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Biomedical subjects

E F Eriksen

Publications and source records attributed to E F Eriksen.

At least 91 records · Page 5Linked to original sources
PubMed1994

Familial isolated primary hyperparathyroidism.

UNLABELLED: Familial primary hyperparathyroidism (PHPT) is usually encountered in the context of multiple endocrine neoplasia (MEN) syndromes. Few families have been reported in the literature where PHPT was the only abnormality. However, in these families no long-term follow-up data were reported and no genetic linkage studies were performed. OBJECTIVE: We investigated a large family with a familial primary hyperparathyroidism for biochemical and genetic markers of multiple endocrine neoplasia syndromes. DESIGN: A family screening study. PATIENTS: Thirty-seven family members participated in this study including 7 patients who had been previously operated upon for PHPT. MEASUREMENTS: Serum calcium (albumin adjusted), was measured in all family members. Hypercalcaemic subjects and patients who had been operated upon for PHPT were assessed for biochemical markers of MEN syndromes (serum gastrin, prolactin, calcitonin, fasting plasma glucose and 24-hours urinary excretion of adrenaline, noradrenaline and vanillylmandelic acid (VMA)). Genetic linkage analysis was performed using DNA markers linked to chromosome 11q13, the presumed MEN type 1 (MEN-1) locus. RESULTS: Four new patients with PHPT and two with probable PHPT were discovered. No clinical or biochemical evidence of MEN syndromes could be detected. DNA marker pMS51(D11S97) was informative, maximum two-point lodscore of 2.12 at a recombination fraction of 0.05 confirming linkage to chromosome 11q13. CONCLUSIONS: Familial PHPT can exist as a separate clinical entity. Isolated familial PHPT is caused by mutation in a gene located in the MEN-1 region on chromosome 11q13, possibly the MEN-1 locus.

Adult↗
PubMed1994

Effects of fluoride on human bone cells in vitro: differences in responsiveness between stromal osteoblast precursors and mature osteoblasts.

The cellular effects of sodium fluoride (NaF) on human bone cells in vitro have been variable and dependent on the culture system used. Variability could be attributed to differences in responsiveness to NaF among different populations of cells at various stages of differentiation in the osteoblastic lineage. In this study we compared the effects of NaF in serum-free medium on cultures of more differentiated human osteoblast-like (hOB) cells derived from trabecular bone explants and on osteoblast committed precursors derived from human bone marrow, i.e. human marrow stromal osteoblast-like (hMS(OB)) cells. Sodium fluoride (10(-5) mol/l) increased proliferation of hMS(OB) cells (p < 0.05, N = 10) but was not mitogenic to hOB cells (p > 0.05, N = 10). Alkaline phosphatase (AP) production increased in both hMS(OB) (p < 0.05, N = 9) and hOB cells (p < 0.05, N = 9). No significant effects on procollagen type I propeptide production were obtained in either culture. In the presence of 1,25-dihydroxycholecalciferol (10(-9) mol/l), NaF enhanced alkaline phosphatase (p < 0.05, N = 8), procollagen type I propeptide (p < 0.05, N = 7) and osteocalcin (p < 0.05, N = 7) production by hMS(OB) cells but not by hOB cells. Our results suggest that osteoblast precursors are more sensitive to NaF action than mature osteoblasts and that the in vivo effects of NaF on bone formation may be mediated by stimulating proliferation and differentiation of committed osteoblast precursors in bone marrow.

Adult↗
PubMed1994

No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis.

To test the hypothesis that a dysfunctional growth hormone (GH)-insulin-like growth factor (IGF) axis may play a role in the pathogenesis of osteoporosis, we compared the levels of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3) in 15 women with spinal osteoporosis (i.e. at least one non-traumatic vertebral fracture) and 15 normal age-matched women. Furthermore, the response to 3 days' treatment with recombinant human GH (r-hGH) (0.2 IU kg-1.day-1) was determined. The basal levels of IGF-I, IGF-II and IGFBP-3 were similar in patients and controls (mean +/- SEM): IGF-I, 16.5 +/- 1.3 versus 16.0 +/- 1.3 nmol/l (NS); IGF-II, 79.9 +/- 3.6 versus 72.5 +/- 4.1 nmol/l (NS); and IGFBP-3, 125.7 +/- 6.5 versus 130.3 +/- 7.8 nmol/l (NS). Stimulation with r-hGH elicited increased levels of IGF-I, IGF-II and IGFBP-3 within both groups (p < 0.001). The maximal values expressed as a percentage of baseline were: IGF-I, 341 +/- 26% versus 369 +/- 22%, IGF-II, 125 +/- 4% versus 119 +/- 5%, IGFBP-3, 141 +/- 5% versus 147 +/- 7% in osteoporotic patients and controls, respectively. No significant differences were observed between patients and controls in either their maximal response or in the area under the response curves. Our results do not support the hypothesis of a dysfunctional GH-IGF axis in women with spinal osteoporosis.

