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Biomedical subjects

F Brown

Publications and source records attributed to F Brown.

At least 109 records · Page 6Linked to original sources
PubMed1993

Early encounters of the repetitive kind: a prelude to cell adhesion in conjugating Tetrahymena thermophila.

The relationship between direct cell contacts and subsequent cell-cell adhesion was studied in the ciliated protozoan, Tetrahymena thermophila. During sexual reproduction, adhesion into pairs begins at approximately 1 hr after mixing starved complementary mating types. However, direct contacts between cells prior to pairing are known to be required for the development of adhesion-readiness. We find here that the initial contact interactions are necessary but not sufficient to drive the cells to adhesion-readiness. Secondary interactions are needed. Two distinct experimental strategies were used. First, we examined the effects of a mutant that is unable to pair but which can stimulate two different wild-type mating type cells to pair when mixed. We showed that stimulation by the mutant is only partial; in response to mutant cells, wild-type cells ceased forming food vacuoles but did not undergo tip transformation or concanavalin A (Con A)-receptor tipping. Further, kinetic analysis shows that when mixed together, pair-formation among partially stimulated wild-type cells is slightly delayed, allowing time for these pre-pairing processes to occur. This indicates that, beyond the initial contact interaction, mutant-stimulated wild-type cells require a subsequent interaction which cannot be fulfilled by the mutants. Secondly, we found that by blocking contact interactions between wild-type mating types at various time intervals after they were mixed, additional increase in tip transformation and Con A receptor tipping was prevented. Further, both processes underwent a regression. This indicates that multiple contact interactions are required to drive the cells to adhesion readiness and to prevent developmental slip-back.

Animals↗
PubMed1993

Antibody-complexed foot-and-mouth disease virus, but not poliovirus, can infect normally insusceptible cells via the Fc receptor.

Poliovirus and foot-and-mouth disease virus (FMDV) initiate infection by binding to specific cell surface receptors, which is followed by a poorly understood disassembly process. To probe these early steps of infection, the ability of poliovirus and FMDV to infect cells following binding through an alternative receptor was examined. For these studies, a Chinese hamster ovary (CHO) cell line expressing the B2 isoform of the murine Fc receptor (FcR) was used. Both viruses were able to bind to this cell line in an antibody-dependent manner, but only FMDV was able to productively infect these cells following binding through the FcR. These results suggest that the natural poliovirus receptor has dual functions in binding and destabilizing the virus particle, whereas the putative FMDV receptor may only be necessary for virion binding. These findings are consistent with differences in virion architecture which predict a more intimate virion-receptor association for poliovirus than for FMDV.

Animals↗
PubMed1993

Early childhood memories: accuracy and affect.

Subjects were asked to report the earliest memories of their lives. Where possible, the memory protocols were submitted to adults present at the time of the original episode for possible confirmation. The majority of memories were characterized by distinct emotion, with a higher count of negative than of positive emotion. The majority of memories proved accurate, with confirmation operating at as high a level in the case of positive or emotionally neutral memories as of negative memories. General memory content showed no differential patterns across negative and positive memories. Thus claims that infantile memories are powered uniquely by trauma, and/or routinely include distortions, were not supported. Evidence was found that some memories recalled as emotionally bland by the subject had involved an originally emotional episode.

Adult↗
PubMed1993

Characterization of the adenosine receptors of the rat superior cervical ganglion.

