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S Dokoh

Publications and source records attributed to S Dokoh.

At least 37 records · Page 2Linked to original sources
PubMed1985

Serum 1,25-dihydroxyvitamin D concentrations in premature infants: preliminary results.

Serum 1,25(OH)2D concentrations were measured in serial serum samples from 19 premature infants of 29.6 +/- 1.3 weeks gestation and 1,129 +/- 159 g birthweight. 1,25(OH)2D was always normal or elevated and mean concentrations increased with age (adult, 55.2 +/- 13; infants, 1-2 weeks, 81.5 +/- 37.7 pg/mg; 3 weeks, 65 +/- 21; 6 weeks, 90.0 +/- 17.3; 9 weeks, 99.0 +/- 25.1; 12 weeks, 103.3 +/- 26.6 pg/ml). No correlation was seen with 25-OHD. Infants given 800 IU D2 supplements had lower 1,25(OH)2D levels than infants given 400 IU D2. Breast fed infants had initially higher 1,25(OH)2D levels; however, this was not sustained. These preliminary data suggest that premature infants regulate 1,25(OH)2D production similar to more mature infants and children. Whether the premature infant has a normal gastrointestinal and/or bone responsiveness to 1,25(OH)2D and whether these elevated 1,25(OH)2D concentrations are "adequately elevated" requires further study.

Age Factors↗
PubMed1985

Vitamin D metabolites in adolescents and young adults with cystic fibrosis: effects of sun and season.

To assess mineral metabolism in patients with cystic fibrosis and to study the effects of season and sunlight exposure on generation of vitamin D metabolites, we quantified serum levels of calcidiol and calcitriol, other measures of bone metabolism, and radiographic bone mass in 20 adolescents and young adults with CF and 20 age-matched normal volunteers. Levels of calcidiol were lower in patients with CF than in controls and lower in Massachusetts than in Arizona in both study groups. Controls in Arizona had higher (P less than 0.05) levels of calcitriol than in Massachusetts throughout the year. All control subjects in both states had higher levels of calcitriol than did patients with CF. Patients in Massachusetts had significantly lower levels of calcitriol in winter than in summer. Summer levels of calcitriol in CF were significantly higher in Massachusetts than in Arizona; during winter, lower levels were found in Massachusetts than in Arizona. Mean bone density in patients with CF was 88% and 89% of normal American standards in Massachusetts and Arizona, respectively. These data indicate a seasonal, sunlight-related influence on levels of vitamin D metabolites in patients with CF receiving approximately 1000 IU vitamin D per day. Older patients with CF with progressively diminishing sunlight exposure may be at increased risk for development of osteopenia. The detected radiographic abnormalities of bone mineralization may also be related to malabsorptive deficiencies of calcium and phosphorus.

25-Hydroxyvitamin D 2↗
PubMed1985

Identification of 1,24(R)-dihydroxyvitamin D3-like bone-resorbing lipid in a patient with cancer-associated hypercalcemia.

A lipid indistinguishable from 1,24(R)-dihydroxyvitamin D3 [1,24(R)-(OH)2D3] was found in serum and tumor extracts from a hypercalcemic patient with a small cell carcinoma of the lung. The lipid comigrated with authentic 1,24(R)-(OH)2D3 on high performance liquid chromatography using both straight and reverse phase columns and competed with tritiated 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3)] for binding to intestinal 1,25-(OH)2D3 receptor. Increasing doses of the lipid factor from tumor and authentic 1,24(R)-(OH)2D3 gave parallel responses in a bone resorption assay, as assessed by 45Ca release from prelabeled mouse calvaria. The lipid factor from the patient's serum and authentic 1,24(R)-(OH)2D3 had identical biological activities in the receptor binding and bone resorption assays. In addition, the mechanisms of action of this lipid factor and 1,24(R)-(OH)2D3 were indistinguishable. Bone resorption by both was inhibited by calcitonin, and neither the lipid factor nor authentic 1,24(R)-(OH)2D3 affected cAMP content in osteoblast-like bone cells derived from mouse calvaria. The estimated concentrations of the 1,24(R)-(OH)2D3-like lipid, expressed as 1,24(R)-(OH)2D3 were 11 ng/g tumor wet wt by the receptor binding assay and 9.2 ng/g tumor wet wt by the bone resorption assay. The mean serum concentration was 1.4 +/- 0.3 (+/- SD) ng/ml (n = 3) by the receptor binding assay. No activity was detected in either bioassay when extracts of nontumor tissues from this patient or tumor extracts and sera from one hypercalcemic and four normocalcemic cancer patients were tested. The mean serum 1,25-(OH)2D level was low (6.4 +/- 0.5 pg/ml; n = 2), and serum 1,24(R),25-(OH)3D in this patient was high (103 pg/ml) compared to normocalcemic cancer patients, in whom the mean serum 1,25-(OH)2D level was 27 +/- 12 pg/ml (n = 4) and the 1,24(R),25(OH)3D level was 28 +/- 1.3 pg/ml (n = 4). Thus, the 1,24(R)-(OH)2D3-like lipid may be a substrate for metabolic conversion to 1,24(R),25-(OH)3D in vivo. These results provide evidence for the presence of a novel metabolite of vitamin D3, 1,24(R)-(OH)2D3. Detection of this bone-resorbing lipid in both tumor and serum suggests, but does not prove, that the tumor secreted this bioactive lipid into the circulation and that the high level of circulating bone-resorbing lipid was related to the hypercalcemia in this patient.

