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C Jone

Publications and source records attributed to C Jone.

14 recordsLinked to original sources
PubMed2000

Selective opiate modulation of nociceptive processing in the human brain.

Fentanyl, a mu-opioid receptor agonist, produces analgesia while leaving vibrotactile sensation intact. We used positron emission tomography (PET) to study the mechanisms mediating this specific effect in healthy, right-handed human males (ages 18-28 yr). Subjects received either painful cold (n = 11) or painless vibratory (n = 9) stimulation before and after the intravenous injection of fentanyl (1.5 microgram/kg) or placebo (saline). Compared with cool water (29 degrees C), immersion of the hand in ice water (1 degrees C) is painful and produces highly significant increases in regional cerebral blood flow (rCBF) within the contralateral second somatosensory (S2) and insular cortex, bilaterally in the thalamus and cerebellum, and medially in the cerebellar vermis. Responses just below the statistical threshold (3.5 < Z < 4.0) are seen in the contralateral anterior cingulate, ipsilateral insular cortex, and dorsal medial midbrain. The contralateral primary sensory cortex (S1) shows a trend of activation. Except for slight changes in intensity, this pattern is unchanged following a saline placebo injection. Fentanyl reduces the average visual analogue scale ratings of perceived pain intensity (47%) and unpleasantness (50%), reduces pain-related cardioacceleration, and has positive hedonic effects. After fentanyl, but not placebo, all cortical and subcortical responses to noxious cold are greatly reduced. Subtraction analysis [(innocuous water + fentanyl) - (innocuous water + no injection)] shows that fentanyl alone increases rCBF in the anterior cingulate cortex, particularly in the perigenual region. Vibration (compared with mock vibration) evokes highly significant rCBF responses in the contralateral S1 cortex in the baseline (no injection) and placebo conditions; borderline responses (3.5 < Z < 4. 0) are detected also in the contralateral thalamus. Fentanyl has no effect on the perceived intensity or unpleasantness of vibratory stimulation, which continues to activate contralateral S1. Fentanyl alone [(mock vibration + fentanyl) - (mock vibration + no injection)] again produces highly significant activation of the perigenual and mid-anterior cingulate cortex. A specific comparison of volumes of interest, developed from activation peaks in the baseline condition (no injection), shows that fentanyl strongly attenuates both the contralateral thalamic and S1 cortical responses to noxious cold stimulation (P < 0.048 and 0.007, respectively) but fails to affect significantly these responses to vibrotactile stimulation (P > 0.26 and 0.91, respectively). In addition, fentanyl, compared with placebo, produces a unique activation of the mid-anterior cingulate cortex during fentanyl analgesia, suggesting that this region of the cingulate cortex participates actively in mediating opioid analgesia. The results are consistent with a selective, fentanyl-mediated suppression of nociceptive spinothalamic transmission to the forebrain. This effect could be implemented directly at the spinal level, indirectly through cingulate corticofugal pathways, or by a combination of both mechanisms.

Adolescent↗
PubMed1988

Effect of cholesterol epoxides on the inhibition of intercellular communication and on mutation induction in Chinese hamster V79 cells.

Cholesterol, cholesterol-5 alpha, 6 alpha-epoxide, cholesterol-5 beta, 6 beta-epoxide and cholestane-3 beta,5 alpha,6 beta-triol were tested for their ability to induce mutations at the Na+/K+-ATPase loci of the Chinese hamster V79 cells. None of these compounds induced ouabain-resistant mutations compared to the background mutation frequency in the control cells. These compounds were further tested for their ability to inhibit intercellular communication, using the Chinese hamster V79 cell metabolic cooperation assay. The diastereomeric epoxides and cholestane-triol, but not cholesterol, were found to be inhibitors of intercellular communication in a manner similar to other known tumor promoters.

Animals↗
PubMed1987

Effect of biological toxins on gap-junctional intercellular communication in Chinese hamster V79 cells.

Since chemical modulation of gap-junctional intercellular communication has been implicated in several toxicological endpoints, a study to examine the ability of several biological toxins to inhibit this process was undertaken. Eight biological toxins were tested for their ability to inhibit metabolic cooperation, a measure of gap-junctional intercellular communication, in the Chinese V79 cell system. Aplysiatoxin, anhydrodebromoaplysiatoxin and debromoaplysiatoxin showed the strongest ability to inhibit metabolic cooperation while T2-toxin and vomitoxin inhibited metabolic cooperation to a lesser degree. Aflatoxin B1, aflatoxin B2 and palytoxin were inactive in the Chinese V79 system. Palytoxin, which was extremely cytotoxic, might act as a tumor promoter if it induces compensatory hyperplasia in vivo.

