expressing CD62L was higher.Infl ammation related cells (IRC), a subset generated by the cytokine activation of naive cells, also tended to be lower in patients who did well.These studies were performed using retrospective samples (with loss of data due to freezing peripheral blood mononuclear cells).The aim of the current study is to take this work to immediate reporting by performing fl ow cytometry analysis within 4 h of blood collection.Methods 23 patients with <12 months infl ammatory arthritis were recruited and treated with methotrexate or methotrexate and infl iximab or etanocept (blinded to treatment received).The clinical response was evaluated based on disease activity score (DAS28) at baseline and 6 months after start of treatment.6 Colour fl ow cytometry was performed using standard protocols.Thirty-six healthy controls were used to build the age relationship with naive cell frequency.Results There was no difference in baseline DAS28 between groups.The authors confi rmed that naive cell frequency
Decreased tumor surveillance in perforin-deficient mice.
Authors: M E van den Broek, D Kägi, F Ossendorp, R Toes, S Vamvakas, W K Lutz, C J Melief, R M Zinkernagel, H Hengartner
Journal: The Journal of Experimental Medicine (1996)

Immune surveillance against tumors usually depends on T cell recognition of tumor antigens presented by major histocompatibility complex (MHC) molecules, whereas MHC class I- tumors may be controlled by natural killer (NK) cells. Perforin-dependent cytotoxicity is a major effector function of CD8+ MHC class I-restricted T cells and of NK cells. Here, we used perforin-deficient C57BL/6 (PKO) mice to study involvement of perforin and Fas ligand in tumor surveillance in vivo. We induced tumors in PKO and normal C57BL/6 mice by (a) injection of different syngeneic tumor cell lines of different tissue origin in naive and primed mice; (b) administration of the chemical carcinogens methylcholanthrene (MCA) or 12-O-tetradecanoylphorbol-13-acetate (TPA) plus 7,12-dimethylbenzanthracene (DMBA), or (c) by injection of acutely oncogenic Moloney sarcoma virus. The first set of models analyzes the defense against a tumor load given at once, whereas the last two sets give information on immune defense against tumors at the very moment of their generation. Most of the tumor cell lines tested were eliminated 10-100-fold better by C57BL/6 mice in an unprimed situation; after priming, the differences were more pronounced. Lymphoma cells transfected with Fas were controlled 10-fold better by PKO and C57BL/6 mice when compared to untransfected control cells, indicating some role for FasL in tumor control. MCA-induced tumors arose more rapidly and with a higher incidence in PKO mice compared to C57BL/6 or CD8-deficient mice. DMBA+TPA-induced skin papillomas arose with similar high incidence and comparable kinetics in both mouse strains. C57BL/6 and PKO mice have a similar incidence of Moloney murine sarcoma and leukemia virus-induced sarcomas, but tumors are larger and regression is retarded in PKO mice. Thus, perforin-dependent cytotoxicity is not only a crucial mechanism of both cytotoxic T lymphocyte- and NK-dependent resistance to injected tumor cell lines, but also operates during viral and chemical carcinogenesis in vivo. Experiments addressing the role of Fas-dependent cytotoxicity by studying resistance to tumor cell lines that were stably transfected with Fas neither provided evidence for a major role of Fas nor excluded a minor contribution of Fas in tumor surveillance.
Biomarkers of infection for the differential diagnosis of pleural effusions
Authors: J. M. Porcel, M. Vives, G. Cao, S. Bielsa, A. Ruiz-González, A. Martínez-Iribarren, A. Esquerda
Journal: European Respiratory Journal (2009)

We aimed to investigate whether pleural fluid concentrations of biomarkers for bacterial infection, namely triggering receptor expressed on myeloid cells (sTREM-1), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP), might identify infectious effusions and discriminate between complicated (CPPEs) and uncomplicated parapneumonic effusions (UPPEs). Stored pleural fluid samples from 308 patients with different causes of pleural effusion were used to measure the four biomarkers. Receiver-operating characteristic analysis determined the accuracy of the new tests. Median pleural fluid levels of CRP, sTREM-1 and LBP were significantly higher in CPPE compared with those in other aetiologies. The area under the curve for distinguishing infectious (parapneumonics and tuberculosis) from noninfectious effusions was 0.87 for CRP, 0.86 for sTREM-1, 0.57 for PCT and 0.87 for LBP. Regarding the discrimination of nonpurulent CPPE versus UPPE, a multivariate analysis found that pleural fluid glucose ≤60 mg·dL −1 , LBP ≥17 μg·mL −1 and CRP ≥80 mg·L −1 were the best parameters. Individually, none of the new biomarkers achieved better performance characteristics than pH, glucose or lactate dehydrogenase in labelling CPPE. In conclusion, elevated pleural fluid levels of CRP, sTREM and LBP identify patients with infectious effusions, particularly those with CPPE. PCT has no value for the differential diagnosis of pleural effusions.
High incidence of cystic fibrosis in children born in Italy to Albanian immigrants
Authors: F Festini
Journal: Thorax (2003)

