PubMed Health⌕ Search

Biomedical subjects

C A Jones

Publications and source records attributed to C A Jones.

At least 19 recordsLinked to original sources
PubMed1992

Skinfold thickness and cardiovascular risk factors in American and Japanese telephone company executives.

Data from a cross-sectional study of cardiovascular disease risk factors in 962 US and 827 Japanese male telephone company executives were used to determine the associations of skinfold thickness measurements (abdominal, subscapular, triceps, ulnar) with blood pressure, blood glucose, serum cholesterol, and serum triglycerides. These associations were assessed within each group of executives and were compared between the groups. Most skinfolds showed association with risk factors in univariate regression. After adjusting for age and body mass index, the abdominal skinfold continued to be significantly associated with blood pressure and triglycerides in both groups, while the subscapular skinfold showed associations only with triglycerides. After adjustment, the peripheral skinfolds showed no association with risk factors in the US men, however, in the Japanese men the ulnar skinfold continued to be associated with blood pressure. These findings suggest that abdominal and ulnar skinfold measurement may be useful in adjusting for the effect of obesity on coronary heart disease risk in epidemiological studies.

Administrative Personnel↗
PubMed1992

Peritoneal macrophages during peritonitis. Phenotypic studies.

The expression of a range of surface molecules/receptors that are important in the host response to infection and foreign antigens was examined using peritoneal macrophages isolated from patients on continuous ambulatory peritoneal dialysis (CAPD) with peritonitis. The macrophage phenotypic profile was compared with that of normal peripheral blood monocytes. Consistently there was increased expression by macrophages of CD14, ICAM-1 (CD54), Fc gamma RI (CD64), Fc gamma RII (CDw32), Fc gamma RIII (CD16), transferrin receptors (CD71) and tissue factor. Increased expression of MHC class II was marginally significant. There was no detectable expression of either the p55 (CD25) or p70 chains of the IL-2 receptor. The expression of the complement receptors, CR1 (CD35) and CR3 (CD11b, CD18), was reduced. The activity of well-known inflammatory cytokines, rather than uraemic molecules, can account for the phenotypic profile of these extravasated peritoneal macrophages. The results of this study indicate that peritoneal macrophages from CAPD patients with peritonitis display a phenotype consistent with them being in vivo-derived inflammatory macrophages, and that they are appropriate for use in studies of anti-inflammatory agents.

Antigens, CD↗
PubMed1992

Regulated tissue- and cell-specific expression of the human renin gene in transgenic mice.

Transgenic mice containing the human renin gene were constructed with the aim of examining the tissue- and cell-specific expression of human renin. The human renin transgene used consisted of a genomic sequence extending approximately 900 bp upstream and 400 bp downstream of the coding region and included all exon and intron sequences. Two assays were developed to differentiate human renin transcripts from endogenous mouse renin transcripts at the whole-tissue level. High level human renin expression was evident in the kidney, adrenal gland, ovary, testis, lung, and adipose tissue of all four transgenic lines examined. Human renin mRNA could also be detected at lower levels in the submandibular gland and heart of two different individual lines. No expression was evident in the liver or brain of any line tested. In situ hybridization revealed the human renin mRNA to be localized and exquisitely restricted to renal juxtaglomerular cells. Treatment of transgenic mice with captopril resulted in an increase in the accumulation of renal renin mRNAs derived from both the mouse and human renin genes. Plasma renin activity assays using synthetic human renin substrate clearly demonstrated the elaboration of active human renin into the systemic circulation of transgenic mice. These data strongly suggest that the human renin transgene exhibits both tissue- and cell-specific expression in transgenic mice. Its expression is entrained to the same regulatory signals as the endogenous renin gene in kidney, and active human renin is released into the plasma of the transgenic mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. III. Biosynthesis.

The biosynthetic origin of the carbon and oxygen atoms of the novel fungal secondary metabolite 1 was studied. Incorporation studies with single and multiple labelled 13C precursors indicated that the major portion of the molecule was derived from two polyketide chains made up of acetate units. One of the chains had benzoic acid (which can be derived from phenylalanine) as a starter unit. The remaining carbons were derived from a four-carbon unit related to succinate and from methionine. Studies with [1-(13)C,18O2]acetate and 18O2 indicated that five of the oxygens, including both of the heterocyclic oxygens, were derived from atmospheric oxygen. The oxygens at the two ester carbonyls were derived from acetate.

Bridged Bicyclo Compounds↗
PubMed1992

Interleukin-4 suppression of monocyte tumour necrosis factor-alpha production. Dependence on protein synthesis but not on cyclic AMP production.

