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C S Jones

Publications and source records attributed to C S Jones.

At least 73 records · Page 4Linked to original sources
PubMed1994

Influenza A subtype cross-protection after immunization of outbred mice with a purified chimeric NS1/HA2 influenza virus protein.

Influenza A/PR/8/34-derived chimeric (D) protein (SK&F 106160) composed of the first 81 amino acids (aa) of NS1 fused to the conserved 157 C-terminal aa of HA2 (NS1 1-81-HA2 65-222) was previously shown to induce H-2d-restricted protective cytotoxic T-lymphocyte (CTL) immunity in inbred mice. However, D protein, like other small peptides, exhibited haplotype dependence and was not immunogenic in H-2b and H-2K mice. A potential use of this antigen in humans and the role of T cells in any protection were evaluated in outbred Swiss and inbred CBF6F1 (H-2d/b) mice. Mice immunized with D protein and challenged by small-particle aerosol with a lethal dose of influenza virus were significantly protected against mortality from influenza A/H1N1 and A/H2N2 (p < 0.05-< 0.0000001), but not from A/H3N2 and influenza B viruses when compared with control mice. D protein did not induce serum virus-neutralizing antibody but caused virus to be cleared faster in immunized mice. Protection was long-lasting. In vivo depletion of either Lyt2 (CD8+) or L3T4 (CD4+) T cells with monoclonal antibodies led to abrogation of in vitro-generated CTL activity in CF6F1 mice and significant reduction in the protective efficacy of D protein against virus challenge in both Swiss and CF6F1 mice. These results suggest that protection was mediated by CD8+ and/or CD4+ cells and not antibody. Thus D protein, via a conserved sequence on the HA2 polypeptide, has the potential to induce partially cross-reactive CTL that may protect against influenza virus disease in humans.

Aerosols↗
PubMed1994

Retinol and beta-carotene concentrations in skin, papillomas and carcinomas, liver, and serum of mice fed retinoic acid or beta-carotene to suppress skin tumor formation.

Using 7,12-dimethylbenz[a]anthracene as the initiator and 12-O-tetradecanoyl-13-acetate as the tumor promoter on the dorsal skin of Sencar mice, we previously showed that pharmacological dietary all-trans-retinoic acid and beta-carotene inhibit the conversion of papillomas to carcinomas in a two-stage system of chemical carcinogenesis. The purpose of this study was to determine the influence of dietary retinoic acid and beta-carotene on retinoid and beta-carotene concentrations in skin and other tissues. We were unable to measure tissue retinoic acid because of the relatively limited amount of tissue available for analysis and the fast rate of metabolism. Different dietary levels of retinoic acid or beta-carotene did not influence total retinol of skin, papilloma, and carcinoma tissues, which all showed a concentration of approximately 1 +/- 0.5 microgram/g wet wt. Equally refractory to dietary retinoic acid or beta-carotene was serum retinol concentration. In contrast, dietary retinoic acid protected loss of liver retinol and retinyl palmitate, and beta-carotene caused an increase in beta-carotene and retinyl palmitate in liver but did not affect serum and liver retinol. We further investigated metabolic and functional aspects of retinoic acid in cultured mouse epidermal keratinocytes (LC-8 cells) and found that these cells actively metabolized [10,11-14C]retinoic acid to polar compounds. Isomers of retinoic acid were a minor product in the presence of cells and the major product when incubated in serum-containing medium in the absence of cells. From the functional point of view, exposure of LC-8 cells to 3 x 10(-6) M all-trans-retinoic acid (RA) caused a 75-fold induction in tissue transglutaminase and an approximately 9-fold induction in 10(-6) M RA at three days of culture. We conclude that retinoic acid spares endogenous retinol and that beta-carotene greatly enhances liver retinyl palmitate levels. Moreover we show that although mouse epidermal cells metabolize retinoic acid at a very high rate, they respond functionally by induction of tissue transglutaminase activity. Because this enzyme has been suggested to be involved in programmed cell death, we are presently investigating the possibility that it may be involved in the inhibition of carcinogenesis in mice fed pharmacological doses of RA.

Animals↗
PubMed1994

Parent and larval RAPD fingerprints reveal outcrossing in freshwater bryozoans.

