tbuckley/cabot-search huggingface dataset:
PMO-115 ANTI-B1-integrin antibodies improve survival of isolated human hepatocytes significantly increasing both adhesion to hepatic sinusoidal endothelium under flow and engraftment in murine liver following transplantation
Authors: D C Bartlett, V S Aldridge, A Wilhelm, N Davies, J Youster, D H Adams, P N Newsome
Journal: Gut (2012)

<h3>Introduction</h3> Hepatocyte transplantation is a potential alternative to orthotopic liver transplantation but is limited by poor survival of transplanted cells. This may be partly due to apoptosis of isolated hepatocytes following detachment from extracellular matrix with loss of β1-integrin-mediated survival signals. Anti-β1-integrin antibodies have been shown to reduce apoptosis of rat hepatocytes<sup>1</sup> and improve their survival in allogeneic transplantation.<sup>2</sup> The purpose of this study was to determine the effect of β1-integrin blocking antibodies on the survival and initial engraftment of transplanted human hepatocytes. <h3>Methods</h3> Hepatocytes were isolated from tissue obtained with ethical approval from Queen Elizabeth Hospital Birmingham. Integrin expression was confirmed using flow cytometry. Cells were incubated in suspension with anti-β1-integrin blocking antibodies or isotype matched control for 1 h. Viability and caspase three activity were assessed using flow cytometry and cleaved caspase 3 ELISA respectively. A modified flow adhesion assay was used to investigate the resistance to flow of cells adherent to sinusoidal endothelium (HSEC). An FC blocking agent was used to exclude the possibility of antibody-treated cells binding via antibody-FC receptor interactions. 1×10<sup>6</sup> fluorescently labelled cells were injected into C57BL/6 mice via the portal vein under general anaesthesia and the mice culled after 15 min. The livers were immediately frozen and sectioned and the number of fluorescent cells per field of view counted. <h3>Results</h3> Mean surface expression of the β1-integrin subunit on human hepatocytes was 86.8% (MFI 46.8). Hepatocytes treated with β1-integrin antibodies showed increased viability (85.4% vs 79.0% p=0.02) and reduced caspase 3 activity as demonstrated by a decrease in cleaved caspase 3 (mean 450 nm absorbance 1.37 vs 1.90, p=0.02). β1-integrin blockade significantly increased the mean percentage of cells remaining adherent to HSEC under flow compared to IgG control (30.6% vs 12.7%, p=0.03) and significantly increased the number of cells per field of view in the livers of mice following transplantation (1.6 vs 0.7, p=0.017). <h3>Conclusion</h3> β1-integrin blocking antibodies increase survival of isolated hepatocytes and improve their ability to remain adherent to HSEC under flow resulting in increased engraftment of transplanted human hepatocytes in mouse liver. The use of β1-integrin blocking antibodies may provide a means to increase the efficacy of human hepatocyte transplantation. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Pinkse</b>, <i>et al</i>. <i>J Hep</i> 2005. 2. <b>Kocken</b>, <i>et al</i>. <i>Lab Invest</i> 1997.
THE RELATIONSHIP BETWEEN SHORT AND LONG–TERM ANTIPLATELET THERAPY USE AND STENT THROMBOSIS FOLLOWING PERCUTANEOUS CORONARY INTERVENTION WITH THE RESOLUTE ZOTAROLIMUS–ELUTING STENT
Authors: Ajay Kirtane, Sigmund Silber, Franz–Josef Neumann, Patrick Serruys, Laura Mauri, Ian Meredith, Stephan Windecker, Jorge Belardi, Petr Widimsky, Alan Yeung, Shigeru Saito, Martin Leon
Journal: Journal of the American College of Cardiology (2013)
A Modified Form of Muscle Testing in Mild Poliomyelitis
Authors: J. C. Mulier, J. C. MacQueen
Journal: New England Journal of Medicine (1954)