The molecular mechanisms by which human interleukin-4 (IL-4) down-regulates tumour necrosis factor-alpha (TNF-alpha) production by monocytes remain unknown. Other studies of IL-4 action in B lymphocytes and large granular lymphocytes (LGL) suggested that IL-4 may suppress mediator production by augmenting intracellular cyclic AMP (cAMP) levels. However, this study did not find evidence for involvement of a cAMP-dependent signalling pathway for expression of IL-4 activity in monocytes. IL-4 reduced TNF-alpha production by monocytes when IL-4 and lipopolysaccharide (LPS) were added concomitantly, or upon subsequent activation by LPS 16 hr after first exposure to IL-4. The continued presence of IL-4 at the time of LPS stimulation was not necessary; however, the suppressive effects of IL-4 were dependent on protein synthesis. This sustained activity of IL-4 for down-regulation of the production of inflammatory signals may be important for control in vivo of excessively activated monocytes/macrophages, and in therapy.

Cells, Cultured↗
PubMed1991

Prokaryotic expression of the thyrotropin receptor and identification of an immunogenic region of the protein using synthetic peptides.

Graves' disease is characterized by hypersecretion of thyroid hormones due to binding of autoantibodies to the thyrotropin receptor (TSHR). In order to study immunological aspects of the TSHR we expressed the extracellular domain of the rat TSHR (ETSHR) as a fusion protein with beta-galactosidase in a prokaryotic system. The identity of this ETSHR-fusion protein was confirmed by Western blot, using antibodies to synthetic peptides derived from TSHR. Patients' sera reacted to a significantly greater extent with the affinity purified ETSHR relative to control sera. Similarly, sera from patients with Graves' disease displayed significant reactivity with only one of five peptides, RH2 (residues 352-366), when compared with normal sera. These data, together with the predicted hydrophilicity of the peptide RH2, suggest that amino acids 352-366 which lie within one of the unique regions of the extracellular domain of the TSHR may be important for antibody binding.

Amino Acid Sequence↗
PubMed1991

Plasmid effects on secondary metabolite production by a streptomycete synthesizing an anthelmintic macrolide.

Transformation of the thermotolerant streptomycete, soil isolate S541, with plasmid cloning vectors of varying size, copy number, and parent replicon (derived from pIJ101, SCP2* and SLP1.2) depressed the biosynthesis of nemadectins (polyketide-derived secondary metabolites possessing anthelmintic activity). However, production of the chemically distinct 21-hydroxyl-oligomycin A, also produced by S541, was either unaffected or increased in plasmid-containing strains. A causal relationship between plasmid carriage and the changes in secondary metabolite yield was confirmed since cured strains were restored to normal production levels and their subsequent retransformation by plasmid DNA was followed by the same effects on nemadectin and oligomycin biosynthesis as before. All the plasmids tested were highly unstable in S541 and it was generally necessary to include an appropriate selective antibiotic (usually thiostrepton) in the growth medium. Thiostrepton was not responsible for the depressive effect, since this was also observed in plasmid-containing strains (i) when grown in antibiotic-free media and (ii) when alternative selective antibiotics such as neomycin were used. In addition, the plasmid-free strain produced both nemadectins and 21-hydroxyl-oligomycin A in the presence of sub-inhibitory levels of thiostrepton. The thiostrepton resistance gene, which was present on many of the plasmids tested, did not mediate the effect since plasmids carrying other selectable markers (pIJ58, neomycin, and pIJ355, viomycin) also depressed nemadectin but not 21-hydroxyl-oligomycin A production. No obvious recombination or integration events between S541 chromosomal DNA and any of the plasmids tested were revealed by DNA-DNA Southern hybridization.

Anti-Bacterial Agents↗
PubMed1991

Pathophysiology of vascular smooth muscle in renin promoter-T-antigen transgenic mice.

The pathophysiological consequence of targeted production of SV-40 T-antigen to renin-expressing cells in the kidney of transgenic mice is reported. A histopathologic analysis of the kidney from adult transgenic mice (12-16 wk old) revealed the presence of severe vascular lesions manifested by marked atypical hyperplasia of vascular smooth muscle. The levels of plasma renin, kidney renin, and kidney renin mRNA were examined in 6- and 9-wk-old transgenic mice and were found to be significantly lower than their age-matched non-transgenic littermates and were nonresponsive to captopril treatment. However, there was no significant difference in conscious mean arterial pressure between transgenic and non-transgenic mice. The levels of renal renin mRNA in transgenics and nontransgenic littermates were compared throughout ontogeny and were found to be equal in newborns, elevated 3- to 5-fold in 1-wk-old transgenics, and yet decreased 10-fold by 6 wk of age in transgenic mice. Expression of the transgene in the kidney exhibited the proper developmental pattern and was properly restricted to juxtaglomerular cells in neonatal mice. Nevertheless, in adult mice, T-antigen-containing cells were found throughout the entire renal arterial tree. The observed ability of renal vascular cells to be recruited to express both renin and T-antigen suggests a mechanism that can explain the development of the renal pathology in these mice.

