tbuckley/cabot-search huggingface dataset:
Towards an Improved anti‐HIV Activity of NRTI via Metal–Organic Frameworks Nanoparticles
Authors: Valentina Agostoni, Tamim Chalati, Patricia Horcajada, Hervé Willaime, Resmi Anand, Nicolas Semiramoth, Tarek Baati, Shaun Hall, Guillaume Maurin, Hélène Chacun, Kawthar Bouchemal, Charlotte Martineau, Francis Taulelle, Patrick Couvreur, Christine Rogez‐Kreuz, Pascal Clayette, Sandra Monti, Christian Serre, Ruxandra Gref
Journal: Advanced Healthcare Materials (2013)

Abstract Nanoscale mesoporous iron carboxylates metal–organic frameworks (nanoMOFs) have recently emerged as promising platforms for drug delivery, showing biodegradability, biocompatibility and important loading capability of challenging highly water‐soluble drugs such as azidothymidine tryphosphate (AZT‐TP). In this study, nanoMOFs made of iron trimesate (MIL‐100) were able to act as efficient molecular sponges, quickly adsorbing up to 24 wt% AZT‐TP with entrapment efficiencies close to 100%, without perturbation of the supramolecular crystalline organization. These data are in agreement with molecular modelling predictions, indicating maximal loadings of 33 wt% and preferential location of the drug in the large cages. Spectrophotometry, isothermal titration calorimetry, and solid state NMR investigations enable to gain insight on the mechanism of interaction of AZT and AZT‐TP with the nanoMOFs, pointing out the crucial role of phosphates strongly coordinating with the unsaturated iron(III) sites. Finally, contrarily to the free AZT‐TP, the loaded nanoparticles efficiently penetrate and release their cargo of active triphosphorylated AZT inside major HIV target cells, efficiently protecting against HIV infection.
Neurodevelopmental Outcomes in Children After the Fontan Operation
Authors: Joseph M. Forbess, Karen J. Visconti, David C. Bellinger, Richard A. Jonas
Journal: Circulation (2001)

Previous studies of patients after the Fontan operation have reported IQ scores lower than population norms. In the past decade, changes have occurred both in surgical methods used and in the patient population undergoing Fontan palliation. The present study examined the impact of these changes on neurodevelopmental outcomes after Fontan.Neuropsychological tests were administered to 27 five-year-old children after Fontan. Mean age at repair was 2 years 4 months. The present sample was compared with an earlier Fontan group (EFG) of 133 patients who underwent surgery in the 1970s and 1980s. Mean age at repair for the EFG was 7 years 3 months. Compared with EFG, the present study sample was younger at Fontan (P=0.0001) and more likely to have undergone a Norwood procedure (P=0.02), a pre-Fontan bidirectional cavopulmonary anastomosis (P<0.001), and Fontan fenestration (P=0.001). Although mean full-scale, verbal, and performance IQ scores were within 1 SD (15 points) of the population mean of 100 (93+/-16, 95+/-15, and 91+/-17, respectively), mean full-scale and performance IQ scores were significantly lower than this population mean (P=0.03 and P=0.01, respectively).Compared with a historical cohort of Fontan patients from this institution, a staged approach to Fontan earlier in life is not detrimental to neurodevelopmental outcome. Neurodevelopmental outcomes in children after Fontan are in the normal range, but performance remains lower than the general population.
Plasticity of Sensory and Motor Maps in Adult Mammals
Authors: J H Kaas
Journal: Annual Review of Neuroscience (1991)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis
Authors: A. Higashi
Journal: European Respiratory Journal (2005)

