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Biomedical subjects

T L Clemens

Publications and source records attributed to T L Clemens.

At least 73 records · Page 4Linked to original sources
PubMed1985

Detection and developmental changes of the 1,25-(OH)2-D3 receptor concentration in mouse skin and intestine.

We investigated [3H]1,25-dihydroxyvitamin D3-specific binding activity in fetal, neonatal, and adult mouse skin to determine (a) during which stage in development the skin develops the capacity to respond to this hormone and (b) whether the hormone binding activity changed during development and maturation. A macromolecule with properties similar to those of the chick intestinal 1,25-dihydroxyvitamin D3 receptor was detected in the skin and intestine of mouse pups at 17 days of fetal life. 1,25-Dihydroxyvitamin D3-specific binding activity from both tissues sedimented on linear sucrose gradients at 3.5-3.7S and eluted from DNA cellulose at 0.22 M KCl. At earlier stages of fetal life (12-14 days) receptor-like activity was detected in cytosols prepared from whole-mouse fetuses. 1,25-Dihydroxyvitamin D3-specific binding activity was quantitated in the skin and intestine throughout development using a chromatin binding assay. Scatchard analysis of saturation binding data showed that the concentration of binding activity in skin increased rapidly after birth and reached a maximum when the mice were 10-19 days old. By contrast, the binding activity that was detected in the fetal and neonatal whole intestine remained low until the mice were weaned. The affinity (Kd) of the binding activity was similar in skin and intestine at all ages studied. It is concluded that 1,25-dihydroxyvitamin D3-specific binding activity appears in both skin and intestine of the mouse prior to birth and increases in these two tissues during different stages in development.

Animals↗
PubMed1984

1 alpha,25-dihydroxyvitamin D3 induces maturation of the human monocyte cell line U937, and, in association with a factor from human T lymphocytes, augments production of the monokine, mononuclear cell factor.

The monocyte factor, interleukin 1, or other factors homologous with interleukin 1, modulates functions of a variety of cells, including T and B lymphocytes, synovial cells, and chondrocytes. We have reported that a human monocyte cell line, U937, produces interleukin 1 when incubated with a soluble factor from lectin-stimulated T lymphocytes. We have also shown that U937 cells have a specific cytosolic receptor for 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25[OH]2D3). We now report that 1 alpha,25(OH)2D3(10(-11)-10(-10) M) induces maturational changes in the U937 cells similar to those produced by conditioned medium from lectin-stimulated T lymphocytes (increase in Fc receptors and OKM1 binding and decrease in proliferation), but does not induce monokine production as measured by mononuclear cell factor activity. 1 alpha,25(OH)2D3 is 200-300-fold more effective than 25-hydroxyvitamin D3, which is consistent with the known biological potency of these vitamin D3 metabolites. 1 alpha,25(OH)2D3 and the lymphokine together markedly augment maturational effects and, in addition, augment monokine production. The specificity of the interaction is further demonstrated by the lack of augmentation of monokine production with 1 beta,25-dihydroxyvitamin D3 in the presence of lymphokine. These interactions of a classical hormone and the hormonelike product(s) of the immune system with U937 cells serve as a model for human monocyte/macrophage differentiation and suggest a role for these interactions in some aspects of inflammation.

Antigens, Surface↗
PubMed1984

Studies of the hypercalcaemia of sarcoidosis: effect of steroids and exogenous vitamin D3 on the circulating concentrations of 1,25-dihydroxy vitamin D3.

