Migration of Langerhans Cells from Carcinogen-Treated Sheep Skin

To define the mechanism(s) of carcinogen depletion of Langerhans cells (LC) from skin, the migration of LC from the skin to the regional lymph node was examined in carcinogen-treated, antigen-treated, and control sheep. This was assessed by cannulation of afferent lymphatic vessels that drain the treated areas of skin or the efferent lymphatic draining the regional lymph node. Cells draining from test or control skin were continuously collected and enumerated by indirect immunofluorescence and flow cytometry using specific anti-CD1 monoclonal antibodies. There was a marked increase in the rate of LC migration in the 8h following the application of the contact sensitizing antigen trinitrochlorobenzene (TNCB). The chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) triggered a tenfold-greater migration of LC compared with TNCB—with the peak response at 5 d. After DMBA treatment LC were also detected in the efferent lymph of the regional lymph node. It is concluded that the depletion of LC from carcinogentreated skin is due to the increased LC migration and not carcinogen-induced cell death

Dc track edge interactions

Includes bibliographical references.We have developed an experimental method for investigating the interaction between two dc track edges by studying the track edge noise. We conclude that two edges do not interact when they are several micrometers apart, but the noise reduces nearly to zero when their separation is less than about half a micrometer. There is a transition region that exists between these two limits. The net track edge noise power from two dc edges is quantized, implying that in our experiment track edges interact around the complete revolution of the disk or not at all.This work was supported in part by NSF Grant No. ECS-880470 and NSF Presidential Young Investigator Award (Indeck) ECS-89-5714

Intermittent Feeding of Tylan Reduces Use of In-Feed Antibiotics While Still Controlling Incidence of Liver Abscesses in Finishing Steers

Liver abscesses are a cause of concern for many feedlots across the country as they lead to a decrease in feedlot performance of finishing cattle as well as a decrease in the final carcass value. Loss in carcass value is due to not only the abscessed liver being condemned, but also due to trim loss associated with the condemned liver. The macrolide drug tylosin phosphate is the drug of choice for metaphylactic treatment of liver abscesses in feedlot cattle. The Food and Drug Administration approved the drug for over-the-counter use, however, from January 2017 all medically important (used in human health) antibiotics that are to be fed in production animal diets will require a veterinary feed directive. The objective of the veterinary feed directive program is to decrease the use of medically important antibiotics in animal production. These veterinary feed directives are similar to a prescription and will encourage the use of the drug in accordance to FDA-guidelines associated with that drug. Macrolide antibiotics are considered medically important and will need a veterinary feed directive. Therefore, it is imperative to look at different methods to control liver abscesses in feedlot cattle. Various studies have noted that macrolide antibiotics (such as tylosin phosphate) are effective against pathogens for moderate to prolonged periods after initial use. The purpose of this study was to determine whether feeding tylosin phosphate periodically throughout the finishing period will have a comparable effect on decreasing liver abscesses as when we would feed tylosin phosphate continuously through the finishing period

Cyclotron resonance of the quasi-two-dimensional electron gas at Hg1-xCdxTe grain boundaries

The magnetotransmission of a p-type Hg0.766Cd0.234Te bicrystal containing a single grain boundary with an inversion layer has been investigated in the submillimetre wavelength range. For the first time the cyclotron resonance lines belonging to the various electric subbands of a quasi-two-dimensional carrier system at a grain boundary could be detected. The measured cyclotron masses and the subband densities determined from Shubnikov-de Haas experiments are compared with theoretical predictions and it is found that the data can be explained very well within the framework of a triangular well approximation model which allows for non-parabolic effects

Rac1 as a therapeutic target in ovarian cancer

Rac1 is a high value therapeutic target for cancer based on its tumor promoting activities, yet clinical applications targeting Rac1 are in their infancy. High expression and hyperactivation of Rac1 in ovarian cancer, along with our identification of R-ketorolac as a novel Rac1 and Cdc42 selective inhibitor with translational potential, prompt us to test the hypothesis that targeting Rac1 has therapeutic utility for ovarian cancer. Ascites tumor cell samples from ovarian cancer patients in a prospective study receiving racemic ketorolac for clinically indicated use in pain relief were previously reported to show time dependent reduction of Rac1 and Cdc42 activities post-treatment. New RNA seq data of these patient samples reveals significant changes of genes involved in cell adhesion, cytokine-mediated signaling and cytokine production pathways. Conversely, the identified downregulated genes were overexpressed and associated with worse survival in ovarian cancer patients analyzed through The Cancer Genome Atlas (TCGA). Among the downregulated genes in the NOD pathway are chemokines and pro-inflammatory cytokines. Follow-up cytokine panels from patients confirm that racemic ketorolac treatment reduces the levels of immunosuppressive cytokines IL-6, IL-10 and RANTES in ascites fluids. Together, these data indicate there may be a benefit to the anti-inflammatory activity of the S- enantiomer, as well as the GTPase inhibitory activity of the R- enantiomer of ketorolac for ovarian cancer treatment

