PubMed Health⌕ Search

Biomedical subjects

S D London

Publications and source records attributed to S D London.

32 records · Page 2Linked to original sources
PubMed1993

An in-frame insertion into the Sindbis virus 6K gene leads to defective proteolytic processing of the virus glycoproteins, a trans-dominant negative inhibition of normal virus formation, and interference in virus shut off of host-cell protein synthesis.

Encoded in the genomes of all alphaviruses is a hydrophobic polypeptide of 55 amino acids, which is post-translationally modified with 4 covalently bound palmitic acids. This protein, noted as 6K, associates with membranes and is transported along with the two virus transmembranal glycoproteins to the site of virus assembly at the infected cell's plasma membrane. Previous studies showed that mutations in the 6K protein led to the slow release of aberrant, multi-cored infectious virions. In this paper, we report that an in-frame insertion of 45 nucleotides into an internal site of the 6K gene of Sindbis virus produced single-cored infectious particles at about 5% the yield of wild-type virus when the mutant was grown on avian, mammalian, and insect cells. Although the 15 amino acids were inserted at position 29 of the 55-amino-acid 6K protein, the mutation interfered with the cotranslational proteolytic processing that cleaves the 6K at its amino terminus from the Sindbis virus p62 glycoprotein and at its carboxyl terminus from the E1 glycoprotein. As a result, the amounts of normal p62 and E1 proteins were only half that made in cells infected with wild-type virus. In addition, the post-translational proteolytic conversion of p62 to E2 occurred at 10% the rate of wild-type proteins and the extensive fatty acylation normally detected on wild-type 6K protein was not found on the altered 6K protein. None of the mutated 6K protein was detected in virions, which were morphologically indistinguishable from wild-type virus. The mutant 6K virions also were similar to wild type in their rate of attachment, uncoating, and formation of an early nonstructural virus protein in avian cells. When compared with the wild-type virus, 6K29-infected cells exhibited a decreased rate of host-cell protein synthesis shut off. However, the rates of virus capsid synthesis were the same, indicating that capsid protein, per se, is not involved in shut off of host-cell protein synthesis. In complementation studies, this mutant exhibited a trans-dominant phenotype. These data provide clues about the topology of 6K protein in the membrane and its function in virus maturation.

Amino Acid Sequence↗
PubMed1992

Infectious enveloped RNA virus antigenic chimeras.

Random insertion mutagenesis has been used to construct infectious Sindbis virus structural protein chimeras containing a neutralization epitope from a heterologous virus, Rift Valley fever virus. Insertion sites, permissive for recovery of chimeric viruses with growth properties similar to the parental virus, were found in the virion E2 glycoprotein and the secreted E3 glycoprotein. For the E2 chimeras, the epitope was expressed on the virion surface and stimulated a partially protective immune response to Rift Valley fever virus infection in vivo. Besides providing a possible approach for developing live attenuated vaccine viruses, insertion of peptide ligands into virion surface proteins may ultimately allow targeting of virus infection to specific cell types.

Amino Acid Sequence↗
PubMed1990

CD8 lymphocyte subpopulations in Peyer's patches induced by reovirus serotype 1 infection.

CD8 lymphocyte population heterogeneity has been examined by using reovirus serotype 1, strain Lang (reovirus 1/L) as a model infection. We have previously reported that gut mucosal infection with reovirus stimulates the appearance of virus-specific cytotoxic T cell precursors (pCTL) in Peyer's patches (PP). The effectors that mediate reovirus-specific cytotoxicity were found to express both the Thy-1 and CD8 Ag and were MHC-restricted in their recognition of reovirus Ag. To further characterize the virus-specific precursor and effector cells we have analyzed PP cells for the expression of a novel surface Ag (termed germinal center and T cell Ag (GCT)) found on germinal center B cells and a subpopulation of CD8+ T cells. Gut mucosal infection with reovirus 1/L is capable of increasing the proportion of GCT+ CD8+ T cells in PP. Positive selection as well as depletion of GCT+ cells has demonstrated that pCTL can express this Ag, and depletion experiments have demonstrated that effector CTL express the GCT Ag. Thus, a subpopulation of GCT+ cells have been identified as Ag-specific precursor and effector CTL. These observations indicate that the expression of the GCT Ag may provide a means to identify recently stimulated pCTL or effector CTL in gut mucosal tissues.

