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Biomedical subjects

F Brown

Publications and source records attributed to F Brown.

At least 235 records · Page 13Linked to original sources

Presence of a covalently linked protein on calicivirus RNA.

The infective RNA of the calicivirus, vesicular exanthema virus, has been shown to contain a protein which is apparently linked to the RNA by a covalent bond. The protein remained bound to the RNA after boiling with SDS-mercaptoethanol-urea or treating with formamide-dimethylsulphoxide but was removed by incubating with proteinase K. The mol. wt. of the protein was estimated to be about 1o X 1O(3) by electrophoresis in highly cross-linked polyacrylamide gels. The infectivity of the RNA was destroyed by removal of the protein with proteinase K.

Animals↗

The mechanism of the hypothermic effect of amantadine in rats and mice.

Amantadine (25--100 mg kg-1, i.p.) given to rats at an ambient temperature of 4 degrees, or mice at 21 degrees, caused a marked fall in rectal temperature. Prior administration of pimozide (1--2 mg kg-1, s.c.) did not block hypothermia due to amantadine in rats or mice; in contrast, hypothermia due to apomorphine (2 mg kg-1, i.p.) and piribedil (10--40 mg kg-1, i.p.) in rats was blocked by pimozide pretreatment. Amphetamine (5 mg kg-1, i.p.) given 2 h after reserpine (2 mg kg-1, i.p.) caused a reversal of the hypothermic effect of reserpine in mice, but a reversal was not obtained with amantadine (50 mg kg-1, i.p.). Direct injection of amantadine (4--8 mg kg-1) into the cerebral ventricles (i.c.v.) of mice caused marked hypothermia which was not blocked by pimozide, but intravenous injection of the same dose of amantadine did not cause hypothermia. Rimantadine, a congener of amantadine but without anti-parkinsonian activity, also caused pimozide insensitive hypothermia in mice at doses of 50 mg kg-1, intraperitoneally or 2--4 mg kg-1, intracerebroventricularly. The main conclusion drawn from these results is that in causing hypothermia amantadine acts in the cns but not on dopamine receptors.

Amantadine↗

More precise location of the polycytidylic acid tract in foot and mouth disease virus RNA.

The polycytidylic acid [poly(C)] tract in foot and mouth disease virus RNA has been located about 400 nucleotides from the 5' end of the RNA by analysis of the products from the digestion of the RNA with RNase H in the presence of oligodeoxyguanylic acid [oligo(dG)]. This treatment produces a small fragment (S) containing the small protein covalently linked to the RNA and a large fragment (L) that migrates faster than untreated RNA on low-percentage polyacrylamide gels, lacks the poly(C) tract as shown by RNase T1 digestion and oligo(dG)-cellulose binding, and is no longer infective. Polyacrylamide gel electrophoresis of fragment S suggests that it is about 400 nucleotides long, in agreement with the size estimated from the proportion of radioactivity in the fragment. Analysis of the RNase T1 digestion products of S shows that it contains only those oligonucleotides mapping close to the poly(C) tract that is situated near the 5' end of the virus RNA.

Aphthovirus↗

Relationship of San Miguel sea lion virus to other members of the calicivirus group.

San Miguel sea lion virus (SMSV) is indistinguishable from vesicular exanthema virus (VEV) and feline calicivirus (FCV) in its morphology and in possessing a single capsid polypeptide with a molecular weight of approximately 65 X 10(3). Neutralization tests readily differentiate the three viruses, but immunodiffusion tests show that SMSV is closely related serologically to VEV but not to FCV. Although the RNAs of the three caliciviruses have similar base compositions, homology tests show that SMSV is closely related to VEV but is not related to FCV. Tryptic peptide maps of the single major polypeptide comprising the capsid of each virus also show that SMSV and VEV are more closely related to each other than to FCV.

Animals↗

Management of 136 consecutive supratentorial berry aneurysms.

