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Biomedical subjects

C S Jones

Publications and source records attributed to C S Jones.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Biochemical and growth inhibition studies of methotrexate and aminopterin analogues containing a tetrazole ring in place of the gamma-carboxyl group.

The biological activities of novel analogues of methotrexate (MTX) and aminopterin (AMT) in which the gamma-carboxyl was replaced by a 1H-tetrazol-5-yl ring, an isosteric group with acidic properties similar to a carboxyl group, were investigated. The tetrazolyl analogues of MTX and AMT were more potent inhibitors of the growth of CCRF-CEM and K562 human leukemia cell lines during continuous (120 h) and 24-h pulse exposure than were the respective parent drugs; only when the exposure time was reduced to 6 h were the parent drugs more potent. These inhibitory effects on growth correlated with the onset of and recovery from inhibition of de novo thymidylate biosynthesis. Growth inhibition by the analogues was protectable by leucovorin. MTX-resistant CCRF-CEM sublines with decreased transport or increased dihydrofolate reductase (DHFR) levels were cross-resistant to the analogues. The analogues were as potent as their parent drugs in inhibiting DHFR activity in vitro and at displacing [3H]MTX from intracellular DHFR. Each analogue was more effective than its parent drug at inhibiting uptake of [3H]MTX into CCRF-CEM cells. The tetrazole analogue of AMT was a linear competitive inhibitor (Kis = 50 microM) of CCRF-CEM folylpolyglutamate synthetase, while the tetrazole analogue of MTX, unlike all other inhibitors, was linear noncompetitive (Kis = 51 microM, Kii = 321 microM). The data suggest that, compared with MTX or AMT, the tetrazole substituent, in place of the gamma-carboxyl group, allows more efficient transport into cells via the reduced folate/MTX carrier and the resulting greater uptake of the analogues leads to inhibition of DNA synthesis and cell death at lower extracellular concentrations during long exposures. The mechanism of cell death could involve inhibition at folypolyglutamate synthetase, but DHFR is the primary target. The low potency of the analogues during short exposure is presumably related to the inability to form the poly-gamma-glutamyl metabolites required for intracellular retention.

Aminopterin↗
PubMed1990

The role of emergent exploration in free-tissue transfer: a review of 150 consecutive cases.

One-hundred and fifty consecutive free-tissue transfers were reviewed to evaluate the role of emergent exploration in flap survival. Eleven flaps exhibited signs of circulatory failure between 1 hour and 6 days postoperatively and required return to the operating room. In eight patients the preoperative diagnosis was venous thrombosis, and in three patients it was arterial thrombosis. The average time from the first abnormal examination to exploration was 1.5 hours. There were no false-positive explorations. All 11 flaps were salvaged following correction of the cause of circulatory compromise. In eight patients this was due to inflow or outflow obstruction in the recipient vessels proximal to the anastomosis, in two patients it was due to extrinsic compression of the flap from a tight wound closure, and in one patient it was due to obstruction of the recipient vein by a drain. Primary anastomotic thrombosis was not encountered as the cause of circulatory compromise in any patient. An aggressive approach to exploration was responsible for an increase in flap survival in the entire series from 90 to 98 percent. The results of this study demonstrate the efficacy of clinical monitoring, the role of early exploration, and the durability of microvascular anastomoses.

Adolescent↗
PubMed1989

Interaction of free porphyrins and metalloporphyrins with mouse ferrochelatase. A model for the active site of ferrochelatase.

The ability of purified mouse ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) to bind and catalytically utilize a variety of porphyrins has been examined. In all, the kd, Km or Ki values for eleven different porphyrins, the Ki values for four metalloporphyrins and the kd values for two metalloporphyrins were determined. The data obtained demonstrate that mouse ferrochelatase binds a wide variety of porphyrins and metalloporphyrins with kd values ranging from 6 nM for N-methylprotoporphyrin to 1.08 microM for coproporphyrin III. However, the enzyme shows a degree of catalytic specificity for the substituents at the 2.4 positions and utilizes only proto-, hemato-, meso-, deutero-, 2,4-monohydroxy-ethylmonovinyl- and 2,4-monohydroxymethylmonovinyl deuteroporphyrin as substrates. The data show that the magnitude of the kd is not an accurate indicator of the ability of the porphyrin to serve as a substrate or inhibitor and, with the exception of N-methylprotoporphyrin, the size of the kd is several orders of magnitude less than that of the Km or Ki. Of the metalloporphyrins examined (Fe, Co, Zn and Sn) all inhibited ferrochelatase at micromolar concentrations, although tin protoporphyrin was the least effective. These data are discussed in terms of an active site model for mammalian ferrochelatase.

Animals↗
PubMed1989

Fee scales.

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Composite Resins↗
PubMed1989

Self referral to an accident and emergency department for another opinion.

