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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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