IN recent years, there has been a great increase in the number of patients admitted to the hospitals of this country with the diagnosis of poliomyelitis. This patient load has grossly taxed the physical facilities of many general hospitals, few of which have sufficient flexibility and resources to provide, without confusion or without outside help, superior medical care during an epidemic.Patients without paralysis frequently constitute 40 to 50 per cent of the patients admitted to hospitals with the diagnosis of poliomyelitis. Some communities assign such mild cases to a designated hospital, sending the more severely involved cases to other . . .
Congenital Cytomegalovirus Infection
Authors: Mohamed El-Amin Abdel-Latif, Ella Sugo
Journal: New England Journal of Medicine (2010)

A baby girl was delivered prematurely, at 30 weeks' gestation, by emergency cesarean section owing to deceleration and no acceleration on fetal heart-rate monitoring. In addition, she had severe intrauterine growth restriction, oligohydramnios, and increased peak systolic velocity of the middle cerebral artery on Doppler ultrasonography. The 39-year-old mother (gravida 7, para 5) had been well during the pregnancy. On examination, the neonate was found to have respiratory distress, an extensive rash (Panel A), and hepatomegaly. The rash consisted of purple-to-magenta, nonblanching macules that were 0.5 to 1.0 cm in diameter, as well as papules and petechiae covering her entire . . .
The role of p21ras in CD28 signal transduction: triggering of CD28 with antibodies, but not the ligand B7-1, activates p21ras.
Authors: J A Nunès, Y Collette, A Truneh, D Olive, D A Cantrell
Journal: The Journal of Experimental Medicine (1994)

CD28 is a 44-kD homodimer expressed on the surface of the majority of human T cells that provides an important costimulus for T cell activation. The biochemical basis of the CD28 accessory signals is poorly understood. Triggering of the T cell antigen receptor (TCR) activates the p21ras proteins. Here we show that ligation of CD28 by a monoclonal antibody (mAb) also stimulates p21ras and induces Ras-dependent events such as stimulation of the microtubule-associated protein (MAP) kinase ERK2 and hyperphosphorylation of Raf-1. One physiological ligand for CD28 is the molecule B7-1. In contrast to the effect of CD28 mAb, the present studies show that interactions between CD28 and B7-1 do not stimulate p21ras signaling pathways. Two substrates for TCR-regulated protein tyrosine kinases (PTKs) have been implicated in p21ras activation in T cells: p95vav and a 36-kD protein that associates with a complex of Grb2 and the Ras exchange protein Sos. Triggering CD28 with both antibodies and B7-1 activates cellular PTKs, and we have exploited the differences between antibodies and B7-1 for p21ras activation in an attempt to identify critical PTK-controlled events for Ras activation in T cells. The data show that antibodies against TCR or CD28 induce tyrosine phosphorylation of both Vav and p36. B7-1 also induces Vav tyrosine phosphorylation but has no apparent effect on tyrosine phosphorylation of the Grb2-associated p36 protein. The intensity of the Vav tyrosine phosphorylation is greater in B7-1 than in TCR-stimulated cells. Moreover the kinetics of Vav tyrosine phosphorylation is prolonged in the B7-1-stimulated cells. These studies show that for CD28 signaling, the activation of p21ras correlates more closely with p36 tyrosine phosphorylation than with Vav tyrosine phosphorylation. However, the experiments demonstrate that Vav is a major substrate for B7-activated PTKs and hence could be important in CD28 signal transduction pathway.
Racial Barriers May Hamper Diagnosis, Care of Patients With Alzheimer Disease
Authors: Joan Stephenson
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Comparative analysis of incidence and clinical features of cutaneous malignant melanoma in Crete (Greece) and southern Germany (central Baden-Württemberg)
Authors: K. Lasithiotakis, U. Leiter, S. Krüger-Krasagakis, A. Tosca, C. Garbe
Journal: British Journal of Dermatology (2006)

