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Biomedical subjects

C J Peters

Publications and source records attributed to C J Peters.

At least 271 records · Page 15Linked to original sources

A serological survey of Rift Valley fever antibodies in the northern Sinai.

In the aftermath of an extensive Egyptian Rift Valley fever (RVF) epidemic during 1977-78, RVF activity in the adjacent Sinai peninsula has been inferred from the presence of haemagglutination-inhibition (HI) antibodies in sera from indigenous humans and rodents. We attempted to confirm these findings by HI testing of sera from Israeli soldiers serving in the region of the El Arish Wadi system in the Sinai, and from indigenous rodents. Six of 199 human sera (3.0%) and two of 88 rodent sera (2.3%) were positive, but none reacted in the more specific plaque-reduction neutralization test. We conclude that there is no definitive serological evidence for RVF activity in the Sinai and that sera reacting in the HI test must be confirmed by a more specific serological procedure.

Animals↗

A rift Valley fever vaccine trial. I. Side effects and serologic response over a six-month follow-up.

A formalin-inactivated Rift Valley fever vaccine, originally produced in primary monkey kidney cells, has been used to protect laboratory workers. A trial of a modified vaccine, newly formulated in well-characterized diploid fetal rhesus lung cells, was conducted with 114 men aged 19--24 years. Of the 107 subjects who received up to three injections of 0.1 to 1 ml vaccine (an additional seven received a placebo) one had a local hypersensitivity-type reaction and another a generalized urticarial syndrome. Both cases had a prior history of hypersensitivity states. No pyrogenicity was detected and only insignificant systemic reactions were recorded. Mild and transient local reactions ranged from 5% at the lowest dose level to 43% at the highest. Serologic response, as assessed by plaque reduction neutralizing antibody titers, was dose dependent. Within a single vaccine lot tested at multiple dose levels, peak (day 42) geometric mean titers ranged from 48 (at 0.1 ml x 3) to 436 (at 1.0 ml x 3). Reciprocal titers of greater than or equal to 40 are considered to be protective. Comparison of three lots at the 0.5 ml level indicated between lot variability, though this was not statistically significant. A sharp decline in antibody titers was observed in all vaccination groups by day 84; six months after vaccination apparently protective antibody titers were present only in groups that received 1 ml x 3 and 0.5 ml x 3 of the most antigenic lot of vaccine. These results suggest that 1) the vaccine is generally nonreactogenic, but individuals with a prior history of hypersensitivity states should be observed for allergic side effects; 2) existing vaccine supplies cannot be extended by using lower dose levels without a lower and less sustained serologic response; 3) a booster dose is necessary six months or more following the primary series; 4) although the current TSI-GSD-200 vaccine is immunogenic, a more potent vaccine is needed.

Adult↗

The spread of Rift Valley fever and approaches to its control.

Rift Valley fever (RVF) is primarily a disease of sheep, cattle, other domestic animals, and man; it was believed to be relatively benign for man until 1977 when it spread to Egypt. There it caused enormous losses of sheep and cattle, and thousands of human cases occurred, with nearly 600 reported deaths. Although mosquitos are known to transmit RVF virus in epizootics and epidemics, the reservoir and means of inter-epizootic maintenance are not known. RVF epizootics can be recognized by a combination of observations: abortions and neonatal death in sheep and cattle at times when mosquitos are abundant, accompanied by cases of fever in man, which are complicated in a minority of patients by haemorrhagic fever, encephalitis, and retinitis with blindness. Vaccination of livestock with available killed or live attenuated vaccines should prevent transmission to both human subjects and animals. Although routine quarantine of animals is not deemed a practical measure, movement of animals should be restricted when an epizootic is in progress. Since it is possible that RVF may spread from Africa in the future, serological surveillance in man and animals is recommended in potentially receptive countries of the Mediterranean Basin and South-West Asia to establish baseline data and to familiarize staff with the methods of RVF diagnosis.

Africa↗

Formation and characterization of an intertypic lymphocytic choriomeningitis recombinant virus.