A series of 103 consecutive cases admitted to the University of Chicago Hospitals with a recently ruptured supratentorial aneurysm were medically managed by antifibrinolytic medication, and, when applicable, by hypotension, intracranial pressure control, and respiratory support. Nine patients deteriorated and died, and six rebled and died before they were judged fit for surgical treatment. Four were treated by carotid occlusion. Nine, because of refusal or medical judgment, did not have surgical treatment. Sixty-nine of these patients and a further 33, electively admitted, underwent craniotomy. In these 102 patients, there was no mortality. Seven developed postoperative hemiparesis or hemiplegia. Six recovered. One has a residual monoparesis.

Adolescent↗

Questions concerning the potency of rabies vaccine.

In pre-exposure immunization the protective effect of rabies vaccines can be correlated with their ability to stimulate the production of neutralizing antibodies and in post-exposure therapy also antibodies would appear to have a major role. Therefore, the potency of the vaccines may conveniently be compared by measuring their antigenicity in animals or by serum blocking tests. Nevertheless, most authorities will license, for human and veterinary use, only those vaccines which reach the required standards in the Habel or NIH tests, both of which depend upon the inoculation of more than 1 dose of vaccine followed by an intracerebral challenge. We have been involved recently in testing batches of vaccine imported into Britain for use in animals and man. Since the U.K. authorities have adopted the NIH test for this purpose we have taken the opportunity to compare some of these vaccines in the NIH test, in a modified NIH test in which the same amount of vaccine was given in a single dose, and in a test in which the production of serum neutralizing antibodies was measured. We have found that one dose of vaccine given on day 0 gave less protection and less neutralizing antibody than the same amount of vaccine given as two separate doses on day 0 and day 7. The greater effect obtained by inoculating the vaccine in two doses could thus be misleading and we suggest the adoption of a test in which a single dose is given.

Animals↗

Biochemical analysis of a virulent and an avirulent strain of foot-and-mouth disease virus.

A comparison has been made of some of the serological and physicochemical properties of a virulent and an avirulent strain of foot-and-mouth disease virus, serotype SAT1. The avirulent strain (SAT1-82) was derived from the virulent strain (SAT1-7) by serial passage in BHK 21 cells. The viruses were indistinguishable in cross-neutralization tests. In immunodiffusion tests a clear spur line was obtained with the SAT1-82 antiserum but not with SAT1-7 antiserum. The major polypeptides of the two viruses were identical when examined by polyacrylamide gel electrophoresis. Hybridization and thermal denaturation experiments failed to distinguish between the RNAs but two-dimensional electrophoresis of the oligonucleotides produced by ribonuclease T1 digestion revealed several differences. Possibly the most significant of these differences was the size of the polycytidylic acid [poly (C)] tract. There were about 170 nucleotides in the poly (C) tract of the SAT1-7 RNA compared with around 100 in the SAT1-82 RNA. Further evidence for this deletion was provided by the slightly different behaviour of the two RNAs when compared by sucrose gradient centrifugation and polyacrylamide gel electrophoresis.

Animals↗

Immunogenic and cell attachment sites of FMDV: further evidence for their location in a single capsid polypeptide.

Chymotrypsin cleaves only one of the four major polypeptides of foot-and-mouth disease virus (FMDV serotype O) in situ. This polypeptide (VP1, mol. wt. 29 X 10(3) was first cleaved into fragments of mol. wt. 20 and 9 X 10(3) and further cleavage could be prevented by the addition of a large excess of bovine serum albumin. The infectivity of the virus particles at this stage was the same as that of the intact virus although the rate of attachment to BHK 21 cells was slower and the immunogenic activity was reduced. If hydrolysis was allowed to continue, VP1 was cleaved into fragments with mol. wt. 18 and less than 9 X 10(3), similar to those obtained with trypsin and the virus particles then had a greatly reduced infectivity and a lower immunogenicity. Treatment of strains from five other serotypes of the virus with the two enzymes cleaved only VP1 in each instance and there was a corresponding loss of infectivity. The results are discussed in relation to the location and biological activity of the virus polypeptides.