Animals↗
PubMed1989

Immune response to a molecularly defined internal image idiotope.

A monoclonal anti-idiotope termed 87.92.6 mimics the neutralization/cell-attachment site of the reovirus type 3 hemagglutinin (HA3). The second complementarity determining regions of the VH and VL of 87.92.6 share sequence similarity with a determinant on the HA3. We have used synthetic peptides (termed VH, VL, and Reo peptides, respectively) to probe the immunologic significance of this sequence similarity. Antibodies specific for Reo peptide or VL peptide neutralized reovirus type 3 infectivity. Although Reo peptide was an effective immunogen by itself, free VL peptide or VH peptide were unable to elicit antibodies unless they were linked to each other (VH-VL peptide). Immunization with reo peptide, 87.92.6, or the HA3 elicited a specific lymphocyte proliferative response to VH peptide, indicating that VH peptide may bear an important TH determinant. As found previously for 87.92.6, VL peptide elicited a delayed-type hypersensitivity response specific for reovirus type 3. Reovirus type 3 specific cytolytic lymphocytes specifically lysed targets coated with VH-VL peptide, but not VH or VL peptide alone. These results suggest that immune cross-reactivity between an external Ag and an internal image antibody can be understood at the primary structural level. These observations may have important implications for understanding the development of autoantibodies, network interactions, and the regulation of immune responses.

Amino Acid Sequence↗
PubMed1989

The reovirus-specific cytotoxic T cell response is not restricted to serotypically unique epitopes associated with the virus hemagglutinin.

Reovirus, a virus that contains neither an envelope nor glycosylated polypeptides, has been found to induce virus-specific, major histocompatibility complex (MHC) class I antigen restricted, cytotoxic T lymphocyte (CTL) responses. The cytotoxic T cells require in vitro stimulation in the presence of virus to phenotypically express cytotoxic activity. Utilizing reovirus types 1 and 3, the CTLs derived from mice infected with one serotype can lyse target cells infected with a second serotype of reovirus. In addition, lymphocytes primed in vivo with one serotype develop into fully functional CTLs during in vitro stimulation with the other serotype of reovirus. Therefore, these results suggest that reovirus induced CTLs are virus, but not serotype specific. Common determinants shared by reovirus polypeptides from reovirus types 1 and 3 are most likely the stimuli for the majority of CTLs responses to reovirus.

Animals↗
PubMed1987

Gut mucosal immunization with reovirus serotype 1/L stimulates virus-specific cytotoxic T cell precursors as well as IgA memory cells in Peyer's patches.

In this report we have shown that reovirus 1/L is an effective mucosal immunogen capable of generating a cytotoxic T cell (CTL) and associated helper T cell response to the nominal antigens associated with reovirus 1/L. The effectors that mediate reovirus-specific cytotoxicity are Thy-1+, Lyt-2+, and major histocompatibility complex (MHC)-restricted in their recognition of reovirus antigens, and can therefore be classified as CTLs. Frequency analysis of precursor CTLs occurring in Peyer's patches (PP) and peripheral lymph nodes (PLN) 6 d and 6 mo after intraduodenal stimulation have demonstrated that a persistent gradient of precursors is established, with higher frequencies present in PP. The generation of a CTL response in PP may be important in preferentially repopulating mucosal tissues with effector CTLs that could result in the local containment of infections in the gut. We also found that reovirus 1/L generates a virus-specific B cell response that is dominated by IgA memory cells after intraduodenal immunization. We hypothesize that the efficacy of reovirus 1/L at stimulating T and B cells in the gut mucosa is related to its ability to selectively enter PP via microfold (M) cells after enteric application. In this study we have also demonstrated that PP cells, upon in vitro culture and unrelated to prior reovirus priming, can generate natural killer-like (NK) cytotoxic activity. This may be an in vitro correlate of the in vivo generation of effectors that may populate mucosal tissues (i.e., the intestinal epithelium) with NK-like effector cells.