An intertypic reassortant arenavirus has been obtained from co-infection of BHK-21 cells by two strains of lymphocytic choriomeningitis virus (LCM virus), WE and Armstrong (ARM), having the large/small (L/S) viral RNA genotype of WE/ARM. The two parental viruses have different virulence characteristics in hamsters and guniea-pigs. The reassortant virus induces LCM-WE-type plaques in Vero cell monolayers, but has the avirulent characteristics of LCM-ARM in hamsters and two strains of guniea-pigs. These results suggest that the LCM plaque phenotype is determined by L RNA gene products, while the pathogenic potential in guinea-pigs may be determined by S RNA gene products.

Animals↗

Adjuvant activity of a novel metabolizable lipid emulsion with inactivated viral vaccines.

Studies were conducted in mice, hamsters, sheep, and two species of nonhuman primates which demonstrate the adjuvant activity of a new metabolizable lipid emulsion with marginally immunogenic doses of Formalin-inactivated viral vaccines. The lipid base consists of highly refined peanut oil emulsified in aqueous vaccines with glycerol and lecithin. Hamsters and mice inoculated with lipid emulsion plus western or Venezuelan equine encephalitis vaccine were significantly more resistant than vaccinated controls to lethal homologous virus challenge. Sheep given one dose of lipid emulsion plus Rift Valley fever vaccine developed significantly higher antibody titers than control sheep receiving only vaccine. Cynomolgous monkeys inoculated with lipid emulsion plus Rift Valley fever vaccine developed 16-fold greater peak primary and 20-fold greater secondary antibody titers than those of vaccine controls. Similar lipid emulsion-Rift Valley fever studies in rhesus monkeys resulted in 37- and 300-fold increases in primary and secondary titers, respectively, compared with monkeys given vaccine alone. Neither the sequence of combining antigen with lipid nor the exact ratio of aqueous phase to lipid phase affected the survival of Venezuelan equine encephalitis-vaccinated mice challenged with homologous lethal virus. This lipid formulation has several advantages over other water-in-oil adjuvants for potential use in humans. The components are metabolizable or normal host constituents, it is easily emulsified with aqueous vaccines by gentle agitation, and it is relatively nonreactogenic in recipients.

Adjuvants, Immunologic↗

Glucan-induced enhancement of host resistance to selected infectious diseases.

We conducted studies with mice, rats, and monkeys which demonstrated the ability of glucan to induce either nonspecific or specific enhancement of host resistance to infectious diseases. Intravenous pretreatment of mice with glucan significantly enhanced the survival of mice challenged with either Venezuelan equine encephalomyelitis (VEE) virus or Rift Valley fever virus. Pretreatment was beneficial when initiated 3 days before challenge with VEE virus and 7 days before challenge with Rift Valley fever virus. Treatment of mice after VEE challenge did not increase their survival compared with controls. Glucan pretreatment of rats provided increased resistance to both intraperitoneal and low-dose aerosol challenges with virulent Francisella tularensis when the glucan was given intravenously, but not when it was administered intranasally. In contrast, intranasal glucan pretreatment enhanced the survival of mice when they were challenged by aerosol with Pseudomonas pseudomallei, whereas intravenous glucan pretreatment did not increase survival. mice given glucan combined with a marginally immunogenic dose of VEE vaccine were more resistant to homologous virus challenge than were mice given either Freund complete adjuvant plus vaccine or vaccine alone. Similarly, both primary and secondary VEE antibody titers in cynomolgus monkeys given glucan with VEE vaccine were significantly greater than titers in vaccine controls.

Adjuvants, Immunologic↗

Baroreflex sensitivity in rabbits during the development of experimental renal hypertension and medial sclerosis.

