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Biomedical subjects

J H Cox

Publications and source records attributed to J H Cox.

At least 19 recordsLinked to original sources
PubMed1992

Isolation and characterization of 115 street rabies virus isolates from Ethiopia by using monoclonal antibodies: identification of 2 isolates as Mokola and Lagos bat viruses.

There were 115 isolates of rabies viruses recovered by tissue culture technique from 119 animal brains collected in Ethiopia. By using 17 selected antinucleocapsid monoclonal antibodies (MAbs), 113 isolates were classic street rabies viruses (serotype 1). An isolate of feline origin (Eth-16) was a Mokola virus (serotype 3) and another isolate (Eth-58, obtained from a rabid dog) was serotype 2 (Lagos bat virus). None of the 16 antiglycoprotein MAbs used neutralized the Eth-16 isolate, whereas Eth-58 was neutralized by 1 (TERA543). Antirabies vaccines prepared from Pitman-Moore and Pasteur virus strains protected mice against homologous challenge, but neither was protective against the 2 rabies-related virus isolates. The isolation of Mokola and Lagos bat viruses from domestic animals in eastern Africa is of public and veterinary concern mainly due to lack of effective vaccines against these agents and the difficulty of proper diagnosis.

Animals↗
PubMed1992

Detection of rabies antibody by ELISA and RFFIT in unvaccinated dogs and in the endangered Simien jackal (Canis simensis) of Ethiopia.

Varying levels of rabies antibody have been detected both by Enzyme Linked Immunosorbent Assay (ELISA) and Rapid Fluorescent Focus Inhibition Test (RFFIT) in the sera collected from wild and domestic canids in the Bale Mountains National Park (BMNP) of Southern Ethiopia. Rabies antibody was detected in 80% (8 out of 10) of domestic dog samples, 13.3% (2 out of 15) of Simien jackal samples and in one common jackal. Rabies virus was isolated from one dog in an area where contact with the Simien jackal could possibly occur. All samples examined from wild rodents as possible reservoir hosts for rabies were found negative. The presence of large proportion of susceptible Simien jackals in the population should be a cause of great concern in saving this endangered species from the ravages of rabies.

Animals↗
PubMed1992

Rabies virus neuritic paralysis: immunopathogenesis of nonfatal paralytic rabies.

Two pathogenetically distinct disease manifestations are distinguished in a murine model of primary rabies virus infection with the Evelyn-Rokitnicky-Abelseth strain, rabies virus neuritic paralysis (RVNP) and fatal encephalopathogenic rabies. RVNP develops with high incidence in immunocompetent mice after intraplantar infection as a flaccid paralysis restricted to the infected limb. The histopathologic correlate of this monoplegia is a degeneration of the myelinated motor neurons of the peripheral nerve involved. While, in this model, fatal encephalopathogenic rabies develops only after depletion of the CD4 subset of T lymphocytes and without contribution of the CD8 subset, RVNP is identified as an immunopathological process in which both the CD4 and CD8 subsets of T lymphocytes are critically implicated.

Animals↗
PubMed1978

Isolation and purification of a polymeric form of the glycoprotein of rabies virus.

Of the three major proteins associated with the rabies virus membrane, only the glycoprotein was found to be located on the external surface of the virus membrane. Glycoprotein prepared by treatment of rabies virus with Triton X-100 and purified by isoelectric focusing was found to be homogeneous with respect to size and isoelectric point. This material, which is free of phospholipids, is able to protect in vaccination experiments against a lethal challenge infection with rabies virus. The apparent mol. wt. of this component isolated under non-denaturing conditions is approx. 400000. The same material analysed by SDS polyacrylamide gel electrophoresis (PAGE) was found to consist solely of polypeptide chains of the G protein (mol. wt. 80000). A minor glycoprotein (gp 50), detected by PAGE of the Triton X-100 released material, appeared to be a breakdown product of the G-protein. Therefore the detergent released material represents homopolymers of the G-protein. Whether the antigenic determinants reside on the monomeric subunit or are a property of the polymeric form of the G-protein is discussed.

Epitopes↗
PubMed1978

Comparison studies on potency tests for rabies vaccines.