Animals↗

Role of sialic acid in infection with vesicular stomatitis virus.

The role of sialic acid in the infection of tissue culture cells and mice with vesicular stomatitis virus has been studied. No loss of infectivity of the Indiana serotype of the virus was detected by incubating with neuraminidase although the virus particles had lost sialic acid as judged by their ability to inhibit the agglutination of red blood cells by influenza virus. The results did not depend on the type of cell used for growth and assay of the virus since essentially similar findings were made in BHK cells, L cells or mice. Similar results were obtained with Brazil virus, a subtype of the Indiana serotype and with the New Jersey serotype. We consider that the sialic acid of the virus which is removed by neuraminidase does not play a major role in the infectivity of the virus.

Aedes↗

Biochemical mapping of the foot-and-mouth disease virus genome.

Four primary cleavage products, mol. wt. 10(3) X 100, 88, 56 and 52 (P100, P85, P56 and P52 respectively) are present in BHK 2I cells infected with foot-and-mouth disease virus (FMDV). However, no precursor polyprotein equal to the sum of their mol. wt. was detected, even when amino acid analogues and proteolytic enzyme inhibitors were used. Three of the primary products were shown to cleave to smaller polypeptides, including the capsid polypeptides of the virus. Polypeptide P88, which was shown to be the precursor of the capsid polypeptides, is translated from the gene located at the 5'-end of the genome. The order of the structural polypeptides, determined by the use of emetine, is VP4, VP2, VP3, VP1. The order of the remaining primary cleavage products is P52, P56 and P100. P56 is a stable product, identical with the virus infection associated (VIA) antigen found in virus harvests. The function of the other two products P52 and P100 is not known. EMDV thus differs from other picornaviruses in that there is an extra primary cleavage product, apparently resulting from translation of more of the virus genome.

Aphthovirus↗

Relationship of a virus from Tellina tenuis to infectious pancreatic necrosis virus.

The physicochemical and serological properties of a virus isolated from the bivalve mollusc, Tellina tenuis, have been examined. The virus has a diam. of 59 nm, sediments at 430S in sucrose gradients and bands at a density of I-32 g/ml in CsCl. The virus contains RNA with a mol. wt. about 2-8 X 10(6) as extimated by polyacrylamide gel electrophoresis but in sucrose gradients the RNA sediments at 14S. The virus RNA is resistant to ribonuclease under conditions in which ribosomal RNA and the single stranded Mengo virus RNA are completely hydrolysed. Two major polypeptides, mol. wt. 67 and 40 X 10(3), and minor polypeptide, mol. wt. 110 X 10(3), are present in the virus particle. These properties are similar to those found in different serotypes of infectious pancreatic necrosis (IPN) virus. Although there was only a very low level of cross-neutralization between Tellina virus and IPN virus. there was some cross-reaction in immune electron microscopy tests and in immunofluorescence tests with infected tissue culture cells. This cross reaction, together with the close similarity in morphology and physiochemical properties, suggests that Tellina virus and IPN virus belong to the same virus group.

Animals↗

An assessment by competition hybridization of the sequence homology between the RNAs of the seven serotypes of FMDV.

A comparison has been made of the RNAs of the seven serotypes of foot-and-mouth disease virus (FMDV) by competition hybridization. Homology among the three European serotypes A, O, C and the Asia I serotype was 60 to 70%. Similar homologies were found among the three Southern African Territories serotypes (SAT I, SAT 2, SAT 3), but homology between the two groups was much lower (25 to 40%). Homology between the RNAs of subtypes within serotypes A and O was greater than 70%. Double competition experiments with the Eropean serotypes indicate sharing of nucleotide sequences.

Aphthovirus↗