tbuckley/cabot-search huggingface dataset:
Abstract 5712: Identification and characterization of high affinity thioaptamer ligands against E-selectin
Authors: Aman Mann, Anoma Somasunderam, Rene Nieves, David Gorenstein, Mauro Ferrari, Takemi Tanaka
Journal: Cancer Research (2010)

Abstract E-selectin (CD62E, ELAM-1 or LECAM-2) is a calcium dependent cell surface glycoprotein that mediates an adhesion of leukocytes on inflamed endothelium through recognition of specific carbohydrate ligands, sialyl Lewis X (sLeX) and sialyl Lewis A (sLeA). E-selectin expression is transcriptionally induced by NF-κB and AP-1 in response to inflammatory cytokines such as IL-1 and TNF-alpha. Accordingly, elevated E-selectin expression was reported in many types of acute and chronic inflammatory diseases including cancer. Aberrant homing of leukocytes to tumor results in tumor progression and local invasion. In addition, E-selectin and its counter ligands have also been reported to trigger the initial adhesive step of circulating cancer cells to endothelial cells. Therefore, blockade of E-selectin is a promising therapeutic strategy to control pathological infiltration of leukocytes and/or metastatic cancer cells. Thioaptamers (TA) are single stranded DNA molecules with thio substitution in the phosphate backbone, which provide stability against nucleases. Thioaptamer can fold into tertiary structures and bind with high affinity and specificity to a target molecule, and thus suitable for in vivo applications. In this study, we aimed to identify thioaptamer ligands that bind to E-selectin with high affinity and specificity. To achieve this goal, we used two-step selection strategies, recombinant protein based thioaptamer selection from a combinatorial thioaptamer library that contains 10E14 random sequences, followed by a cell based binding to tetracycline inducible E-selectin endothelial cells. We selected 14 different groups of thioaptamer candidates following 10 iterative cycles of binding to recombinant E-selectin protein. Using Tet-on inducible E-selectin endothelial cells, we identified the lead three TA candidates that bind to E-selectin on the surface of endothelial cells at high affinity (nM range) and specificity. In addition, the TA bound to tumor associated vasculature that express E-selectin. Moreover, the TA selected demonstrated significant inhibition of leukocyte adhesion to E-selectin positive endothelial cells at low nanomolar concentrations. In summary, we identified antagonistic TA against E-selectin that binds to endothelial cells and interferes with leukocyte bindings at nM range. Potential applications of this TA could be for 1) inflamed tumor vasculature selective targeted delivery of therapeutic molecules or drug delivery carriers 2) the prevention of pathological diapedesis of leukocytes and/or metastatic cancer cells. We are currently investigating potential clinical applications of the TA. 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 5712.
Similar Progression of Fibrosis Between HIV/HCV–Infected and HCV–Infected Patients: Analysis of Paired Liver Biopsy Samples
Authors: Richard K. Sterling, Jacob A. Wegelin, Paula G. Smith, R. Todd Stravitz, Velimir A. Luketic, Michael Fuchs, Puneet Puri, Mitchell L. Shiffman, Melissa A. Contos, A. Scott Mills, Arun J. Sanyal
Journal: Clinical Gastroenterology and Hepatology (2010)
Integrin-targeted nanocomplexes for tumour specific delivery and therapy by systemic administration
Authors: Aristides D. Tagalakis, Stephanie M. Grosse, Qing-Hai Meng, M. Firouz Mohd Mustapa, Albert Kwok, Shahla E. Salehi, Alethea B. Tabor, Helen C. Hailes, Stephen L. Hart
Journal: Biomaterials (2010)
Dissection of compartments in rat hepatocytes involved in the intracellular trafficking of high-density lipoprotein particles or their selectively internalized cholesteryl esters
Authors: Stefan Jäckle, Franz Rinninger, Thomas Lorenzen, Heiner Greten, Eberhard Windler
Journal: Hepatology (1993)