The pathophysiology of extrinsic allergic alveolitis (EAA) involves oxidative lung damage as well as interstitial and alveolar inflammation. Macrophages and mast cells are inflammatory components of EAA that produce both leukotrienes (LTs) and prostaglandin D2 (PGD2). In addition, PGD2 is also produced by the free-radical-catalysed peroxidation of arachidonic acid during oxidative stress. Urinary 8-iso prostaglandin F2alpha (8-isoPGF2alpha) and serum surfactant protein D (SP-D) are considered appropriate biomarkers of oxidative stress and interstitial lung disease activity, respectively. The present study aimed to assess the association of these biomarkers with the pathophysiology of EAA. Two cases of acute EAA caused by the inhalation of fungi spores were reported. Eight asthmatic patients and six healthy control subjects were also enrolled in the current study. The serum SP-D and urinary eicosanoid (LTE4, PGD2 metabolite (9alpha,11betaPGF2), 8-isoPGF2alpha) concentrations markedly increased during the acute exacerbation phase. These concentrations decreased following corticosteroid therapy in the EAA patients. There was a significant correlation between serum SP-D and urinary 9alpha,11betaPGF2 concentrations in the EAA patients. In conclusion, although the present study proposes that serum surfactant protein-D and urinary eicosanoids are new biomarkers involved in the various immunological responses in extrinsic allergic alveolitis, further large-scale studies are needed to investigate the role of these compounds, not just as biomarkers, but also as biological potentiators of extrinsic allergic alveolitis.
Atrial Natriuretic Peptide: A New Factor in Hormonal Control of Blood Pressure and Electrolyte Homeostasis
Authors: S A Atlas, J H Laragh
Journal: Annual Review of Medicine (1986)

Recent research has led to the discovery and characterization of a hormone secreted by the atria that has powerful vasodepressor and natriuretic properties. A series of atrial peptides varying only in length and exhibiting these activities have been isolated, so that it is not yet clear which of these is the active hormone. The factors that determine its secretion remain to be characterized although preliminary evidence suggests that sodium-volume loading and/or intraatrial distension may be centrally involved. Atrial hormone acts in four different ways to oppose or counter the actions of the renin angiotensin aldosterone system. Thus, it produces vasorelaxation, which is especially pronounced in angiotensin-preconstricted blood vessels; it blocks angiotensin-induced aldosterone secretion by the adrenal cortex; it inhibits renin secretion by the kidneys; and its natriuretic action opposes the sodium-retaining action of aldosterone. Accordingly, the atrial-natriuretic and vasorelaxant hormone may play a role complementary to the renin angiotensin-aldosterone system in the long-term regulation of sodium balance and arterial pressure. In this construction the renin system acts primarily to defend sodium balance and blood pressure, with the atrial hormone playing an increasingly active counterpart in situations involving sodium-volume surfeit and/or high blood pressure. The physiologic properties of the new atrial hormone already suggest a major role for it in sodium-volume, blood pressure homeostasis, and for understanding and treating hypertensive-cardiovascular diseases.
The development and validation of a scoring system for shoulder injuries in rugby players
Authors: Simon Benedict Roberts, Lennard Funk
Journal: British Journal of Sports Medicine (2013)

Shoulder injuries are relatively common among professional rugby players and result in a large proportion of days absent from training and competition. No instrument exists that is designed and validated to assess function or outcome following therapeutic interventions in rugby players sustaining shoulder injuries. The objective was to develop and validate an athlete-reported scoring system to assess shoulder function in rugby players following shoulder injuries.Potential items for the scoring system were identified by a literature review of shoulder-specific scoring systems (n=46), and by interviewing professional rugby players (n=38) and medical staff (n=12). Redundant and clinician-assessed items were excluded. A second set of interviews with rugby players (n=8) determined the frequency importance product (FIP) of potential items. The 20 items with the highest FIPs were selected for the provisional Rugby Shoulder Score (RSS) that was tested for internal consistency and reliability by administering to rugby players with stable shoulder injuries (n=11).The literature review and interviews identified 575 items, of which 105 items were neither clinician-assessed nor redundant. Twenty items with the highest FIPs were selected for the RSS. The RSS demonstrated excellent internal consistency (Cronbach's α=0.96) and reliability (intraclass correlation coefficient= 0.941, paired student t test p>0.05).A reliable athlete-reported scoring system for assessing shoulder injuries in rugby players has been developed that incorporates the most important factors for rugby players recovering from shoulder injuries. Further prospective testing of the instrument is being undertaken to determine its discriminative and evaluative functions and construct validity.
Bulimia nervosa, binge eating, and psychogenic vomiting: a controlled treatment study and long term outcome.
Authors: J H Lacey
Journal: BMJ (1983)

