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Biomedical subjects

C A Reed

Publications and source records attributed to C A Reed.

At least 19 recordsLinked to original sources
PubMed1999

Intramuscular injection of plasmid DNA encoding cottontail rabbit papillomavirus E1, E2, E6 and E7 induces T cell-mediated but not humoral immune responses in rabbits.

To test the efficacy of genetic vaccination against papillomavirus infection, plasmid DNA encoding cottontail rabbit papillomavirus (CRPV) E1, E2, E6, E7 or without insert were intramuscularly injected into five groups of rabbits. Peripheral blood mononuclear cells (PBMCs) showed specific proliferation upon in vitro stimulation with E1, E2, E6 or E7 proteins in a majority of vaccinated rabbits but Western blot analysis did not detect antibodies specific for these viral proteins in rabbit serum. All rabbits grew papillomas after virus challenge and none of the rabbits showed systemic papilloma regression. These observations showed that intramuscular injection of plasmid DNA encoding CRPV E1, E2, E6 or E7 induced CD4+ T cell-mediated but not humoral immune responses, and did not result in the protection of rabbits from virus infection.

Animals↗
PubMed1999

A broad-spectrum microbicide with virucidal activity against sexually transmitted viruses.

Sodium dodecyl sulfate (SDS), an alkyl sulfate surfactant derived from an organic alcohol, possesses surfactant properties but also denatures and unfolds both monomeric and subunit proteins. In preliminary experiments, we demonstrated that SDS is a potent inactivator of herpes simplex virus type 2 and human immunodeficiency virus type 1 at concentrations comparable to those used for the surfactant nonoxynol-9. We hypothesized that SDS might be capable of denaturing the capsid proteins of nonenveloped viruses. In this report, we demonstrate inactivation of rabbit, bovine, and human papillomaviruses after brief treatment with dilute solutions of SDS. Effective concentrations were nontoxic to rabbit skin and to split-thickness grafts of human foreskin epithelium. This is the first report of a microbicidal surfactant that will inactivate papillomaviruses. We propose that SDS is now a candidate microbicide for formulation and testing with humans.

Animals↗
PubMed1998

Characterization of transformation function of cottontail rabbit papillomavirus E5 and E8 genes.

Cottontail rabbit papillomavirus (CRPV) induces rabbit skin papillomas, which progress to invasive carcinoma in some animals. Two early genes, E7 and E6, have been demonstrated previously to be oncogenes. In this study, we identified two additional transforming genes, E8 and E5. Both E8 and E5 stimulated C127 and BALB/c A31 (A31) cell proliferation and affected cell cycle transition. The E8 and E5 transfectants lost cell contact inhibition, reaching a high saturation density when cultured up to 2 weeks. E8-C127 transfectants formed colonies in soft agar in the presence of platelet-derived growth factor (PDGF) while E5-C127 transfectants formed colonies without the requirement for PDGF. E8-C127 transfectants were highly tumorigenic whereas E5-C127 transfectants showed a weak tumorigenicity in nude mice. Both E8 and E5 A31 transfectants failed to form colonies in soft agar even in the presence of platelet-derived growth factor (PDGF) and did not develop tumors in nude mice. These results clearly showed that CRPVE8 and E5 are oncogenes and that the PDGF beta-receptor signaling pathway may be involved in E8-mediated C127 cell transformation. The difference in colony formation in soft agar and tumorigenicity in nude mice between C127 and A31 cell lines indicates that additional alterations in cellular gene expression are needed for E5- and E8-transfected cells to acquire a malignant phenotype.

3T3 Cells↗
PubMed1997

Dissimilar spine and femoral Z-scores in premenopausal women.

The purpose of this study was to determine if differences exist in premenopausal women between z-scores for lumbar spine and proximal femoral bone mineral densities (BMD). Participants were 237 women ranging in age from 20 to 45 years. BMDs of the lumbar spine and proximal femur (femoral neck, Ward's area, and trochanter) were assessed using dual-energy X-ray absorptiometry (Lunar DPX). Mean (+/-SD) age, height, and weight of the participants were 29.4 +/- 6.9 years, 164.4 +/- 6.1 cm, and 64.9 +/- 12.1 kg, respectively. Lumbar spine BMD and BMD at the femoral neck, Ward's area, and trochanter were significantly correlated with large SEEs (r = 0.59-0. 65; SEE = 0.09-0.11). No positive correlation with age and BMD at any site was seen in this population but a significant negative correlation with age was seen in the proximal femur beginning at age 30. Twenty to 24% of the 20-29-year-olds exhibited a difference in z-scores of greater than 1 between the spine and sites in the proximal femur. This percentage increased to 32-46% in the 30-45-year-olds but the nature of the observed differences changed. The differences in spine and proximal femoral z-scores that are seen in the older age group appear to be the result of the earlier onset of bone loss in the proximal femur rather than an initial difference in peak bone mass which has been maintained.

