tbuckley/cabot-search huggingface dataset:
The Use of Lymphocyte Function–Associated Antigen (Lfa)-1–Deficient Mice to Determine the Role of Lfa-1, Mac-1, and α4 Integrin in the Inflammatory Response of Neutrophils
Authors: Robert B. Henderson, Lina H.K. Lim, Philippe A. Tessier, Felicity N.E. Gavins, Meg Mathies, Mauro Perretti, Nancy Hogg
Journal: The Journal of Experimental Medicine (2001)

After injury or infection, neutrophils rapidly migrate from the circulation into tissues by means of an orderly progression of adhesion receptor engagements. Neutrophils have been previously considered to use selectins exclusively to roll on vessels before an adhesion step mediated by the β2 integrins, lymphocyte function–associated antigen (LFA)-1, and Mac-1. Here we use LFA-1−/− mice, function blocking monoclonal antibodies, and intravital microscopy to investigate the roles of LFA-1, Mac-1, and α4 integrins in neutrophil recruitment in vivo. For the first time, we show that LFA-1 makes a contribution to neutrophil rolling by stabilizing the transient attachment or tethering phase of rolling. In contrast, Mac-1 does not appear to be important for either rolling or firm adhesion, but instead contributes to emigration from the vessel. Blocking Mac-1 in the presence of LFA-1 significantly reduces emigration, suggesting cooperation between these two integrins. Low levels of α4β1 integrin can be detected on neutrophils from LFA-1+/+ and −/− mice. These cells make use of α4β1 during the rolling phase, particularly in the absence of LFA-1. Thus LFA-1 and α4β1, together with the selectins, are involved in the rolling phase of neutrophil recruitment, and, in turn, affect the later stages of the transmigration event.
Coronary ostial stenosis.
Authors: C L Pritchard, J G Mudd, H B Barner
Journal: Circulation (1975)

Symptomatic, nonsyphilitic, acquired coronary ostial stenosis is a rare angiographic finding and was found in 0.13% of 3000 coronary angiograms. Three females with this lesion have been treated surgically. Two had left coronary ostial involvement. Coronary angiography may result in catheter tip occulsion of the ostium with chest pain, dyspnea, diaphoresis, systemic hypotension and abrupt fall in pressure at the catheter tip. Recognition of this entity is necessary for safe coronary angiography. Involvement of the left ostium carries the same serious prognosis as does left main coronary disease.
The Immunology of Epstein-Barr Virus–Induced Disease
Authors: Graham S. Taylor, Heather M. Long, Jill M. Brooks, Alan B. Rickinson, Andrew D. Hislop
Journal: Annual Review of Immunology (2015)

Epstein-Barr virus (EBV) is usually acquired silently early in life and carried thereafter as an asymptomatic infection of the B lymphoid system. However, many circumstances disturb the delicate EBV-host balance and cause the virus to display its pathogenic potential. Thus, primary infection in adolescence can manifest as infectious mononucleosis (IM), as a fatal illness that magnifies the immunopathology of IM in boys with the X-linked lymphoproliferative disease trait, and as a chronic active disease leading to life-threatening hemophagocytosis in rare cases of T or natural killer (NK) cell infection. Patients with primary immunodeficiencies affecting the NK and/or T cell systems, as well as immunosuppressed transplant recipients, handle EBV infections poorly, and many are at increased risk of virus-driven B-lymphoproliferative disease. By contrast, a range of other EBV-positive malignancies of lymphoid or epithelial origin arise in individuals with seemingly intact immune systems through mechanisms that remain to be understood.
Statin therapy might be beneficial for patients with ankylosing spondylitis
Authors: J C van Denderen
Journal: Annals of the Rheumatic Diseases (2005)

Therapeutic options for patients with the chronic inflammatory disease ankylosing spondylitis (AS) are limited. Treatment was, until recently, mainly based on non-steroidal anti-inflammatory drugs and physical therapy. The efficacy of disease modifying antirheumatic drugs, such as sulfasalazine and methotrexate, is less beneficial in AS than in other rheumatic diseases such as rheumatoid arthritis.1 Recently, tumour necrosis factor α blocking agents, have been proved to be very effective in a high proportion of patients with AS. However, these agents are expensive and their use is sometimes accompanied by severe adverse events, as opportunistic infections. Moreover, tumour necrosis factor α blocking agents are not effective in about 30% of patients.2 Hence, there is a continuing need for alternative therapeutic options.