Aged↗
PubMed1994

Growth hormone stimulates proliferation of normal human bone marrow stromal osteoblast precursor cells in vitro.

In this study the effects of growth hormone (GH) in human marrow stromal osteoblast-like [hMS(OB)] cell cultures containing a population of osteoblast precursors, were tested. GH (dose range 0.1-500 ng/ml) stimulated hMS(OB) cell proliferation in a dose-dependent fashion as evidenced by increased 3H-thymidine incorporation into DNA and increased cell number. Maximal stimulation was 173 +/- 35% (P < 0.001, n = 12) and 145 +/- 6% (P < 0.0001, n = 10) of no-treatment controls for 3H-thymidine incorporation and cell number, respectively. GH did not exert major effects on differentiation markers in hMS(OB) cell cultures. 1,25-dihydroxy vitamin D3 (10(-9) M) alone increased cellular production of alkaline phosphatase (AP) and induced expression of osteocalcin. When GH was tested in combination with 1,25(OH)2D3, it tended to inhibit vitamin D-stimulated effects on differentiation markers but these effects were not statistically significant. Our results suggest that GH induces proliferation of less differentiated cells in the osteoblast lineage and this mechanism may in part mediate the in vivo effects of GH on bone formation.

Adult↗
PubMed1993

Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry.

Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy-terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high- and low-turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S-ICTP on volume-referent resorption rate (BRs/R/BV) was significant (r = 0.61, p < 0.01, SEM/Y = 56%). S-ICTP also showed a significant regression on the volume-referent cancellous bone balance (r = -0.45, p < 0.05, SEM/Y = 412%). S-PICP was significantly correlated to the mineral appositional rate (r = 0.53, p < 0.05) and volume-referent bone formation rate (r = 0.61, p < 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r = 0.61, p < 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease.

Adult↗
PubMed1993

1,25-dihydroxyvitamin D3 potentiates fluoride-stimulated collagen type I production in cultures of human bone marrow stromal osteoblast-like cells.

In this study we tested the effects of sodium fluoride (NaF) in serum-free cultures of human marrow stromal osteoblast-like [hMS(OB)] cells. NaF (10(-5) M) stimulated hMS(OB) cell proliferation up to 220% of control cultures. NaF alone did not increase type I collagen production, but in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] (10(-9) M), NaF enhanced type I collagen production in a dose-dependent way to 300% of 1,25-(OH)2D3-treated control cultures. The production of alkaline phosphatase (ALP) and osteocalcin (bone gla protein, BGP) was also enhanced in the presence of 1,25-(OH)2D3 to 170 and 200%, respectively, of 1,25-(OH)2D3-treated controls. Our results suggest that 1,25-(OH)2D3 potentiates fluoride-mediated anabolism in hMS(OB) cell cultures and suggest that osteoblast precursors in bone marrow are targets for fluoride action.

Alkaline Phosphatase↗
PubMed1993

The von Kossa reaction for calcium deposits: silver lactate staining increases sensitivity and reduces background.

The classical von Kossa method has been modified: the high silver nitrate concentration in the original was replaced by 0.05% silver lactate with hydroquinone remaining the reducing agent of choice. The present modification stained calcification nodules with a sensitivity comparable to the original von Kossa reaction, but resulted in a reduced background staining in cultured osteoblasts. The method works well also with plastic- or paraffin-embedded tissue sections.

Calcification, Physiologic↗
PubMed1993

Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro.

In this study we investigated the direct, short-term effects of human growth hormone (hGH) on the biology of normal adult human osteoblast-like (hOB) cells cultured from trabecular bone explants. In Subconfluent cultures, hGH stimulated hOB proliferation in a dose-dependent fashion (P < 0.001, n = 15) with half-maximal effects at a concentration of 10 ng/ml. These mitogenic effects were detectable within 24 hours as shown by bromodeoxyuridine labeling. In confluent cultures containing mainly quiescent cells, hGH increased levels of alkaline phosphatase (P < 0.05, n = 10) and to a lesser degree levels of procollagen type I carboxyterminal propeptide (PICP) (P = 0.07, n = 9). Effects on osteocalcin (bone GLa protein, BGP) levels were highly variable among different cell strains and only 7 of 10 cell strains showed a stimulatory response (P = 0.16). We also studied the effects of hGH on osteoblastic production of insulin-like growth factor I (IGF-I) and IGF-II as well as the production of GH-dependent, insulin-like growth factor binding protein 3 (IGFBP-3). Under basal conditions, human osteoblasts produced IGF-II and IGFBP-3 in the conditioned medium. When stimulated with hGH, minor insignificant increase in both IGF-II and IGFBP-3 (125% and 126% of control, respectively) were detectable. No IGF-I was detectable in the conditioned medium under basal conditions or after stimulation with hGH. In conclusion, the results obtained in this study suggest that GH exerts direct anabolic effects on human osteoblasts.