Animals↗
PubMed1984

Development of a radioligand immunoassay for 1,25-dihydroxycholecalciferol receptors utilizing monoclonal antibody.

A radioligand immunoassay for 1,25-dihydroxycholecalciferol [1,25(OH)2D3] receptors was developed utilizing a specific, high-affinity (Kd = 1.8 X 10(-11 M) monoclonal antibody (9A7 gamma) obtained from suspension cultures of rat spleen X mouse myeloma hybrid SP2/0-9A7. A standard curve was established, based on the competition between 1,25(OH)2[3H]D3-receptor (18 fmol/tube) and increasing concentrations of radioinert 1,25(OH)2D3-receptor (0-240 fmol/tube) for the binding site on 9A7 gamma. Samples, prepared in identical buffer, contained 0-100 fmol of receptor/tube. After an equilibrium incubation of 1,25(OH)2[3H]D3-receptor with either standard or sample (16 h at 4 degrees C), antibody-bound receptor was immunoprecipitated with rabbit anti-(rat immunoglobulin) prelinked to Staphylococcus aureus and quantified. The assay is statistically sensitive to 2 fmol of receptor/tube, with intra- and inter-assay variations of 7 and 12% respectively. Occupied, unoccupied and denatured receptor were observed to compete equally in the assay. This quantitative technique has been successfully applied to the characterization of receptors after fractionation by sedimentation analysis and DNA-cellulose chromatography. Finally, the measurement of total receptor by this assay, in conjunction with 1,25(OH)2D3 binding assays, has revealed that rachitic, normal and 1,25(OH)2D3-injected chicks have respectively 13, 20, and 56% of receptor in the occupied form. From these results we consider that this radioligand immunoassay will be a useful tool in further research focusing on quantifying 1,25(OH)2D3 receptors in tissue and cell extracts.

Animals↗
PubMed1984

Vitamin D3--resistant fibroblasts have immunoassayable 1,25-dihydroxyvitamin D3 receptors.

Cultured fibroblasts obtained from patients with tissue resistance to 1,25-dihydroxyvitamin D3 (vitamin D3--dependent rickets, type II) contain normal, low, or undetectable concentrations of this hormone's receptor protein as measured by a ligand-binding assay. Extracts from these cells were evaluated for receptors by immunoassay with a recently developed monoclonal antibody to the chick receptor. The results show that a protein sedimenting at 3.7S and recognizable by the antibody exists in comparable concentrations in cells from both normal and resistant patients, irrespective of the hormone-binding abnormalities of the cells. This implies that deficiencies in hormone binding associated with inherited tissue resistance to 1,25-dihydroxyvitamin D3 probably arise from structural variations in the receptor molecule and not from defective receptor synthesis.

Antibodies, Monoclonal↗
PubMed1984

Hypercalcemia in coccidioidomycosis.

Two patients with disseminated coccidioidomycosis and hypercalcemia are presented. One patient studied showed normal levels of 25-hydroxyvitamin D with depressed levels of 1 alpha,25-dihydroxyvitamin D. The serum calcitonin level was appropriate for the level of serum calcium, and the serum parathyroid hormone level was suppressed with elevation of the nephrogenous cAMP level. Intestinal absorption of calcium was elevated at 63 percent. Hypercalcemia and hypercalciuria persisted despite a 300 mg calcium diet. An osteotropic substance similar to the humoral hypercalcemia of malignancy is postulated.

25-Hydroxyvitamin D 2↗
PubMed1984

Phosphorus administration in patients with profound hypophosphatemia.