Hypercalcaemia in six patients with sarcoidosis was associated with elevated circulating 1,25-dihydroxy vitamin D3 (187-475 pmol/l): the concentration of this metabolite of vitamin D was a function of the concentration of its precursor, 25-hydroxy vitamin D which remained within the normal range. Corticosteroids, in reducing serum calcium, eliminated this abnormal substrate--product relationship by rapidly reducing circulating 1,25-dihydroxy vitamin D3 while having no effect on 25-hydroxy vitamin D. The fall in circulating 1,25-dihydroxy vitamin D3 preceded the fall of calcium. Studies on the clearance of exogenous 1,25-dihydroxy vitamin D3 indicated that during hypercalcaemic episodes, the plasma disappearance time of the sterol was delayed and that this reverted to normal with steroid therapy. Administration of vitamin D3 to these patients with sarcoidosis increased the circulating concentration of 1,25-dihydroxy vitamin D3 and this resulted in hypercalcaemia, thus accounting for their hypersensitivity to vitamin D and sunlight.

Adult↗
PubMed1983

A simple method for generation of antibodies with specificity for 1,25-dihydroxyergocalciferol and 1,25-dihydroxycholecalciferol.

A simple method for production of antisera with high affinity and selectivity for 1 alpha, 25-dihydroxyergocalciferol and 1 alpha, 25-dihydroxychole-calciferol is described. 1 alpha-Hydroxy-25,26,27-trisnorcholecalciferol-24-oic acid was coupled directly to bovine serum albumin. Rabbits immunized with this conjugate rapidly produced antibodies that bound 3H-1 alpha,-25-dihydroxycholecalciferol with high affinity and demonstrated nearly equal reactivity with 1 alpha, 25-dihydroxyergocalciferol and poor reactivity with 25-hydroxycholecalciferol; 24,25-dihydroxycholecalciferol; 25,26-dihydroxycholecalciferol; and 1 beta,25-dihydroxycholecalciferol. The use of one of these antisera has led to the development of a specific assay for 1 alpha,25-dihydroxyergocalciferol and 1 alpha,25-dihydroxycholecalciferol in human serum.

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

Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation.

Human peripheral blood monocytes have high affinity binding sites for 1,25-(OH)2D3 (Kd 0.14 nM, sedimentation coefficient 3.7S). Resting human peripheral blood T lymphocytes, however, do not have a demonstrable 1,25-(OH)2D3 receptor. After activation with phytohemagglutinin the T cells exhibit the receptor within 24 h, and this expression is blocked by cycloheximide. The receptor in activated T lymphocytes has a sedimentation coefficient of 3.7S and a high affinity (Kd 0.10 nM) for the ligand.

Calcitriol↗
PubMed1982

Measurement of circulating vitamin D in man.

An assay for vitamin D consisting of high-pressure liquid chromatography (HPLC) and ultraviolet (UV) absorbance detection has been developed and used to measure circulating vitamin D concentrations in human subjects during summer and winter and after deliberate exposure to ultraviolet radiation. Extracts of 2-4 ml of serum were initially fractionated on silica Sep-Pak cartridges followed by reverse-phase HPLC and finally quantitated by UV-absorbance during straight-phase HPLC. Using these methods, we determined the normal range for circulating vitamin D in Boston subjects to be less than 0.5 ng/ml to 25 ng/ml (n = 30); subjects sampled during summer months had higher concentrations of vitamin D than those sampled during winter months. In subjects exposed to a single quantitative dose of ultraviolet radiation (UVR), large transient increases in circulating vitamin D3 were observed. Concentrations rose 30-50 fold over the first days after exposure before returning to basal levels by one week.

Adult↗
PubMed1982

Increased skin pigment reduces the capacity of skin to synthesise vitamin D3.

To determine the effect of increased skin pigment on the cutaneous production of vitamin D3, circulating vitamin D concentrations were determined in two lightly pigmented Caucasian and three heavily pigmented Negro volunteers after exposure to a single standard dose of ultraviolet radiation (UVR). Exposure of Caucasian subjects to 1 minimal erythemal dose of UVR greatly increased serum vitamin-D concentrations by up to 60-fold 24-48 h after exposure, whereas this dose did not significantly change serum vitamin-D concentrations in Negro subjects. Re-exposure of one Negro subject to a dose of UVR six times larger than the standard dose increased circulating vitamin D to concentrations similar to those recorded in Caucasian subjects after exposure to the lower dose. These results indicate that increased skin pigment can greatly reduce the UVR-mediated synthesis of vitamin D.