Animals↗
PubMedDate not supplied

Biomechanical performance of cutting edge surgical needles.

The purpose of this study was to compare the biomechanical performance of cutting edge needles made of S45500 stainless steel alloy to Surgalloy stainless steel. The new high-nickel stainless steel alloy, Surgalloy, has superior performance characteristics over that of the other high-nickel stainless steel alloy, S45500. The Surgalloy needle is produced from a stronger stainless steel alloy than the S45500 needle. The Surgalloy needle has considerably greater resistance to bending than the needle produced from S45500 alloy. In addition, Surgalloy stainless steel has almost a twofold greater resistance to fracture than the S45500 stainless steel alloy.

Biomechanical Phenomena↗
PubMedDate not supplied

Adaptive clothing for persons with mobility disorders after burn injury.

Smart-looking clothes have been designed for wheelchair users. These clothes make dressing faster and easier, and the clothes fit better than the standard garments. The special features for new adaptive clothing for wheelchair users include easy handling fastenings, quick-access garment openings, conveniently placed pockets, custom-curved trousers, slacks, and jackets, custom-shaped dresses and skirts, ponchos or custom-made coats, easy-fit undergarments, and durable styled fabrics. These clothing adaptations are attractive and give the wearer and the observer the feeling that the person with the disability is not set apart by the clothing he or she wears.

Burns↗
PubMedDate not supplied

Reoviruses as probes of the gut mucosal T cell population.

Reovirus, serotype 1, causes a transient, asymptomatic infection of the murine intestine when given intraduodenally or orally. However, this infection markedly perturbs both B- and T- cell populations in Peyer's patches (PP) resulting in: 1) a rapid and persistent increase in specific precursors for cytotoxic T cells (pCTL) and a gradient of frequencies highest in PP and lowest in distal lymphoid tissue; 2) a similar increase in memory B cells committed to IgA; 3) the transient appearance of a subset of germinal center B cells identified by MAb, GC-T; 4) the appearance of pCTL among intraepithelial lymphocytes; and 5) the antigen non-specific alteration in Ig isotype potential of B cells previously primed and found in PP. The pCTL appearing upon acute gut mucosal infection with reovirus are Thyl+, Lyt2+, virus-specific, viral serotype non-specific, class I MHC haplotype restricted and occur within the subset of T cells which newly appears also identified by MAb GC-T. Infections of both neonatal and severe-combined immunodeficient mice indicate that the elements of the immune system may operate at many levels to resist, limit, contain, and resolve viral infection.

Animals↗
PubMedDate not supplied

Intraepithelial lymphocytes contain virus-specific, MHC-restricted cytotoxic cell precursors after gut mucosal immunization with reovirus serotype 1/Lang.

Reovirus 1 has been intraduodenally administered to mice to determine whether virus-specific cytotoxic cells can be elicited within the intestinal epithelium. We have found that reovirus-stimulated, but not control mice, generate virus-specific cytotoxic effector cells when isolated intraepithelial lymphocytes are restimulated in vitro. These effector cells are restricted by major histocompatibility complex (MHC) class I determinants and thus appear to utilize the T cell antigen receptor and to be of the T cell lineage. These results raise the possibility that cytotoxic T lymphocytes (CTL) may be an important component of the host immune response in the intestinal epithelium.

Animals↗
PubMedDate not supplied

The evolution of functional endoscopic sinus surgery in the Commonwealth of Virginia.

This is the largest retrospective analysis of sinus surgery ever reported involving 5,860 surgical as well as 6,769 diagnostic sinus procedures during a six year period, 1988-1993. During this time interval, the frequency of endoscopic procedures has increased dramatically. Because of the increased frequency of this procedure, we see the need for strict definition of the clinical indications for surgery for patients with chronic or acute sinusitis. In addition, the number of open procedures, namely the Caldwell-Luc procedure, as a treatment for sinusitis remained relatively constant despite the frequent use of endoscopic technique. Because of the endoscopic surgery's increased acceptance and advantages over the open surgical technique, we emphasize the need for continuing educational programs to train surgeons to perform the endoscopic procedure or referral of the patient to an otolaryngologist experienced in this technique.

Adult↗