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Biomedical subjects

E F Eriksen

Publications and source records attributed to E F Eriksen.

At least 127 records · Page 7Linked to original sources
PubMed1988

The effects of short-term, high-dose treatment with prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in monocytes from normal human subjects.

Animal and cell culture studies indicate glucocorticoid regulation of 1,25-dihydroxyvitamin D3 receptors and interference with cellular effects of vitamin D. These investigations prompted us to examine the effects of prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in freshly isolated human monocytes. Eighteen normal subjects were studied in a randomized, double-blind, placebo-controlled study. Analysis of receptor kinetics revealed that the maximal nuclear uptake (Bmax) of (3H)-1,25-dihydroxyvitamin D3 in monocytes decreased 40% (P less than .001) after prednisone treatment. In the group treated with prednisone (40 mg/d for 5 days) s-1,25-dihydroxyvitamin D increased 46% (P less than .01). S-25-Hydroxyvitamin D, S-phosphat, S-calcium, and S-iPTH remained unchanged. Osteoblastic production of the matrix protein, bone gla protein (BGP) is stimulated by 1,25-dihydroxyvitamin D3. However, despite increased serum levels of 1,25-dihydroxyvitamin D3, the prednisone-treated group revealed a 75% reduction in s-BGP. The present data indicate that corticosteroids decrease the nuclear uptake of 1,25-dihydroxyvitamin D3 in human monocytes. Further investigations are necessary, however, to elucidate the biologic mechanism for this observation and whether the mechanism is operative in other human tissues including bone.

Adult↗
PubMed1988

Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers.

In 12 younger (age, 30-41 yr) and 11 older (age, 55-73 yr) normal women we assessed bone formation rate using multiple methods. Bone formation (mean +/- SE) was higher in the older women than in the younger women, based on measurements of serum bone Gla-protein (1.67 +/- 0.07 vs. 1.14 +/- 0.10 nmol/L; P less than 0.01), serum bone-specific alkaline phosphatase activity (388 +/- 42 vs. 223 +/- 22 nanokatal/L, P less than 0.01), and bone formation rate by histomorphometry of iliac biopsy (31.1 +/- 4.9% vs. 15.1 +/- 2.7%/yr; P less than 0.01), but was similar in the two groups when accretion rates were assessed by calcium kinetics (5.9 +/- 1.0 vs. 7.5 +/- 1.2; P = NS). This latter discrepancy may have been caused by several age-related factors, especially reduced mineralization of completed osteons, and by not correcting for the decrease in total skeletal calcium in the older group. Our data call into question the traditional belief that bone turnover decreases in older women.

Adult↗
PubMed1988

Epitopes of the human erythrocyte Ca2+-Mg2+ ATPase pump in human osteoblast-like cell plasma membranes.

Human osteoblast-like cells were examined for the presence of the Ca2+-Mg2+ ATPase pump. The osteoblast-like cells had characteristic features of the osteoblast phenotype, including the presence of osteonectin, bone GLA protein, and type I collagen. The cells were able to mineralize matrix, their production of cAMP increased in response to PTH, and their alkaline phosphatase activity increased in response to 1,25-dihydroxyvitamin D3. Immunocytochemical staining of the osteoblast-like cells with a monoclonal antibody against human red cell Ca2+-Mg2+ ATPase demonstrated the presence of an epitope of the Ca2+-Mg2+ ATPase in these cells; staining of paraffin-embedded osteoblast-like cell sections demonstrated anti-Ca2+-Mg2+ ATPase staining only in cell plasma membranes. Western blot analysis of osteoblast-like cell homogenates showed that the monoclonal antibody to human erythrocyte Ca2+-Mg2+ ATPase bound to a major band at 140,000 mol wt, similar to the mol wt of known plasma membrane Ca2+-Mg2+ ATPases. The presence in the osteoblast-like cells of a Ca2+-Mg2+ ATPase similar to the human red cell calcium pump suggests that this enzyme may play a role in osteoblast intracellular calcium homeostasis.

