Gene/Protein Disease Symptom Drug Enzyme Compound
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Serum 25-hydroxycholecalciferol (25[OH]D3) levels and other parameters of vitamin D nutriture were examined in 58 subjects aged 70 or more, living in Jerusalem. They were compared with those of 54 young adults living in the same neighbourhood. No evidence was obtained of a lower level of vitamin D nutriture in the elderly compared to younger adults. Serum 25 (OH)D3 of the elderly adults was 18.4 (SEM: 1.4) ng/ml and in the younger adults, 17.8 (1.0) ng/ml. There was no seasonal variation in serum 25(OH)D3, nor could a strong association be found between reported vitamin D intake nor with exposure to sunshine. There was a negative correlation between serum alkaline phosphatase and the calcium-phosphorus product in serum. High values of alkaline phosphatase were associated with reported low exposure to sunlight and, in elderly persons, with a reported low consumption of vitamin D.
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PMID:Biochemical parameters of vitamin D nutriture in old people in Jerusalem. 42 85

The mean +/- SEM of the cord, 48-hr, and 7-day values for serum calcium, magnesium, human calcitonin (HCT), parathyroid hormone (PTH), and 25-hydroxy-vitamin D (25-OHD) for premature and term infants can be seen in Table 1. Mean cord calcium concentrations were similar for term and premature infants. Serum calcium concentrations fell in both term and premature infants at 48 hr, but decreased more in the premature infants (from 10.23 +/- 0.30 to 8.74 +/- 0.19 mg/dl) than in the term infants (from 10.5 +/- 0.26 to 9.6 +/- 0.23 mg/dl). Serum calcium values increased from 48 hr to 7 days in both groups, and there was no significant difference between term and premature infants' serum calcium concentrations (10.6 +/- 0.28 and 10.12 +/- 0.3 mg/dl, respectively) at that time. There was no significant difference between term and premature cord serum magnesium concentrations. Serum magnesium concentrations increased similarly by 48 hr in both groups and remained at these concentrations at 7 days of life. Serum HCT concentrations were elevated above normal adult levels (71.9 +/- 6.6 pg/ml, 81% less than 100 pg/ml, n = 63) in both premature and term cord sera, but premature cord concentrations (146 +/- 24 pg/ml) were significantly higher than term cord concentration (91 +/- 21 pg/ml). Both term and premature infants displayed a 2-3-fold increase in serum HCT by 48 hr and a partial fall by 7 days to concentrations still above those seen in cord sera (Fig. 1). Nine of 10 premature and 9 of 10 term infants had undetectable PTH concentrations in cord sera. In two premature infants, PTH serum concenttration remained undetectable at 48 hr. However, the majority of both premature and term infants had elevated levels of PTH at 48 hr. The mean PTH concentrations were lower but still elevated at 7 days with the suggestion of higher concentrations in premature infants (Fig 2). There were no significant differences in serum 25-OHD concentrations between term and premature sera at birth or at 7 days. There was a weakly positive correlation between 25-OHD and cord calcium (r = 0.45, P less than 0.05), and a negative correlation between cord calcium and 48-hr PTH (r = -0.53, P less than 0.01). Calcium and magnesium were significantly positively correlated in 48-hr (r = 0.83) and 7-day (r = 0.84) sera in premature infants but not in term infants. Cord 25-OHD and cord HCT levels were significantly positively correlated (r = 0.80, P less than 0.01) in the term infants but not the premature infants.
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PMID:Serial measurements of serum calcium, magnesium, parathyroid hormone, calcitonin, and 25-hydroxy-vitamin D in premature and term infants during the first week of life. 86 19

Fractional intestinal absorption of calcium was measured in 41 haemodialysed patients 4 hours after an oral dose of 47 Ca. Fractional intestinal calcium absorption was 40.3 +/- 1.9% (SEM) when measured 10 to 12 hours after a haemodialysis session (dialysate calcium concentration: 1.75 mmol/litre). This value was significantly lower (p less than 0.001) than that in 26 healthy controls (56.8 +/- 1.8%) and higher (p less than 0.05) than that of 35 patients with chronic renal failure treated conservatively (34.5 +/- 2.1%). In 17 patients, fractional intestinal calcium absorption was measured just before and just after a dialysis session. Pre-dialysis fractional intestinal calcium absorption (33.7 +/- 3.0%) was not significantly different from fractional intestinal calcium absorption in uraemic patients treated conservatively, while after dialysis fractional intestinal calcium absorption had increased significantly to 42.0 +/- 2.6% (p less than 0.001). It is suggested that the transient increase in fractional intestinal calcium absorption observed after dialysis could be related to dialysis induced volume depletion rather than to a vitamin D-dependent mechanism.
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PMID:Effects of haemodialysis on fractional intestinal absorption of calcium in uraemia. 93 48