The trafficking of apolipoprotein E-deficient highdensity lipoprotein particles and of their component cholesteryl esters in rat hepatocytes was studied. Human high-density lipoprotein 3, labeled with two nondegradable, intracellularly trapped tracers in their apolipoprotein A-I and their cholesteryl esters, were injected into rats, and five subcellular hepatocytic fractions were isolated at various time intervals. In control experiments with homologous lipoproteins, doubly labeled rat high-density lipoproteins depleted of apolipoprotein E were used. In endosomes and lysosomes the two labels were recovered at near unity, indicating that high-density lipoproteins are endocytosed as particles, transported to early and late endosomes and finally subjected to lysosomal degradation. No significant amounts of label were found in receptorrecycling endosomes. In contrast to label of those of low-density lipoproteins, label of component protein and cholesteryl esters of high-density lipoproteins from isolated endosomes floated at different densities in gradient ultracentrifugation, indicating early disintegration of high-density lipoprotein particles. In contrast to the endocytic organelles, in the whole liver, label of high-density lipoprotein-associated cholesteryl esters exceeded the label of high-density lipoprotein-associated apolipoprotein A-I twofold to threefold. This finding is compatible with selective uptake of high-density lipoprotein cholesteryl esters in addition to uptake of high-density lipoprotein particles. The excess cholesteryl esters accumulated in a nonendosomal fraction, whose major proteins differed from the integral proteins of endosomes. These data suggest two distinct intracellular routes of hepatocytic high-density lipoprotein trafficking in vivo . Highdensity lipoproteins free of apolipoprotein E are internalized intact by hepatocytes, are predominantly transported to early and late endosomes and are finally subjected to lysosomal degradation. High-density lipo-protein particles do not undergo retroendocytosis in hepatocytes. In addition, high-density lipoprotein-associated cholesteryl esters can be taken up by hepatocytes selectively. They, however, accumulate in a nonendosomal, nonlysosomal compartment. (Hepatology 1993;17:455-465.)
Drug Addiction and Logic
Authors: Frederic Hoffman
Journal: JAMA (1967)

To the Editor:—  It is quite evident that conventional methods and, for that matter, even radical means have not provided a real solution to the problem of addiction. Finding a  answer to this enigma has not evolved to date. Perhaps this lack of success has been due to our eagerness to find a logical solution to a problem which cannot be approached by conventional logic. All forms of behavior ultimately can be explained. It may very well be, however, that certain facets in in the behavior of the addict may lend themselves to explanation only at a molecular level. If this is true, then it is not unreasonable to assume that addictive behavior could have components which are nonrational in nature.  Psychiatry can interpret the needle, the ceremony of the fix, and the premorbid personality of the heroin addict. Alcohol and food addictions have their own spectrum of interpretations.
Relaxing prescribing of naloxone could save lives of drug users, expert says
Authors: D. Henderson
Journal: BMJ (2009)

A leading pharmacologist has called for more widespread availability of a drug that could save the lives of users of opiates. 

Leslie Iverson, professor of pharmacology at the University of Oxford, believes that naloxone should be made more freely available to families of drug addicts so that they can give an intramuscular injection after a respiratory arrest while waiting for paramedics or other professional treatment.

“Naloxone needs to be much …
The Chinese Herbal Formula CUF2 Modulates Th1/Th2 Responses in a Rat Model of Allergic Asthma
Authors: Y.O. Wong, R.Y.T. Sung, K. Li, Y. Zhao, A.M. Li, Y.X. Bao, T.F. Fok, K.P. Fung
Journal: Journal of Allergy and Clinical Immunology (2006)
The influence of HTLV-III infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers
Authors: Kim Krogsgaard, Bjarne ÖRskov Lindhardt, Jens Ole Nielsen, Poul Andersson, Peter Kryger, Jan Aldershvile, Jan Gerstoft, Court Pedersen
Journal: Hepatology (1987)

The presence of antibodies to HTLV-III and markers of active hepatitis B virus replication was examined in a longitudinal study of 33 consecutive male homosexual HBsAg carriers. The mean follow-up time was 37 months (range = 4 to 109 months). All patients were initially hepatitis B virus DNA-positive and HBeAg positive. Antibodies to HTLV-III were detectable in eight patients while they were positive for both of these markers. One of them cleared hepatitis B virus DNA and seroconverted from HBeAg to anti-HBe. This corresponds to an annual clearance/seroconversion rate of 4% (95% confidence limits = 0 to 15%). In two patients, antibodies to HTLV-III appeared after clearance of hepatitis B virus DNA and HBeAg, and in one of them, hepatitis B virus DNA reappeared. Among the 25 patients negative for HTLV-III antibodies, the annual hepatitis B virus DNA clearance rate was 20% and HBeAg to anti-HBe seroconversion rate was 11% (95% confidence limits = 11 to 31% and 4 to 20 % respectively). The observed hepatitis B virus DNA clearance rates in the two groups were significantly different (p &lt; 0.05). Disease activity, as determined by transaminase levels, was significantly lower in HTLV-III infected individuals as compared to individuals without HTLV-III infection (p &lt; 0.05). Infection with HTLV-III may extend the period of active viral replication or even reactivate hepatitis B virus replication and seems to diminish inflammatory disease activity in chronic HBsAg carriers.
SUPPRESSION OF LACTATION BY TESTOSTERONE
Authors: PAUL V. DUFFY
Journal: JAMA (1941)