Comparative analysis of the incidence rates and epidemiological features of cutaneous malignant melanoma (CMM) between different ethnic groups exposed to varying environmental factors is critical for consideration of the causes of CMM but can also be utilized in a public health approach to control of the disease.To compare incidence rates and clinical features of CMM in a Greek and a central European population (central Baden-Württemberg, Germany).Incident cases of CMM were traced in all hospitals of the island of Crete for the period 1999-2002. Age-standardized incidence rates per 100 000 inhabitants per year for the European Standard Population were calculated based on the Cretan population statistics. A comparison was performed between the Cretan findings and those of southern Germany as registered by the hospital-based Central Malignant Melanoma Registry, which likewise documents more clinical features than normally recorded by population-based cancer registries.Mean incidence rates in Crete for 1999-2002 were 4.01 per 100 000 inhabitants per year for males and 4.05 for females as compared with 10.6 for males and 11.1 for females in southern Germany. There were striking differences in the clinical characteristics of CMMs, with significantly higher tumour thickness in Crete (median 1.4 mm vs. 0.7 mm in southern Germany). Correspondingly, significantly more nodular melanomas were observed in Crete (29%) as compared with southern Germany (11%).Incidence of CMM in Crete, with about four cases per 100 000 inhabitants per year, is clearly higher than previously estimated, and there is an urgent necessity for earlier recognition of CMM in Crete. However, the incidence of CMM in southern Germany is much higher.
Liver Preservation by Single Passage Hypothermic "Squirt" Perfusion
Authors: R. Y. Calne, D. C. Dunn, B. M. Herbertson, E. M. Gordon, H. Bitter-Suermann, A. J. Robson, A. S. Macdonald, D. R. Davis, D. P. Smith, F. H. Reitter, L. M. Webster
Journal: BMJ (1972)

A single passage, hypothermic, intermittent squirt perfusion of the pig's liver is described which has allowed preservation of porcine livers for up to 17 hours. After preservation, orthotopically allografted livers can maintain recipient animals in good health. If this technique can be applied to clinical liver transplantation it should be possible to move livers from one hospital to another in the same way that kidneys are transported. This should increase the availability of donor livers for transplantation and avoid the serious disadvantages of moving the sick recipient just before the operation to the hospital where the donor has died.
Inflammatory bowel disease, drug therapy and pregnancy: awareness in female IBD patients of reproductive age
Authors: G. Chakrabarty, A. Poullis
Journal: Gut (2011)

<h3>Introduction</h3> Inflammatory bowel disease (IBD) often affects women during their child bearing age. Management of a pregnant IBD patient or any women contemplating pregnancy poses unique challenge. Patient understanding of the disease and its changes during pregnancy and breastfeeding is vital for a successful outcome. It is important to discuss the issues related to pregnancy and conception either at diagnosis or when medication is initially prescribed. In our experience some pregnant women tend to stop their medication in fear of the side effect of the drugs on the developing fetus, with an inherent risk of disease flare up. <h3>Aim</h3> To evaluate understanding and awareness in women of the reproductive age about IBD, its medication, and there effects on pregnancy. <h3>Method</h3> A questionnaire was designed to assess the understanding of the disease and its effect on pregnancy in our IBD clinic patients in 2010. <h3>Results</h3> 71 women, age 18–45 years completed the questionnaire (Mean age 33.03 ± 5.96 years). 40 had Crohn9s disease, 27 ulcerative colitis and 4 indeterminate colitis. 38 were on 5-ASA, 11 on oral steroid, 23 on immunomodulators (Azathioprine or 6MP), 3 on Anti-TNF treatment. 34 had prior pregnancy and 8 of them stopped their drugs during pregnancy. 3 had flare up of disease during pregnancy while the treatment was stopped. One woman had pre term delivery with loss of baby, although her disease was not active at that time. 26 women continued their treatment during the pregnancy, out of them one had preterm delivery and other had intrauterine growth retardation. Three women were pregnant at the time of the assessment and 2 were continuing their treatment. One is not on any regular medication. 36 women were planning future pregnancy – and out of them 10 (27.7%) had no knowledge of how the disease may affect the pregnancy. 20 (55.5%) did not know how pregnancy may affect their disease. 35 (53.8%) did not know if their medication effected breast feeding. 6 women had pre pregnancy counseling (8.95%) – 5 in hospital and 1 in private setting. 45 women (70.3%) would be keen on a formal pre pregnancy counseling service. Only 43 women (65.15%) knew the beneficial effect of folic acid pre-conception and during the first trimester of pregnancy. <h3>Conclusion</h3> This study highlights the lack of knowledge and understanding in the women of reproductive age about their disease, medication and effects of these on pregnancy. Pre pregnancy counseling should form an integral part of IBD service, as only 8.96% of our IBD patient had received pre pregnancy counseling. 70.3% of women suggested a dedicated pre pregnancy counseling service would be desirable. Better understanding of the disease, effects of drug and pregnancy would ensure better outcomes. Education about the benefits of preconception folic acid is required in this patient group.
Abstract 5246: Use of near infrared fluorescence imaging to determine tumor burden in genetically engineered mice
Authors: Kazuhiro Yoshikawa, Marco A. De Velasco, Motoyoshi Tanaka, Yuka Miyazaki, Hiroshi Ushida, Chiori Asahi, Kazuto Nishio, Hirotsugu Uemura
Journal: Cancer Research (2010)

