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Biomedical subjects

D Peterson

Publications and source records attributed to D Peterson.

At least 163 records · Page 9Linked to original sources
PubMed1994

Development of recombinant Salmonellae expressing hybrid hepatitis B virus core particles as candidate oral vaccines.

This paper provides a review on the development of hepatitis core antigen as a vaccine carrier moiety and the use of recombinant Salmonella vaccine strains expressing hybrid HBcAg particles as live oral vaccines. Salmonella spp. can be attenuated by defined genetic means so that they become avirulent, yet preserve invasiveness after oral uptake. Oral immunization of mice with such avirulent candidate Salmonella typhimurium vaccine strains elicited serum antibody responses against a limited number of bacterial antigens. A highly immunogenic viral nucleocapsid antigen, hepatitis B virus core antigen (HBcAg) that can be expressed in prokaryotes was used as a carrier moiety for B-cell epitopes. Insertion sites with an enhanced immunogenicity for the carried epitopes were defined using HBV envelope protein virus neutralizing epitopes. An internal insertion site in HBcAg was found that drastically enhanced the immunogenicity of the foreign (pre-S1) epitope while reducing the immunogenicity of the carrier protein. Internally fused HBc/pre-S hybrid particles were expressed in Salmonella typhimurium and S. typhi vaccine strains. A single oral immunization of mice with such live recombinant S. typhimurium strains elicited a high titred serum anti-pre-S1 IgG response. Similarly, circumsporozoite repeat epitopes of three different malaria parasites were expressed as HBcAg/CS hybrids in recombinant S. spp. and were found to be highly immunogenic.

Administration, Oral↗
PubMed1993

Structure of hepatitis B virus core and e-antigen. A single precore amino acid prevents nucleocapsid assembly.

The hepatitis B virus core gene codes for two polypeptides: the core protein, which assembles to form particles (HBcAg), and the secreted precore protein (HBeAg). Expression vectors directing the synthesis in Escherichia coli of a recombinant HBeAg corresponding in sequence to serum-derived HBeAg encompassing the 10 precore amino acids remaining after cleavage of the precursor and residues 1-149 of HBcAg (PC-HBeAg) were constructed. Recombinant PC-HBeAg, HBcAg, and C-terminally truncated HBcAg were isolated from E. coli and analyzed by sucrose velocity sedimentation, electron microscopy, anti-HBc/e specific monoclonal antibody analysis, and for immunogenicity. HBcAg and truncated HBcAg formed 27-nm particles and displayed HBc antigenicity. In contrast, PC-HBeAg was nonparticulate and did not band in sucrose gradients. PC-HBeAg was recognized efficiently by HBeAg-specific antibodies and displayed little HBc antigenicity. Immunogenicity studies including T and B cell recognition confirmed that PC-HBeAg demonstrates HBe antigenicity. The presence of the 10 precore amino acids therefore prevented particle formation. To analyze which precore amino acids might be responsible for the prevention of particle formation a cysteine to glutamine substitution at amino acid position -7 was introduced into PC-HBeAg (-7C-->Q)PC-HBeAg. This single amino acid change at position -7 restored particle formation and HBc antigenicity. The evolutionarily conserved cysteine at position -7 thus appears responsible for the prevention of particle assembly in the HBeAg biosynthesis pathway.

Animals↗
PubMed1993

Simulation of stochastic micropopulation models--II. VESPERS: epidemiological model implementations for spread of viral infections.

This second paper concerning stochastic micropopulation simulations describes VESPERS, which can serve as a framework for simulation models of the epidemic spread of infection. The versions described are implemented using the simulation shell, SUMMERS, which includes the generic commonalities of several micropopulation models. Population members in VESPERS move through states related to the individual's status relative to the infective agent. Features of the models include mixing groups, member demographics, susceptibility and infectiousness, and co-circulation of infectious agents. The sensitivity of the simulation outcomes to quantitative features of the model has been analyzed. The user can select reports of desired distributions and averages of simulation outcomes.

Demography↗
PubMed1993

A virulent Salmonella expressing hybrid hepatitis B virus core/pre-S genes for oral vaccination.

