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G Jones

Publications and source records attributed to G Jones.

At least 487 records · Page 27Linked to original sources
PubMed1983

The isolation and identification of two new metabolites of 25-hydroxyvitamin D3 produced in the kidney.

We have demonstrated in this paper the isolation and identification of two new metabolites of 25-hydroxy-vitamin D3 (25(OH)D3) from the kidney of the vitamin D-replete rat. These are 24-oxo-23(25-(OH)2D3 and 24,25,26,27-tetranor-23(OH)D3. Both compounds logically fit on the same metabolic pathway. 25(OH)D3 leads to 24(R),25-(OH)2D3 leads to 24-oxo-25(OH)D3 leads to 24-oxo-23,25-(OH)2D3 leads to leads to 24,25,26,27-tetranor-23(OH)D3 Each metabolite on this pathway was isolated and identified from kidneys perfused with pharmacological concentrations of 25(OH)D3. All metabolites were identified by techniques involving high performance liquid chromatography, UV spectrophotometry, and mass spectrometry. Use of 24(R),25-(OH)2D3 as the substrate gave rise to increased amounts of 24-oxo-25(OH)D3, 24-oxo-23,25-(OH)2D3, and 24,25,26,27-tetranor-23(OH)D3. In vitro studies involving perfusion of a vitamin D-replete kidney with 25(OH)D3 at a concentration of 25 nM suggest that 24-oxo-23,25-(OH)2D3 is also formed under physiological conditions. At this substrate concentration, 24(R),25-(OH)2D3 represented the major metabolite accumulating in the perfusate over the initial 2-h period but at subsequent times the concentration of 24-oxo-23,25-(OH)2D3 increased so that by the end of 6 h it was the major product remaining in the perfusate. Our work also suggests that the rate of synthesis of 25(OH)D3-26,23-lactone is measurable in the intact mammalian kidney but that it is slower than the synthesis of 24(R),25-(OH)2D3 and its metabolites.

Animals↗
PubMed1983

A & E in USA--OK?

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Ambulances↗
PubMed1983

Chromatographic separation of 24(R),25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3-26,23-lactone using a cyano-bonded phase packing.

A high-performance liquid chromatographic system is described for the baseline resolution of 25-hydroxyvitamin D3, 24(R),25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3-26,23-lactone, the three principal circulating metabolites of vitamin D3 in the vitamin D-replete animal. The system is based upon a cyano-bonded phase packing and the solvent hexane--isopropanol--methanol (94:5:1). Of particular interest is the strong retention of carbonyl-containing vitamin D metabolites. The new system can be used for unequivocal analysis of vitamin D metabolites in plasma samples from clinical and animal studies and in the separation and identification of renal metabolites generated in vitro.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Inhibition by vesicular stomatitis virus of herpes simplex virus-directed protein synthesis.

Infection of mammalian cells with either herpes simplex virus (HSV) or vesicular stomatitis virus (VSV) results in a marked inhibition of host protein synthesis. These viruses employ different mechanisms to turn off the host. In previous studies we showed that following infection with HSV, cellular mRNA was degraded and host polyribosomes were dissociated (Nishioka and Silverstein, Proc. Nat. Acad. Sci. USA 74, 2370-2374, 1977; Nishioka and Silverstein, J. Virol. 25, 422-426, 1978a). Degradation required synthesis of an HSV-specified polypeptide whereas dissociation appeared to be mediated by a heat-labile virion associated function (Nishioka and Silverstein, J. Virol. 27, 619-627, 1978b). In contrast, when cells are infected with VSV, host mRNAs are not degraded and polyribosome profiles are not drastically altered (Nishioka and Silverstein, 1978a). We have exploited the properties of these two viruses by infecting cells either simultaneously or sequentially in an effort to test our previous hypotheses. Analyses of the distribution of polyribosomes, stability of mRNA, synthesis of mRNA, and patterns of protein synthesis in coinfected cells permit us to conclude that dissociation of polyribosomes in cells infected with HSV results from expression of a virion associated function, degradation of cellular mRNA requires expression of the HSV genome, and VSV is dominant in doubly infected cells because it inhibits de novo transcription of the HSV genome.

Animals↗
PubMed1983

Cell and virus sensitivity studies with recombinant human alpha interferons.