Suppression of lactation in the puerperal breast frequently is desirable or necessary. After premature or still births, toxemia of pregnancy and some cesarean sections, when there is malformation or abscess of the breast or cracked nipples and in the presence of certain constitutional diseases, such as tuberculosis, diabetes and heart disease, there is valid reason to prohibit lactation. The measures employed for this purpose, until recently, were empiric and generally consisted of application of tight breast binders, with camphor liniment or belladonna unctions, restriction of fluids, saline purges and numerous other procedures of questionable value.  Kurzrok and O'Connell 1 first demonstrated that it is possible to inhibit lactation in women by administering androgen in the form of testosterone propionate. They reported successful results in 19 of 21 cases.  Birnberg, Kurzrok and Klor 2 later reported using testosterone propionate to inhibit lactation in a series of 56 cases, with successful results
Book Review McAlpine's Multiple Sclerosis Third edition. By Alastair Compston, George Ebers, Hans Lassmann, Ian McDonald, Bryan Matthews, and Hartmut Wekerle. 592 pp., illustrated. New York, Churchill Livingstone, 1998. (Distributed by W.B. Saunders, Philadelphia.) $165. 0-443-05008-2
Authors: Massimo Filippi
Journal: New England Journal of Medicine (1999)
Antiphospholipid syndrome: Laboratory testing and diagnostic strategies
Authors: Thomas L. Ortel
Journal: American Journal of Hematology (2012)

Abstract The antiphospholipid syndrome (APS) is diagnosed in patients with recurrent thromboembolic events and/or pregnancy loss in the presence of persistent laboratory evidence for antiphospholipid antibodies. Diagnostic tests for the detection of antiphospholipid antibodies include laboratory assays that detect anticardiolipin antibodies, lupus anticoagulants, and anti‐β 2 ‐glycoprotein I antibodies. These assays have their origins beginning &gt;60 years ago, with the identification of the biologic false positive test for syphilis, the observation of “circulating anticoagulants” in certain patients with systemic lupus erythematosus, the identification of cardiolipin as a key component in the serologic test for syphilis, and the recognition and characterization of a “cofactor” for antibody binding to phospholipids. Although these assays have been used clinically for many years, there are still problems with the accurate diagnosis of patients with this syndrome. For example, lupus anticoagulant testing can be difficult to interpret in patients receiving anticoagulant therapy, but most patients with a thromboembolic event will already be anticoagulated before the decision to perform the tests has been made. In addition to understanding limitations of the assays, clinicians also need to be aware of which patients should be tested and not obtain testing on patients unlikely to have APS. New tests and diagnostic strategies are in various stages of development and should help improve our ability to accurately diagnose this important clinical disorder. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
Early Inhibition of Mycobacterial Growth by Human Alveolar Macrophages is not Due to Nitric Oxide
Authors: CHRISTOPHER ASTON, WILLIAM N. ROM, ANITA T. TALBOT, JOAN REIBMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Phagocytic cells provide the first line of defense against mycobacteria. We examined the relative mycobacteriostatic contributions of normal human alveolar macrophages (HAM), peripheral blood monocytes (PBM), and polymorphonuclear leukocytes (PMN) in the early time period after infection with mycobacteria (48 h). Cells were infected with Mycobacterium bovis (BCG) or M. tuberculosis H37Ra and their ability to inhibit growth was determined by mycobacterial incorporation of [3H]uracil. HAM inhibited the growth of both mycobacteria (44.2 ± 7.9 and 37.6 ± 10.5% inhibition, respectively). Two populations of HAM donors were subsequently defined: inhibitors and noninhibitors. The ability to inhibit growth of H37Ra correlated with that of BCG. In contrast to HAM, PBM and PMN did not inhibit mycobacterial growth. Because nitric oxide (NO) has been proposed to mediate growth inhibition in murine models, we examined whether NO was responsible for the early growth inhibition of mycobacteria by HAM. As expected, in murine peritoneal macrophages (MPM) IFN- γ (2,500 U / ml) enhanced growth inhibition of BCG; the effect was abolished by the nitric oxide synthase (NOS) inhibitor NMMA. In contrast, IFN- γ failed to enhance growth inhibition by HAM or PBM and NMMA had no effect. MPM expressed inducible nitric oxide synthase (NOS2) mRNA in response to LPS and IFN- γ and produced NO. Neither NOS2 mRNA nor NO could be detected in HAM stimulated with LPS and IFN- γ or mycobacteria. These data demonstrate that HAM, but not PBM or PMN, have NO-independent mycobacteriostatic activity in the early time period after infection with mycobacteria.
Splenic Avulsion and Bleeding Shown on Radiocolloid Images
Authors: HOWARD A. LEVY, JOHN J. SZIKLAS, RICHARD P. SPENCER, RONALD J. ROSENBERG
Journal: Clinical Nuclear Medicine (1983)