The occurrence of outcrossing in benthic hermaphroditic colonial invertebrates has received much historical debate and little demonstration. Direct genetic study of this question using routine techniques has been limited by both the amount of material required and the detection of adequate DNA polymorphisms. However, the recent development of molecular techniques that require no a-priori sequence data provides new approaches to the characterization of both tiny and genetically similar individuals. Random amplification of polymorphic DNA (the RAPD assay) was used to amplify fragments of DNA (via the polymerase chain reaction) to obtain fingerprints of parental colonies and larval offspring of the hermaphroditic freshwater bryozoan Cristatella mucedo. Here we report the first positive and direct genetic evidence for outcrossing in bryozoans. However, we find that outcrossing generates only low levels of genetic variation in populations that are highly clonal.

Animals↗
PubMed1993

Female multiple mating behaviour in the common shrew as a strategy to reduce inbreeding.

Three hypotheses concerning potential genetic benefits of female multiple mating behaviour are evaluated for the common shrew. In a high-density population, many successful copulations took place between individuals estimated to be close relatives (e.g. full or half siblings). Juveniles resulting from such matings tended to be relatively small at weaning, and were generally less likely to survive to sexual maturity than more outbred individuals. Multiple paternity was discovered in eight of nine litters examined. The incidence of matings between close relatives, the cost of inbreeding, and the high incidence of multiple paternity presented are each consistent with the hypothesis that female multiple mating is a strategy to reduce inbreeding. That is, if females cannot always distinguish close kin, then they may copulate with several different males and so reduce the risk that all their offspring will be sired by a close relative.

Animals↗
PubMed1993

Randomly amplified polymorphic DNA analysis of clonal population structure and geographic variation in a freshwater bryozoan.

The randomly amplified polymorphic DNA (RAPD) assay was used to identify genetic polymorphisms in three clonal populations of the freshwater bryozoan, Cristatella mucedo, a species with few useful biochemical genetic markers. Of the 19 decamer oligonucleotide primers screened, 13 gave clear, reproducible RAPD profiles. Clonal population structure was evident, and one clone was dominant at each site. Cluster analysis grouped populations from more distant localities separately (Thames Valley and Norfolk), whereas populations from the Thames Valley clustered together. However, even at the regional scale a high degree of relatedness pertained. This work is one of the first RAPD studies of natural populations, and demonstrates the suitability of the technique for examining population structure and geographic variation in clonal taxa.

Animals↗
PubMed1993

Effects of dietary retinoic acid on skin papilloma and carcinoma formation in female SENCAR mice.

Previously we have shown that dietary retinoids are essential for papilloma formation induced by either an initiation-promotion or a complete skin carcinogenesis protocol. The present study was conducted to further determine the effect of dietary retinoic acid (RA) on papilloma formation and the conversion of papillomas to carcinomas. Skin tumors were induced in 3 week old female SENCAR mice by an initiation-promotion protocol with one application of 20 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA), followed by 20 weekly applications of 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed RA at one of the three doses: 0.3 (nutritionally marginal dose), 3 (near physiological) and 30 (pharmacological) micrograms/g of diet. Mice fed 30 micrograms of RA/g of diet had the same survival rate as the other two groups despite a lower body weight and all three groups had similar papilloma incidence, which reached 100% at age 18 weeks. Mice fed 3 micrograms of RA/g of diet had the highest papilloma yield (approximately 14 papillomas/mouse) of all groups and it peaked between weeks 18 and 38 of age. These papillomas later regressed such that mice from all three groups had about the same papilloma yield at week 44 of age. Mice fed 30 micrograms of RA/g of diet failed to develop any visible carcinoma, while mice fed 0.3 or 3 micrograms/g showed 1.9% conversion of papillomas to carcinomas. Therefore, dietary RA at 30 micrograms/g of diet inhibited the conversion of papillomas to carcinomas without affecting papilloma incidence. In addition, dietary RA at 30 and 0.3 micrograms/g of diet lowered papilloma yield.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Differential effects of dietary beta-carotene on papilloma and carcinoma formation induced by an initiation-promotion protocol in SENCAR mouse skin.