Animals↗
PubMed1987

Characterization of a rat liver epithelial cell line to detect inhibitors of metabolic cooperation.

A normal rat liver epithelial cell line, with phenotype characteristics of "oval" cells (WB-F344), was examined for its ability to perform gap-junctional intercellular communication as measured by metabolic cooperation. To test for gap-junctional intercellular communication, 6-thioguanine-sensitive cells were cocultivated with 6-thioguanine-resistant cells. It was found that the recovery of 6-thioguanine-resistant cells depended on the densities of the 6-thioguanine-sensitive cells. Higher densities of 6-thioguanine-sensitive cells reduced the recovery of 6-thioguanine-resistant cells. These observations demonstrate that rat liver epithelial cells could metabolically cooperate, implying they could perform gap-junctional intercellular communication. Two tumor-promoting organochlorine pesticides, aldrin and dieldrin, were potent inhibitors of metabolic cooperation for these cells, but 12-0-tetradecanoyl-phorbol-13-acetate and teleocidin, known mouse skin tumor promoters, were not significantly effective in inhibiting metabolic cooperation. The results suggest that these cells might provide the basis for an in vitro assay specifically to study liver tumor promoters.

Animals↗
PubMed1985

Further characterization of the in vitro assay for inhibitors of metabolic cooperation in the Chinese hamster V79 cell line.

12-O-Tetradecanoylphorbol-13-acetate (TPA) has been previously shown to inhibit metabolic cooperation in Chinese hamster V79 cells. An in vitro assay, based on this phenomenon, has been developed to study tumor promoters. Several parameters concerning the metabolic cooperation assay using V79 Chinese hamster cells were further investigated in this report. Pretreatment of the cells with TPA in situ for different periods of time did not result in any detectable change in the inhibition of metabolic cooperation. If cells were replated after TPA treatment, a different result was obtained. There was an apparent decrease in the ability of TPA to inhibit metabolic cooperation when TPA was added back to the TPA-pretreated cultures. However, when TPA was omitted from the TPA pretreated cultures after replating, the inhibition of metabolic cooperation remained high. It was also found that pretreatment of the cells with another chemical, aldrin, exhibited the same pattern as the in situ TPA pretreatment effect on inhibition of metabolic cooperation. In order to obtain a high level of inhibition of metabolic cooperation when using aldrin in this assay, it was determined that the chemical needed to be present for more than one day. Our studies also showed that a 24 h treatment with 6-thioguanine did not kill 6-thioguanine-sensitive cells quickly, nor did it prevent them from performing metabolic cooperation. The relationship of cell density and TPA concentration was also studied. It was observed that a higher cell density required higher TPA concentration to inhibit, maximally, metabolic cooperation. A 'down regulation' type effect was noted when culture was challenged with different concentrations of TPA. These results were interpreted to be consistent with the hypothesis that inhibited gap-junctional intercellular communication is one of the components of tumor promotion.

Aldrin↗
PubMed1984

Inhibition of intercellular communication in cultures of Chinese hamster V79 cells by 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid.

Using the Chinese hamster V79 in vitro cell system designed to measure intercellular communication, 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and several mixtures of these compounds were tested for their ability to inhibit this biological process. The ability of these chemicals to inhibit colony-forming ability of these cells was tested prior to the studies to measure intercellular communication. 2,4-D was less cytotoxic than 2,4,5-T. Both 2,4,5-T and 2,4-D were able to inhibit intercellular communication at their respective noncytotoxic dose ranges. Various mixtures of both chemicals were also able to inhibit intercellular communication, showing some kind of additivity. No-effect levels were also noted in the intercellular communication assay. These results were interpreted as being consistent with the hypothesis that these compounds might be teratogenic by their ability to inhibit intercellular communication during development.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1984

Further studies on a rapid protein hydrolysis method.

Proteins may be hydrolysed for amino-acid analysis by a trifluoroacetic acid/HCl mixture at 166 degrees C for 25 or 50 min. A number of uncommon amino acids and certain amino-acid derivatives were subjected to this procedure and their decomposition rates were determined.

Amino Acids↗
PubMed1984

Promotion of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis by high dietary fat in the rat: possible role of intercellular communication.