Animals↗
PubMed1990

Isolation and characterization of renin-expressing cell lines from transgenic mice containing a renin-promoter viral oncogene fusion construct.

We constructed transgenic mice containing a renin-promoter SV40 T antigen fusion transgene with the intention of inducing neoplasia in renin-expressing cells and isolating renin-expressing cell lines in vitro. We examined six kidney tumors from mice representing three different transgenic lines and found they expressed their endogenous renin gene. Initially, five nonclonal kidney tumor-derived cell lines were established which expressed their endogenous renin gene in addition to the transgene. They retained active renin intracellularly and constitutively secreted an inactive form of renin (prorenin). One of these cell lines was cloned to homogeneity. This line maintained high level expression of renin mRNA throughout 3 months of continuous culture. Although the cells contained an equal proportion of active and inactive renin, the species constitutively secreted into the media was predominantly (95%) prorenin. However, active renin secretion was stimulated 2.3- and 4.6-fold by treatment with 8-bromo-cAMP after 4 and 15 h, respectively. In addition, the presence of multiple secretory granules was confirmed by ultrastructural analysis. These cells, which express renin mRNA and can regulate secretion of active renin, should provide an excellent tool for studying renin gene regulation and secretion. Furthermore, these mice should provide a useful source for the establishment of renin-expressing cell lines from a variety of renin-expressing tissues.

Animals↗
PubMed1990

Tissue and cell specific expression of a renin promoter-reporter gene construct in transgenic mice.

The tissue specific expression of a fusion transgene consisting of 4.6 kb of Ren-2 5' flanking sequence and the SV40 T antigen viral oncogene was analyzed by northern hybridization and immunocytochemistry. Among the 10 tissues examined, endogenous renin transcripts were identified in and restricted to kidney, submandibular gland, testes and ovary consistent with the expression pattern of the Ren-1c gene. In addition to these tissues, significant levels of transgene mRNA were detectable in the brain. Expression of the transgene was restricted to juxtaglomerular cells in the kidney and the granular convoluted tubule cells of submandibular gland. These results suggest that 4.6 Kb of Ren-2 5' flanking sequence is sufficient to confer tissue and cell specific expression upon an exogenous reporter gene.

Animals↗
PubMed1990

Modulation of gene expression in Syrian hamster embryo cells following ionizing radiation.

We examined the modulation of gene expression in Syrian hamster embryo (SHE) cells at various times following exposure to low doses of ionizing radiation. Early passage SHE cells were irradiated in plateau phase (greater than 95% G0-G1 cells) with 21-cGy fission-spectrum neutrons, 75-cGy X-rays, or 90-cGy gamma-rays, none of which induced more than 10% loss in cell viability. RNA harvested at various times after exposure was examined for levels of particular RNA species by dot blot and Northern blot hybridizations. Levels of beta-actin-specific RNA decreased within 15 min after exposure of the cells. The kinetics of repression of beta-actin mRNA were similar for all qualities of radiation (X-rays, gamma-rays, and neutrons) for 12 h post-irradiation. Within 1 h after neutron exposure (21 cGy), we observed a decrease in accumulation of RNA species (relative to RNA from nonirradiated cells) encoding the enzyme ornithine decarboxylase; this decrease continued for up to 12 h. Similar results were obtained with gamma- and X-rays. RNA encoding interleukin 1, however, was induced by 3 h after neutron irradiation but reduced to background levels by 7 h. Amounts of rRNA remained constant in all experiments, although total transcription on a per cell basis was reduced within 15 min following irradiation and did not return to normal until 7 h post-irradiation. No alterations, relative to untreated control cells, in overall cell viability or the rate of cell cycle progression were observed in cells either immediately or within 24 h post-irradiation. Our results demonstrate modulation of specific genes following low-dose irradiation. In addition, our findings suggest that some molecular responses to different qualities of ionizing radiation (X-rays, gamma-rays, and neutrons) may be similar.

Actins↗
PubMed1990

Changes in adrenal cortisol secretion as reflected in the urinary cortisol/creatinine ratio in dogs.