1. Adenosine analogues caused hyperpolarization and inhibition of the depolarizing response to muscarine of the rat isolated superior cervical ganglion (SCG) measured by a 'grease gap' recording technique. The receptors mediating these responses have been characterized by use of a range of selective adenosine analogues and adenosine receptor antagonists. 2. In decreasing order of potency N6-cyclopentyladenosine (CPA), 2-chloroadenosine (2CA), adenosine, 2-phenylaminoadenosine (PAA), caused concentration-dependent hyperpolarizations whilst N6-(9-fluorenylmethyl)adenosine (PD 117,413) was inactive at up to 100 microM. 3. The order of potency of adenosine analogues in depressing depolarization caused by a submaximal concentration of muscarine (100 nM) was: CPA > R-PIA = 2CA > NECA > S-PIA > BZA > adenosine > PAA, where R- and S-PIA = R(-)- and S(+)-N6-(2-phenylisopropyl)adenosine, NECA = 5'N-ethylcarboxamidoadenosine and BZA = N6-benzyladenosine. PD 117,413 was inactive at concentrations up to 100 microM. The maximum inhibitions of the muscarine-induced depolarization by CPA, 2CA, NECA and BZA were similar. R-PIA, S-PIA and PAA produced similar maximal inhibitions which were significantly smaller than those produced by CPA. 4. Hyperpolarizations caused by adenosine were antagonized by the P1-purinoceptor selective antagonist 1,3-dimethyl-8-phenylxanthine (8PT) and by the selective A1-adenosine receptor antagonist, 1,3-dipropyl-8-(4-((2-aminoethyl)amino)carbonylmethyloxyphenyl++ +)xanthine (XAC). Hyperpolarizations caused by CPA, adenosine and PAA were antagonized by the A1-selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) but not by the A2-selective antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX). 5. Inhibition of the muscarinic-induced depolarization by CPA was antagonized by 8PT and DPCPXbut not by DMPX.6. It is concluded that the neurones of the rat SCG possess P1-purinoceptors of the Al-adenosine receptor subtype which mediate hyperpolarization and inhibition of depolarization caused by muscarine.

Adenosine↗
PubMed1993

Genetically engineered foot-and-mouth disease viruses with poly(C) tracts of two nucleotides are virulent in mice.

To determine the role of the poly(C) tract found at the 5' end of the genome of foot-and-mouth disease virus, synthetic RNAs (in vitro transcripts) with poly(C) tracts of different lengths have been produced and evaluated. RNAs with poly(C) tracts of 35, 25, 16, 6, or 2 residues displayed similar specific infectivities in baby hamster kidney (BHK) cells. Viruses recovered from cells transfected with in vitro transcripts containing 6 to 35 Cs had properties similar to those of the wild-type virus in cell culture, and poly(C) tracts present in the synthetic RNA-derived viruses ranged from 75 to 140 bases in length. Viruses recovered from transcripts containing only two Cs showed very different properties. Specifically, viruses grew to much lower levels in cell culture and maintained a poly(C) tract of only two residues. The pool of viruses harvested from cells transfected with the synthetic C2 RNA also contained a small amount of a virus with a 42-base deletion in the region of the poly(C) tract, which appeared to have arisen by recombination. Taken together, these data suggest that recombination provides the mechanism of poly(C) elongation and that viruses with poly(C) tracts over 75 bases in length have a selective advantage in cell culture. Interestingly, all of the in vitro transcript-derived viruses [including viruses with poly(C) tracts of only two residues] were equally virulent in mice, indicating that poly(C) tract length has no effect on virulence in this animal model.

Animals↗
PubMed1993

Review of accidents caused by incomplete inactivation of viruses.

Inactivation of viruses and bacterial toxins with formaldehyde for the preparation of vaccines has been a favourite method for most of this century. The Cutter incident in 1955 with poliovaccine focussed attention on the problems accompanying the procedure for inactivating viruses although it had been known since the 1930s that the method was not without its dangers. It had also been known since about the same time that foot-and-mouth disease vaccines prepared in this way could carry residual infectivity. The molecular methods of analysis introduced in the 1970s proved without any doubt that the outbreaks in France in 1981 and in other countries of Western Europe in the 1980s were caused by improperly inactivated vaccines. Recent molecular evidence has now shown that formaldehyde-inactivated Venezuelan equine encephalitis vaccines were the probable cause of the outbreaks of the disease during the 1969-1972 pandemic in Central America. In the author's opinion it is remarkable that formaldehyde is still used for the preparation of inactivated vaccines, particularly since it is known that the procedure also affects the immunogenic epitopes of the viruses.

Accidents↗
PubMed1992

Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives.