The incidence of cystic fibrosis (CF) can vary significantly among different racial groups; within white populations it has been reported to vary from 1/3419 in the USA to 1/2500 in the UK and 1/4700 in Italy. According to Lewis,1 the highest incidence that can be reliably expected in white populations is 1/2500, although a value as high as 1/936 has been reported in a well defined community.2

Italy and other European countries have experienced a heavy influx of immigrants from Albania in the last 10 years following political and economic upheaval occurring in that country. Although precise numbers are not available, since 1989 some tens of thousands of Albanian immigrants have settled in Tuscany, a region of central Italy populated by 3.5 million people in an area of 23 000 sq km. There are no data on the incidence of CF in Albanians, so we have calculated the incidence …
Surgical techniques in orthopaedics and sports traumatology
Authors: P McCrory
Journal: British Journal of Sports Medicine (2005)

Edited by J Duparc et al. Published by Elsevier (Harcourt Publishers), April 2003, £396.00 paperback,

This impressive set of volumes is enough to make any orthopaedic surgeon salivate. Try to imagine an eight volume set of …
Compartmentalization of Cardiac β-Adrenergic Inotropy Modulation by Phosphodiesterase Type 5
Authors: Eiki Takimoto, Diego Belardi, Carlo G. Tocchetti, Susan Vahebi, Gianfrancesco Cormaci, Elizabeth A. Ketner, An L. Moens, Hunter C. Champion, David A. Kass
Journal: Circulation (2007)

Recent cell-based studies have found that cGMP synthesis and hydrolysis by phosphodiesterase (PDE) appear compartmentalized, with nitric oxide synthase-derived and/or PDE type 5 (PDE-5)-hydrolyzable cGMP undetected at the sarcolemmal membrane in contrast to cGMP stimulated by natriuretic peptide. In the present study, we determine the functional significance of such compartments with a comparison of beta-adrenergic modulation by PDE-5 inhibition to that of natriuretic peptide stimulation in both cardiomyocytes and intact hearts. The potential role of differential cGMP and protein kinase G stimulation by these 2 modulators was also studied.Intact C57/BL6 mouse hearts were studied with pressure-volume analysis, and adult isolated myocytes were studied with fluorescence microscopy. PDE-5 inhibition with 0.1 to 1 micromol/L sildenafil (SIL) suppressed isoproterenol (ISO)-stimulated contractility, whereas 10 micromol/L atrial natriuretic peptide (ANP) had no effect. ISO suppression by SIL was prevented in cells pretreated with a protein kinase G inhibitor. Surprisingly, myocardial cGMP changed little with SIL+ISO yet rose nearly 5-fold with ANP, whereas protein kinase G activation (vasodilator-stimulated protein phosphorylation; ELISA assay) displayed the opposite: increased with SIL+ISO but unaltered by ANP+ISO. PDE-5 and ANP compartments were functionally separated, as inhibition of nitric oxide synthase by N(w)-nitro-L-arginine methyl ester eliminated antiadrenergic effects of SIL, yet this was not restorable by co-stimulation with ANP.Regulation of cardiac beta-adrenergic response by cGMP is specifically linked to a nitric oxide-synthesis/PDE-5-hydrolyzed pool signaling via protein kinase G. Natriuretic peptide stimulation achieves greater detectable increases in cGMP but not protein kinase G activity and does not modulate beta-adrenergic response. Such disparities likely contribute to differential cardiac regulation by drugs that modulate cGMP synthesis and hydrolysis.
Imaging Breast Cancer Chemotherapy Response with Light
Authors: Bruce J. Tromberg, Albert E. Cerussi
Journal: Clinical Cancer Research (2010)

Diffuse optical spectroscopy (DOS), which is used to image tumor metabolic response to neoadjuvant chemotherapy (NAC), shows large changes in tumor functional parameters with significant reductions in oxy- and deoxyhemoglobin for responders versus nonresponders. Although investigational, DOS may provide a cost-effective, risk-free method for optimizing NAC drug and dosing strategies for individual patients.
Rates of Sunburn Among Dermatology Patients
Authors: Kimberly A. Mallett, Sarah Ackerman, Rob Turrisi, June K. Robinson
Journal: JAMA Dermatology (2014)