An "epidemic" prevalence of binge eating and vomiting (bulimia nervosa) has been reported, and treatment has been claimed to be difficult. This paper describes a short term outpatient treatment programme of eclectic orientation capable of being conducted by non-specialist staff, under medical supervision, in local centres. The treatment programme was evaluated in a controlled trial and in long term follow up. In 30 women with severe bulimia the treatment programme significantly reduced their incidence of dietary manipulation without producing weight gain, weight disorder, or neurotic illness. After treatment all the women had fewer symptoms; 24 stopped binge eating and vomiting at the end of treatment, and a further four stopped shortly afterwards. During formal follow up 20 showed no dietary abuse and a further eight reduced their attacks to an average of three episodes a year: all judged treatment to be a success. Pretreatment indicators of poorer prognosis include alcohol abuse and a history of anorexia nervosa. Married patients experienced marital difficulties or illness in the spouse.
Dicumarol Therapy and Platelet Turnover
Authors: E. A. MURPHY, J. F. MUSTARD
Journal: Circulation Research (1961)

Platelet survival and turnover were studied by the use of diisopropyl fluorophosphate, which contains phosphorus as P 32 (DFP 32 )in atherosclerotic male subjects. Twenty-nine were given dicumarol in doses sufficient to diminish platelet function in vitro and 31 were used as controls. Platelet survival was prolonged and platelet turnover was decreased by dieumarol therapy. Of the coagulation tests, the platelet adhesive index showed the best correlation with platelet turnover. These findings indicate that platelet function in vitro and in vivo is diminished by adequate dicumarol therapy. Evidence is presented that the survival of the platelet, at least in the atherosclerotic subject, is largely determined by factors external to the platelet, among which the activity of the coagulation mechanism is important.
Markedly Different Pathogenicity of Four Immunoglobulin G Isotype-Switch Variants of an Antierythrocyte Autoantibody Is Based on Their Capacity to Interact in Vivo with the Low-Affinity Fcγ Receptor III
Authors: Liliane Fossati-Jimack, Andreea Ioan-Facsinay, Luc Reininger, Yves Chicheportiche, Norihiko Watanabe, Takashi Saito, Frans M. A. Hofhuis, J. Engelbert Gessner, Carsten Schiller, Reinhold E. Schmidt, Tasuku Honjo, J. Sjef Verbeek, Shozo Izui
Journal: The Journal of Experimental Medicine (2000)

Using three different Fcgamma receptor (FcgammaR)-deficient mouse strains, we examined the induction of autoimmune hemolytic anemia by each of the four immunoglobulin (Ig)G isotype-switch variants of a 4C8 IgM antierythrocyte autoantibody and its relation to the contributions of the two FcgammaR, FcgammaRI, and FcgammaRIII, operative in the phagocytosis of opsonized particles. We found that the four IgG isotypes of this antibody displayed striking differences in pathogenicity, which were related to their respective capacity to interact in vivo with the two phagocytic FcgammaRs, defined as follows: IgG2a > IgG2b > IgG3/IgG1 for FcgammaRI, and IgG2a > IgG1 > IgG2b > IgG3 for FcgammaRIII. Accordingly, the IgG2a autoantibody exhibited the highest pathogenicity, approximately 20-100-fold more potent than its IgG1 and IgG2b variants, respectively, while the IgG3 variant, which displays little interaction with these FcgammaRs, was not pathogenic at all. An unexpected critical role of the low-affinity FcgammaRIII was revealed by the use of two different IgG2a anti-red blood cell autoantibodies, which displayed a striking preferential utilization of FcgammaRIII, compared with the high-affinity FcgammaRI. This demonstration of the respective roles in vivo of four different IgG isotypes, and of two phagocytic FcgammaRs, in autoimmune hemolytic anemia highlights the major importance of the regulation of IgG isotype responses in autoantibody-mediated pathology and humoral immunity.
Imaging Atherosclerotic Plaque Inflammation With [ <sup>18</sup> F]-Fluorodeoxyglucose Positron Emission Tomography
Authors: J.H.F. Rudd, E.A. Warburton, T.D. Fryer, H.A. Jones, J.C. Clark, N. Antoun, P. Johnström, A.P. Davenport, P.J. Kirkpatrick, B.N. Arch, J.D. Pickard, P.L. Weissberg
Journal: Circulation (2002)