There is growing evidence that statins possess anti-inflammatory properties, as indicated by lowering of C reactive protein …
Prophylactic Antibiotics and Dog Bite Wounds
Authors: Robert M. Elanbaas
Journal: JAMA (1981)

<h3>To the Editor.—</h3> Regarding the concise review of the management of dog bite injuries by Michael Callaham, MD (1980;244:2327), he has nicely summarized many important aspects of the appropriate treatment of these common wounds. We would, however, like to offer a different opinion of the use of prophylactic antibiotics in their care. We recently completed a prospective, double-blind, placebo-controlled study designed to determine the value of prophylactic oxacillin administration in the treatment of dog bite wounds. Adult patients having uninfected, full-thickness wounds seen within 24 hours of injury were considered for inclusion. Patients requiring hospitalization, having open fractures, already receiving antibiotics for some other medical problem, or stating an allergy to penicillin were excluded. Emergency department management consisted of cleansing, irrigation, debridement, and closure as indicated; no topical antibiotics were applied. Patients were initially classified as having all open or one or more closed wounds and then randomly assigned to receive eithers
Phase II Study of Pemetrexed and Carboplatin Plus Bevacizumab With Maintenance Pemetrexed and Bevacizumab As First-Line Therapy for Nonsquamous Non–Small-Cell Lung Cancer
Authors: Jyoti D. Patel, Thomas A. Hensing, Alfred Rademaker, Eric M. Hart, Matthew G. Blum, Daniel T. Milton, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2009)

This study evaluated the efficacy and safety of pemetrexed, carboplatin, and bevacizumab followed by maintenance pemetrexed and bevacizumab in patients with chemotherapy-naive stage IIIB (effusion) or stage IV nonsquamous non-small-cell lung cancer (NSCLC).Patients received pemetrexed 500 mg/m(2), carboplatin area under the concentration-time curve of 6, and bevacizumab 15 mg/kg every 3 weeks for six cycles. For patients with response or stable disease, pemetrexed and bevacizumab were continued until disease progression or unacceptable toxicity.Fifty patients were enrolled and received treatment. The median follow-up was 13.0 months, and the median number of treatment cycles was seven (range, one to 51). Thirty patients (60%) completed > or = six treatment cycles, and nine (18%) completed > or = 18 treatment cycles. Among the 49 patients assessable for response, the objective response rate was 55% (95% CI, 41% to 69%). Median progression-free and overall survival rates were 7.8 months (95% CI, 5.2 to 11.5 months) and 14.1 months (95% CI, 10.8 to 19.6 months), respectively. Grade 3/4 hematologic toxicity was modest-anemia (6%; 0), neutropenia (4%; 0), and thrombocytopenia (0; 8%). Grade 3/4 nonhematologic toxicities were proteinuria (2%; 0), venous thrombosis (4%; 2%), arterial thrombosis (2%; 0), fatigue (8%; 0), infection (8%; 2%), nephrotoxicity (2%; 0), and diverticulitis (6%; 2%). There were no grade 3 or greater hemorrhagic events or hypertension cases.This regimen, involving a maintenance component, was associated with acceptable toxicity and relatively long survival in patients with advanced nonsquamous NSCLC. These results justify a phase III comparison against the standard-of-care in this patient population.
The Cognitive Neuroscience of Human Memory Since H.M.
Authors: Larry R. Squire, John T. Wixted
Journal: Annual Review of Neuroscience (2011)

Work with patient H.M., beginning in the 1950s, established key principles about the organization of memory that inspired decades of experimental work. Since H.M., the study of human memory and its disorders has continued to yield new insights and to improve understanding of the structure and organization of memory. Here we review this work with emphasis on the neuroanatomy of medial temporal lobe and diencephalic structures important for memory, multiple memory systems, visual perception, immediate memory, memory consolidation, the locus of long-term memory storage, the concepts of recollection and familiarity, and the question of how different medial temporal lobe structures may contribute differently to memory functions.
837 OBESITY-RELATED INCREASE IN SERUM PLASMINOGEN ACTIVATOR INHIBITOR-1 IS INDEPENDENTLY CORRELATED TO THE PRESENCE AND SEVERITY OF NON-ALCOHOLIC STEATOHEPATITIS
Authors: S. Francque, A. Verrijken, I. Mertens, E. Van Marck, G. Hubens, L. Van Gaal, P. Pelckmans, P. Michielsen
Journal: Journal of Hepatology (2011)
Inhibition of αvβ3 Integrin Survival Signaling Enhances Antiangiogenic and Antitumor Effects of Radiotherapy
Authors: Amir Abdollahi, David W. Griggs, Heike Zieher, Alexandra Roth, Kenneth E. Lipson, Rainer Saffrich, Hermann-Josef Gröne, Dennis E. Hallahan, Ralph A. Reisfeld, Juergen Debus, Andreas G. Niethammer, Peter E. Huber
Journal: Clinical Cancer Research (2005)