The influence of severe hypophosphatemia (less than or equal to 1.0 mg/dl) on vitamin D metabolism was prospectively determined in 11 patients before and after intravenous phosphorus administration. Evidence of liver dysfunction was present in ten patients. The mean (+/- SE) plasma 25 hydroxycholecalciferol [25(OH)D] was significantly decreased before phosphorus therapy when compared to control subjects (9.4 +/- 1.3 vs. 17.8 +/- 1.3 ng/ml, P less than 0.001). With phosphorus administration, serum phosphorus increased from 0.59 +/- 0.07 to 2.58 +/- 0.09 mg/dl while 1,25 dihydroxycholecalciferol [1,25(OH)2D] decreased from 34.6 +/- 4.3 to 14.3 +/- 2.9 pg/ml (P less than 0.001). Plasma 25(OH)D, plasma immunoreactive PTH (both amino and carboxyterminal) and serum calcium did not change after phosphorus administration, suggesting that phosphorus alone was responsible for the change in plasma 1,25(OH)2D concentration. An inverse correlation was found between serum phosphorus and plasma 1,25(OH)2D (r = -0.62, P less than 0.005). In addition, a direct correlation was observed between plasma 25(OH)D and 1,25(OH)2D both before (r = 0.66, P less than 0.005) and after (r = 0.74, P less than 0.005) phosphorus administration. Thus, the decrease in 1,25(OH)2D levels with phosphorus therapy suggests a role of serum phosphate in the regulation of this sterol, and hypophosphatemia or phosphorus depletion may change the relationship of substrate [25(OH)D] to product [1,25(OH)2D].

Adult↗
PubMed1984

Influence of 1,25-dihydroxyvitamin D3 on cultured osteogenic sarcoma cells: correlation with the 1,25-dihydroxyvitamin D3 receptor.

We have characterized the effects of the steroid hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on a series of rat osteogenic sarcoma cell lines of increasing osteoblastic-like nature (ROS 24/1, ROS 2/3, and ROS 17/2.8). When these cells were grown in monolayer culture in the presence of 10 nM 1,25-(OH)2D3, there was a dramatic and selective inhibition of proliferation in the ROS 17/2.8 line. Similar concentrations of other vitamin D metabolites did not elicit this effect. Furthermore, the aggregated cuboidal ROS 17/2.8 cells showed a marked change after 6 days of treatment with 10 nM 1,25-(OH)2D3 to an apparently less transformed spindle-like morphology. In contrast, ROS 2/3 displayed only a slight morphological alteration, and ROS 24/1 was unchanged by treatment with 1,25-(OH)2D3. Anchorage-independent growth studies performed in soft agar indicated that 1,25-(OH)2D3 inhibited colony formation to the greatest degree in ROS 17/2.8, with a lesser effect in ROS 2/3. Based upon analyses by sucrose gradient centrifugation, DNA cellulose chromatography, and saturation of specific binding, the level of the 1,25-(OH)2D3 receptor was quantitated in these cells. ROS 17/2.8 cells possess 18,000 copies of the receptor per cell, while ROS 2/3 contains only 500 binding sites per cell, and no detectable high-affinity 1,25-(OH)2D3 receptor is found in ROS 24/1. The receptor in ROS cells is indistinguishable from other mammalian 1,25-(OH)2D3 receptors in that it is a DNA-binding protein that sediments on sucrose gradients at 3.3S, and specifically binds the hormone with high affinity (Kd = 2 to 3 X 10(-11) M). Since the biological responses of these three cell lines to 1,25-(OH)2D3 exhibit a strong correlation with the respective number of receptor molecules per cell, we propose that the actions of this hormone are mediated by the specific 1,25-(OH)2D3 receptor.

Animals↗
PubMed1983

The ovary: a target organ for 1,25-dihydroxyvitamin D3.

Using both clonal Chinese hamster ovary (CHO) cells in culture and the hen ovary, we have searched for the presence of specific 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors. Receptor analyses were carried out on high salt cytosols of CHO cells and high salt extracts of hen ovarian nuclei that were originally isolated in low salt buffer. Both CHO and hen ovary contain a specific high affinity 1,25-(OH)2D3 receptor (Kd = 10(-10) - 10(-11) M), which sediments (3.3S) in high salt sucrose gradients identically to the chick intestinal receptor for 1,25-(OH)2D3. This 3.3S macromolecule from both sources absorbed to DNA-cellulose at 0.1 M KCl and eluted during a linear salt gradient at 0.2-0.22 M KCl, a property characteristic of the 1,25-(OH)2D3 receptor. Saturation analysis indicated that there are approximately 2000 copies of the receptor molecule per CHO cell. We also investigated the effect of 1,25-(OH)2D3 on ovarian cell growth in monolayer culture of CHO cells. Significant inhibition of CHO cell growth (up to 60%) was observed in the presence of physiological (100 pM) levels of 1,25-(OH)2D3 in the culture medium. This inhibition of growth was dose dependent and was accompanied by a parallel decrease in total cell protein. Concentrations of 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 as high as 1 nM did not affect CHO cell growth, indicating that, like receptor binding, cell proliferation is selectively influenced by 1,25-(OH)2D3 over other vitamin D metabolites. These data demonstrate that ovarian cells in mammals and birds possess the 1,25-(OH)2D3 receptor which may play a role in the effect of 1,25-(OH)2D3 on the growth of these cells in culture.