The cell sensitivity of recombinant human alpha interferons (rIFN-alpha) of greater than 95% purity (A,D and the hybrid A/D) and crude nature (B and F) was studied in human (WISH, HeLa, AG1732), bovine (MDBK, BT), monkey (Vero), mouse (L), rabbit (RK-13), and hamster (BHK-21) cells. Based on an activity of 100% in WISH cells, the other cells responded to rIFN-alpha A as follows: AG1732 (90%), HeLa (94%), and MDBK and BT cells (170-190%). Rabbit, mouse, and hamster cells had a relative sensitivity of less than 1%. rIFN-alpha B and F were essentially equivalent to rIFN-alpha A in terms of cell sensitivity, but MDBK and BT cells were about 20 times more sensitive to rIFN-alpha D than were WISH cells and rIFN-alpha D was 1/5 to 1/10 as active on L cells as on WISH cells. The activity of the hybrid IFN A/D on bovine, mouse, and human cells was similar. The inhibitory dose50 (U/ml) of rIFN-alpha A, B, D, and F against virus infections in WISH cells were: vesicular stomatitis virus (1-4), rhinovirus types 1 and 42 (2-18), and herpes simplex virus (HSV) type 2 (45-70). Type 1 HSV, Semliki Forest (SFV) and encephalomyocarditis (EMC) viruses were tested against only rIFN-alpha A and D where SFV and EMC were the most sensitive to both IFNs (ID50-SFV, 0.2 U/ml, EMC, 1.2 U/ml) while 13 U/ml of rIFN-alpha A and D inhibited Type 1 HSV. The various rIFN-alpha s did not exhibit different antiviral spectra in vitro. When tested in mice rIFN-alpha A did not protect against infections with SFV, EMC, HSV, or influenza viruses. rIFN-alpha D and A/D protected mice infected with EMC, SFV, or HSV.

Animals↗
PubMed1983

Radioimmunoassay of 1,25-dihydroxy vitamin D2: studies on the metabolism of vitamin D2 in man.

A sensitive radioimmunoassay for 1,25-dihydroxy vitamin D2 was developed using a sheep antiserum which preferentially reacts with 1-hydroxylated forms of vitamin D. An improved isolation procedure was also developed using acetonitrile for the initial extraction of serum followed by chromatography on cartridges of C18 silica and high pressure liquid chromatography eluted with a ternary solvent system to separate 1,25-dihydroxy vitamin D2 and 1,25-dihydroxy vitamin D3. 25-hydroxy vitamin D2 and 25-hydroxy vitamin D3 were separated by further reverse phase high pressure liquid chromatography prior to competitive protein binding assay. The limits of detection were 4.3 pmol/1 (2.0 pg/ml) for the 1,25-dihydroxy metabolites and 1.25 nmol/1 (0.5 ng/ml) for both 25-hydroxy vitamin D2 and 25-hydroxy vitamin D3. 25-hydroxy vitamin D2 ranged from 2.0 to 11.3 nmol/1 (0.8-4.5 ng/ml) with a mean of 4.75 nmol/1 (1.9 ng/ml) in thirteen healthy British adults and this accounted for 9.0% of the mean total 25-hydroxy vitamin D. 1,25-dihydroxy vitamin D2 was detected in the sera of only one of these subjects whereas 1,25-dihydroxy vitamin D3 was present in all ranging from 48 to 163 pmol/1 (20-65 pg/ml) with a mean of 100 pmol/1 (42 pg/ml). Both 1,25-dihydroxy vitamin D2 and 1,25-dihydroxy vitamin D3 were detected in the sera of hypoparathyroid patients treated with vitamin D2 but the relationship between 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D was complex. For example, when an excess of 25-hydroxy vitamin D2 was present the serum concentration of 1,25-dihydroxy vitamin D3 was disproportionately high. Conversely, in patients who had previously been treated with vitamin D2 but were receiving only vitamin D3 at the time of study, the major 25-hydroxy metabolite was in the vitamin D3 form and there was a disproportionately high amount of 1,25-dihydroxy vitamin D2. Total 1,25-dihydroxy vitamin D ranged from 110 to 400 pmol/1 (45-165 pg/ml) and was above the upper limit of normal for 1,25-dihydroxy vitamin D3 in half of these hypoparathyroid patients treated with pharmacological doses of vitamin D.

25-Hydroxyvitamin D 2↗
PubMed1983

Stimulation of 24R,25-dihydroxyvitamin D3 synthesis by metabolites of vitamin D3.

Previously we have shown that the isolated perfused kidney from vitamin D-deficient rats converts [3H]25(OH)D3 into [3H]1 alpha,25(OH)2D3. When certain vitamin D metabolites were added to perfusate the same kidney began to synthesize [3H]24R,25(OH)2D3. In this study we investigated the structural requirements of the vitamin D molecule necessary to stimulate synthesis of [3H]24R,25(OH)2D3 in a 1-hydroxylating kidney. Kidneys were perfused with tracer [3H]25(OH)D3 (450 pM) alone and in the presence of a variety of hydroxylated metabolites and fluorinated analogues of vitamin D3 at concentrations of 450 pM to 25 microM. Tracer [3H]25(OH)D3 alone resulted in synthesis of only [3H]1 alpha,25(OH)2D3 during the 6-h perfusion period. 25-Hydroxylated metabolites [25(OH)D3, 25 nM; 1 alpha,25(OH)2D3, 25 nM; 24R,25(OH)2D3, 25 nM; 24(F)2,25(OH)D3, 50 nM] stimulated [3H]24R,25(OH)2D3 production at 2 h of perfusion. On the other hand, analogues without the 25-hydroxyl group [D3; 1 alpha(OH)D3; 25(F)D3; 1 alpha(OH),25(F)D3; 1 alpha(F)D3; 1 beta(F)D3]; did not stimulate [3H]24R,25(OH)2D3 synthesis. We conclude that the 25-hydroxyl group is an essential determinant of 24-hydroxylation.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Quantitative evaluation of fluorescein angiograms: microaneurysm counts.