The involvement of alpha(v)beta3 and alpha(v)beta5 integrins in angiogenesis and the use of integrin antagonists as effective antiangiogenic agents are documented. Radiotherapy is an important therapy option for cancer. It has been shown that ionizing radiation exerts primarily antiangiogenic effects in tumors but has also proangiogenic effects as the reaction of the tumor to protect its own vasculature from radiation damage. Here, we show that combined treatment with S247, an Arg-Gly-Glu peptidomimetic antagonist of alpha(v)beta3 integrin, and external beam radiotherapy are beneficial in local tumor therapy. We found that radiation up-regulates alpha(v)beta3 expression in endothelial cells and consecutively phosphorylates Akt, which may provide a tumor escape mechanism from radiation injury mediated by integrin survival signaling. In the presence of S247, the radiation-induced Akt phosphorylation is strongly inhibited. Our studies on endothelial cell proliferation, migration, tube formation, apoptosis, and clonogenic survival show that the radiosensitivity of endothelial cells is enhanced by the concurrent administration of the integrin antagonist. The in vitro data are successfully translated into human glioma (U87), epidermoid (A431), and prostate cancer (PC3) xenograft models growing s.c. on BALB/c-nu/nu mice. In vivo, the combination of S247 treatment and fractionated radiotherapy (5 x 2.5 Gy) leads to enhanced antiangiogenic and antitumor effects compared with either monotherapies. These results underline the importance of alpha(v)beta3 integrin when tumors protect their microvasculature from radiation-induced damage. The data also indicate that the combination of integrin antagonists and radiotherapy represents a rational approach in local cancer therapy.
Castration-Resistant Prostate Cancer: Locking Up the Molecular Escape Routes
Authors: Ricardo M. Attar, Chris H. Takimoto, Marco M. Gottardis
Journal: Clinical Cancer Research (2009)

Abstract The understanding of the key role that androgens play on the normal and pathological physiology of the prostate guided the development of different therapies for the treatment of locally advanced or metastatic prostate cancer (PCa). These so-called androgen deprivation therapies include surgical or chemical castration, achieved by the administration of gonadotropin-releasing hormone analogs; inhibition of steroidogenic enzymes; and finally, blocking of the binding of androgens to their receptor (AR) by the use of antiandrogens. Despite an excellent initial response, in approximately 2 to 3 years, most of these patients will succumb to the castration resistant form of the disease. Remarkably, even in the presence of castration levels of circulating androgens, these tumors are still dependent on a functional AR, and several molecular mechanisms have been proposed to explain this phenomenon. These include: (1) gene amplification and increased expression of the AR mRNA and protein, (2) selection of mutations in the AR that confer broader ligand specificity, (3) changes in the ratios or expression between the AR and its coregulators, (4) increased expression of steroidogenic enzymes, and (5) up-regulation of cross-talk signal transduction pathways that can activate the AR in a ligand-independent manner. We will summarize how these molecular hypotheses are being tested in the clinic by the latest therapeutic modalities.
Authors' reply to Williams
Authors: M. Jun, B. R. Hemmelgarn
Journal: BMJ (2015)

Regarding our use of the number needed to treat to harm (NNH),1 2 we aimed to determine the association between kidney function (different stages of chronic kidney disease) and the rate of major bleeding (safety of warfarin therapy) in older adults with atrial fibrillation, specifically those starting warfarin.