The association between excessive UV light (UVL) exposure and skin cancer is well documented.1 Therefore, it is essential that individuals with a history of skin cancer or other risk factors are able to successfully implement precautions to protect their skin. While studies show that many dermatology patients, particularly those who have a history of skin cancer, are motivated to engage in UVL protective behaviors,2 it is unclear how successful they are in avoiding excessive UVL exposure (ie, frequency of sunburns). Patients who are motivated to use sun protection may encounter a range of barriers preventing the successful use of sunscreen that result in unintended sunburns (eg, they forget to reapply it). Other patients do not use sun protection despite awareness of the risks associated with unprotected UVL exposure.2 A recent study3 found that dermatologists assessed patients’ sunscreen use in 30% of office visits involving a skin examination; however, they did not assess frequency of sunburns. Identifying patients who vary in their ability to successfully protect their skin and avoid sunburns is an important step in reducing overall risk by allowing physicians to provide behavioral intervention.

The present study had 3 aims: (1) to identify whether dermatology patients report lower rates of high-risk UVL exposure compared with the general population, (2) to examine the frequency of sunburns reported by dermatology patients over the course of a year in relation to the general population to determine the need for additional sun protection counseling, and (3) to examine the relationship between a history of skin cancer and frequency of sunburns to assess if higher-risk patients use UVL protection more proficiently.
ARTHOSCOPIC REDUCTION AND FIXATION OF FRACTURES OF THE GREATER HUMERAL TUBEROSITY IN ATHLETES: A CASE SERIES
Authors: Georgios Tsikouris, Panagiotis Intzirtis, Emmanouil Zampiakis, Sotirios Plessas, Loukas Taprantzis, Panayiotis Kourougenis, Dimitrios Tsikouris, Lefteris Tsikouris
Journal: British Journal of Sports Medicine (2013)

Background Arthroscopy is nowadays a well-establish method to treat a wide range of injuries and overuse syndromes of the shoulder. The role of arthroscopy is extremely important for the treatment of soft-tissue injuries and specific-type fractures of the shoulder. Aim to estimate the applicability of shoulder arthroscopy as an effective method for the treatment of fractures of the greater tuberosity in athletes. Patients–Methods Twelve athletes (six professional–six recreational, four skiers–two horse riders–two motorcycle racers–one cyclist–one football player–one hardle jumper–one judoka, eight males-four females) with a mean age of 29 (20–45) years, sustaining an avulsion fracture of the greater humeral tuberosity were treated arthroscopically over a 5-year period. Nine were managed acutely and three as malunion and rotator cuff dysfunction cases. For the imaging evaluation, standard plain radiographs (anteroposterior and axillary views), CT scans (with 3D reconstruction) and MRI were performed. In three patients the fragment dislocation was found ≤5 mm, in four was 6–10 mm and in two was more than 10 mm. Anchors were used to fix the avulsed fragment. In nine patients, accompanying soft-tissue lesions (seven rotator cuff tears and two Bankart lesions) were recognized and properly treated. Postoperatively a shoulder abduction brace 30° was applied for six weeks and a careful rehabilitation plan was utilized. Passive external rotation exercises were started immediately. Results During the follow up period no major complication was observed. Radiographic outcome was assessed on plain X-rays. No patient developed non-union. All patients achieved UCLA scores over 30 at six months. Professionals returned to practicing at 10–12 weeks with customized programs. All athletes returned to their pre-operative activity level with no residual pain. Discussion The investigation of indications of shoulder arthroscopy is a continuous process. Surgical familiarity is important to perform advanced techniques in shoulder arthroscopy. Arthroscopic treatment of minimally displaced greater tuberosity fractures should be considered for athletes or people who perform overhead activities. Conclusions Arthroscopic treatment of fractures of the greater humeral tuberosity can offer excellent functional results and permits the treatment of concomitant critical lesions.
Choice of detection site for the determination of cardiac output by thermal dilution: the injection-thermistor-catheter
Authors: A. C. A. P. VLIERS, B. OESEBURG, K. R. VISSER, W. G. ZIJLSTRA
Journal: Cardiovascular Research (1973)

