A circadian rhythm in 5-hydroxytryptophan decarboxylase? [proceedings].
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Biomedical subjects
Publications and source records attributed to F Brown.
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Inactivated defective interfering and complete particles of vesicular stomatitis virus given intracerebrally to adult mice protect them against challenge with homologous virus whether this is given at the same time or several days later. Two separate protective processes appear to be involved. The first, which comes into operation immediately after inoculation, is also effective against heterologous strains of vesicular stomatitis virus, rabies (another rhabdovirus), and a neurotropic strain of foot-and-mouth disease virus. The second, later effect, which is strain specific, appears to be correlated with the appearance of circulating neutralizing antibody. Our results suggest that the protective effect that Holland and his colleagues described using defective interfering particles of vesicular stomatitis virus may also be accounted for by an immunological mechanism rather than one involving interference.
The physicochemical properties of two serologically distinct equine rhinoviruses have been examined. Each virus sedimented at approximately 160S but co-centrifugation of the two viruses in a sucrose gradient revealed a small difference in their sedimentation coefficients. The two viruses also have different buoyant densities in cesium chloride. The equine rhinovirus type 1 equilibrated as a sharp peak at 1.45 g/ml whereas the type 2 virus equilibrated as a heterogeneous band with a peak at 1.44 g/ml but ranging in density from 1.41 to 1.45 g/ml. The relative sedimentation coefficients of the two virus RNAs were 35S for rhinovirus 1 and 37S for rhinovirus 2. A limited number of base composition analyses also showed differences between the two virus RNAs. The polypeptide profile of each serotype in polyacrylamide gels was generally similar to those of other picornaviruses but the two serotypes could be distinguished readily from each other.
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The structure of rabies virus and the importance of its glycoprotein in immunization are discussed. The improvement in vaccines for use in man, culminating in the production of the human diploid vaccine is described. Nevertheless problems remain, particularly with regard to post-exposure therapy. Possible disadvantages in the use of subunit vaccines are mentioned and attention is drawn to the discovery of the rabies-related viruses.
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With the exception of phage Qbeta, the RNAs of all the other small icosahedral RNA viruses so far examined contain a poly (A) tract. This tract has been implicated in the infectivity of poliovirus RNA. We have now shown that Nodamura virus, a divided genome virus from which infective RNA can be extracted, does not contain any poly (A) tracts. This evidence with Nodamura virus shows that poly (A) is not a necessary requirement for the infectivity of virus RNA molecules.
In addition to the four major polypeptides VP1 and VP4, foot-and-mouth disease virus particles contain two minor polypeptides, mol. wt. 40 X 10(3) (P40) and 52 X 10(3) (P52). Extensive purification procedures failed to remove these minor polypeptides from the virus particles. Polypeptide P40 co-electrophoresed in SDS-polyacrylamide gels with VP0, the probable precursor of VP2 and VP4 and was inaccessible to iodination in situ. The second minor polypeptide, P52, co-electrophoresed with the virus infection associated (VIA) antigen found in large amounts in harvests of the virus grown in BHK 21 cells. Polypeptide P52 was shown to be located near the surface of the virus particle by iodination experiments and by its removal on incubating the particles with trypsin or chymotrypsin. Pactamycin mapping showed that this polypeptide was not a precursor of the structural polypeptides. About one copy of P52 and 4 copies of P40 were found in the virus particles sedimenting at 146S. However a larger number of copies was found in those virus particles sedimenting faster than the 146S peak.
The relatedness of swine vesicular disease virus (SVDV) and Coxsackie B5 virus has been studied by virus neutralization and immunodiffusion tests and by hybridization of the virus RNAs. Clearly defined differences between the two viruses were found by the three methods. Isolates of SVDV from several countries were very closely related but could be differentiated. Recent isolates of Coxsackie B5 virus also appeared to be similar but clear differences could be detected between these and the prototype (Faulkner) strain of the virus. The SVDV isolates were more closely related to the Faulkner strain than to the recent isolates of Coxsackie B5 virus. Perhaps of more importance, the Faulkner strain was more closely related to SVDV than it was to the recent Coxsackie B5 isolates. The significance of these observations in relation to the recent emergence of swine vesicular disease is discussed.