We focused on assessing the risk of major bleeding in these patients because reluctance to use warfarin mostly relates to uncertainties about its safety in this setting, and data on its use …
Japan's answer to the economic demands of an ageing population
Authors: Y. Takasaki, I. Kawachi, E. J. Brunner
Journal: BMJ (2012)

Japan's ageing population and prolonged recession are putting enormous strain on the national budget. <b>Yohsuke Takasaki</b>, <b>Ichiro Kawachi</b>, and <b>Eric Brunner</b> explain the problems and what the government is doing to tackle them
Aquatic toxicology: past, present, and prospects.
Authors: J B Pritchard
Journal: Environmental Health Perspectives (1993)

Aquatic organisms have played important roles as early warning and monitoring systems for pollutant burdens in our environment. However, they have significant potential to do even more, just as they have in basic biology where preparations like the squid axon have been essential tools in establishing physiological and biochemical mechanisms. This review provides a brief summary of the history of aquatic toxicology, focusing on the nature of aquatic contaminants, the levels of contamination in our waters, and the origins of these agents. It considers the features of the aquatic environment that determine the availability of xenobiotics to aquatic life and the fate of foreign chemicals within the organism. Finally, toxic effects are considered with primary emphasis on the potential of aquatic models to facilitate identification of the underlying mechanisms of toxicity.
VITAMIN C CONTENT OF MONKEY TISSUES IN EXPERIMENTAL POLIOMYELITIS
Authors: Claus W. Jungeblut, Rose R. Feiner
Journal: The Journal of Experimental Medicine (1937)

1. The concentrations of reduced ascorbic acid present in the tissues of normal rhesus monkeys are of a magnitude in keeping with the values found for other animal species which are incapable of synthesizing vitamin C. These concentrations are subject to distinct increase by prolonged parenteral administration of ascorbic acid. 2. The amounts of vitamin C present in nervous tissue and the suprarenals of monkeys, paralyzed as the result of poliomyelitis infection, are slightly below the normal average when examined at the height of paralysis or in early convalescence. The figures show a tendency for a return to normal or slightly hypernormal levels concomitant with the progress of convalescence. 3. Vitamin C titrations of the tissues of monkeys which had received parenteral injections of ascorbic acid during the incubation period of poliomyelitic infection give different results according to whether such animals develop paralysis or survive without paralytic symptoms. In paralyzed C-treated monkeys the vitamin C levels are practically identical with those of normal C-prepared monkeys. Markedly higher values, however, are obtained with non-paralytic survivors in the early stages of their survival. As the period of survival lengthens normal figures prevail again. 4. The data are discussed in their relationship to the success or failure of vitamin C therapy in experimental poliomyelitis.
Genetic Structure and Evolutionary History of a Diploid Hybrid Pine Pinus densata Inferred from the Nucleotide Variation at Seven Gene Loci
Authors: Xiao-Fei Ma, Alfred E. Szmidt, Xiao-Ru Wang
Journal: Molecular Biology and Evolution (2006)

Although homoploid hybridization is increasingly recognized as an important phenomenon in plant evolution, its evolutionary genetic mechanisms are poorly documented and understood. Pinus densata, a pine native to the Tibetan Plateau, represents a good example of a homoploid hybrid speciation facilitated by adaptation to extreme environment and ecological isolation from the parents. Its ecologically and reproductively stabilized nature offers excellent opportunity for studying genetic processes associated with hybrid speciation. In this study, we investigated the levels and patterns of nucleotide variation in P. densata and its putative parents. Haplotype composition, gene genealogies, and the levels and patterns of nucleotide variation gave further support to the hybrid nature of P. densata. Allelic history, as revealed by our data, suggests the ancient nature of the hybrid preceding elevation of the Tibetan Plateau. We detected more deviations from neutrality in P. densata than in the parental species. Thus, at least some of the evolutionary forces that have shaped the genetic variation in P. densata are likely to be different from those acting upon parental species. We speculate that when populations of P. densata invaded new territories, they had elevated rates of response to selection in order to develop traits that help them to survive and adapt in the new environments.
Improved key health outcomes in women with fibromyalgia undergoing different supervised exercise programmes: a randomised controlled trial
Authors: B Sañudo, L Carrasco, J Saxton, D Galiano, M de Hoyo
Journal: British Journal of Sports Medicine (2010)