Baroreflex sensitivity was assessed in 9 normotensive (N), 8 renal wrap (one kidney model, RH) and 16 medial sclerotic rabbits (MS, fed on calciferol 50,000 i.u. and calcium lactate 1g for 10 days) before (mean BP;N, 79 +/- 3.3 mm Hg; RH, 80 +/- 7.4 mm Hg; and MS, 83 +/- 1.0 mm Hg) and at monthly intervals for up to 16 weeks after the induction of the disease processes (mean BP;N, 87 +/- 3.9 mm Hg; RH, 127 +/- 7.2 mm Hg and MS, 99 +/- 3.8 mm Hg). Blood pressure was elevated by i.v. phenylephrine (5 and 10 micrograms.kg-1) or angiotensin (250 ng.kg-1) and baroreflex sensitivity assessed by the increase of pulse interval per unit rise of pressure. The pressor response was greater in the RH and MS than in the N rabbits. The baroreflex sensitivity showed a progressive reduction with time and with the elevation of blood pressure in both MS and RH rabbits. The difference was significantly greater (P < 0.01) than in the aged related control rabbits (P < 0.05). There was an inverse relationship between baroreflex sensitivity and the pressor response in MS rabbits. Results indicated progressive baroreceptors dysfunction in hypertensive and medial sclerotic rabbits.

Angiotensin II↗

Evaluation of a formalin-inactivated Rift Valley fever vaccine in sheep.

A formalin-inactivated Rift Valley fever (RVF) vaccine prepared in cell culture for human use was immunogenic in sheep. Vaccine was administered as a single dose of diluted (1:5) or undiluted vaccine with or without an adjuvant. Serum-neutralizing antibodies induced by RVF vaccine persisted for at least 7 months. Seven of 11 vaccinated sheep with prechallenge plaque-reduction neutralization (PRN80) antibody titers of less than or equal to 10 were protected against challenge exposure with 10(6) plaque-forming units of Zagazig 501 strain of RVF virus. Challenge exposure induced abortion in 2 of 2 pregnant sheep. Five sheep with PRN80 titers greater than or equal 1:20 were protected from detectable viremia after challenge exposure. Additionally, 5 of 6 lambs (3 months old) were protected (by maternal antibodies) against challenge exposure. Challenge control sheep developed clinical disease and detectable viremia after exposure. Virus was isolated from saliva of 1 challenge control sheep and virus was transmitted by contact exposure to 1 of 4 seronegative contact-control sheep. Immunization of sheep with formalin-inactivated RVF vaccine induced a priming effect against RVF viral antigens. Challenge exposure with RVF virus resulted in significantly higher neutralizing titers in vaccinated sheep than in nonvaccinated sheep.

Animals↗

Male determined accelerated autoimmune disease in BXSB mice: transfer by bone marrow and spleen cells.

Autoimmune disease in BXSB mice progresses more rapidly in male animals. We have investigated the cellular basis of this effect by transferring male and female bone marrow and spleen cells into male and female lethally irradiated BXSB recipients. The rate of development of disease was measured by the overall mortality rate, mortality from glomerulonephritis, and development of serologic abnormalities. We found that the pace of disease in the BXSB sex chimeras was determined entirely by the sex of the donor of the transferred cells. Lethally irradiated BXSB animals receiving male cells had rapidly progressive disease, whether the recipients were themselves male or female, whereas female-cell recipients of either sex had slowly progressive disease. The male-specific effect that accelerates autoimmune disease in the BXSB is thus not hormonally mediated, but rather is expressed in the hematopoietic stem cell populations.

Aging↗

Natural thymocytotoxic autoantibodies in autoimmune and normal mice.

Natural thymocytotoxic autoantibodies (NTA) were found in all mouse strains. Among those strains that show autoimmune syndromes resembling human systemic lupus erythematosus (SLE), the NZB and NZBxNZW had high levels of NTA, the BXSB had moderate levels, and the MRL/1 and MRL/n had very low levels. In addition, some normal strains had high levels, sometimes even higher than the autoimmune strains. The NTA were mostly IgM and were present, but not concentrated, in the cryoprecipitates of teh autoimmune mouse strains. In most strains, they were directed toward an antigen shared by thymocytes and brain. The failure to find high levels of NTA in all autoimmune mouse strains, as well as the finding of very high levels in some normal strains, make it unlikely that such auto-antibodies are a fundametnal etiologic factor in all murine SLE.

Absorption↗