What is your diagnosis? Dorsopalmar slab fracture of the medial aspect of the third carpal bone.
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Animals↗
Biomedical subjects
J H Cox
Publications and source records attributed to J H Cox.
Frequency analysis of cytolytic T lymphocyte precursors (CTL-P) generated in vivo during lethal rabies infection of mice. II. Rabies virus genus specificity of CTL-P.
Cytolytic T lymphocyte precursors (CTL-P) were sensitized in vivo by intraplantar infection of C57BL/6 mice with a lethal dose of rabies virus, strain ERA (ERA). As a result of sensitization CTL-P matured to interleukin-receptive CTL-P (IL-CTL-P) that could be expanded in vitro to Thy-1+, Lyt-2+ CTL clones in the presence of IL without subjection to antigen-driven selection. After infection with ERA, IL-CTL-P-derived CTL lysed fibroblasts infected with rabies virus but not those infected with another rhabdovirus, the vesicular stomatitis virus. These CTL, however, did not discriminate between fibroblasts infected with the serologically closely related laboratory strains of classic rabies virus, ERA and HEP-Flury, and the serologically distinct rabies-related African isolate Mokola. This finding implies that in vivo sensitized IL-CTL-P recognize common genus-specific determinants expressed on cells infected with members of the lyssavirus genus.
Animals↗
The kinetics and specificity of lymphocyte infiltration of cardiac allografts in unmodified and cyclosporin-treated rats.
Lymphocyte infiltration of heart grafts has been monitored using pulses of Indium-111-labelled syngeneic lymphocytes. The cells were injected into cyclosporin (CSA)-treated or untreated rats that had received an allograft 1, 2, 4, 6, and 8 days previously Accumulation of the labelled cells in the graft was measured 24 hr after injection, and was compared with that in the animal's own heart. For the first three days after grafting, Indium-111-labelled lymphocytes accumulated to the same extent in the grafts of untreated and CSA-treated rats. However, the substantial rapid increase in lymphocyte accumulation in the graft that occurs in the untreated recipient between days 4 and 5 did not occur in CSA-treated recipients. From day 5 until day 9 the accumulation of labelled cells in CSA-maintained grafts was not greater than in syngeneic non-rejecting grafts, and it was significantly less than in the untreated rejecting grafts. At early times after grafting, removal from the labelled cell population of lymphocytes with reactivity against the histocompatibility antigens of the graft resulted in a reduction in the extent to which these lymphocytes accumulated in the graft.
Animals↗
The anti-arthritic and immunosuppressive effects of cyclosporine on arthritis induced in the rat by type II collagen.
The influence of cyclosporine (CsA) on the induction and pathogenesis of type II collagen-induced arthritis has been investigated in inbred and outbred Wistar rats. The proportion of animals developing disease and the severity of disease they developed were both diminished by treatment with CsA. These effects were accompanied by a marked suppression of the antibody response to both the immunizing collagen and also to rat type II collagen. CsA treatment also resulted in a decreased accumulation of lymphocytes in arthritic joints. The results indicate that the anti-arthritic and immunosuppressive effects of CsA probably result from a modification of both systemic antibody-mediated and local cell-mediated immunity.
Animals↗
The migration of lymphocytes across specialized vascular endothelium. IV. Prednisolone acts at several points on the recirculation pathways of lymphocytes.
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Adrenocorticotropic Hormone↗
Frequency analysis of cytolytic T cell precursors (CTL-P) generated in vivo during lethal rabies infection of mice. I. Distinction of CTL-P with different interleukin 2 sensitivity.
The aim of this study was to determine the number and state of activity of cytolytic T lymphocytes (CTL) and their precursors (CTL-P) present in vivo during the early stages of viral infection. The local response to lethal infection with rabies virus was used as a model system that is not accessible to analysis by secondary activation in vitro. The local response to alloantigen served as a control. Experimental protocols were established that allow frequency estimates of in vivo antigen-triggered CTL-P. Data allow a distinction between CTL-P activated in vivo by alloantigen and viral antigen with respect to their different capacity to utilize T cell growth factors (interleukins). In vivo alloantigen-primed CTL-P generate, in vitro, an active effector progeny in the presence of interleukins of xenogeneic origin, whereas the majority of virus-specific CTL-P, in spite of considerable expansion in vivo, fail to generate CTL in vitro unless antigen is added.
Animals↗
The structural proteins of rabies virus.
The five structural proteins of rabies virus, L, G, N, M1 and M2 have been re-evaluated in light of recent results. It has been found that the M1 protein is associated with the N protein which together with the L protein and the RNA forms the nucleocapsid complex. Only the G and M2 proteins could be visualized on the surface of infected cells. Therefore, it is proposed that the M1 protein be renamed NS analogous to vesicular stomatitis virus and that the M2 protein, being the only membrane protein, now be called simply the M protein.
Electrophoresis, Polyacrylamide Gel↗
Preparation and characterization of rabies virus hemagglutinin.
Rabies virus glycoprotein, released by treatment with Triton X-100, was isoelectrically focused in a sucrose gradient containing the nonionic detergent octylglucoside. Removal of the detergent by dialysis resulted in aggregates of variable size and shape. The hemagglutinating activity of this preparation was approximately sixfold higher than that of the intact virus. The protein with hemagglutinating activity and with a buoyant density of 1.237 consisted solely of polypeptide chains of the G-protein and contained 0.38% phospholipids and 16 ng of Triton X-100 per mg of protein. In the National Institutes of Health test the hemagglutinin conferred a significantly higher protective activity than detergent-associated glycoprotein and was as effective as an inactivated virus vaccine. However, after the application of a single dose of hemagglutinin, the onset of protection was delayed by approximately 7 days when compared with inactivated virus vaccine.
Centrifugation, Density Gradient↗
Rabies virus strains: a comparison study by polypeptide analysis of vaccine strains with different pathogenic patterns.
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Electrophoresis, Polyacrylamide Gel↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