SENCAR mice were used to determine the effects of the provitamin A compound beta-carotene on papilloma formation and the conversion of papillomas to carcinomas in a two-stage protocol with one application of the initiator 7,12-dimethylbenz[a]anthracene (DMBA, 20 micrograms) and 20 weekly applications of the promotor 12-O-tetradecanoylphorbol-13-acetate (TPA, 2 micrograms). A purified vitamin A-free diet was supplemented with beta-carotene at four levels (0.6, 6, 60 and 600 micrograms/g of diet) for female mice and two levels (60 and 600 micrograms/g) for male mice. Dietary supplementations of beta-carotene did not result in significant changes in body weight and survival of female and male mice. However, papillomas developed more rapidly and papilloma incidence (% mice with papillomas) reached its maximum (100%) sooner in male mice fed 600 micrograms of beta-carotene/g of diet than those fed 60 micrograms/g. There were smaller differences in papilloma incidence among the dietary groups in female mice, but the papilloma incidence again reached 100% sooner in mice fed 600 micrograms of beta-carotene/g of diet. Female and male mice fed 600 micrograms of beta-carotene/g of diet had significantly higher papilloma yields (average number of papillomas/mouse) than other dietary groups and a very low percentage of these papillomas converted to carcinomas in these mice. Thus, beta-carotene at 600 micrograms/g inhibited the conversion of papillomas to carcinomas in both sexes. In addition, papilloma yields were higher in female mice and these papillomas regressed more quickly than those in the corresponding groups of male mice. In conclusion, dietary beta-carotene caused differential effects on papilloma and carcinoma yields and sex-dependent differences in papilloma formation in female and male SENCAR mice treated with DMBA and TPA in a two-stage carcinogenesis protocol.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Safety and immunogenicity of a recombinant protein influenza A vaccine in adult human volunteers and protective efficacy against wild-type H1N1 virus challenge.

A recombinant influenza A vaccine (D protein), comprising a carboxy-terminal sequence from the hemagglutinin HA2 subunit of A/Puerto Rico/8/34 virus (H1N1, A/PR/34) fused to 81 amino-terminal residues of the NS1 nonstructural protein, has previously protected mice against influenza A challenge by inducing H1N1/H2N2 cross-reactive cytotoxic T cells (CTL) without hemagglutination-inhibiting (HI) or neutralizing antibody. In our dose-escalating study, the vaccine was safe in humans and induced both IgG and T cell proliferative responses to D protein but little antibody to A/PR/34 or A/Kawasaki/8/86 (H1N1, A/KW/86) viruses. Among an additional group of A/KW/86-seronegative volunteers immunized with 500 micrograms of D protein, none had a rise in serum HI or neutralizing antibody to A/KW/86, 20% had minimal IgG responses to A/KW/86 by EIA, and a minority had any increase in A/KW/86-specific CTL activity. However, viral shedding and clinical illness score were reduced in vaccines relative to A/KW/86-seronegative unimmunized controls after intranasal challenge with wild-type A/KW/86. D protein immunization conferred significant protective immunity not currently explained by any of the immune parameters measured.

Adolescent↗
PubMed1993

Prevention of bicycle-related injuries in childhood: role of the caregiver.

To assess perceptions of bicycle-related head injuries, helmet use, and safety practices, we had questionnaires distributed to caregivers of 2,500 children in the third through sixth grades; 1,006 (40.2%) completed surveys were returned. Eight hundred thirty-two caregivers (82.7%) indicated that they had a child cyclist in their household; approximately 65% responded that they believed head injury was likely if their child was involved in a bicycle mishap. A majority (approximately 70%) also said that a bicycle helmet may prevent head injury in between 25% and 75% of all occurrences. Yet 758 (91.1%) students did not own or have access to a bicycle helmet. Among the caregivers whose child did not have a bicycle helmet, 530 (69.9%) stated that they had never thought about purchasing one. Caregivers of both helmeted and nonhelmeted youngsters indicated concern for bicycle safety (100% versus 94%, respectively). Most caregivers (approximately 64%) stated that they would encourage their child to attend a bicycle safety camp. These findings suggest that caregivers perceive the dangers associated with bicycling but are not cognizant of available programs and methods that prevent the risk of serious injury to bicyclists.

Accident Prevention↗
PubMed1993

Molecular comparison of the IncX plasmids allows division into IncX1 and IncX2 subgroups.