Abstract Tumor imaging in mice revolutionized the ability to detect and quantify tumor burden in pre-clinical studies. However, this technology has been limited for the most part to the use of cancer cell lines manipulated to express specific fluorescence or bioluminescence in xenograft models. Recent advances in the generation of genetically engineered mouse (GEM) models have resulted in notable improvements as platforms for pre-clinical models. Variables such as initial tumor detection, size and location have influenced and limited objectivity in study design and interpretation. In this study we introduce a new modality for determining tumor burden using a commercially available recombinant EGF polypeptide labeled with a near infrared (NIR) fluoroprobe to identify and quantify tumor burden in a knockout mouse model. We evaluated the sensitivity and accuracy EGF-labeled IRDye using our prostate specific PTEN conditional gene-targeting mouse model using intact and castrated mice. Mice were administered the EGF-labeled IRDye by tail vein injection 72 h prior to imaging in vivo imaging. The genitourinary tact (GUT), consisting of the prostate, urethra, bladder, seminal vesicles and coagulating gland, was collected, weighed, fixed in formalin and imaged and cryosectioned. EGFR expression was detected by immunohistochemistry and expression levels were measured by image analysis. To determine tumor burden, adjacent cryosections were analyzed by NIR fluorescence and by histology for size and distribution of tumor glands in H&amp;E stained slides. Closed abdomen in vivo imaging was not possible due to low signal and interference of the preputial gland. However, prostates surgically exposed revealed the presence of tumor nests in the prostate as small as 0.2 mm. Furthermore, formalin fixed GUTs retained fluorescence and were imageable up to 48 h post-fixation. EGFR overexpression was found to be concentrated in cancerous glands and expression was directly proportional to the NIR fluorescent signal. Tumor burden determined by GUT weight correlated poorly to NIR expression in castrated mice. Our data shows that EGF-labeled IRDye NIR imaging is a precise and sensitive method for the determination of tumor burden; however, at the present time, this technology is limited to invasive imaging or ex vivo applications. This study is the first to use NIR fluorescence to measure prostate tumor growth and response in GEM and thus provides a feasible alternative to conventional methods. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5246.
Cofactor Question Divides Codiscoverers of HIV
Authors: Paul Cotton
Journal: JAMA (1990)