Adolescent↗
PubMed1988

The effects of high-dose glucocorticoid administration on serum bone gamma carboxyglutamic acid-containing protein, serum alkaline phosphatase and vitamin D metabolites in normal subjects.

The effects of 40 mg of prednisone given daily for 5 days to normal individuals on serum levels of bone Gla-protein (BGP), alkaline phosphatase, calcium phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone (S-iPTH) and on renal excretions of calcium, phosphate and hydroxyproline were evaluated in a double-blind, placebo controlled study. In the prednisone group a 75% decrease (P less than 0.001) was found in serum BGP compared to a 6% decrease (P less than 0.05) in serum alkaline phosphatase. The renal hydroxyproline excretion remained unchanged. Serum calcium was unchanged while the fasting urinary calcium excretion showed a 2-fold increase (P less than 0.001). Serum 1,25-dihydroxyvitamin D increased (P less than 0.01) in spite of unchanged serum 25-hydroxyvitamin D, serum phosphate and parathyroid function (as judged by S-iPTH and the maximal tubular reabsorption capacity for phosphate (TmP/GFR]. The data suggest a direct inhibition of osteoblast number and/or function by short-term glucocorticoid administration with unchanged bone resorption leading to a negative bone mineral balance. The increase in serum 1,25-dihydroxyvitamin D is probably due to a direct stimulation by glucocorticoids of the renal 1 alpha-hydroxylase. The effects of the vitamin D metabolite, however seem to be blunted.

Adult↗
PubMed1987

Treatment of cervical disc disease using Cloward's technique. Part V. The effect of reoperations.

Among 1,106 patients with cervical disc disease in whom Cloward's operation had been performed over a fifteen-year period, 145 patients were reoperated upon with a new Cloward procedure. In the 1st year after the first operation 3/4 of the patients were operated upon on the previous level, whereas reoperations performed later mainly were done on new levels. The effect of the reoperation was poorer than the effect of the 1st operation. Early reoperations--which were due to: an initially unsatisfactory clinical course, postoperative complications or graft problems--had a poor result, but late reoperations--which were caused by relapses--showed a result corresponding to the first operation. The frequency of relapses leading to a 2nd Cloward operation was 8.8% in the first year falling to 0.2% in the following years of observation.

Cervical Vertebrae↗
PubMed1987

The significance of preoperative radiological examinations in patients treated with Cloward's operation.

During a fifteen-year period 1,106 patients with symptoms and signs of cervical disc disease underwent Cloward's operation. Plain x-rays were performed in 94%, but the severity and extension of degenerative changes had no prognostic value. In 91% of the patients myelography was performed and in recent years mainly metrizamide was used as it was found to be more accurate. The findings on the myelograms were correlated according to age, severity and number of affected disc levels, but were independent of the duration of symptoms. Patients with medullary symptoms were found more often than not to have an anterior indentation into the spinal canal whereas most patients with radicular symptoms had wide cervical root sleeves or lateral compression. The best outcome was found among patients with monosegmental symptoms and signs and one affected disc level on the myelogram underlining that the indication for surgery in cervical disc disease should be based on both clinical and radiological findings.

Adult↗
PubMed1987

Bone turnover and balance evaluated by a combined calcium balance and 47calcium kinetic study and dynamic histomorphometry.

Bone resorption and formation rates were evaluated at the organ level using calcium kinetic methods and at the trabecular bone tissue level using dynamic histomorphometry in 20 patients with various metabolic bone diseases (primary hyperparathyroidism (N = 9), hyperthyroidism (N = 6), and hypothyroidism (N = 5). Highly significant correlations were demonstrated between resorption and formation rates at organ level (r = .90, P less than .001) and at tissue level (volume referent) (r = .93, P less than .001), indicating a high degree of coupling between resorption and formation within the three disease states. Tissue level resorption rates (surface referent, as well as volume referent) both correlated significantly (P less than .01) to organ level resorption rate (r = .60 and r = .63, respectively). Fractional active resorption surface and cellular level resorption rate did not reveal significant correlations to calcium kinetic estimates. No correlation could be demonstrated between organ level mineralization rate and formative or labeled trabecular surfaces. However, all tetracycline based tissue level formation rates revealed highly significant correlations (P less than .01) to organ level mineralization rate (calcification rate, r = .71; surface referent bone formation rate, r = .59; volume referent bone formation rate, r = .68). Based on histomorphometric parameters for resorption and formation, actual and predicted tissue level trabecular bone balances were calculated. Both the actual and predicted bone balance correlated significantly to the organ level calcium balance (P less than .05). Correction for skeletal size based on BMC measurements did not improve any of the correlations significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Exogenous triiodothyronine activates bone remodeling.