A case is discussed of a man who presented with trauma to the chest and abdomen. A radiocolloid image showed uptake by the liver. However, the spleen was not identified. Areas of activity outside of the spleen were noted. The patient had splenic avulsion; extra sites of activity likely represented bleeding sites in the abdomen. Failure to identify the spleen on a radiocolloid image, after trauma, should be an alerting sign to possible splenic avulsion (especially when there are also ectopic sites of accumulation of the radiocolloid).
Restoration of Collagen Formation in Photodamaged Human Skin by Tretinoin (Retinoic Acid)
Authors: Christopher Griffiths, Andrew N. Russman, Gopa Majmudar, Robert S. Singer, Ted A. Hamilton, John J. Voorhees
Journal: New England Journal of Medicine (1993)

Topical tretinoin (retinoic acid) modifies fine wrinkles and certain other features of human skin damaged by exposure to the sun (photodamage), but histologic changes do not account for this improvement. In mice with photodamage induced by ultraviolet light, effacement of fine wrinkles by tretinoin is correlated with dermal collagen synthesis but not with histologic changes. We investigated whether collagen synthesis was reduced in photodamaged human skin and, if so, whether it could be restored by treatment with topical tretinoin.Biopsies of photodamaged skin from the extensor aspect of the forearm and skin from the buttocks, which had been protected from the sun, were performed on 26 healthy subjects. In addition, 29 patients with photodamaged skin were treated for 10 to 12 months with a daily application of 0.1 percent tretinoin cream (15 patients) or vehicle cream (14 patients). Skin-biopsy specimens obtained at base line and after treatment were assessed immunohistologically for evidence of dermal collagen I formation (collagen synthesis).Collagen I formation was 56 percent less in the papillary dermis of photodamaged skin than in skin protected from the sun (P < 0.001) and was correlated with the clinical severity of photodamage (r = -0.58, P = 0.002). Treatment of photodamaged skin with tretinoin produced an 80 percent increase in collagen I formation, as compared with a 14 percent decrease in collagen formation with the use of vehicle alone (P = 0.006).The formation of collagen I is significantly decreased in photodamaged human skin, and this process is partly restored by treatment with tretinoin.
Hyperthyroidism and Urticaria
Authors: Norman H. Ertel
Journal: JAMA (1985)

<h3>To the Editor.—</h3> In answer to a question requesting clarification of the relationship between chronic urticaria and thyroid disease, MacKechnie<sup>1</sup>described a case report and mentioned other cases of urticaria in thyrotoxicosis, emphasizing the rarity of the association. He did not point out that urticaria or pruritus may be so severe as to be the presenting complaint in patients with thyrotoxicosis. In 1971, Isaacs and I<sup>2</sup>described six patients who presented because of chronic urticaria (four patients) or severe pruritus (two patients). The case of a 12-year-old girl, treated on several occasions with methimazole, was particularly instructive in that on several occasions she discontinued use of medication and each time had a recurrence of urticaria along with an exacerbation of hyperthyroidism; with the effective treatment of the thyrotoxicosis, the urticaria disappeared. A 61-year-old woman complained of weight loss, weakness, and mild pruritus for 24 months and consulted a
An Address on the Work of a Medical Officer of Health, and How to do it
Authors: T. J. Dyke
Journal: BMJ (1872)