This report reviews and extends data on the use of hepatitis B virus (HBV) core (HBcAg) particles as a carrier moiety for B-cell epitopes of the HBV envelope proteins. Virus-neutralizing epitopes of the HBV pre-S region were inserted at the N-terminus, the N-terminus through a precore linker sequence, the C-terminus and an internal position of HBcAg by genetic engineering in Escherichia coli. The hybrid HBc/pre-S proteins were purified and their antigenicity and immunogenicity analysed. All purified HBc/pre-S particles were particulate. Pre-S epitopes inserted at the N-terminus through a precore polylinker, the truncated C-terminus and at the internal position between HBcAg amino acids 75 and 81 were accessible on the particle surface. N-terminal fusions required the presence of the linker sequence to become surface accessible and immunogenic. Fusions to the N- and C-termini of HBcAg did not interfere with HBcAg antigenicity and immunogenicity. In contrast, insertion at the internal site abrogated recognition of HBcAg by five out of six monoclonal antibodies and diminished recognition by human polyclonal anti-HBc antibodies as well as HBcAg immunogenicity. A pre-S(2) sequence fused to the C-terminus of HBcAg was surface accessible and weakly immunogenic. Pre-S(1) sequences fused to the N-terminus through a precore linker were surface accessible and highly immunogenic. The same sequence fused to the core methionine was not surface accessible or immunogenic. Insertion of the same pre-S(1) sequence at an internal position of HBcAg resulted in the most efficient anti-pre-S(1) antibody response.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Immunization with recombinant woodchuck hepatitis virus nucleocapsid antigen or hepatitis B virus nucleocapsid antigen protects woodchucks from woodchuck hepatitis virus infection.

Woodchucks were immunized with recombinant woodchuck hepatitis virus (WHV) nucleocapsid antigen (WHcAg) or hepatitis B virus (HBV) nucleocapsid antigen (HBcAg) and challenged with 10(6) WHV ID50. Six out of six woodchucks immunized with WHcAg and four out of six immunized with HBcAg were protected from WHV infection. Woodchucks immunized with WHcAg or HBcAg developed high serum antibody titres against WHcAg or HBcAg. Antibodies against WHc and HBc displayed little cross-reactivity (< 1%). This confirms and extends previous reports of protection against homologous challenge after immunization with HBcAg/WHcAg which are both internal viral antigens. As the dominant B-cell epitope(s) on particulate WHcAg and HBcAg appear not to be conserved it also demonstrates that antibodies against HBcAg/WHcAg are not important for this protection. Woodchucks immunized with WHcAg/HBcAg reacted with a fast serum antibody response against viral envelope proteins upon challenge with WHV, indicative of functional intrastructural/intermolecular T-cell help as one potential mechanism of protection after immunization with an internal viral antigen.

Animals↗
PubMed1993

New enzyme immunoassays for the serologic detection of woodchuck hepatitis virus infection.

The woodchuck and the woodchuck hepatitis virus (WHV) have been used as a model of hepatitis B virus infection and its disease sequelas. Serologic responses to WHV infection have been described in previous reports from this laboratory by using virus-specific radioimmunoassays (RIAs) for WHV surface antigen, antibody to WHV core antigen, and antibody to WHsAg. In this study, we developed and evaluated new enzyme immunoassays (EIAs) for these WHV serologic markers. Relative to the established RIAs, the EIAs were either improved or comparable in their sensitivity and specificity, and in their utility for monitoring experimental WHV infection and classifying woodchucks into serological diagnostic categories. These EIA systems are amenable to the quantitative titration of antibodies and quantitation of WHV antigens in serum, and ultimately should allow improved resolution of virologic and humoral immune responses of woodchucks to WHV infection.

Animals↗
PubMed1993

A redox-based O2 sensor in rat pulmonary vasculature.

The effector mechanism of hypoxic pulmonary vasoconstriction (HPV) involves K+ channel inhibition with subsequent membrane depolarization. It remains uncertain how hypoxia modulates K+ channel activity. The similar effects of hypoxia and mitochondrial electron transport chain (ETC) inhibitors on metabolism and vascular tone suggest a common mechanism of action. ETC inhibitors and hypoxia may alter cell redox status by causing an accumulation of electron donors from the Krebs cycle and by decreasing the production of activated O2 species (AOS) by the ETC. We hypothesized that this shift toward a more reduced redox state elicits vasoconstriction by inhibition of K+ channels. Pulmonary artery pressure and AOS, measured simultaneously using enhanced chemiluminescence, were studied in isolated perfused rat lungs during exposure to hypoxia, proximal ETC inhibitors (rotenone and antimycin A), and a distal ETC inhibitor (cyanide). Patch-clamp measurements of whole-cell K+ currents were made on freshly isolated rat pulmonary vascular smooth muscle cells during exposure to hypoxia and ETC inhibitors. Hypoxia, rotenone, and antimycin A decreased lung chemiluminescence (-62 +/- 12, -46 +/- 7, and -148 +/- 36 counts/0.1 s, respectively) and subsequently increased pulmonary artery pressure (+14 +/- 2, +13 +/- 3, and +21 +/- 3 mm Hg, respectively). These agents reversibly inhibited an outward, ATP-independent, K+ current in pulmonary vascular smooth muscle cells. Antimycin A and rotenone abolished subsequent HPV. In contrast, cyanide increased AOS and did not alter K+ currents or inhibit HPV. The initial effect of rotenone, antimycin A, and hypoxia was a change in redox status (evident as a decrease in production of AOS). This was associated with the reversible inhibition of an ATP-independent K+ channel and vasoconstriction. These findings are consistent with the existence of a redox-based O2 sensor in the pulmonary vasculature.