Eleven laboratories from eight countries and four continents took part in a collaborative study to evaluate experimental procedures to be used in selecting the new standard reference rabies vaccine prepared in human diploid cell cultures. The following procedures were used : (a) the NIH potency test in mice, (b) the antibody binding technique (by either mouse inoculation or the tissue culture method), (c) virus-neutralizing antibody levels in mice used for the NIH test, and (d) antibody induction in human volunteers treated with vaccine alone and in combination with human rabies gamma globulin. The four methods used for determination of rabies antibodies were mouse inoculation, rapid fluorescent focus inhibition, plaque reduction and complement fixation techniques. All results were expressed in International Units as compared to the standard WHO serum and vaccine preparations. In general, a close correlation was noted in results from different laboratories, and it was recommended that the future rabies standard vaccine should be evaluated by three testing procedures, the NIH test, the antibody-binding technique, and antibody levels in mice used for the NIH test.

Animals↗
PubMed1978

Studies on candidate reference preparations of rabies vaccine.

Two candidate reference rabies vaccines were tested in a collaborative study involving seven laboratories. Using four different testing procedures it was determined that both vaccine preparations were highly potent and demonstrated satisfactory stability in the thermal degradation test.

Animals↗
PubMed1978

Comparative study on antibody determination by different methods in sera of persons vaccinated with HDCS rabies vaccine.

The comparative studies undertaken by 7 laboratories in 6 countries show that the calculation of I.U.'s did not, as anticipated, minimize but actually enhanced the variability of results of rabies antibody estimations in the sera of HDCS vaccinees. The high biological variance in the method(s) may not have been considered by individual laboratories and any neglect of fundamental biostatistical laws unfortunately diminishes the theoretical advantage of using the "International Standard (I.S.)" as a "tertium comparationis". Perhaps the intrinsic variability of the I.S. should be re-evaluated and it is conceivable that a pure IgG fraction of rabies antiserum would show less variability. Intralaboratory variation might be reduced by agreeing that only a geometric mean of the I.S., and not a single value obtained in an individual test, should be used for calculation of I.U.'s. Application of the principles of biochemical and pharmacological methods, such as test-to-test control of the I.S. and its analytical variances might well enhance the reproducibility of the results. MNT, RFFIT, PRT and CFT were unable to detect antibodies in HDCS vaccinees until 7 days after the first vaccination. The establishment of methods for detecting early antibody requires further investigation.

Analysis of Variance↗
PubMed1978

Rabies post-exposure treatment and side-effects in man using HDC (MRC 5) vaccine.

126 patients underwent a post-exposure antirabies treatment using the beta-propiolactone inactivated (HDC) MRC-5 vaccine. The immunization schedule consisted of single doses of 1 ml of vaccine administered on days 0, 3, 7, 14, 30 and 90. Within the post-exposure group several patients suffered wounds from known rabid animals. Serum samples were collected on days 0, 14, 30, 90 and 104. Neutralizing antibodies against the rabies virus were determined in the rapid-fluorescent-focus-inhibition (RFFI) test. The rise in neutralizing antibodies was steeper than that in the prophylactic group whereas the mean titer at day 30 did not significantly exceed the values obtained with the preventive immunization scheme. A 1 ml booster injection on day 90 resulted in a three-fold increase of antibody titer within two weeks. Although no major side-effects were observed, an analysis of questionnaires filled out by the patients is presented.

Adolescent↗
PubMed1978

Human rabies immunoprophylaxis using HDC (MRC-5) vaccine.

In a field trial 181 high risk persons of both sexes between ages of 2--71 years were prophylactically vaccinated against rabies with the beta-propiolactone inactivated rabies-vaccine (hdc) mrc-5. 1 ml of vaccine was administered intramuscularly on days 0, 7 and 21. Serum samples were collected on days 0, 7, 21 and 35. Neutralizing antibody titers against the rabies virus were determined in the rapid fluorescent focus inhibition test, 7 days after the first injection measurable titers of antibodies were found in all sera with one exception. On day 21 all persons showed a 100% seroconversion with a mean titer of 1:1000 (8,3 IU/ml). On day 35 the final mean titer measured 1:2400 (20 IU/ml). Major side effects during the prophylactic vaccination were not observed.