Black People↗
PubMed1982

Regulation of calcium absorption by 1,25,dihydroxy-vitamin D--studies of the effects of a bisphosphonate treatment.

In 10 patients with Paget's disease of bone and 2 patients with osteoporosis, we studied the effects of hypocalcemia and hypophosphatemia induced by disodium-(3-amino-1-hydroxypropylidene)-1,-bisphosphonate (APD) treatment on the serum concentration of PTH and 1,25-dihydroxy-vitamin D [1,25(OH)2D3] and on calcium absorption and balance. The fall in serum calcium and phosphate was associated with a rise in the serum concentration of PTH and 1,25(OH)2D3, coupled with increases in net calcium absorption and calcium balance. The concentration of 1,25(OH)2D3 was significantly related (P less than 0.001) to the serum calcium (r = 0.66), the serum phosphate (r = 0.78), and the serum PTH (r = 0.71), confirming the interrelated control of these parameters on 1,25(OH)2D3 production. Moreover the rise in 1,25(OH)2D3 caused an appropriate rise in calcium absorption (r = 0.74) and calcium balance (r = 0.86), showing that this vitamin D metabolite contributes as a hormone to calcium homeostasis.

Aged↗
PubMed1982

Chronic acidosis with metabolic bone disease. Effect of alkali on bone morphology and vitamin D metabolism.

Chronic metabolic acidosis and osteomalacia developed in two patients following urinary diversion. Good clinical, biochemical, and histologic responses were seen following treatment with alkali alone (vitamin D was not given), despite the presence of markedly impaired glomerular filtration in one of the patients. Plasma 25-hydroxyvitamin D and 1 alpha, 25-dihydroxyvitamin D concentrations were normal before and during treatment in one of the patients and in the other were low before and normal during treatment. The results show that successful treatment of the osteomalacia of chronic acidosis is not necessarily accompanied by changes in the plasma levels of vitamin D metabolites and that even when marked glomerular dysfunction coexists with acidosis and osteomalacia, treatment with alkali may be more appropriate than the administration of vitamin D analogues.

Acidosis↗
PubMed1982

The effect of renal function on changes in circulating concentrations of 1,25-dihydroxycholecalciferol after an oral dose.

1. 1,25- Dihydroxycholecalciferol [1,25-(OH)2D3] was administered orally to four normal subjects and six patients with chronic renal failure not on dialysis. The serum concentration of 1,25-(OH)2D3 was measured by radioimmunoassay in both groups from samples taken before, and at regular intervals up to 48 h after, the oral dose. 2. The plasma half-time for the disappearance of the administered 1,25-(OH)2D3 was estimated by determining the time for a 50% reduction from the peak increment of the sterol. In normal subjects the calculated value ranged from 5 to 8 h compared with 18 to 44 h in uraemic patients. 3. It appears from our studies that in uraemic subjects there is impaired ability to metabolize or excrete 1,25-(OH)2D3.

Adult↗
PubMed1982

Demonstration of circulating 1,24,25-trihydroxyvitamin D3 in man by radioimmunoassay.

1,24,25-trihydroxyvitamin D3 has been detected in human serum using a sensitive radioimmunoassay. Tritiated 1,24,25-trihydroxyvitamin D3 was synthesized biologically and used as tracer to monitor the recovery of endogenous metabolite during isolation from serum. Circulating 1,24,25(OH)3D3 in normal subjects ranged from 9.3 to 18.5 pmol/l but was not detectable (less than 2.3 pmol/l) in serum from nephrectomized subjects. The trihydroxymetabolite was elevated in three out of four vitamin D deficient subjects who were being treated with vitamin D3.

Cholecalciferol↗