Absorptiometry, Photon↗
PubMed1997

Coinfection of human foreskin fragments with multiple human papillomavirus types (HPV-11, -40, and -LVX82/MM7) produces regionally separate HPV infections within the same athymic mouse xenograft.

The athymic mouse xenograft system was used to prepare infectious stocks of two additional anogenital tissue-targeting human papillomaviruses (HPVs) in a manner similar to that for the development of infectious stocks of HPV-11. An anal condyloma from a transplant patient was used as material for extraction of infectious virus, and human foreskin fragments were incubated with the virus suspension and transplanted subrenally into athymic mice. Partial viral sequencing indicated that two rare HPV types (HPV-40 and HPVLVX82/MM7) were concurrently present in both the patient condyloma and the foreskin xenografts, and passage of both types was achieved as a mixed infection with HPV-40 predominating. Xenografts that developed from simultaneous infection of human foreskin fragments with HPV-11, -40, and -LVX82/MM7 virions produced regionally separate areas of HPV-11 and -40 infection as determined by in situ hybridization. In addition, in situ hybridization with HPV-40 and HPVLVX82/MM7 DNA probes demonstrated that both of these HPV types were present as adjacent but separate infections within the same anal condyloma of the transplant patient. These studies indicate that multiple HPV types can simultaneously infect genital tissue and that each HPV type predominantly maintains regional separation within the same papilloma.

Animals↗
PubMed1996

Monoclonal antibodies to HPV-6 L1 virus-like particles identify conformational and linear neutralizing epitopes on HPV-11 in addition to type-specific epitopes on HPV-6.

A set of 13 monoclonal antibodies (MAbs) was generated against HPV-6 L1 virus-like particles (VLPs), screened for reactivity to HPV-6 and HPV-11 L1 VLPs by ELISA, and tested for neutralization of HPV-11 infection. Both cross-reactive and type-specific epitopes were detected such that 4 of 13 MAbs reacted to surface conformational sites on HPV-6 L1 VLPs and the remaining 9 MAbs were cross-reactive to both HPV-6 and HPV-11 L1 VLPs. four of the 9 cross-reactive MAbs were able to neutralize HPV-11 infectivity, and 3 of 4 of these neutralizing MAbs (N-MAbs) identified shared surface conformational sites. One N-MAb therefore recognized a surface linear epitope as judged by positive binding to L1 in a Western blot assay. The neutralization status of these cross-reactive MAbs with regard to HPV-6 could not be assayed. These results demonstrated that the closely related HPV types 6 and 11 contain both type-specific and shared neutralizing epitopes.

Animals↗
PubMed1996

Surface conformational and linear epitopes on HPV-16 and HPV-18 L1 virus-like particles as defined by monoclonal antibodies.

A panel of 24 monoclonal antibodies (MAbs) was generated against human papillomavirus (HPV) types 16 and 18 L1 virus-like particles (VLPs). The MAbs were screened for reactivity to a variety of VLPs prepared from HPV-6, -11, -16, -18, -31, -33, -35, and -45, cottontail rabbit papillomavirus, bovine papillomavirus type 1, and a set of 35 overlapping 20-amino-acid peptides spanning the entire HPV-16 L1 gene. Type-specific linear and conformational surface epitopes were detected as well as several cross-reactive linear epitopes that showed various levels of cross-reactivity between different genital HPV and animal papillomavirus L1s. Most of the linear epitopes were mapped using synthetic peptides, and the epitopes were identified as being either surface or buried within the VLP as defined by the pattern of reactivity in ELISA using intact and disrupted VLP antigen. These MAbs may be useful reagents to help define neutralizing epitopes of HPV-16 and -18 when infectivity assays become available, and to define the regions of L1 that are exposed on the surface or buried within the assembled capsid.

Amino Acid Sequence↗