Adolescent↗
PubMed1978

Structure and function of rabies virus glycoprotein.

Of the three major proteins associated with the rabies virus membrane, only the glycoprotein (G-protein) was found to be located on the external surface of the viral membrane. A minor glycoprotein (gp 50) detected by SDS-polyacrylamide gel electrophoresis (PAGE) of rabies virus appeared to be a breakdown product of the G-protein. Glycoprotein prepared by treatment of rabies virus with Triton X100 and purified by isoelectric focusing was found to be homogeneous with respect to size and isoelectric point. The apparent molecular weight of this component isolated under nondenaturing conditions is approximately 400,000 daltons. The same material analyzed by PAGE was found to be comprised solely of polypeptide chains of the G-protein (MW 80,000 daltons). Therefore, the Triton X100-released material represents homopolymers of the G-protein. The purified rabies virus glycoprotein (G) is only structural protein of the virus that induces the formation of virus-neutralizing antibodies and which confers immunity to animals. The total protective activity of the virus was recovered in the purified G protein preparation. The protective activity of G protein increased with purification : 9 ng of G protein was required to protect 50% of the mice as compared to 1.63 microgram of the virus. The number of oligosaccharide side chains on rabies virus glycoprotein was investigated. Analysis of glycopeptides obtained by protease digestion of desialated glycoprotein revealed three discrete glycopeptides. Comparison of the protease digestion products from desialated and from untreated glycoprotein indicated a heterogeneity among the glycopeptides in the sialic acid content. Two major tryptic glycopeptides were isolated from desialated rabies virus glycoprotein and were analyzed after protease digestion; one contained two oligosaccharide side chains and the other contained a single oligosaccharide side chain.

Chemical Phenomena↗
PubMed1978

Comparative study on antibody determination by different methods in sera of persons vaccinated with HDCS-vaccine.

The comparative studies undertaken by 7 laboratories in 6 countries show that the calculation I.U.s did not as anticipated minimize but actually enhanced the variability of results of Rabies antibody estaminations in the sera of HDCS vaccines. The high biological variance in the method(s) may not have been considered by individual laboratories and any neglect of fundamental biostatistical laws, unfortunately, diminishes the theoretical advantage of using the "International Standard (I.S.)" as a "tertium comparationis". Perhaps the intrinsic variability of the I.S. should be re-evaluated and it is conceivable that a pure IgG fraction of Rabies antiserum would show less variability. Intralaboratory variation might be reduced by agreeing that only a geometric mean of the I.S., and not a single value obtained in an individual test, should be used for calculation of I.U.s. Application of the principles of biochemical and pharmacological methods, such as test-to-test control of the I.S. and its analytical variances might well enhance the reproducibility of the results. MNT, RFFIT, PRT and CFT were unable to detect antibodies in HDCS vaccinees until 7 days after the first vaccination. The establishment of methods for detecting early antibody requires further investigation.

Antibodies, Viral↗
PubMed1977

Comparison of the ribonucleoproteins of different rabies virus serotypes by radioimmunoassay.

Radioimmunoassay (RIA) provides a sensitive serological procedure for detecting rabies virus ribonucleoprotein (RNP) as well as its specific antibodies, RIA was carried out using highly purified RNPs labelled by the chloramine-T method. This paper describes optimal conditions for iodination of RNP with high specific activity. The optimal concentrations of 125I, RNP, chloramine-T, and reducing agent as well as the effect of pH on the reaction were investigated. RIA proved to be extremely sensitive for detection of homologous antibodies. In competition experiments the part-relationship of the group-specific RNPs of the three rabies virus serotypes (HEP, MOK and LBV) was confirmed.

Chloramines↗
PubMed1977

Rabies virus glycoprotein. II. Biological and serological characterization.

Purified rabies virus glycoprotein (G) was shown by complement fixation and immunodiffusion tests to be a second distinct antigen of the virus. It it the only structural protein of the virus that induces the formation of virus-neutralizing antibodies and which confers immunity to animals. When the G protein is taken as antigen, the complement fixation test can be used for the assay of virus-neutralizing antibodies. The total protective activity of the virus was recovered in the purified G protein preparation. The protective activity of G protein increased with purification: 9 ng of G protein was required to protect 50% of the mice as compared to 1.63 micrograms of the virus. Selective immunofluorescent membrane staining and immunocytolysis of rabies virus-infected cells were shown to be G protein specific. Due to its purity and potency, the G protein preparation can be considered the ideal human antirabies vaccine.