We have investigated molecular relationships and evolution of plasmids classified genetically to incompatibility (Inc) group X, in particular by comparison of plasmids from the pre-antibiotic era (PAE) with contemporary R-plasmids. On the basis of restriction analysis, R6K, the best-described and 'prototype' plasmid of the IncX group, exhibited little similarity with the other plasmids in this Inc group. Other contemporary IncX R-plasmids exhibited a substantial degree of interrelationship, and were also related to PAE IncX plasmids. When the origin of plasmid replication of R6K was used as a replicon probe, R6K was the only plasmid tested which exhibited homology. Other contemporary and PAE IncX plasmids exhibited homology with the origin of plasmid R485. These data suggest that the IncX group should be subdivided. R485 may be regarded as representative of the major subgroup present before and after the advent of antibiotic selection pressure. Plasmids of this subgroup, IncX1, possess an internal region which yields five characteristic EcoRV fragments. R6K may be regarded as representative of subgroup IncX2, of which it is presently the sole well-described member. The antibiotic resistances encoded by contemporary IncX R-plasmids are due to insertion of identifiable transposons in progenitor plasmids identical to the R485 subgroup of PAE IncX plasmids.

Biological Evolution↗
PubMed1992

Dietary retinoids are essential for skin papilloma formation induced by either the two-stage or the complete tumorigenesis model in female SENCAR mice.

Our previous work has shown that dietary retinoic acid (RA) is necessary for skin tumor formation induced by the two-stage protocol with the initiator 7,12-dimethylbenz[a]anthracene (DMBA) and the promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) (De Luca et al., Cancer Res., 36 (1976) 2334-2339). Here we report that retinoids are required for tumorigenesis by the two-stage as well as by the complete tumorigenesis protocol. Mice were treated with a single dose of DMBA (20 micrograms), followed by 20 applications of TPA (2 micrograms), or by 20 applications of DMBA (25 micrograms for 2 weeks and 51 micrograms thereafter). Regardless of the tumor induction protocol, tumor formation was inhibited by vitamin A-deficiency, while RA (3 micrograms/g of diet) or retinyl palmitate (RP, 6 micrograms/g) supplementation permitted the appearance of tumors. In addition, in comparison to the purified diets and regardless of their RA levels, the non-purified Purina chow diet enhanced tumor yield especially in the two-stage tumorigenesis protocol. This effect was less striking in mice with tumors induced by the complete tumorigenesis protocol. In summary, dietary retinoids are essential for skin tumor formation induced either by the two-stage or the complete tumorigenesis protocol.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Acute alcohol intoxication, body composition, and pharmacokinetics.

The present study compared alcohol pharmacokinetics associated with body weight, anthropometrically estimated total body water, and body mass index in men and women in two experimental sessions, single dose and double dose. All subjects were given the same amount of alcohol (2.3 and 4.6 oz. 86 proof vodka for single dose and double dose, respectively). Data analyses found a significant correlation between body mass index and peak blood alcohol concentration (BAC). Weight and total body water were not significantly correlated with peak BAC. The findings suggested that body mass index may be considered a better criterion than body weight for equating alcohol doses.

Adult↗
PubMed1992

Induction of protective class I MHC-restricted CTL in mice by a recombinant influenza vaccine in aluminium hydroxide adjuvant.

Induction of class I MHC-restricted cytotoxic T lymphocyte (CTL) responses by soluble proteins or peptides requires complex adjuvants or carrier systems which are not licensed for use with human vaccines. The data presented in this report show that vaccination with a highly purified recombinant influenza protein antigen in aluminium hydroxide adjuvant, the only adjuvant currently licensed for clinical use, elicited class I restricted CTL and protection from lethal challenge with H1N1 and H2N2 viruses. The antigen (D protein, SK&F 106160) is produced by expression of H1N1 influenza virus-derived cDNA (strain A/PR/8/34) in Escherichia coli, and is composed of the first 81 N-terminal amino acids (aa) of the non-structural protein 1 (NS1) fused via a nine nucleotide non-viral linker sequence to the 157 C-terminal aa of the haemagglutinin 2 subunit (HA2). Previous work by Kuwano et al demonstrated that in vitro stimulation of spleen cells from influenza virus-primed mice, with a partially purified preparation of the D protein, selected for CD8+ CTL clones which facilitated lung clearance of H1N1 and H2N2 viruses. In the current study, these results were extended by studying the responses of mice actively immunized with highly purified D protein in the presence or absence of adjuvants. Vaccination of CB6F1 (H-2dxb) mice with D protein in aluminum hydroxide or Freund's complete adjuvant generated H1N1 cross-reactive, H-2d-restricted, CD8+ CTL directed against an immunodominant HA2 epitope (aa 189-199). D protein without adjuvant did not elicit CTL, regardless of the route of injection. However, long-lived (greater than 6 months) splenic memory CTL were elicited by boosting mice intraperitoneally (i.p.) with the D protein in the absence of adjuvant. In mice injected subcutaneously with D protein in aluminium hydroxide at weeks 0 and 3, survival was increased relative to controls up to 16 weeks beyond the second vaccination, after which time additional boosting was required for protection. Studies in H-2b and H-2k mice vaccinated with the D protein showed that induction of CD4+ T-cell or antibody responses, in the absence of CD8+ CTL, did not correlate with protection. Passive transfer of immune sera from CB6F1 mice was also not protective. This prototype H1N1 recombinant subunit vaccine in aluminium adjuvant should directly address the feasibility of achieving a protective cell-mediated immune response in human influenza.