Background — Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication of plaque inflammation. The glucose analogue [ 18 F]-fluorodeoxyglucose ( 18 FDG) can be used to image inflammatory cell activity non-invasively by PET. In this study we tested whether 18 FDG-PET imaging can identify inflammation within carotid artery atherosclerotic plaques. Methods and Results — Eight patients with symptomatic carotid atherosclerosis were imaged using 18 FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in 18 FDG-PET images acquired 3 hours post- 18 FDG injection. The estimated net 18 FDG accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher than in contralateral asymptomatic lesions. There was no measurable 18 FDG uptake into normal carotid arteries. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas of the plaque. Conclusions — This study demonstrates that atherosclerotic plaque inflammation can be imaged with 18 FDG-PET, and that symptomatic, unstable plaques accumulate more 18 FDG than asymptomatic lesions.
Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart
Authors: G. S Liu, S. C Richards, R. A Olsson, K. Mullane, R. S Walsh, J. M Downey
Journal: Cardiovascular Research (1994)

Objective: Agonists selective for the A1 adenosine receptor mimic the protective effect of ischaemic preconditioning against infarction in the rabbit heart. Unselective adenosine antagonists block this protection but, paradoxically, the A1 adenosine receptor selective antagonist 8-cyclopentyl-l,3-dipropylxanthine (DPCPX) does not. The aim of this study was to test the hypothesis that the newly described A3 adenosine receptor, which has an agonist profile similar to the A1 receptor but is insensitive to DPCPX, might mediate preconditioning. Methods: Isolated rabbit hearts perfused with Krebs buffer experienced 30 min of regional ischaemia followed by 120 min of reperfusion. Infarct size was measured by tetrazolium staining. Results: In control hearts infarction was 32.2(SEM 1.5)% of the risk zone. Preconditioning by 5 min ischaemia and 10 min reperfusion reduced infarct size to 8.8(2.3)%. Replacing the regional ischaemia with 5 min perfusion with 10 μM adenosine or 65 nM N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA), an adenosine A3 receptor agonist, was equally protective. The unselective antagonist 8-p-sulphophenyl theophylline at 100 μM abolished protection by preconditioning, adenosine, and APNEA, but 200 nM DPCPX did not block protection by any of the interventions. Likewise the potent but unselective A3 receptor antagonist 8-(4-carboxyethenylphenyl)-1,3-dipropylxanthine (BW A1433) completely blocked protection from ischaemic preconditioning. Conclusions: Because protection against infarction afforded by ischaemic preconditioning, adenosine, or the A3 receptor agonist APNEA could not be blocked by DPCPX and because the potent A3 receptor antagonist BW A1433 blocked protection from ischaemic preconditioning, these data indicate that the protection of preconditioning is not exclusively mediated by the adenosine A1 receptor in rabbit heart and could involve the A3 receptor. Cardiovascular Research 1994;28:1057-1061
Eosinophilic Leukocyte Accumulation during Vagally Induced Bronchoconstriction
Authors: YUJI SAITO, MITSUSHI OKAZAWA
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Eosinophilic leukocytes (eosinophils) are important effector cells in allergic inflammatory diseases such as asthma, in which significant accumulation of these cells is observed in the bronchial mucosa. However, there is little information about the relationships between bronchoconstriction and accumulation of eosinophils. We hypothesized that eosinophils are retained in the bronchial vasculature in the inner airway wall during bronchoconstriction because of deformation of the mucosal membrane. To test this hypothesis we induced unilateral bronchoconstriction in open chest guinea pigs by stimulating the right vagus nerve and compared the accumulation of eosinophils in the airway wall of the constricted and contralateral unconstricted lungs using histologic specimens. Results show that the density of eosinophils (number of cells/wall area) significantly increased in the inner wall and decreased in the adventitia of the constricted airways compared with the contralateral unconstricted airways. There was a positive relationship between the amount of smooth muscle shortening and the eosinophil density in the inner wall. On the other hand, this relationship was significantly negative in the adventitia. Atropine completely inhibited the eosinophil accumulation in the inner wall. These data suggest that eosinophils can accumulate in the airway inner wall during bronchoconstriction because of geometrical factors.
Antigen persistence and the control of local T cell memory by migrant respiratory dendritic cells after acute virus infection
Authors: Taeg S. Kim, Matthew M. Hufford, Jie Sun, Yang-Xin Fu, Thomas J. Braciale
Journal: The Journal of Experimental Medicine (2010)