The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]quinuclidinyl benzilate. Potency and efficacy were found in compounds in which the azole moiety was attached to the azabicyclic ring either through a carbon atom or a nitrogen atom. Electrostatic potential maps of both the C-linked and the novel N-linked series of compounds were calculated. A relationship between position and depth of the electrostatic minima relative to the azabicyclic ring and the potency and efficacy of the compounds was determined.

Animals↗
PubMed1992

Independent effect of various facial mimetic muscles on the nasolabial fold.

The independent effect of the contraction of various facial mimetic muscles on the nasolabial fold was defined through study of cadaver dissections. The four major lip elevator muscles were identified and the effect of traction of these muscles on the nasolabial fold was studied. This study identified the levator alae muscle (levator labii superioris alaeque nasi) as the primary facial muscle responsible for creating the medial nasolabial fold. The levator labii superioris muscle was found to define the middle nasolabial fold. These two facial muscles may be significant in the etiology of the prominent nasolabial fold that occurs with aging.

Aged↗
PubMed1992

Characterization of neutralizing antibodies to bovine enterovirus elicited by synthetic peptides.

Six synthetic peptides corresponding to regions of bovine enterovirus (BEV), strain VG-5-27, elicited antibodies in mice which reacted with the virus in various assays. These antibodies have been characterised on the basis of their ability to (1) neutralize the virus, (2) bind to the intact virus particle in an immunoprecipitation test, (3) react with the denatured viral proteins, and (4) give immunofluorescent staining of virus infected cells. We have also determined the proportion of antipeptide antibody which binds to the virus in each case. All of the sera immunoprecipitated the virus and neutralized its activity to varying extents. Two of the sera specific for VP 1 sequences failed to react with denatured VP 1 whereas all the other antisera reacted with their respective parental proteins. All of the sera reacted with VG-5-27 infected cells in an immunofluorescence test. The proportion of antibodies to each peptide recognizing intact virus was variable and did not appear to correlate with neutralizing activity. In addition, the ability of each of the sera to react with and neutralize three other strains of the virus was analysed. With one of these strains significant cross-neutralization was observed.

Amino Acid Sequence↗
PubMed1992

New approaches to vaccination against foot-and-mouth disease.

The economically important foot-and-mouth disease has been successfully controlled in Western Europe by comprehensive immunization using killed vaccine. The author discusses the wisdom of abandoning this policy, and outlines research into alternative vaccines using recombinant DNA technology, in particular using synthetic peptides.

Animals↗
PubMed1991

Correlations between the conformations elucidated by CD spectroscopy and the antigenic properties of four peptides of the foot-and-mouth disease virus.

The conformational features of four related antigenic peptides (A, B, C and USA) from the foot-and-mouth disease virus (FMDV) (VP1; 141-160 of serotype A, subtype 12), assessed by CD, were found to correlate with the serological properties of these peptides. The CD spectra of the four peptides, obtained under cryogenic and solvent titration conditions, were consistent with three conformational components (a left-handed extended helix, an alpha-helix and a 3(10) helix) for peptides A and C and four components (a beta-turn of type II, an alpha-helix, a gamma-turn and a 3(10) helix) for peptides B and USA. The amino acid substitutions at positions 148 and 153, which distinguish the peptides, are therefore responsible for both their conformational and antigenic differences.

Amino Acid Sequence↗
PubMed1991

Designing future vaccines.

Vaccination is one of the major preventive measures against infectious diseases. With the exception of the hepatitis B vaccine, the vaccines in use today are produced from the infectious agents themselves, either by attenuation or inactivation. Although these products have been successful in controlling many diseases, there are several reasons why efforts are being made to improve their quality. In addition there are some infectious diseases for which vaccines are not available because the causal agents cannot be grown in sufficient quantities. New approaches will be required to obtain effective vaccines against these diseases. In this paper, these approaches to the design of new vaccines are described using hepatitis B, rabies and foot-and-mouth disease as examples.

Animals↗
PubMed1991

Vaccines.

Much progress has been made towards reaching an understanding of immune responses at the molecular level. This has provided much needed information for identifying the antigens which will afford protection against diseases such as rabies, malaria, whooping cough, hepatitis and acquired immune deficiency syndrome, and for presenting them to the immune system.

Animals↗