This study describes a method for quantifying microaneurysms (MA) from fluorescein angiograms. The method was validated by the reproducibility of the number of MA in 30 angiograms read twice each by two independent observers; and by the absolute difference in MA counts between two readings by the same observer, and difference in numbers counted by two different observers. The precise location of each MA on two readings was also studied and the reproducibility of location varied from 60 to 71%, depending on the quality of the angiograms. Clinicians and technicians working in the same or in different centers obtained similar results. The coefficient of correlation between observers and between readings was satisfactory, r greater than 0.9. The method is easy to learn and the reproducibility allows for its use in clinical trials.

Aneurysm↗
PubMed1982

Inhibition by nonsteroidal antiinflammatory drugs of luminol-dependent human-granulocyte chemiluminescence and [3H]FMLP binding. Effect of sulindac sulfide, indomethacin metabolite, and optical enantiomers (+) and (-) MK830.

A system is described to evaluate for nonsteroidal antiinflammatory drugs by means of luminol-dependent human-granulocyte chemiluminescence (CL) is described. The CL is produced using either opsonized zymosan (yeast cells) or the soluble chemotactic peptide f-Met-Leu-Phe as the perturbant of the granulocyte membrane. Using either system, the following drug effects 2 x 10(-5) M were noted: only sulindac sulfide, and not sulindac sulfone or sulindac, displayed marked inhibition of chemiluminescence, following the in vivo data regarding inflammatory effects. The 5-OH indomethacin metabolite was likewise inactive as an inhibitor of CL mirroring in vivo effects. MK(+)410, MK(-)830 and MK835 all showed approximately 50% inhibition of CL, displaying deviation from in vivo data. MK(+)830 markedly stimulated CL, 4-6 times the control (without drug), which is clearly different from its enantiomer, MK(-)830. The reasons for this behavior are unclear. However, receptor binding studies with [3H]FMLP were accomplished in the presence and absence of the various drugs at 2 x 10(-5) M that were effective inhibitors of chemiluminescence (CL). Indomethacin, MK(-)830 and MK(+)410 had equivalent percent control binding and percent control CL. Sulindac sulfide and MK(+)835 both had higher percent control binding than percent control CL, with MK(+)835 displaying apparent increased numbers of available receptors relative to control. MK(+)830, which produces large increases in CL, produced a minor effect on percent control binding. A direct relationship between binding and CL does not exist with each drug. Chemiluminescence is dependent on ion movement and oxidative metabolism and is a secondary event to agonist-receptor occupation.

Anti-Inflammatory Agents↗
PubMed1982

Plasma vitamin D metabolite levels in phosphorus deficient rats during the development of vitamin D deficient rickets.

Plasma levels of the vitamin D metabolites were related to changes in bone morphology during the development of rickets in rats deprived of phosphorus and vitamin D. Weanling rats were studied at 1, 3, and 5 wk after onset of diets deficient in phosphorus or in both phosphorus and vitamin D. Bone histology and morphometry were carried out and measurements were made of 45Ca and 32P absorption, serum Ca and P, and plasma 25(OH)D3, 24,25(OH)2D3 and 1,25(OH)2D3. After 1 wk of vitamin D restriction, the plasma levels of 25(OH)D3 and 24,25(OH)2D3 were non-detectable (less than 0.5 and less than 0.8 ng/ml). The plasma 1,25(OH)2D3 level was elevated at 1 wk (105.5 pg/ml) and fell to 19 pg/ml by 5 wk. At 1 wk mild rachitic lesions in epiphyseal cartilage were observed despite the elevated 1,25(Oh)D3 level. Serum Ca and P levels and values for 45CA and 32P absorption decreased and the severity of the rickets increased with the fall in plasma levels of 1,25(OH)2D3. In Vitamin D replete, phosphate deficient rats the epiphyseal cartilage was normal throughout the 5 wk study period. Our results provide further evidence that physiological levels of 1,25 (OH)2 D3 will not prevent rickets without adequate plasma concentrations of either 25(OH)D3 or 24,25(OH)2D3.

Animals↗
PubMed1982

The biological activity of 25-hydroxycholecalciferol and 1,25--dihydroxycholecalciferol for rainbow trout (Salmo gairdneri).

Dietary 25-hydroxycholecalciferol (25-hydroxycholecalciferol (25-OH-D3) and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] showed vitamin D activity in rainbow trout. However, inclusion of dietary cholecalciferol (vitamin D3 or D3), ergocalciferol (vitamin D2 or D2), 25-OH-D3 or 1,25-(OH)2D3 did not result in the presence of detectable levels of vitamin D or 25-OH-D in the blood plasma of the fish. Fish fed the diet devoid of vitamin D over an extended period of time showed symptoms of a droopy-tail or "lordosis-like" syndrome that appeared to be related to muscle weakness since x-ray examination indicated no abnormality in vertebral development. The requirement for vitamin D as cholecalciferol was in excess of 1600 IU/kg diet and may be as high as, or higher than 2400 IU/kg diet.

Animals↗