The effect of exogenous triiodothyronine (T3) as an activator of bone remodeling was investigated by measuring biochemical marker levels. Fourteen people received 100-160 micrograms of T3 for 1 week and were followed for a total of 10 weeks. Serum T3 increased markedly during the first week, whereas serum TSH and serum thyroxine (T4) decreased. Bone resorption was stimulated during the first week as evaluated from serum calcium and renal excretion of calcium, phosphate, and hydroxyproline. Serum osteocalcin showed an increase in the first week, probably caused by stimulation of existing osteoblasts. Serum alkaline phosphatase increased from week 6 to week 8, and serum osteocalcin increased at week 8 to a level higher than the initial level. The results indicate that T3 acts as an activator of bone remodeling and initiates bone resorption followed by bone formation. The observed timetable for the remodeling sequence is in accordance with that obtained by bone histomorphometry. Osteopenic states may be treated by synchronizing the skeletal remodeling processes and then selectively depressing bone resorption with calcitonin or diphosphonates (ADFR treatment). Synchronization may be achieved by short-term treatment with a drug that stimulates the formation rate of new remodeling cycles (an activator). The results from this study indicate that exogenous T3 may be used as an activator.

Adult↗
PubMed1987

Prostaglandin-E2 receptors in the rat kidney: biochemical characterization and localization.

A radiohistochemical technique yielding data on the distribution and characteristics of PGE2-receptor binding in tissue sections is described. The binding of tritiated PGE2 (3H-PGE2) to slide-mounted tissue sections had all the characteristics associated with ligand-receptor interactions: it was saturable, of high affinity and displayed high specificity for PGE2 binding. From the binding curves a Hill coefficient of 1.1 was calculated which suggests the presence of a homogeneous receptor population. Pretreatment with indomethacin for four days resulted in a 66% increase in maximal binding capacity (Bmax) without any change in affinity. The distribution of receptor was mapped in rats with and without indomethacin pretreatment and compared to the distribution of Tamm-Horsfall glycoprotein, a specific marker for the thick ascending limb of Henle. In both groups the PGE2 receptor showed striking regional variation. In the untreated group the distribution of PGE2 receptors was similar to that of the thick ascending limb of Henle, with maximal density in the outer medullary zone. After indomethacin pretreatment, however, a striking increase in inner medullary binding was observed together with increased binding in the cortex. Thus, in accordance with the main action of PGE2 being regulation of renal water and sodium excretion, we found the highest receptor density in areas of the kidney dominated by the thick ascending limb of Henle and collecting tubules, and much less binding to glomeruli and cortical vessels. In order to investigate characteristics and distribution of PGE2 receptor binding, however, it was mandatory that endogenous prostanoid synthesis is blocked.

Animals↗
PubMed1986

Trabecular bone remodeling and balance in primary hyperparathyroidism.