In Experiment 1, voided urine samples were collected from 12 adult dogs at 0500, 1400, and 2200 hr for 4 days. Cortisol was measured in unextracted urine by radioimmunoassay, creatinine by spectrophotometry, and the cortisol/creatinine ratio (UCCR) was calculated for each sample. There was considerable variation both within and among dogs in UCCR but there was no consistent time of day fluctuation in UCCR. In Experiment 2, these dogs were randomly assigned to 1 of 4 groups. The groups received each of 4 treatments (saline, dexamethasone, ACTH gel, and aqueous ACTH) at 7 day intervals in Latin square design. All urine was collected from 0 through 8 hr. Blood samples were collected at 20 minute intervals from 0 through 8 hr. Plasma cortisol exposure was determined by quantifying area under the curve (AUC). UCCR measurement was shown to differentiate basal from elevated, but not lowered, cortisol secretion. A positive linear relationship between UCCR and AUC was seen for all treatments except dexamethasone. These results indicate that changes in cortisol secretion are reflected in changes in UCCR, but measurement of UCCR may lack sensitivity to differentiate basal from reduced states of cortisol secretion. In Experiment 3, urine was collected daily before and during induction therapy with o,p'-DDD from dogs with pituitary-dependent hyperadrenocorticism. Successful suppression of the adrenal glands was accompanied by a progressive decrease in UCCR. There was considerable variation in the rate of adrenal suppression.

Adrenal Cortex↗
PubMed1990

Expression of murine renin genes in subcutaneous connective tissue.

A renin promoter-large tumor antigen (T antigen) fusion gene was constructed to provide a reporter function for renin expression in transgenic mice. These transgenic mice gave rise to tumors in subcutaneous soft tissue, which was attributed to transgene expression at this site. An immunohistochemical analysis of transgenic fetuses from several independent lines revealed scattered T-antigen-containing mesenchymal cells and fibroblasts in the subcutaneous layer of the skin between the panniculus carnosus muscle of the skin and the skeletal muscle of the body wall. This localization is consistent with the location of overt tumorigenesis in adult mice. This pattern was specific for the renin-T antigen fusion gene as no immunohistochemical staining was observed in transgenic fetuses containing a heterologous promoter-T antigen fusion gene. Northern blot analysis of tumor RNA indicated that most of the tumors expressed both T antigen and the endogenous renin gene Ren-1c. In addition, when multiple renin genes were introduced by crossing transgenic mice with nontransgenic DBA/2J mice, which contain another allele of the Ren-1 locus as well as the duplicated locus Ren-2, the resultant tumors expressed the Ren-2 gene. Northern blots were then used to analyze renin expression in the subcutaneous tissue of normal mice. Fully processed renin mRNA was detected in eviscerated 15.5-day postcoitus fetal and newborn carcasses and in newborn skin. Our data indicate that there is a renin-expressing cell population in fetal and newborn subcutaneous tissue.

Animals↗
PubMed1990

Fission-neutron-induced expression of a tumour-associated antigen in human cell hybrids (HeLa x skin fibroblasts): evidence for increased expression at low dose rate.

The induction of a tumour-associated antigen in a human cell hybrid line (HeLa x skin fibroblast) following exposure to fission neutrons of average energy 0.85 MeV (Janus reactor, Argonne National Laboratory) at two dose rates, 0.086 and 10.3 cGy/min, has been examined. The dose-response data obtained indicate the lower dose rate to be 2.9-fold more effective than the higher in inducing expression of the tumour-associated antigen, while there was no significant dose-rate effect in terms of cell killing. These results are qualitatively in agreement with previous observations using neutrons from the Janus reactor for the neoplastic transformation of C3H10T1/2 cells and Syrian hamster embryo cells.

Antigens, Neoplasm↗
PubMed1990

Expression of murine renin genes during fetal development.

Fetuses were examined to produce a developmental profile of renin expression in the kidneys and adrenal glands in single renin gene and two renin gene strains of mice. Sites of renin expression were detected by in situ hybridization using an 35S-labeled antisense RNA probe complimentary to the renin cDNA. Accumulation of renin transcripts in the adrenal gland reached a maximum at 15.5 days post coitum for all strains examined, but declined to undetectable levels by birth in one gene strains, while in two gene strains, the levels of renin transcripts lessened and by birth became limited to the developing inner cortex. Kidney renin transcripts were first detected at 14.5 days post coitum in the newly developing arteries in fetuses of both genotypes of mice. As the renal arterial tree developed, renin mRNA containing cells were progressively localized to more distal blood vessels and finally to the specialized cells of the afferent arteriole (juxtaglomerular cells). These results were confirmed by examining the localization of immunoreactive T antigen in transgenic fetuses. These mice carried a transgene which placed the SV40 T antigen structural gene under control of renin regulatory elements. Expression of T antigen occurred at the same sites in the kidneys and adrenal glands as renin mRNA. Furthermore, in strains with two renin genes, primer extension analysis indicated transcripts from both genes were present in equal proportion in combined kidney and adrenal gland extracts of total RNA. These transcripts were full length in size. The transient localization of renin mRNA in cells of the fetal intrarenal arteries is consistent with the notion that renin may be a useful marker for the developing renal vasculature.

Adrenal Glands↗