I AM induced to lay before you the following remarks, from the fact of my having received lately very many inquiries from my brother asso- ciates, as to what the duties of a Medical Officer of Health were, and how they were to be done.I will hope that it will not be considered presumptuous on my part to thus lay my views before you, when I tell you that, for the last twenty-four years, I have been a watchful stu- dent of the causes deteriorating the Public Health, and for the last seven years have held the medical officership of health in my native town, Merthyr Tydfil.The Duities of a Healt4z Oficer.-Thesehave been briefly, yet com- prehensively, stated in the minute adopted by the Local Board of Health of Merthyr, in January, I866." I. To ascertain what local causes prejudicially affect the public health in this district, to inform the Board of these discovered causes, and to suggest such means for their removal as medical science can advise." 2. To seek information of the occurrence of cases of epidemic, en- demic, or contagious diseases, and when informed to visit the localities, ascertain the extent of the malady, the local causes likely to conduce to the diffusion thereof, and give such warning as may induce the persons affected to have recourse to medical treatment.In case of an outbreak of small-pox, to inquire into the history thereof, and as to the practice of vaccination in the neighbourhood." 3. To inspect any meat exposed for sale for human food, whenever required so to do by an officer of this Board, or any police officer, and to give his opinion as to the fitness or otherwise of such meat being used for human food, whenever required by a Justice of the Peace." 4. Upon any complaint received by him of the emission of any noxious or offensive smell from any process of trade carried on in any manufactory, yard, house, or premises, or of atmospheric pollution from any drains ox sewers, to inquire into the causes, and report upon the means for the prevention thereof." 5. To perform any duties imposed by any Act of Parliament on the Officer of Health, or Sanitary Inspector."6.To attend the meetings of the Local Board when necessary."7.To report quarterly the nature and amount of sickness and
Viral warts in organ transplant recipients: new aspects in therapy
Authors: T. Schmook, I. Nindl, C. Ulrich, T. Meyer, W. Sterry, E. Stockfleth
Journal: British Journal of Dermatology (2003)

The long-term success of organ transplantation depends on the prevention of allograft rejection and improvement in quality of life for the patients. This has been achieved through better immunosuppressive regimens with lower dosages and a new generation of immunosuppressive drugs. However, these immunosuppressive agents not only impair the patient's reactivity to the graft, but also to infectious organisms, thereby making them more susceptible to opportunistic pathogens. Because of this, organ transplant recipients are predisposed to epithelial malignancies and infections. The majority of transplant recipients will develop warts induced by human papillomavirus (HPV). Some of these viral warts may present with atypical histological features and may progress into squamous cell carcinomas. The risk for cutaneous cancers after transplantation is much higher than in the immunocompetent population. Current therapies for HPV-associated skin tumours mainly depend on the destruction of affected skin areas. These treatment modalities are of limited efficacy and are usually painful for the patients. A promising novel therapeutic agent is imiquimod, an immune response modifier. Clinical efficacy of imiquimod has been observed for different skin lesions, including viral warts in both immunocompetent and immunosuppressed patients.
TCT-426 “Balloon angioplasty tamponade facilitated seal” of large diameter arteriotomy vascular access during Endovascular interventions, from the SIMPLIPHieDE Study (Single center IMPella LVAD supported Pci in High Risk group of patients–Detroit Medical Center Experience)
Authors: Obrad Kokanovic, Haroon Faraz, Rohit Amin, Antwon Robinson, Hassan Ismail, Ahmed Munir, Theodore Schreiber
Journal: Journal of the American College of Cardiology (2012)
Rehabilitation of Patients with Oral Cancer
Authors: P. F. Corso
Journal: CA A Cancer Journal for Clinicians (1968)

The increased use of surgery for patients with oral cancer combined with the increasing use of irradiation and chemotherapy, alone or in com bination with surgery, will signifi cantly increase the needs and demands for reconstructive and rehabilitative surgery.Approximately 12,000 new cases of intraoral cancer occur an nually in the United States.Four per cent of cancers occur in the head and neck area.This gives some indication of the magnitude of the problem.The opportunities for rehabilitation and reconstruction should be evaluated in dividually, logically, and unemotion ally, remembering that reconstructed tissue is only a substitute, as perfect or imperfect as it may be.