A radioimmunoassay for the binding protein for vitamin D and its metabolites (DBP) has been developed. Suitable rabbit anti-DBP antiserum was elicited after primary and one booster injection. Anti-DBP antisera, as well as antigroup-specific component antisera, produced a single, monospecific line of percipitation when reacted against purified DBP and human serum. DBP was iodinated with 125I and 125I-DBP was purified by gel filtration on Sephadex G-200. Binding of 125I-DBP by 20 nl of rabbit anti-DBP antisera was approximately 50% and was sharply competed for by 0.4-4.0 ng of DBP standard. Displacement of 125I-DBP by human serum dilutions or standard DBP gave identical curves, and only weak competition was observed with old and new world primate sera. Apo- and holo-DBP possessed indistinguishable immunoreactivity. The assay detects DBP in 1-10 nl of human serum with reasonable accuracy and with reasonable intra- and interassay precision. The mean serum concentration (+/- SEM) for a group of 40 normal adults was 525 +/- 24 mug/ml and no sex difference was observed. Higher levels were found in sera from pregnant women and women receiving oral contraceptives, and decreased concentrations were observed in premature cord and hypoproteinemic sera. No significant correlation between serum DBP levels and serum 25-hydroxycalciferol levels was found, and the DBP content of sera from vitamin D-deprived and vitamin D-treated subjects was indistinguishable from that of normal adults. DBP accounts for 6- of the alpha globulin in normal human serum. Considering the normal serum content of the parent vitamin and its metabolites to be approximately 0.1-0.2 mum, these immunoassay data confirm previous saturation analyses of human serum antiricketic sterol-binding capacity and suggest that greater than 95% of DBP circulates as the apoprotein under normal conditions.
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PMID:Radioimmunoassay of the binding protein for vitamin D and its metabolites in human serum: concentrations in normal subjects and patients with disorders of mineral homeostasis. 108 57

The mechanism for the transfer of fat-soluble vitamin D3 from the avascular basal cellular layers of the epidermis to dermal capillaries and peripheral circulation is unknown, although vitamin D-binding protein (DBP) is thought to mediate this process. To evaluate the effect of increased occupancy of vitamin D carrier(s) on vitamin D3 removal from the skin, serial serum vitamin D2 and D3 concentrations were determined in three groups of six healthy volunteers given combinations of an oral dose of vitamin D2 (50,000 IU) and a fixed dose of UVB radiation (27 mJ/cm2). Serum vitamin D3 levels increased significantly following UVB (time effect, P < .01 by ANOVA), but the response remained unchanged after pretreatment with vitamin D2, increasing from 3 +/- 1 to 14 +/- 5 ng/mL (mean +/- SEM), versus UVB alone, 5 +/- 1 to 16 +/- 5 ng/mL. Elevation of serum vitamin D2 levels was also similar in the groups given vitamin D2 alone (< 1 to 64 +/- 8 ng/mL) and vitamin D2 + UVB (< 1 to 45 +/- 8 ng/mL). There was no time or treatment effect for changes in serum levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, or (DBP) levels (P > .1). We conclude that vitamin D3 egress from the skin is not affected by elevated circulating vitamin D concentrations; thus, the cutaneous release of vitamin D is probably mediated by a protein such as DBP with a high carrying capacity for the vitamin.
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PMID:Elevation of blood vitamin D2 levels does not impede the release of vitamin D3 from the skin. 133 3

The most active metabolite of vitamin D is 1,25-dihydroxyvitamin D [1,25(OH)2D]. Its level in the bone may play a role in the pathogenesis of metabolic bone diseases such as osteoporosis. To assess this, and to see whether there is correlation between serum and bone levels, we studied serum and bone samples taken from 43 patients (18 men and 25 women) undergoing different orthopedic procedures. Patients were studied according to sex and age groups (less than 45 years, 46-60 years, greater than 61 years). Serum level of 1,25(OH)2D was found to be 29.7 +/- 2.61 pg/ml (mean +/- SEM) for women, 32.2 +/- 3.86 pg/ml for men, and 30.7 +/- 2.18 pg/ml for the group as a whole. No significant statistical differences were found among age subgroups in either sex or between sexes. Bone level of 1,25(OH)2D was found to be 31.5 +/- 4.46 pg/g for women, 26.5 +/- 3.06 pg/g for men, and 29.4 +/- 2.81 pg/g for the entire group. No significant statistical difference was found between the age subgroups for men. However, the level of 1,25(OH)2D was found to be higher in the group of younger women (less than 45 years) compared with the older women (46-60 years and greater than 61 years) (P less than 0.005).
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PMID:Decrease in bone level of 1,25-dihydroxyvitamin D in women over 45 years old. 139 72