The total remodeling sequences in 19 primary hyperparathyroid patients and 16 approximately age-matched and sex-matched controls were reconstructed from histomorphometric analyses of bone specimens obtained after intravital tetracycline double labeling. In the primary hyperparathyroid group the total amount of work performed by resorptive cells was reduced, as indicated by the significantly lower three-dimensional mononuclear and preosteoblast-like cell resorption depths (35.8 microns vs 44.5 microns in normals, P less than 0.01 and 45.3 microns vs 56.6 microns in normals, P less than 0.01, respectively). The active resorption period (i.e., the function period for osteoclasts and mononuclear cells) was reduced to 19 days compared to 29 days in normals (P less than 0.05), but no difference with respect to bone resorption rates could be demonstrated between the two groups. The median bone formation period (Sigmaf) in primary hyperparathyroid patients was not different from the value obtained in normals (172 days vs 134 days, respectively), and the matrix appositional rate (Ama), as well as the mineralization lag time (tm), were also unchanged. The initial mineralization rate (Ami(i)) was not significantly different from the value obtained in normals, but averaged over the total bone formation period, a reduced mineralization rate could be demonstrated (0.32 micron3/micron2 per day vs 0.46 micron3/micron2 per day in normals, P less than 0.01). The measured final three-dimensional thickness of bone formed during Sigmaf (mcwTm) was reduced in the primary hyperparathyroid group (51.1 microns vs 55.9 microns in normals, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

A histomorphometric determination of iliac bone structure and remodeling in obese subjects.

Quantitative histomorphometric analyses of iliac crest biopsies were performed after tetracycline double labeling in 24 patients with morbid obesity and in 30 age- and sex-matched controls. The amount and structure of bone were determined from measurements of total biopsy length, fractional length of medullary space, fractional trabecular bone volume, trabecular thickness, and the intertrabecular distance. Static and dynamic variables of bone resorption and formation were determined, and the balance of the BMU level was estimated from final resorption depth and mean wall thickness of trabecular structural units. In the obese patients the total biopsy length was increased, with a normal proportion of medullary space to total biopsy length. The mean fractional trabecular bone volume was reduced due to an increased distance between trabeculae of normal mean thickness. The total biopsy length in the obese patients was found to be positively related to the intertrabecular distance and inversely related to the fractional trabecular bone volume. The remaining histomorphometric variables describing bone formation rate at tissue, BMU, and cellular levels, the amount of bone formed, the mineralization process, mineralization lag time, bone resorption, and the balance between resorption and formation were all normal in the obese group.

Adult↗
PubMed1986

Kinetics of trabecular bone resorption and formation in hypothyroidism: evidence for a positive balance per remodeling cycle.

Using a recently described model for reconstruction of the entire remodeling sequence in trabecular bone after tetracycline double labeling, bone remodeling was investigated in 18 hypothyroid female patients and 11 age- and sex-matched controls. In the hypothyroid group, the final resorption depth was reduced to 42 microns vs 53 microns in the control group (P less than 0.01). The total resorption period was increased to 76 days vs 32 days in the control group (P less than 0.001), and the resorption rate was lowered to 0.8 micron/day vs 2.1 microns/day in the control group (P less than 0.001). The function period for preosteoblast-like cells was 22 days compared to 14 days in normals (P less than 0.05). The total bone formation period was prolonged to 620 days in the hypothyroid group compared to 151 days in the control group (P less than 0.001), and the matrix and mineral appositional rates were lowered to 0.7 and 0.5 micron3/micron2 per day compared to 1.8 (P less than 0.001) and 1.4 (P less than 0.001) micron3/micron2 per day, respectively. The mineralization lag time in the hypothyroid group was 48 days vs 25 days in the control group (P less than 0.001), and at the start of bone formation this difference was even more pronounced (63 and 16 days, respectively, P less than 0.001). The mean completed wall thickness was increased in the hypothyroid group to 59.5 microns compared to 54 micron in the control group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Nuclear uptake of 1,25-dihydroxy[3H]-cholecalciferol in peripheral blood monocytes.

