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Related post: Jhis project concerns the new lymphotropic human herpesviruses 6 (HHV-6) , HHV-7 and HHV-S . The overall goal of these studies has been Toprol 200 Mg to determine virus involvement in human disease (s) . The results of these studies during the past year can be summarized at follows: (i) HHV-6 and HHV-8 . Characterization of multiple virus isolates have revealed that the herpesviruses previously designated as HHV-6 Toprol Xl Cost fall into two distinct categories. These viruses differed in restriction enzyme pattern of Beta Blockers Toprol viral DNA, antigenically and epidemiologically. As per these studies, and confirmed by others, these viruses will be classified as Exanthem Subitum Virus (ESV) , prototyped by the HHV-6 Z29 strain, Toprol Xl Er and HHV-8, prototyped by the U1102, or by the GS strains. (ii) Disease association of ESV or HHV-6 . In addition to ^^iruses from ES patients, we have also analyzed viruses from patients with fatal encephalitis and fatal fulminant hepatitis. All of these viruses were similar to ESV strain Z29. They were distinct from the U1102 strain, as well as from HHV-7 DNA. (iii) Virus reactivation from latency : Analyses of viruses from 8 renal transplant patients and 10 bone marrow transplant patients revealed similarity to the Z29 Toprol Interactions virus, except minor strain variations in the terminal repeat sequences. In one case of renal transplant the reactivated virus originated from the donor icidneys, in as much as identical viruses were derived from two transplanted kidneys . rom the same donor. In ES patients, virus can only be recovered during 3-4 days of the acute (high fever) Toprol X phase, in BMT patients virus Toprol Coupon could be repeatedly isolated ^'or lengthy time, revealing long term viremia. We conclude that ESV (rather than IHV-8) , can be associated with morbidity and mortality in immunocompromised latients. Further studies are designed with additional clinical centers, in the 'SA, Japan and Israel, to extend these conclusions, as well as Metoprolol Vs Toprol to allow early letection of reactivated virus, for more timely therapy with potent anti-viral irugs which are too toxic for lengthy therapy. 19-36 PHi) dU4U (Hev. bflS) DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE NOTICE OF INTRAMURAL RESEARCH PROJECT PROJECT NUMBER ZOl AI 00652-01 LVD PERIOD COVERED October 1, 1991 to September 30, 1992 TITLE OF PROJECT (BO chamctan or lass. Tits must II on on* line batween tf)e boniera.) Structure and Function of Peptide Transporters PRINCIPAL INVESTIGATOR (Ust otttar prnfesskmal pafsonnal Toprol Xl Recall balow tha Toprol Xr Principel Investlgabr.) (Nama, title, laboratory, and institute affiliation) PI J.R. Bennink Microbiologist LVD, NIAID J.W. Yewdell Others: F. Esquivel I. Ba-ik L. Eisenlohr R. Anderson Medical Officer (Research) LVD, NIAID visiting Fellow LVD, NIAID Visiting Fellow LVD, NIAID Staff Fellow Toprol Generic Name LVD, NIAID NRC Fellow LVD, NIAID COOPERATING UNITS (it any) T. Spies, Dana Farber Cancer Institute, Boston, MA R. Demars, University of Wisconsin, Madison, WI LAB/BRANCH Laboratory of Viral Diseases SECTION Viral Immunology Section INSTITUTE AND LOCATION NIAID, NIH, Bethesda, MP 20892 TOTAL STAFF YEARS: 2 . 44 Staff years PROFESSIONAL; 0.22 staff year OTHER: 2 .22 staff years CHECK APPROPRIATE BOX(ES) n (a) Human subjects n (a1) Minors D (a2) Interviews n (b) Human tissues E (c) Neither SUMMARY OF WORK (Use standanJ urvaducad type. Do not exceed the space fxovidad.) CD8+ T cells (Ten,. ) play an important role in controlling virus infections. recognize peptides of 8 to 10 residues derived from viral proteins located in the cytosol of virus infected cells. These peptides are recognized in a complex with class I Toprol Xl Price molecules encoded by the major histocompatibility complex (MHC). In the past 2 years it was discovered that the MHC also encodes two molecules, termed Tapl and Tap2, that seem to specifically transport Toprol Xl 100 peptides from the cytosol into the intracellular compartment that contains class I molecules. Tap genes have been found to be polymorphic in humans, although to a much lesser extent than the class I molecules. The existence of these putative peptide pumps and their polymorphism raises a number of important questions: Where in the cells are the pumps located? Do Toprol Vs Metoprolol the pumps influence the types of peptides presented by class I molecules? Are the pumps Toprol Xi tethered to the proteases Toprol Xl 12.5 that produce antigenic peptides in the cytosol? How do the pumps work? Are there individuals with immune deficiencies based on mutations in the Tap genes? Can cells transport peptides via other mechanisms? To help characterize the structure and function of the Tap genes we have inserted them into vaccinia virus. We have demonstrated that a Vac Toprol Beta Blocker recombinant encoding Tapl produces a fully functional gene, and have begun the biochemical and immunocytochemical characterization of the gene. We have just begun characterization of a vac recombinant that contains the Tap 2 gene. Additionally, we have examined the specificity of the antigen transporters. Toprol Xl 200 We found that the transporters can transport the exact peptides presented by class I molecules. Also we examined whether expression of the human Tap2 gene in mouse cells adversely affects the ability of the cells to present viral proteins to T^^^. We found that the human Tap2 gene functions in a indistinguishable manner from its mouse counterpart. Finally, we explored the presentation of peptides in cells Toprol 12.5 Mg that fail to Beta Blocker Toprol express one or both Tap genes. 19-37 PHtJ BU40 (Hav. 5/92)
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