Methods for the purification of African swine fever virus (ASFV) and its dissection into two fractions are described. The difficulties which have been encountered previously in attempts to purify the virus, namely contamination with large amounts of cellular constituents and aggregation of the virus particles, have been overcome by treatment with Tween 80 and by the use of 1 M-NaCl in the sucrose gradients. Five major polypeptides, mol. wt. 10(3) X 125 (VP1), 76 (VP2), 50 (VP3), 44 (VP4) and 39 (VP5) were found in the purified particles. The virus was dissected by treatment with Nonidet NP 40 into (a) a fraction which had the appearance of an empty capsid shell and capsid shell and contained the polypeptides VP2 and VP3 and (b) a structure containing VP1 and VP4. The location of VP5 was not ascertained.
Fragments of foot-and-mouth disease virus RNA of decreasing size, containing the 3' poly(A) sequence have been prepared by alkali treatment and sucrose gradient centrifugation followed by oligo(dT)-cellulose affinity chromatography. Polyacrylamide gel electrophoresis of the ribonuclease T1 resistant oligonucleotides from these polyadenylated fragments has enabled us to locate the position of some of the longer oligonucleotides on the RNA. In particular the poly C tract has been shown to be near the 5' end of the RNA; The possible function of the poly(C) tract is discussed in the light of these findings.
1 The effect of amantadine hydrochloride on various aspects of catecholamine metabolism in the rat brain has been investigated. 2 Amantadine failed to have any significant effect on brain concentrations of dopamine or noradrenaline even when administered daily for 9 days. 3 Amantadine had no effect on the rate of decline of noradrenaline and dopamine concentrations after alpha-methyl-p-tyrosine. 4 In vitro amantadine inhibited dopamine uptake into synaptosomes only at high concentrations, and caused little release of dopamine from synaptosomes. 5 There is no evidence from these results to suggest that the anti-Parkinsonian effect of amantadine is related to an action on dopaminergic mechanisms.
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Correlations between Bender-Gestalt scores and WISC IQs were obtained for three ethnic groups of 123 Puerto Rican, 82 white, and 61 Negro children in the first grade. The Bender-Gestalt test did not show any significant relationship with the WISC scores of the Puerto Rican children. Significant correlations (p less than .01) between the Bender and all the WISC scores were found for the Negro group. For the white Ss, the WISC-Bender relationship was significant (p less than .01) only for the Performance and Full Scale scores. The absence of a significant correlation between the Bender and the WISC Verbal IQ in these children was attributed to the relative superiority of their Verbal scores.
Fifty children, ranging in age from 6 to 16 years, and their mothers were interviewed using the same structured interview, which in its content follows the usual psychiatric examination of a child. Their answers were compared and it was found that there was an 80% average agreement on all questions. The agreement (between child and parent) was highest on questions relating to factual information (84%) and the agreement (between child's interviewer and parent) was lowest in the section dealing with mental status (69%). Girls were more reliable informants than boys.
The chemical and serological properties of the full, naturally occurring empty and artificially produced empty particles of foot-and-mouth disease virus, serotype A(subtype 10, strain 16) have been studies. The full 146S particles comprised the virus RNA, three polypeptides (VP1 to VP3) mol. wt. about 30 X 10-3, one polypeptide (VP4) mol. wt. about 13-5 X 10-3, and a small amount of a polypeptide (VPo) mol. wt. about 43 X 10-3. The naturally occurring 75S empty particles contained no RNA and much less VP1 and VP4 than were found in the fall particles. However they contained a much greater proportion of VPo than the full particles. Dialysis of purified full particles against tris-EDTA, pH 7-6, produced artificial 75S empty particles which contained only a small amount of RNA and no VP4; otherwise the polypeptide composition was similar to that of the full particles. Immunological and serological tests showed that the full particles were antigenically similar to the naturally occurring empty particles but distinct from the artificial empty particles. The latter particles, however, had serological properties similar to those of the 12S protein subunit of the virus. Both the full and naturally occurring empty particles attached efficiently to susceptible cells, whereas the artificial empty particles attached only to a limited extent. The results are related to the function of the individual polypeptides of the virus particle and compared with published work on other picornaviruses.