Animals↗
PubMed1993

Personal marketing during a job hunt.

Understanding and facing new employment realities can help individuals recognize the changing needs of employers and match their skills with available opportunities. Individuals should exploit the healthcare industry's new realities by refining their personal product package and promoting it effectively.

Career Mobility↗
PubMed1993

Reactivity of leg alignment to articular pressure testing: evaluation of a diagnostic test using a randomized crossover clinical trial approach.

OBJECTIVE: A study was undertaken to assess the reliability of detecting leg alignment changes (reactivity) and to determine if the observed leg alignment reactivity can be attributed to a rotatory articular pressure challenge. DESIGN: Prospective double-blind crossover trial of a diagnostic test. SETTING: Laboratory: Center for Technique Research. PARTICIPANTS: Forty-two chiropractic college students, faculty and staff. INTERVENTIONS: A standardized force of 2 or 3 kg was applied with a 1 cm2 rubber-tipped pressure algometer on the lateral aspect of the T3-T7 spinous processes and the posterior aspect of the lateral masses of C1. MAIN OUTCOME MEASURES: Leg alignment reactivity: an increase in leg alignment discrepancy (yes or no) following a diagnostic intervention. RESULTS: The reliability for detecting leg alignment reactivity was poor: on average, Kappa = 0.05 in the thoracics and 0.06 at C1. On average, the attributable risk of leg alignment reactivity (pressure test risk--sham test risk) was less than 4%. In many cases, the sham rate was greater than the pressure test rate. CONCLUSIONS: For the population investigated, leg alignment reactivity to rotatory pressure testing can, in the majority of cases, be attributable to background noise. This procedure was not found to be viable for identifying vertebrae for adjustment. Further research with different subject populations, regions of investigation, leg alignment measurement techniques and vertebral challenge techniques are indicated.

Adult↗
PubMed1993

Responsiveness of leg alignment changes associated with articular pressure testing to spinal manipulation: the use of a randomized clinical trial design to evaluate a diagnostic test with a dichotomous outcome.

OBJECTIVE: A study was undertaken to assess the stability of leg alignment reaction to a pressure challenge and its responsiveness to an adjustive intervention. DESIGN: Prospective, double-blind clinical trial of a diagnostic test. SETTING: Laboratory: Center for Technique Research. PARTICIPANTS: Forty-two chiropractic college students, faculty and staff. INTERVENTIONS: A high-velocity, low-amplitude, short lever adjustment of a single vertebra from among C1 and T3-T7; or a sham adjustment similar to a manual diagnostic pressure test at C1, T3-T7 or T9-T10. MAIN OUTCOME MEASURES: Leg alignment reactivity: An increase in leg alignment discrepancy (yes or no) following a metered pressure challenge to a vertebra. RESULTS: On average, stability was poor at T3-T7 (Kappa = 0.04), moderate at C1 (K = 0.47), and fair for sham pressure tests (K = 0.30). Responsiveness: The proportion of positive baseline leg alignment reactions that responded (became negative) to sham adjustment was 95% at T3-T7 and 55% at C1. Further analysis was untenable since too few vertebrae were implicated for an adjustment. CONCLUSIONS: For the population investigated, the majority of the responsiveness of the leg alignment diagnostic test to a rotatory adjustment appears to be a diagnostic illusion (i.e., background noise unrelated to a treatment intervention). Further research with different subject populations, regions of investigation, leg alignment measurement techniques and vertebral challenge techniques are indicated.

Adult↗
PubMed1992

Does chronic fatigue syndrome predispose to non-Hodgkin's lymphoma?

Chronic fatigue syndrome, an illness that frequently is associated with abnormalities of cellular immunity, has been reported anecdotally to be associated with an increased incidence of lymphoid hyperplasia and malignancy. This report describes an initial analysis of population-based cancer incidence data in Nevada, focusing on the patterns of non-Hodgkin's lymphoma prior to and subsequent to well described, documented outbreaks of chronic fatigue syndrome during 1984-1986. In a study of time trends in four age groups, the observed time trends were consistent with the national trends reported in the Surveillance, Epidemiology, and End Results Program. No statistically significant increase attributable to the chronic fatigue syndrome outbreak was identified at the state level. Additional studies are in progress analyzing the data at the country level, reviewing patterns in other malignancies, and continuing to monitor the cancer patterns over subsequent years.

Adolescent↗