OBJECTIVE: To determine whether patients referring themselves to an accident and emergency department for another opinion after consulting their general practitioner present with serious illness, show any risk factors for being admitted, or are more likely to be patients of particular practitioners. DESIGN: Six month prospective survey. SETTING: District general hospital's accident and emergency department, receiving 42,000 new patients a year. PATIENTS: 180 Patients identified as attending for another opinion having already consulted a general practitioner. INTERVENTIONS: Classified as admission, referral to specialist clinic, follow up in accident and emergency department, or referral back to general practitioner. END POINT: Admission, with an analysis of admitted patients. MEASUREMENTS AND MAIN RESULTS: General outcome, diagnostic category, age, time of attendance, time since seen by general practitioner, and name of general practitioner were recorded. Forty seven patients were admitted, 99 were discharged back to the general practitioner (62 without a letter), and two died. Patients were most likely to be admitted if they attended within 24 hours after seeing a general practitioner, were aged under 5, or presented with respiratory or gastrointestinal complaints. Some general practitioners were overrepresented. CONCLUSIONS: Important disorders present in this way, and therefore these patients should be seen by a doctor. Information about these attendances could be useful to general practitioners in reviewing their performance.

Adolescent↗
PubMed1989

Growth phase dependency of chromatin cleavage and degradation by bleomycin.

Preferential cleavage of Saccharomyces cerevisiae chromosomes in internucleosomal (linker) regions and nonspecific degradation of chromatin by an anticancer antibiotic which degrades DNA were investigated and found to increase in consecutive stages of growth. Cleavage of DNA in internucleosomal regions and intensities and multiplicities of nucleosomal bands were dependent on drug concentration, growth phase of the cells, and length of incubation. Cellular DNA was least degraded during logarithmic phase. After cells progressed only one generation in logarithmic phase, low concentrations (6.7 x 10(-7) to 3.4 x 10(-6) M) of bleomycin produced approximately three to seven times more DNA breaks. Internucleosomal cleavage was highest, and the most extended oligonucleosomal series and extensive chromatin degradation were observed during stationary phase. It is concluded that the growth phase of cells is critical in determining amounts of the highly preferential cleavage in internucleosomal regions and overall breakage and degradation of DNA. Mononucleosomal bands were most intense, indicating the greatest accumulation of DNA of this size. Mean mononucleosomal lengths were 165.9 +/- 3.9 base pairs, in agreement with yeast mononucleosomal lengths. As high-molecular-weight chromatin was digested by bleomycin, oligonucleosomes and, eventually, mononucleosomes became digested. Therefore, it is also concluded that bleomycin degradation of oligonucleosomes and trimming of DNA linker regions proceed to degradation of the monosomes (core plus linker DNA).

Bleomycin↗
PubMed1988

Peptidyl O-acyl hydroxamates: potent new inactivators of cathepsin B.

Peptidyl O-acyl hydroxamates having appropriate active-site recognition features are very potent time-dependent inhibitors of the cysteine proteinase cathepsin B. The inhibition is irreversible, and the inactivation rate is strongly dependent on peptide structure and correct positioning of the P1 amino acid carbonyl group. Lipophilic O-acyl groups provide the most rapid inactivators, as exemplified by the inhibitor O-mesitoyl N-benzyloxycarbonyl-L-phenylalanyl-L-alanine hydroxamate (kmax/Ki = 640,000 M-1s-1).

Animals↗
PubMed1988

Mammary blood flow and cardiac output during initiated involution of the mammary gland in the rabbit.

1. Cardiac output and its distribution to the mammary gland, kidneys, heart, liver and gastrointestinal tract were measured in conscious rabbits at day 1, day 3 and day 6 after removal of the young at day 0. 2. There was no change in cardiac output, proportion of cardiac output delivered to the mammary gland or mammary blood flow 24 hr after the last suckling period. After a further 48 hr there was a significant reduction in the cardiac output, proportion of the cardiac output and blood flow to the mammary gland compared to the values measured in lactating animals. 3. There was no significant difference in blood flow to the other organs although there were changes in the proportion of the cardiac output delivered to the heart, kidney and liver during this period. 4. The change in uptake of glucose, acetate, non-esterified fatty acids and triacylglycerols by the mammary gland are discussed in relation to the reabsorption of milk components.

Animals↗
PubMed1988

Development of neuroendocrine (Merkel cell) carcinoma mixed with squamous cell carcinoma in erythema ab igne.

Squamous cell carcinoma and neuroendocrine (Merkel cell) carcinoma are cutaneous neoplasms that have only occasionally been reported to coexist. Squamous cell carcinoma, but not neuroendocrine (Merkel cell) carcinoma, is a rare complication of erythema ab igne. This report describes the development of both neoplasms arising within the same tumor mass in an area of erythema ab igne.

Aged↗