Alkaline Phosphatase↗
PubMed1993

Growth hormone and insulin-like growth factors as anabolic therapies for osteoporosis.

Growth hormone (GH) and insulin-like growth factors (IGFs) play a central role in skeletal growth and bone remodeling. In vitro, both agents display anabolic properties, and patients with acromegaly exhibit increased bone mass. Recent in vivo studies have demonstrated profound activation of bone remodeling that lasted for months after a single 1-week dose of GH or IGF-I. Despite these positive effects, the few clinical studies conducted with GH in osteoporotic patients have shown disappointing results in terms of bone mass changes. Changes in dosing regimens and other adjuvant therapies may, however, lead to more efficient use of these agents.

Animals↗
PubMed1993

Effects of triiodothyronine on DNA synthesis and differentiation markers of normal human osteoblast-like cells in vitro.

To study the direct effects of thyroid hormones on human osteoblasts we examined the effects of triiodothyronine (T3) on proliferation and differentiation of human osteoblast-like (hOB) cells in vitro. T3 increased 3H-thymidine incorporation in DNA of hOB cells (p < 0.05, n = 10). Half maximal effects obtained at a T3 concentration of 1-10 nM which lies within the physiological concentration of the hormone. In addition, T3 increased alkaline phosphatase production (p < 0.05, n = 13) and inhibited procollagen type I carboxyterminal propeptide (PICP) production (p < 0.05, n = 13). T3 interaction with 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was also studied. 1,25-(OH)2D3 (10(-9)M) alone doubled AP production and induced osteocalcin expression by hOB cells. Concurrent addition of T3 and 1,25-(OH)2D3 did not further increase production of AP, PICP or osteocalcin by hOB cells. In conclusion, T3 exerts significant effects on osteoblast proliferation and differentiation, suggesting that human osteoblasts are targets for thyroid hormones.

Alkaline Phosphatase↗
PubMed1992

Assessment of bone formation by biochemical markers in metabolic bone disease: separation between osteoblastic activity at the cell and tissue level.

In this study , serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as well as the fraction: standard error of estimate/mean dependent variable (SEE/Y) were determined. In a group of 19 normals, only the regression of S-PICP on m reached significance (r = 0.53, P < 0.02, SEE/Y = 0.44), whereas regressions of S-AP and S-BGP on m were nonsignificant. In a pooled material of high- and low-turnover bone diseases without mineralization defects or spinal fracture [myxedema, thyrotoxicosis, and primary hyperparathyroidism (n = 48)], a highly significant positive regression of S-PICP on m was demonstrable (r = 0.50, SEE/Y = 0.63, P < 0.001). The regression coefficients obtained for S-BGP and S-AP were 0.74 (P < 0.001, SEE/Y = 0.41) and 0.42 (P < 0.01, SEE/Y = 0.55), respectively. When analyzing individual diseases in this group, significant differences among the three markers were detectable. In a group of 52 osteoporotics, S-PICP correlated significantly to m (r = 0.49, P < 0.001, SEE/Y = 0.50). Corresponding r-values for S-BGP and S-AP were 0.21 (NS) and 0.48 (P < 0.001, SEE/Y = 0.61), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Reconstruction of the formative site in trabecular bone by a new, quick, and easy method.

Ordinary measurements of the wall thickness (the end result of the osteoblastic work) of trabecular bone packets (completed remodeling sites) describe the average thickness of walls formed during the previous two to three years. If the bone biopsy is obtained shortly after onset of disease or initiation of treatment, only a few of the measured sites will represent walls formed under the new conditions. With a reconstruction of the formative site true information of the performed osteoblastic work can be obtained, since it is based upon observations of the actual formative events and not the end result (completed walls). Previously published methods have the disadvantage of being time consuming and technically difficult. Furthermore, the method by Eriksen et al. includes rather complicated mathematical calculations. In the present study a new method for reconstruction of the formative phase is presented, which can be performed from measurements normally obtained in a routine histomorphometric analysis and from paired values of osteoid thicknesses and uncompleted wall thickness. The method does not introduce a new time consuming step in the histomorphometric analyses of the bone biopsy. Furthermore, calculations needed to reconstruct the events of the formative phase can easily be performed using a personal computer and a spread-sheet. The new method for reconstruction presented in this paper gives growth curves for matrix and bone mineral, which are virtually identical with the growth curves previously published by Eriksen et al. for the same 20 normal individuals.