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.
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PMID:Normal 24-hydroxylation of vitamin D metabolites in patients with vitamin D-dependency rickets type I. Structural implications for the vitamin D hydroxylases. 154 47

This study was undertaken to evaluate the effects of dietary K intake, independent of whether the accompanying anion is Cl- or HCO3-, on urinary Ca excretion in healthy adults. The effects of KCl, KHCO3, NaCl and NaHCO3 supplements, 90 mmol/day for four days, were compared in ten subjects fed normal constant diets. Using synthetic diets, the effects of dietary KCl-deprivation for five days followed by recovery were assessed in four subjects and of KHCO3-deprivation for five days followed by recovery were assessed in four subjects. On the fourth day of salt administration, daily urinary Ca excretion and fasting UCa V/GFR were lower during the administration of KCl than during NaCl supplements (delta = -1.11 +/- 0.28 SEM mmol/day; P less than 0.005 and -0.0077 +/- 0.0022 mmol/liter GFR; P less than 0.01), and lower during KHCO3 than during control (-1.26 +/- 0.29 mmol/day; P less than 0.005 and -0.0069 +/- 0.0019 mmol/liter GFR; P = 0.005). Both dietary KCl and KHCO3 deprivation (mean reduction in dietary K intake -67 +/- 8 mmol/day) were accompanied by an increase in daily urinary Ca excretion and fasting UCaV/GFR that averaged on the fifth day +1.31 +/- 0.25 mmol/day (P less than 0.005) and +0.0069 +/- 0.0012 mmol/liter GFR (P less than 0.005) above control. Both daily urinary Ca excretion and fasting UCaV/GFR returned toward or to control at the end of recovery. These observations indicate that: 1) KHCO3 decreases fasting and 24-hour urinary Ca excretion; 2) KCl nor NaHCO3, unlike NaCl, do not increase fasting or 24-hour Ca excretion and 3) K deprivation increases both fasting and 24-hour urinary Ca excretion whether the accompanying anion is Cl- or HCO3-. The mechanisms for this effect of K may be mediated by: 1) alterations in ECF volume, since transient increases in urinary Na and Cl excretion and weight loss accompanied KCl or KHCO3 administration, while persistent reductions in urinary Na and Cl excretion and a trend for weight gain accompanied K deprivation; 2) K mediated alterations in renal tubular phosphate transport and renal synthesis of 1.25-(OH)2-vitamin D, since KCl or KHCO3 administration tended to be accompanied by a rise in fasting serum PO4 and TmPO4 and a fall in fasting UPO4 V/GFR, a fall in serum 1,25-(OH)2-D and a decrease in fasting UCa V/GFR, while dietary KCl or KHCO3 deprivation were accompanied by a reverse sequence.
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PMID:Potassium administration reduces and potassium deprivation increases urinary calcium excretion in healthy adults [corrected]. 164 46

Progressive systemic sclerosis (PSS) is a predominantly dermal disorder which may be associated with epidermal atrophy. We investigated epidermal function in 8 patients with PSS and their healthy controls matched for age, sex and racial group. We measured the vitamin D3 photosynthetic response to whole body irradiation with ultraviolet light B (UVB). There were no significant differences in basal serum vitamin D3 levels (mean +/- SEM: PSS 1.2 +/- 0.2 ng/ml; controls 0.8 +/- 0.1 ng/ml; p greater than 0.1) or post UVB blood values (PSS 5.2 +/- 1.4 ng/ml; controls 6.9 +/- 1.1 ng/ml; p greater than 0.1); although the increases post-UVB were significant in both groups (p less than 0.01). In an additional group of 19 patients with PSS and their corresponding matched healthy controls, we performed determination of random levels of the active vitamin D metabolites, 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D [1,25-(OH)2-D]. Similar levels were observed in both groups: 25-OH-D PSS 28 +/- 3 ng/ml, controls 29 +/- 3 ng/ml; 1,25-(OH)2-D PSS 27 +/- 2 pg/ml, controls 31 +/- 2 pg/ml (p greater than 0.1). None of the correlations between skin area involved and vitamin D3 formation or active circulating metabolites reached statistical significance (p greater than 0.1). We conclude that global epidermal synthesis of vitamin D is retained in PSS and, that the hepatic and renal vitamin D hydroxylating mechanisms function normally in that condition.
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PMID:Cutaneous vitamin D3 formation in progressive systemic sclerosis. 165 23

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.
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PMID:Serum erythropoietin and erythropoiesis in primary and secondary hyperparathyroidism: effect of parathyroidectomy. 175 26


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