The active vitamin D metabolite, 1,25-dihydroxycholecalciferol induces differentiation of monocytes into macrophages. The pharmacological induction of differentiation of primitive, rapidly proliferating cell lines into more mature cells with lower proliferative potential is a new dimension in the treatment of myeloproliferative disorders, which may prove to be an important alternative to more traditional regimens. Furthermore, the cell primarily engaged in bone resorption--the osteoclast--represents another differentiated form of mononuclear phagocytes, and 1,25-dihydroxycholecalciferol increases the number of osteoclasts. Since the cellular action of 1,25-dihydroxycholecalciferol is exerted mainly through its binding to nuclear receptors, a detailed knowledge of ligand-receptor interactions is mandatory for future work in this area. In order to investigate the interaction between 1,25-dihydroxycholecalciferol and its receptor in mononuclear cells, the nuclear uptake of the hormone was studied using a whole cell assay. The nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in human monocytes at physiological temperature and pH was saturable, specific, and fully reversible. When eight normal individuals were investigated, the maximal binding capacity (Bmax) was 0.4-8.4 fmol/10(6) cells and the dissociation constants (Kd) were 0.12-0.45 nmol/l. The characterization of the nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in intact human monocytes shows that it is mediated by binding of the ligand to a specific nuclear receptor. The binding to the nuclear receptor is the result of the passage of ligand across the cytoplasmic membrane and of the cytoplasmic transport of ligand. In contrast to conventional receptor assays in hypertonic cellular extracts, this system provides information on the role of the cytoplasmic membrane in relation to the nuclear uptake of 1,25-dihydroxycholecalciferol, which may be closer to in vivo cellular conditions.

Binding, Competitive↗
PubMed1985

Trabecular bone resorption depth decreases with age: differences between normal males and females.

The resorption depth below osteoclasts, mononuclear cells, and preosteoblast-like cells can be estimated by counting the number of lamellae of known thickness eroded below the three cell types. In a previous study on bone resorption in young normal individuals, we demonstrated that the mean depth below osteoclasts was smaller than the mean depth below mononuclear cells, which again was smaller than the mean depth below preosteoblast-like cells, the last taken as the final depth reached. In order to investigate the variation in resorption depth with age in both sexes, we examined bone biopsy specimens from 42 normal females and 34 normal males aged 17-90 years. For each patient the mean osteoclastic, mononuclear, and preosteoblast-like cell resorption depths were calculated, and the surface extensions of the three types of resorption lacunae were determined. The surface extent of preosteoblast-like cell lacunae increased with age in females (p less than 0.05). Osteoclastic resorption depth was constant throughout the ages in females as well as in males. Mononuclear and preosteoblast-like cell resorption depths decreased significantly with age in females (p less than 0.01 and p less than 0.05, respectively) as well as in males (p less than 0.05 and p less than 0.01, respectively). The mean depth of lacunae where resorption had terminated (i.e., preosteoblast-like cell resorption depth) was larger in females aged 30-60 years than in men of the same age (p less than 0.05). The reduction in final resorption depth with age is parallel to the decrease in mean thickness of completed walls previously described.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Trabecular bone remodeling and bone balance in hyperthyroidism.

In vivo tetracycline double-labeled iliac crest bone biopsies from 15 hyperthyroid patients were used for the reconstruction of curves describing the variation of resorption depth and formation thickness with time. The curves emerging were compared to curves reconstructed from 13 age- and sex-matched normal individuals (mean age 44 years). The median function period for resorptive cells in hyperthyroid patients (16 days) was about one-third the resorptive period in normals (51 days). No significant difference between the osteoclast-, mononuclear-, or preosteoblast-like cell resorption depths could be demonstrated between the two groups. Consequently, the median resorption rate in hyperthyroid patients (3.8 microns/day) was more than 3 times higher than the value in the control group (1.1 micron/day). Median Sigma, was shorter in the hyperthyroid group (109 days) than in the control group (151 days, P less than 0.05), as was the median initial mineralization lag time (5 and 16 days, respectively, P less than 0.01). No significant difference between the measured mean completed wall thickness (mcwT) values in the hyperthyroid groups and the control group could be demonstrated (58.1 and 60.5 micron respectively). Median initial mineralization rate in the hyperthyroid group (1.2 micron3/micron2 per day) was not significantly higher than the value calculated in the control group (0.9 micron3/micron2 per day), but median initial matrix appositional rate in hyperthyroid (4.8 microns3/micron2 per day) was 3 times higher than the value calculated for normals (1.6 micron3/micron2 per day) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