Use of the ODD-Luciferase Transgene for the Non-Invasive Imaging of Spontaneous Tumors in Mice

In humans, imaging of tumors provides rapid, accurate assessment of tumor growth and location. In laboratory animals, however, the imaging of spontaneously occurring tumors continues to pose many technical and logistical problems. Recently a mouse model was generated in which a chimeric protein consisting of HIF-1α oxygen-dependent degradation domain (ODD) fused to luciferase was ubiquitously expressed in all tissues. Hypoxic stress leads to the accumulation of ODD-luciferase in the tissues of this mouse model which can be identified by non-invasive bioluminescence measurement. Since solid tumors often contain hypoxic regions, we performed proof-of-principle experiments testing whether this transgenic mouse model may be used as a universal platform for non-invasive imaging analysis of spontaneous solid tumors.ODD-luciferase transgenic mice were bred with MMTV-neu/beclin1+/- mice. Upon injection of luciferin, bioluminescent background of normal tissues in the transgenic mice and bioluminescent signals from spontaneously mammary carcinomas were measured non-invasively with an IVIS Spectrum imaging station. Tumor volumes were measured manually and the histology of tumor tissues was analyzed.Our results show that spontaneous mammary tumors in ODD-luciferase transgenic mice generate substantial bioluminescent signals, which are clearly discernable from background tissue luminescence. Moreover, we demonstrate a strong quantitative correlation between the bioluminescent tumor contour and the volume of palpable tumors. We further demonstrate that shrinkage of the volume of spontaneous tumors in response to chemotherapeutic treatment can be determined quantitatively using this system. Finally, we show that the growth and development of spontaneous tumors can be monitored longitudinally over several weeks. Thus, our results suggest that this model could potentially provide a practical, reliable, and cost-effective non-invasive quantitative method for imaging spontaneous solid tumors in mice

P183 Establishing the epidemiology of rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis in England using primary care electronic health record data

Abstract Background/Aims The substantial personal and socioeconomic costs associated with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) make understanding their epidemiology crucial. The Clinical Practice Research Datalink (Aurum) is an electronic healthcare record (EHR) database, containing primary care records from ∼20% of English practices (&amp;gt;13 million patients currently registered). To determine RA/PsA/axial SpA epidemiology using EHR data, validated methods need to be applied to ascertain patients with these diagnoses. To address this, we updated and applied approaches validated in other primary care EHR databases in Aurum and described the annual incidence/point-prevalence of RA/PsA/axial SpA alongside patient characteristics (providing indirect evidence of coding accuracy). Methods Diagnosis and synthetic disease-modifying anti-rheumatic drug (DMARD) prescription code lists were constructed, and pre-defined approaches for ascertaining patients with RA/axial SpA/PsA applied. The annual incidence and point-prevalence of RA/PsA/axial SpA were calculated from 2004-2020. Samples were stratified by age/gender, and mean age and gender/ethnic-group relative frequencies described. The study was approved by the CPRD Independent Scientific Advisory Committee (reference 20_000244). Results From 2004-2019 the point-prevalence of RA/PsA increased annually, peaking in 2019 (RA 7.79/1,000; PsA 2.87/1,000) then falling slightly. From 2004-2020 the point-prevalence of axial SpA increased annually (except in 2018/2019), peaking in 2020 (1.13/1,000). Annual RA incidence was higher between 2013-2019 (when included in the Quality Outcomes Framework, ranging 0.491 to 0.521/1,000 person-years) than 2004-2012 (ranging 0.345 to 0.400/1,000 person-years). The annual incidence of PsA and axial SpA increased from 2006 (0.108 to a peak of 0.172/1,000 person-years) and 2010 (0.025 to a peak of 0.045/1,000 person-years), respectively. These years were when new disease classification criteria were introduced. Marked falls in the annual incidence of RA, PsA and axial SpA between 2019 and 2020 were seen, reducing by 40.1%, 67.4% and 38.1%, respectively, reflecting the impact of the COVID-19 pandemic on arthritis diagnoses. Stratifying incidence/prevalence by age/gender broadly showed expected patterns (although the incidence of axial SpA/PsA in women increased over time), and the mean age and gender proportions followed those previously reported. Conclusion The approaches we used to determine patients with RA, PsA, and axial SpA in Aurum led to incidence/prevalence estimates broadly consistent with published studies, and patient characteristics as would be expected. These data support the potential of the Aurum-updated ascertainment approaches for use in further studies of RA, PsA and axial SpA. Disclosure I. Scott: None. R. Whittle: None. J. Bailey: None. H. Twohig: None. S. Hider: None. C. Mallen: None. S. Muller: None. K. Jordan: None. </jats:sec