The aim of this study was to compare the relative effects of supervised aerobic exercise (AE) with a combined programme of supervised aerobic, muscle strengthening and flexibility exercises on important health outcomes in women diagnosed with fibromyalgia (FM). Sixty-four women diagnosed with FM were randomly allocated to one of three groups: AE, combined exercise (CE) or usual care control. They were assessed at baseline and after 24 weeks using the Fibromyalgia Impact Questionnaire (FIQ), Short-form Health Survey (SF-36) and Beck Depression Inventory (BDI). Functional outcomes were aerobic capacity (6-min walk test), hand-grip strength and range of motion. A 14%-15% improvement from baseline in total FIQ score was observed in the exercise groups (p≤0.02), and was accompanied by reductions in BDI scores of 8.5 (p&lt;0.001) and 6.4 (p&lt;0.001) points in the AE and CE group, respectively. Relative to nonexercising controls, CE evoked improvements in the SF-36 physical function (p=0.003) and bodily pain (p=0.003) domains and was more effective than AE for evoking improvements in the vitality (p=0.002) and mental health (p=0.04) domains. Greater improvements were also observed in shoulder/hip range of motion and handgrip strength in the CE group. The magnitude of improvement in FIQ scores constitutes a clinically relevant change in FM and is similar to those reported previously after AE interventions in some studies. The improvement in average BDI score in the AE group is comparable to that previously reported after AE interventions suggesting that the changes in BDI scores evoked by this exercise modality are less pronounced. Although changes in global SF-36 scores were similar across exercising groups, improvements in a broader range of SF-36 domains were observed. Furthermore, effect size changes in relation to the controls were generally greater than those observed after the programme of AE. Given the equivalent time commitment required for AE and CE, our results suggest that women with FM can gain additional health benefits by engaging in a similar volume of combined strength, flexibility and AE.
Comparative study of different enzyme immunoassays for measurement of IgM and IgA rheumatoid factors
Authors: S Bas
Journal: Annals of the Rheumatic Diseases (2002)

Objective: To compare the value of various IgM and IgA rheumatoid factor (RF) tests for the diagnosis of rheumatoid arthritis (RA). Methods: Firstly, the latex test, one global assay (for IgM, IgA, and IgG RF), six IgM, and four IgA RF assays were compared in a particularly challenging situation—that is, with 67 patients with RA, many of whom were latex negative, and 91 non-RA controls, many of whom were latex positive. More detailed evaluation followed with three IgM RF tests (two commercially available kits and one assay developed in our laboratory) and two IgA RF tests (one commercially available and one from our laboratory) in two more representative samples of rheumatological patients (146 RA and 75 non-RA controls). Results: Diagnostic performance differed considerably between the assays. For IgM RF detection the highest sensitivity (88%) was obtained with the Diamedix kit (specificity 67%) and for IgA RF with the Inova kit (sensitivity 65%, specificity 88%). Combining one IgM and one IgA RF test improved diagnostic performance when both tests were in agreement, but at the cost of yielding 15–27% of discrepant results which did not help in ruling RA in or out. Mean concentration values differed significantly among IgM RF tests, and in most cases concentrations were not correlated. Conclusions: Available tests for IgM RF isotype vary in accuracy, and none is uniformly better than all the others. For IgA RF isotype, the Inova kit appears to be the best. Quantitative results cannot be compared across tests. Combination of one IgM and one IgA RF test may improve diagnostic accuracy.
Validation of Continuous Glucose Monitoring in Children and Adolescents With Cystic Fibrosis
Authors: Stephen M.P. O'Riordan, Peter Hindmarsh, Nathan R. Hill, David R. Matthews, Sherly George, Peter Greally, Gerard Canny, Dubhfeasa Slattery, Nuala Murphy, Edna Roche, Colm Costigan, Hilary Hoey
Journal: Diabetes Care (2009)

OBJECTIVE To validate continuous glucose monitoring (CGM) in children and adolescents with cystic fibrosis. RESEARCH DESIGN AND METHODS Paired oral glucose tolerance tests (OGTTs) and CGM monitoring was undertaken in 102 children and adolescents with cystic fibrosis (age 9.5–19.0 years) at baseline (CGM1) and after 12 months (CGM2). CGM validity was assessed by reliability, reproducibility, and repeatability. RESULTS CGM was reliable with a Bland-Altman agreement between CGM and OGTT of 0.81 mmol/l (95% CI for bias ± 2.90 mmol/l) and good correlation between the two (r = 0.74–0.9; P &amp;lt; 0.01). CGM was reproducible with no significant differences in the coefficient of variation of the CGM assessment between visits and repeatable with a mean difference between CGM1 and CGM2 of 0.09 mmol/l (95% CI for difference ± 0.46 mmol/l) and a discriminant ratio of 13.0 and 15.1, respectively. CONCLUSIONS In this cohort of children and adolescents with cystic fibrosis, CGM performed on two occasions over a 12-month period was reliable, reproducible, and repeatable.