The effect of high levels of dietary fat on the promotion phase of rat mammary tumorigenesis and the effect of unsaturated and saturated fatty acids on metabolic cooperation in hamster cells were examined. Female Sprague-Dawley rats were given iv injections of 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) and subsequently placed on 20% high-fat (HF) and 4.5% corn oil control (CF) diets. Rats treated with DMBA and fed HF diet for the entire duration of the experiment developed more tumors with shorter latency than rats fed CF diet for the entire experiment. Rats fed HF diet for 3 weeks at different times after DMBA treatment showed similar, enhanced mammary tumor development. Lengthening the duration of HF diet treatment (0, 3, 6, 16 wk) increased mammary tumor development, suggesting a time dose-response relationship. Removal of the HF diet treatment partially reversed its stimulatory effects on tumor development. These results indicate that dietary fat acts as a classical tumor promoter to enhance mammary tumorigenesis. The influence of unsaturated and saturated fatty acids on metabolic cooperation between 6-thioguanine-sensitive (6-TGS) and 6-thioguanine-resistant (6-TGr) Chinese hamster V79 cells was examined. Linoleic acid, palmitoleic acid, and arachidonic acid significantly increased the recovery of 6-TGr cells at noncytotoxic concentrations. Stearic acid, palmitic acid, and arachadic acid had no effect on the recovery of 6-TGr cells at either cytotoxic or noncytotoxic concentrations. These results demonstrate that unsaturated fatty acids but not saturated fatty acids can inhibit metabolic cooperation between Chinese hamster V79 cells, and suggest, mechanistically, that high dietary levels of polyunsaturated fat could promote tumorigenesis by inhibition of intercellular communication.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Oncogenes, inhibited intercellular communication and tumor promotion.

Homeostatic control of proliferation and differentiation is characteristic of normal, but not malignant, cells. Gap junction-mediated intercellular communication provides one mode of this homeostatic control for cells in physical juxtaposition. Many chemicals, both natural and human-made, can modulate the function of gap-junctional communication and by doing so, alter the control of proliferation and differentiation of cells. Many of these chemicals are known tumor promoters. Oncogenes appear to be highly conserved genes influencing proliferation and differentiation of cells. We have speculated that certain oncogenes might play a role in tumor promotion by their influence on the regulation of gap-junctional intercellular communication. If this hypothesis is correct, a mechanism would exist to unify radiation, chemical and viral carcinogenesis.

Animals↗
PubMed1982

Elimination of metabolic cooperation is associated with the tumor promoters, oleic acid and anthralin.

Inhibition of intercellular communication, as measured by metabolic cooperation between 6-thioguanine-sensitive and resistant Chinese hamster V79 cells, has been previously shown to be correlated with a large variety of known tumor promoters in many species and organ systems. The effects of anthralin and oleic acid, at non-cytotoxic concentrations, were shown to eliminate metabolic cooperation in Chinese hamster cells. Moreover, increased serum levels appear to reduce the effectiveness of 12-O-tetradecanoylphorbol-13-acetate, a powerful tumor promoter and inhibitor of metabolic cooperation, to eliminate metabolic cooperation. Results are consistent with the hypothesis that inhibition of metabolic cooperation is associated with an aspect of the complex tumor promotion process and indicate that in vitro culture conditions are critical for the proper assessment of potential tumor promoters.

Animals↗
PubMedDate not supplied

Inhibition of gap junctional-mediated intercellular communication in vitro by aldrin, dieldrin, and toxaphene: a possible cellular mechanism for their tumor-promoting and neurotoxic effects.

Several mechanisms have been postulated to be responsible for the pleiotropic effects of toxic chemicals. Although the cytotoxicity and mutagenicity of chemicals are well studied and relatively easily detected, the noncytotoxic and nonmutagenic (i.e., epigenetic) mechanisms of chemical toxicity are less well understood. An in vitro assay, using cocultures of Chinese hamster cells to measure metabolic cooperation between V79 6-thioguanine-sensitive (6TGs) and resistant (6TGr) cells, has been developed to detect noncytotoxic and nonmutagenic chemicals that inhibit, quantitatively, gap junctional communication. The insecticides aldrin, dieldrin, and toxaphene, known to have pleiotropic toxic effects in animals, were shown to inhibit gap junctional communication. Interpretation of results suggests that chemical inhibition of gap junctional communication could be a possible mechanism to explain their tumor-promoting and neurotoxic effects.

Aldrin↗