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Biomedical subjects

G Jones

Publications and source records attributed to G Jones.

At least 343 records · Page 19Linked to original sources
PubMed1992

Metabolism of 25-hydroxydihydrotachysterol3 in bone cells in vitro.

Dihydrotachysterol3, a reduced (or hydrogenated) analog of vitamin D3 in which the A ring has been rotate through 180 degrees , is, after hepatic 25-hydroxylation, converted in vivo to a dihydroxylated metabolite, termed peak H, which is at present unidentified but with good affinity for the vitamin D receptor. Although peak H is made in relatively large amounts in vivo, it has not yet been possible to synthesize it in vitro. Mass spectrometric evidence suggests that peak H is 25-hydroxylated and the presumption that it is a metabolite of 25-hydroxydihydrotachysterol3 was confirmed by the demonstration that radiolabeled peak H was formed in vivo in the rat after injection of 25-hydroxy-[10,19-3H]dihydrotachysterol3, produced from [10,19-3H]dihydrotachysterol3 in a hepatic cell model. The metabolism of 25-hydroxy-[10,19-3H]dihydrotachysterol3 was also studied in a rat osteosarcoma cell UMR-106, a known target cell for vitamin D, using high (11 microM) and low (10 nM) substrate concentrations. Metabolic products were isolated by lipid extraction, purified by high-performance liquid chromatography, and characterized by direct-probe mass spectrometry and gas chromatography/mass spectrometry. The formation of peak H from 25-hydroxydihydrotachysterol3 could not be demonstrated in UMR-106 cells. However, 25-hydroxydihydrotachysterol3 was metabolized to at least seven side-chain modified metabolites, each of which was extensively characterized and tentatively identified. It is concluded that the vitamin D enzyme system present in UMR-106 cells is able to metabolize dihydrotachysterol3 very efficiently to a series of metabolites but is incapable of producing peak H.

Animals↗
PubMed1992

Combined treatment with oral etretinate and electron beam therapy in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome).

BACKGROUND: Total skin irradiation for early-stage mycosis fungoides produces clinical remission in 90% of patients, but the median duration of remission is only 2 to 4 years. Etretinate has proven efficacy in advanced mycosis fungoides. Its potential as adjuvant therapy to radiation could be limited by toxicity from the combination. OBJECTIVE: Our purpose was to determine whether oral etretinate at 1 mg/kg can be combined with 35 Gy of radiation without intensifying or prolonging the radiation reaction and to determine the relapse-free survival rate. METHODS: Twenty-three patients began etretinate on day one of radiation and the dose was reduced for nose bleeds, dry skin, or hyperlipidemia. During the reaction skin toxicity questionnaires were completed weekly. Nine concurrent patients receiving only radiation completed identical forms. RESULTS: Etretinate did not intensify the skin reaction but did prolong it by 2 weeks. At a median follow-up of 2 years the relapse-free survival rate in complete responders was similar to stage-matched concurrent and historic control subjects. CONCLUSIONS: Both radiation and etretinate can be given together with acceptable toxicity and without compromising either therapy.

Administration, Oral↗
PubMed1992

Regulation of phospholipase C isozymes.

Phosphatidylinositol bisphosphate hydrolysis is an immediate response to many hormones, including growth factors. The hydrolysis of phosphatidylinositol bisphosphate is catalyzed by phosphatidylinositol-specific phospholipase C. A number of phospholipase C isozymes have been identified. Different isozymes are activated by different receptor classes. This review will summarize the different isozymes of phospholipase C, and the current knowledge of the mechanisms by which phospholipase C activity is modulated by growth factors.

Animals↗
PubMed1992

The metabolism of dihydrotachysterols: renal side chain and non-renal nuclear hydroxylations in vivo and in vitro.

The metabolism of dihydrotachysterol (DHT), a hydrogenated analogue of vitamin D, has been studied in vivo using man and rat and in vitro using the perfused rat kidney, and hepatoma (3B) and osteosarcoma (UMR-106) cell lines. In vivo a large number of metabolites appeared in the plasma of rats given DHT2 and DHT3. Of particular interest was a compound more polar than 25-hydroxy-DHT, which has been designated compound H. Further study of this compound showed that it was composed of two components, one (Ha) being in much lower concentration than the other (Hb). The production of T2/H (peak H from DHT2) was demonstrated in human plasma after administration of oral DHT2. Comparison of the metabolites formed in vivo with those isolated from the rat kidney perfused with 25-hydroxy-DHT3 in vitro showed that 25-hydroxy-DHT3 was metabolized along two metabolic pathways previously described for vitamin D, culminating in the production of 25-hydroxy-DHT3-23,26-lactone and 23,25-dihydroxy-24-oxo-DHT3. The osteosarcoma cell line metabolized 25-OH-DHT3 in vitro along the same two metabolic pathways already demonstrated in the perfused rat kidney. More polar metabolites than compound H seen in rat plasma in vivo were shown to be metabolites of compound H and similar metabolites were also produced in the osteosarcoma cell line from chemically synthesized 1 alpha,25-dihydroxy-DHT3. The hepatoma cell line 25-hydroxylated DHT and no feed-back inhibition was observed. Use of the hepatoma cell to 25-hydroxylate a number of chemically synthesized 1-hydroxy-DHTs indicated that compound Ha was indistinguishable from 1 alpha,25-dihydroxy-DHT whereas compound Hb is possibly 1 beta,25-dihydroxy-DHT. Studies with the VDR in both chick gut and calf thymus indicated that 1 alpha,25-dihydroxy-DHT is very effective in displacing radiolabelled 1 alpha,25-dihydroxyvitamin-D3 and is thus most likely to be the calcaemic metabolite of DHT.