Animals↗
PubMed1976

Methoxychlor effects on hepatic storage of vitamin A in rats.

Sixty Sprague-Dawley rats were fed diets containing 0, 10, 100, 1,000, and 10,000 ppm of methoxychlor for 16 weeks under ad libitum- and restricted-feeding regimens. Methoxychlor at 10,000 ppm was lethal to some rats, reduced food consumption and growth, and increased liver weight relative to body weight. Methoxychlor at 1,000 ppm reduced food consumption and growth of rats fed ad libitum but did not reduce growth of restricted-fed rats. Reduced hepatic storage of vitamin A was detectable when methoxychlor was fed at levels of 100 ppm or higher.

Animals↗
PubMed1976

P,p-DDT and p,p'-DDE effects on egg production, eggshell thickness, and reproduction of Japanese quail.

p,p' -DDT and p,p' -DDE were investigated for effects on egg production and eggshell thickness in Japanese quail. p,p' -DDT was examined for effects on hatchability and fertility. DDE was tested at 0, 2, 10, 40, and 200 ppm in the diet. No evidence suggested that DDE affected number of eggs laid, egg weight, or eggshell thickness at any level of DDE tested. DDT was tested at 1,2.5, 10 and 40 ppm in the diet. In one experiment, quail fed DDT at 40 ppm and caged in male-female pairs broke more eggs than quail caged similarly but fed lower amounts of DDT or than quail fed an equal amount of DDT but caged alone. DDT did not detectably reduce eggshell thickness, number of eggs laid, fertility, or hatchability. However, paired quail laid fewer eggs than did single quail in two experiments and laid eggs with thinner shells in one experiment.

Animals↗
PubMed1976

Mirex-induced hepatic changes in chickens, Japanese quail, and rats.

Mirex was fed in the diet to chickens at 0 to 160 ppm for 12 and 16 weeks, to Japanese quail at 0 to 80 ppm for 12 weeks, and to rats at 0 to 100 ppm for 2 and 4 weeks. Mirex did not affect the concentration of protein or cytochrome P450 in hepatic microsomes of chickens or Japanese quail, nor did it affect hydroxylation of aniline or demethylation of aminopyrine. However, structural changes were apparent in livers of chickens fed mirex at 10 ppm and above and included regions of necrosis and nonspecific cellular aberrations and alterations of sinusoids and bile canaliculi. Mirex caused liver enlargement in rats and increased microsomal protein and cytochrome P450 but did not affect hydroxylation of aniline or demethylation of aminopyrine. Hepatic structural changes in rats that were associated with mirex included proliferation of smooth endoplasmic reticulum and degeneration of some bile canaliculi.

Animals↗
PubMed1976

Prophylactic immunization of humans against rabies by intradermal inoculation of human diploid cell culture vaccine.

The antirabies human diploid cell vaccine produced by 1'Institute Merieux, Lyon, France, was administered intradermally to 35 high-risk volunteers using 0.2-ml amounts and various immunization schedules. Three groups never before vaccinated against rabies developed virus-neutralizing antibodies, the titer of which was dose dependent. A single injection stimulated the formation of antibodies. Four inoculations induced the highest antibody levels and the longest persistence of antibody. The administration of a single intradermal booster inoculation was sufficient, even in the case of low-persisting antibody, to elicit a rapid increase of antibodies to high levels. A primary inoculation course of two injections induced a sufficient antibody level which, in case of exposure, could apparently be rapidly elevated by a 0.2-ml intradermal booster inoculation. Adverse side reactions were observed in 7 of 14 individuals after a 1- or 1.5-year intradermal booster inoculation. We therefore suggest that the intramuscular and subcutaneous routes continue to be used for primary vaccinations and that the highly effective intradermal route be restricted to booster inoculations. This is the first long term study of this vaccine and should be a guideline for the pre-exposure treatment of high-risk personnel.

Antibodies, Viral↗