The extravascular distribution of thermal indicator in the pulmonary vascular bed has been demonstrated. For the determination of cardiac output by thermal dilution, right atrial injection and pulmonary arterial detection should be preferred. An injection-thermistorcatheter for use in this method has been constructed.
Effect of payments for health care on poverty estimates in 11 countries in Asia: an analysis of household survey data
Authors: Eddy van Doorslaer, Owen O'Donnell, Ravi P Rannan-Eliya, Aparnaa Somanathan, Shiva Raj Adhikari, Charu C Garg, Deni Harbianto, Alejandro N Herrin, Mohammed Nazmul Huq, Shamsia Ibragimova, Anup Karan, Chiu Wan Ng, Badri Raj Pande, Rachel Racelis, Sihai Tao, Keith Tin, Kanjana Tisayaticom, Laksono Trisnantoro, Chitpranee Vasavid, Yuxin Zhao
Journal: The Lancet (2006)
VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain
Authors: Nicholas van Bruggen, Harold Thibodeaux, James T. Palmer, Wyne P. Lee, Ling Fu, Belinda Cairns, Daniel Tumas, Robert Gerlai, Simon-Peter Williams, Menno van Lookeren Campagne, Napoleone Ferrara
Journal: Journal of Clinical Investigation (1999)

VEGF is mitogenic, angiogenic, and a potent mediator of vascular permeability. VEGF causes extravasation of plasma protein in skin bioassays and increases hydraulic conductivity in isolated perfused microvessels. Reduced tissue oxygen tension triggers VEGF expression, and increased protein and mRNA levels for VEGF and its receptors (Flt-1, Flk-1/KDR) occur in the ischemic rat brain. Brain edema, provoked in part by enhanced cerebrovascular permeability, is a major complication in central nervous system pathologies, including head trauma and stroke. The role of VEGF in this pathology has remained elusive because of the lack of a suitable experimental antagonist. We used a novel fusion protein, mFlt(1-3)-IgG, which sequesters murine VEGF, to treat mice exposed to transient cortical ischemia followed by reperfusion. Using high-resolution magnetic resonance imaging, we found a significant reduction in volume of the edematous tissue 1 day after onset of ischemia in mice that received mFlt(1-3)-IgG. 8-12 weeks after treatment, measurements of the resultant infarct size revealed a significant sparing of cortical tissue. Regional cerebral blood flow was unaffected by the administration of mFlt(1-3)-IgG. These results demonstrate that antagonism of VEGF reduces ischemia/reperfusion-related brain edema and injury, implicating VEGF in the pathogenesis of stroke and related disorders.
Inhibition of von Willebrand factor–platelet glycoprotein Ib interaction prevents and reverses symptoms of acute acquired thrombotic thrombocytopenic purpura in baboons
Authors: Hendrik B. Feys, Jan Roodt, Nele Vandeputte, Inge Pareyn, Harald Mottl, Sam Hou, Seb Lamprecht, Walter J. Van Rensburg, Hans Deckmyn, Karen Vanhoorelbeke
Journal: Blood (2012)
Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory
Authors: Ganesh M Shankar, Shaomin Li, Tapan H Mehta, Amaya Garcia-Munoz, Nina E Shepardson, Imelda Smith, Francesca M Brett, Michael A Farrell, Michael J Rowan, Cynthia A Lemere, Ciaran M Regan, Dominic M Walsh, Bernardo L Sabatini, Dennis J Selkoe
Journal: Nature Medicine (2008)
Circulatory Response to Intra-abdominal Manipulation During Ether Anesthesia in Man
Authors: Leroy D. Vandam, Hans J. Schweizer, Yukio Kubota
Journal: Circulation Research (1962)

Of 38 patients studied during a steady state of ether anesthesia before performance of the definitive phase of operation, hypotensive episodes were produced in 8 by deliberate intra-abdominal stimulation of various types. The production of hypotension was therefore not only unpredictable in the group as a whole, but it was also possible that a positive response in each case could have been mediated by a different circulatory mechanism. The protocol of these experiments was not designed either by method employed or time interval chosen to detect rapid or early changes responsible for the final steady-state measurements that were made. Arterial systolic, diastolic, mean, and pulse pressures decreased with a decline in pulse rate in several cases. As a result of a decreased stroke volume or slowing of the pulse, the cardiac output declined and was responsible for the pressure alterations observed. There was no directional change in the calculated overall peripheral resistance. The remainder of the circulatory measurements, including central venous pressure and central blood volumes, suggest that the circulatory changes are by no means simply explained and that vasodilation in peripheral vascular beds cannot be ruled out.