Animals↗
PubMed1982

[Studies on the measurement of vitamin D derivatives in human plasma. III. Plasma concentrations of vitamin D derivatives in various diseases (author's transl)].

Plasma concentrations of vitamin D3, 25-OH-D3, 24, 25(OH)2D3 and 1, 25(OH)2D3 were measured in patients with various diseases using the multiple assay system previously reported. In patients with hyperparathyroidism, the plasma levels of 1, 25(OH)2D3 tended to increase, while the levels of 24, 25(OH)2D3 tended to decrease in many cases. On the other hand, plasma 1, 25(OH)2D3 levels were low, while 24, 25(OH)2D3 levels were high in patients with hypoparathyroidism. No significant differences in the levels of plasma D3 derivatives among idiopathic-, postoperative- and pseudo- hypoparathyroidism were observed. In a majority of hemodialyzed patients with advanced renal failure who showed no overt bone changes on X-ray films, both the plasma 1, 25(OH)2D3 and 24, 25(OPH)2D3 levels were distributed from normal to very low. In a majority of patients with osteoporosis and hypoparathyroidism, plasma 1, 25(OH)2D3 levels rose quickly after the administration of 1 alpha-OH-D3. In hypophosphatemic vitamin D resistant rickets, however, the response to the relatively large amounts of 1 alpha-OH-D2 was poor, although the concentrations of plasma 24, 25(OH)2D3 were elevated by the 1 alpha-OH-D3 administration in most of these cases. The plasma 1, 25(OH)2D3 and 24, 25(OH)2D3 concentrations in patients with senile osteoporosis were distributed from lower to higher range than those of normal adults. There was a relatively good correlation between plasma levels of 25-OH-D3 and D3 only in cases with plasma D3 levels higher than 5 ng/ml. In addition, a hyperbolic regression curve was obtained between the plasma D3 and 25-OH-D3 ratio. These results may indicate that a possible negative feedback homeostatic mechanism exists between plasma levels of D3 and 25-OH-D3, but only with low plasma levels of D3.

Calcitriol↗
PubMed1981

[Studies on the measurement of vitamin D derivatives in human plasma. I. A competitive protein binding assay for 25-hydroxyvitamin D in plasma (author's transl)].

A simple and precise method has been developed for the determination of 25-hydroxyvitamin D in 1 ml of human plasma. The method consists of methanol/chloroform extraction, purification by high pressure liquid chromatography and a competitive protein binding assay using vitamin D deficient rat serum. The ethanol extract from vitamin D deficient chick serum was added to the sample before CPBA to eliminate the non-specific interference in the CPBA system as a vitamin D free serum extract. The assay was sensitive to 0.72 ng/ml of plasma. Satisfactory results were obtained in the dilution and recovery tests. The coefficients of variation were 5.8 approximately 9.1% for the within-assay, and 7.4 approximately 10.3% for the between-assay. Plasma concentrations of 25-hydroxyvitamin D in 46 samples of normal human plasma were 21 +/- 10.5 ng/ml (mean +/- SD), and the seasonal variation was demonstrated. Plasma levels for 25-hydroxyvitamin D were high in patients receiving vitamin D2 and low in patients suffering from liver cirrhosis.

25-Hydroxyvitamin D 2↗
PubMed1981

Adenylate cyclase activation and competitive binding with renal tissue using synthetic eel calcitonin analog and its fragments.

The structure-function relationship of calcitonin (CT) was investigated using a synthetic eel CT (E-CT) analog and its fragments. Adenylate cyclase activation and competitive binding to rat renal receptors were used as parameters of function. [Asu1,7]E-CT analog, synthesized by replacing the S-S bond of Cys1-Cys7 in the natural hormone with ethylene linkage of 1-amino suberic acid (Asu), and E-CT fragment 11-32 had about 1/5th and 1/50th the potencies of synthetic E-CT, respectively, in both adenylate cyclase activation and competitive inhibition of 125I-labeled [Asu1,7]iodo-E-CT binding on rat renal plasma membranes. The minimal chain length required to activate adenylate cyclase in rat renal plasma membranes was between 12-18 amino acids, and the minimal chain length required to affect the CT receptor binding was between 6-12 amino acids, near the C-terminus. Fragments, including the C-terminus, show a disproportionate and potent inhibition of the binding compared with the potency required for adenylate cyclase activation. Thus, the amino acid sequence near the C-terminus probably plays an important role in the binding of CT to the receptor. (Endocrinology 108: 698, 1981.)

Adenylyl Cyclases↗