Acute viral infections induce robust adaptive immune responses resulting in virus clearance. Recent evidence suggests that there may be depots of viral antigen that persist in draining lymph nodes (DLNs) after virus clearance and could, therefore, affect the adaptive immune response and memory T cell formation. The nature of these residual antigen depots, the mechanism of antigen persistence, and the impact of the persistent antigen on memory T cells remain ill defined. Using a mouse model of influenza virus infection of the respiratory tract, we identified respiratory dendritic cells (RDCs) as essential for both sampling and presenting residual viral antigen. RDCs in the previously infected lung capture residual viral antigen deposited in an irradiation-resistant cell type. RDCs then transport the viral antigen to the LNs draining the site of infection, where they present the antigen to T cells. Lastly, we document preferential localization of memory T cells to the DLNs after virus clearance as a consequence of presentation of residual viral antigen by the migrant RDC.
Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial
Authors: Robert J. Motzer, Brian I. Rini, David F. McDermott, Bruce G. Redman, Timothy M. Kuzel, Michael R. Harrison, Ulka N. Vaishampayan, Harry A. Drabkin, Saby George, Theodore F. Logan, Kim A. Margolin, Elizabeth R. Plimack, Alexandre M. Lambert, Ian M. Waxman, Hans J. Hammers
Journal: Journal of Clinical Oncology (2014)

Purpose Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. Results A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Conclusion Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting.
Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis
Authors: Frank M. Brunkhorst, Christoph Engel, Frank Bloos, Andreas Meier-Hellmann, Max Ragaller, Norbert Weiler, Onnen Moerer, Matthias Gruendling, Michael Oppert, Stefan Grond, Derk Olthoff, Ulrich Jaschinski, Stefan John, Rolf Rossaint, Tobias Welte, Martin Schaefer, Peter Kern, Evelyn Kuhnt, Michael Kiehntopf, Christiane Hartog, Charles Natanson, Markus Loeffler, Konrad Reinhart
Journal: New England Journal of Medicine (2008)

The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids.
Application of Nanotechnology in Cancer Therapy and Imaging
Authors: X. Wang, L. Yang, Z. Chen, D. M. Shin
Journal: CA A Cancer Journal for Clinicians (2008)

Recent developments in nanotechnology have provided researchers with new tools for cancer imaging and treatment. This technology has enabled the development of nanoscale devices that can be conjugated with several functional molecules simultaneously, including tumor-specific ligands, antibodies, anticancer drugs, and imaging probes. Since these nanodevices are 100 to 1,000-fold smaller than cancer cells, they can be easily transferred through leaky blood vessels and interact with targeted tumor-specific proteins both on the surface of and inside cancer cells. Therefore, their application as cancer cell-specific delivery vehicles will be a significant addition to the currently available armory for cancer therapeutics and imaging.