Animals↗
PubMed1992

Normal 24-hydroxylation of vitamin D metabolites in patients with vitamin D-dependency rickets type I. Structural implications for the vitamin D hydroxylases.

The steady state serum concentration of 1,25-dihydroxyvitamin D [1,25-(OH)2D] is determined by the relative rates of its biosynthesis via the renal mitochondrial 1-hydroxylase and catabolism via renal and target cell 24-hydroxylases. It is not yet known whether the two catalytic activities are mediated by the product of a single gene or products of distinct genes. To address this question, we undertook to assess 24-hydroxylase function in patients with vitamin D-dependency rickets type I (VDDR-I), a Mendelian disorder of 1,25-(OH)2D synthesis attributable to a defect in renal 1-hydroxylase activity. To assess renal 24-hydroxylase activity, we measured the serum concentration of 24,25-dihydroxyvitamin D [24,25-(OH)2D] and its 25-hydroxyvitamin D (25OHD) precursor. We also measured target cell, 1,25-(OH)2D3-inducible 24-hydroxylase activity and calcitroic acid production in skin fibroblasts from VDDR-I patients and age- and sex-matched controls. Serum levels of 24,25-(OH)2D and 25OHD were similar in VDDR-I patients and controls [ratio of product to substrate, 0.062 +/- 0.013 (n = 5) vs. 0.067 +/- 0.005 (n = 10), mean +/- SEM, for patients and controls, respectively]. Circulating levels of 1,25-(OH)2D were also comparable in both groups [80.6 +/- 15.5 (n = 5) vs. 86.1 +/- 5.2 (n = 10) pmol/L, for patients and controls, respectively], presumably indicative of compliance with calcitriol therapy. Skin fibroblasts from VDDR-I patients exhibited 24-hydroxylase activity which was indistinguishable from that observed in control fibroblasts [108 +/- 14 (n = 5) vs. 96 +/- 25 fmol/10(6) cells.min (n = 6), for patients and controls, respectively]. Similarly, calcitroic acid production was comparable in fibroblast cultures derived from the two groups of subjects [31 +/- 6 vs. 33 +/- 3 fmol/10(6) cells.min (n = 3), for patients and controls, respectively]. Our data demonstrate that renal and target cell 24-hydroxylase activities are normal in patients with VDDR-I and suggest that the renal 1- and 24-hydroxylases likely represent, or contain, distinct polypeptides encoded by different genes.

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Intensity and direction as dimensions of competitive state anxiety and relationships with competitiveness.

This study examined differences in intensity and direction of symptoms of competitive state anxiety in high and low competitive subjects from the sports of rugby union, basketball, soccer, and field hockey. The 69 men were dichotomized via a median-split into high and low competitive groups based on their scores on the Sport Orientation Questionnaire. All subjects completed a modified version of the Competitive State Anxiety Inventory-2 30 minutes prior to competition. This inventory included the original intensity scale plus a direction scale on which subjects rated the extent the experienced intensity of each symptom was either facilitative or debilitative to subsequent performance. There were no significant group differences on intensity of cognitive anxiety or of somatic anxiety or on direction of somatic anxiety; however, the highly competitive group of 34 subjects reported their anxiety as more facilitative and less debilitative than the low competitive group (n = 35). This supports the proposal that sports performers' directional perceptions of their anxiety symptoms may provide further understanding of the competitive state-anxiety response.

Adult↗
PubMed1992

Further metabolism of 1 alpha,25-dihydroxyvitamin D3 in target cells.

Calcitriol-inducible C-24 oxidation in target cells gives rise to calcitroic acid in a variety of cells. The pathway probably involves a transient C23-aldehyde intermediate. The pathway appears to play a crucial role in the duration of the 1,25-(OH)2D3 signal in target cells. New analogs can be designed to render the molecule more susceptible or more resistant to target cell catabolism. However, these changes do not guarantee survival of the drug due to alternative degradatory pathways.

Animals↗
PubMed1992

Postconcussion symptoms and daily stress in normal and head-injured college populations.

The postconcussion syndrome is a term invoked to describe a constellation of cognitive (decreased memory and concentration), emotional (increased irritability and nervousness or anxiety), and physical (increased headaches and dizziness) changes that are commonly reported following minor or severe head injuries. The first section presents the development and validation of the Postconcussion Syndrome Checklist. The second section describes the daily changes in symptom reports as a function of daily stress levels. A population of head-injured subjects and controls monitored postconcussion symptoms and stress across a 6-week period. The frequency, intensity, and duration of symptoms reported were correlated with daily stress levels as measured by the Daily Stress Inventory for both groups. Yet, the number of symptoms reported by our head-injured group did not vary significantly from the normal subjects. The data support models which predict that postconcussion syndrome varies with stress, but the evidence for a reduction in the cerebral reserve capacity after head injury was not supported with this population. Explanations for this finding are presented and implications of this research and directions for future research are outlined.

Journal Article↗
PubMed1991

Rubella vaccination in pregnancy.

Ninety-two pregnancies complicated by rubella vaccination were reported to the Rubella Vaccination in Pregnancy Study between 1981 and 1990. These pregnancies resulted in 87 live births, 3 stillbirths and two spontaneous abortions. One infant had serological evidence of congenital rubella infection but was healthy and normal with no indication of rubella damage at the age of two and half years. These findings suggest that the risk of rubella-associated damage following inadvertent rubella vaccination in pregnancy or shortly before is low, and support the current advice that termination of pregnancy should not be routinely recommended in these circumstances.

Antibodies, Viral↗