Adjuvants, Immunologic↗
PubMed1992

Enterobacterial tetracycline resistance in relation to plasmid incompatibility.

Sixty-eight well-characterized antibiotic resistance (R) plasmids belonging to 19 Incompatibility groups were screened with probes representing heterologous classes (A-E) of the enterobacterial tetracycline resistance (TcR) determinant. The Class B determinant was shown to be predominant in the IncF and IncH complexes and the IncC group. The Class A determinant was shown to be predominant in the IncP and IncM groups. There was no correlation between distribution of the class of TcR gene and the genus or the species of the host bacterial strain. The plasmids R714a (IncFI) and pHH1465 (IncC) contained TcR determinants which had no homology with any of these five probes.

Enterobacteriaceae↗
PubMed1992

Cloning of a probe for a previously undescribed enterobacterial tetracycline resistance gene.

An 8.35 kb BamHI fragment was cloned from the plasmid R714a. It encoded resistances to chloramphenicol, streptomycin, spectinomycin and tetracycline. Tetracycline resistance was determined by a locus without homology to the known enterobacterial gene classes, TetA-TetE. Further subcloning of the fragment located an unusual tetracycline resistance gene on a 4.7 kb BamHI-BglII fragment. A physical-genetic map of this fragment indicated that the gene was bisected by a PstI site. Deletion analysis and insertion mutagenesis were used to define a suitable probe. An intragenic PstI-AvaI fragment of 1.2 kb was identified, and used as a non-radioactive probe, being specific for this previously undescribed enterobacterial Tet gene.

Cloning, Molecular↗
PubMed1991

Evolutionary lines among Salmonella enteritidis phage types are identified by insertion sequence IS200 distribution.

A survey was made of the presence, copy number and location of the Salmonella-specific DNA insertion element IS200, within the genomes of the 27 phage type strains of Salmonella enteritidis. All the phage type strains contained copies of IS200 revealed by genomic Southern blot hybridizations with a 300-bp DNA probe internal to the element. Restriction site variation around IS200 insertion sites was examined. Three fundamental patterns of hybridization corresponding to chromosomal IS200 loci were found. In terms of population genetics, these 'IS200 profiles' correspond to clonal lineages of recent evolutionary origin, and underline the phage-typing scheme for epidemiological subdivision of S. enteritidis. The molecular analysis is consistent with genetic selection pressures which are apparent in the observed epidemiological distribution of S. enteritidis, since each clonal lineage contained one of the phage types of major clinical importance in the U.K.

Biological Evolution↗
PubMed1991

Identification of contemporary plasmid virulence genes in ancestral isolates of Salmonella enteritidis and Salmonella typhimurium.

Six epidemiologically distinct ancestral strains of Salmonella enteritidis and 5 of S. typhimurium from the pre-antibiotic era were examined for plasmid content, and for presence of plasmid genes implicated in mouse-virulence. Five sizes of plasmid were detected in S. enteritidis varying from 1 to 60 MDa. Two sizes of plasmid were found in S. typhimurium, 28 and 60 MDa. Plasmids of the same size were not common to both serovars. The HindIII restriction patterns of 3 of the ancestral S. enteritidis plasmids were identical to the modern 38 MDa plasmid, while all contained identical bands of 3.5, 2.7 and 1.9 kb. All the 60-MDa S. typhimurium plasmids, ancestral and contemporary, had an identical restriction pattern. Three different sized S. enteritidis plasmids and one size S. typhimurium plasmid contained a 3.5-kb DNA fragment carrying the virulence locus VirA. The VirB virulence locus was located on a 2.7-kb DNA fragment in S. enteritidis and on a 2.5-kb fragment in S. typhimurium. Both loci were precisely conserved between the ancestral strains and the modern representatives of both serovars.

DNA Fingerprinting↗