THE CODISCOVERERS of the virus linked to acquired immunodeficiency syndrome (AIDS) are again at odds, now over the possible role of cofactors in AIDS (<i>JAMA</i>. 1990;264:665-666). Robert Gallo, MD, and Luc Montagnier, MD, appeared together in Los Angeles, Calif, to receive a joint award from the American Association of Blood Banks for improving blood supply safety. Neither would comment on allegations, now under investigation by the National Institutes of Health (NIH) (Bethesda, Md), that Gallo may have misappropriated some of Montagnier's work in staking a claim to discovery of the human immunodeficiency virus (HIV). But the dispute over cofactors gave them plenty on which to disagree. Gallo, senior researcher at the NIH's National Cancer Institute, says HIV is
Do We Need the Oral Glucose Tolerance Test to Identify Future Cases of Type 2 Diabetes?
Authors: Michael P. Stern, Ken Williams, Steven M. Haffner
Journal: Diabetes Care (2003)

In our recent article (1), in which we presented a predicting model based on readily available clinical variables for identifying individuals at high risk of future type 2 diabetes, we concluded with the words: “… we hope that this report will stimulate other researchers with suitable databases to evaluate (similar) prediction models… ” The first group to take up this challenge is McNeely et al. (2), whose report appears in this issue of Diabetes Care . The results of their analyses in Japanese Americans raise the interesting possibility that the predicting model performs better in younger than older individuals.

A major difference between the Japanese-American cohort and our San Antonio cohort was the older age range of the former (34–75 years, mean ∼52 vs. 25–64, mean 43.5). One reason why 2-h glucose might play a larger role in predicting future diabetes in older subjects is that the other risk factors for diabetes, notably, lipids and blood pressure, are also risk factors for cardiovascular disease. Thus, the older the cohort, the greater the likelihood that individuals with risk factors will fail to return for follow-up glucose tolerance testing as a result of having developed either cardiovascular morbidity or mortality. It thus becomes less likely that these same risk factors will emerge as predictive of diabetes. The finding by McNeely et al. that BMI is a stronger risk factor in individuals <55 years of age supports this concept. Based on their suggestion, we have reanalyzed our data and have also observed an interaction in the same direction between age and BMI. McNeely et al. also observed an interaction between age and HDL, although we did not.

All of the above points notwithstanding, however, it must be acknowledged that the fact that only eight individuals in the study by McNeely et al. died …
Involuntary movements in patients taking oral contraceptives
Authors: P. D. Lewis, M. J. G. Harrison
Journal: BMJ (1969)

Involuntary movements developed in five women taking oral contraceptives. In one, the sudden onset of a unilateral disturbance suggested a cerebral thrombosis; this case is considered to be a further example of the increased risk of cerebrovascular disease associated with oral contraception. The four other patients suffered a relapse of Sydenham's chorea between one and four months after starting an oral contraceptive regimen. Possibly an underlying vascular mechanism was responsible for these relapses.
Objectives, methods and content of patient education programmes for adults with asthma: systematic review of studies published between 1979 and 1998
Authors: P. Sudre, S. Jacquemet, C. Uldry, T. V Perneger
Journal: Thorax (1999)

<h3>Abstract</h3> Quaternary climate fluctuations drove many species to shift their geographic ranges, in turn shaping their genetic structures. Recently, it has been argued that adaptation may have accompanied species range shifts via the "sieving" of genotypes during colonisation and establishment. However, this has not been directly demonstrated, and knowledge remains limited on how different evolutionary forces, that are typically investigated separately, interacted to jointly mediate species responses to past climatic change. Here, through whole-genome resequencing of over 1200 individuals of the carnation <i>Dianthus sylvestris</i> coupled with integrated population genomic and gene-environment models, we reconstruct the past neutral and adaptive landscape of this species as it was shaped by the Quaternary glacial cycles. We show that adaptive responses emerged concomitantly with the post-glacial range shifts and expansions of this species in the last 20 thousand years. This was due to the spatial sorting of adaptive alleles through time, as populations expanded out of restrictive glacial refugia into the broader and more heterogeneous range of habitats available in the present-day inter-glacial. Our results reveal a tightly-linked interplay of migration and adaptation under past climate-induced range shifts that has acted to shape the spatial patterns of adaptive genetic variation we see in the species today.