Adult↗
PubMed1992

Ultrastructure of human osteoblasts and associated matrix in culture.

The ultrastructure, as visualized by transmission electron microscopy, of cells obtained from human bone explants and subsequently cultured is described along with the electron microscopic appearance of the associated intercellular matrix. The cells were characterized as osteoblasts on the basis of immunohistochemical, enzymatic, and functional criteria. Although the osteoblasts could be cultured in standard culture media and always appeared singly, not forming syncytia, the cultures were eventually confluent and formed multilayers. The cells were fusiform or cuboidal with diameters ranging between 10-15 microns. The cytoplasm was characterized by numerous large mitochondria, and especially by a very prominent RER. The intercellular matrix was woven with collagen fibres surrounding large numbers of matrix vesicles. In areas with matrix vesicles, evidence for osteoblast activity, i.e. mineralization related to matrix vesicles, could be observed after incubation with beta-glycerophosphate. In conclusion, we provide evidence that human osteoblasts cultured in vitro synthesize collagen and produce a matrix with vesicles capable of initiating mineralization processes.

Calcification, Physiologic↗
PubMed1991

Nuclear estradiol binding in rat adipocytes. Regional variations and regulatory influences of hormones.

The nuclear estrogen receptor was characterised in isolated rat adipocytes. The binding reaction with [3H]estradiol was performed with intact isolated rat adipocytes and the radioactivity associated with the nucleus was subsequently determined after cell lysis. The nuclear uptake of [3H]estrogen in rat adipocytes was temperature dependent and steroid specific. The steady-state binding was achieved after 30 min at 37 degrees C and was constant for several hours. Estradiol was found to bind to a homogeneous class of nuclear receptors in epididymal adipocytes with an apparent Kd of 3.1 +/- 0.76 nM and a Bmax of 7.98 +/- 1.11 fmol/10(6) cells corresponding to about 4800 receptors per nucleus. The estradiol binding exhibited regional variations in isolated adipocytes. In lean rats the highest receptor number was found in epididymal adipocytes, whereas there was a significantly lower number of nuclear binding sites in perirenal and subcutaneous adipocytes (P less than 0.05), unlike in older and more obese rats where the nuclear estradiol binding was greatest in adipocytes from the perirenal fat depot. Incubations with isoproterenol (10 microM) and dibutyryl-cAMP (2.5 mM) both reduced estradiol binding by 56% (P less than 0.005), while insulin (1 nM) enhanced the estradiol binding by 37% (P less than 0.01). In conclusion, a specific and high affinity nuclear estradiol receptor was demonstrated in rat adipocytes and regional differences in nuclear estradiol binding were detected. Furthermore, it was demonstrated that nuclear estradiol binding could be modulated by other agents known to affect adipocyte metabolism.

Adipose Tissue↗
PubMed1991

Effects of a combined estrogen-gestagen regimen on serum levels of the carboxy-terminal propeptide of human type I procollagen in osteoporosis.

Estrogen stimulates osteoblastic collagen production in vitro, but whether the same stimulation takes place in vivo is still unknown. To test the stimulatory effects of a combined estrogen-gestagen regimen in vivo we monitored serum levels of the carboxy-terminal propeptide of human type I procollagen (S-PICP) in a group of 12 osteoporotic women over a 150 week treatment period. Spinal bone mineral content (BMC) increased to a maximum of 5% over pretreatment values around week 90. Serum alkaline phosphatase (S-AP) and serum bone gla protein (S-BGP) both fell from initial values of 220 U/liter and 39 ng/ml, respectively, to 146 U/liter (p less than 0.01) and 27.2 ng/ml (NS) around week 60 and remained reduced over the remaining treatment period. S-PICP also fell from 117 to 68 micrograms/liter at week 60 and 70 micrograms/ml at week 150 (P less than 0.01). This is equal to a reduction to 32 +/- 10% pretreatment levels. The reduction in S-PICP was not significantly different from that of the other two markers of bone formation (S-AP and S-BGP). Thus, provided the metabolic clearance of PICP remains unaltered after hormone replacement therapy, no major stimulation of osteoblastic collagen type I synthesis was demonstrable during estrogen-gestagen treatment in this population of osteoporotic women. The changes in bone markers seen in this study are therefore consistent with an estrogen-mediated reduction in the frequency of remodeling activation. Because of the reduction in bone turnover and methodologic limitations of bone marker assays, however, smaller increases in the amount of bone formed per activation could remain undetectable.

Aged↗
PubMed1991

A reconstruction of the remodelling cycle in normal human cortical iliac bone.

This paper describes the reconstruction of the remodelling cycle in normal iliac crest cortical bone from static and dynamic variables after double labelling with tetracycline in 10 young normal individuals. The average duration of the resorptive period was 27 days during which the average rate of resorption was 4.7 microns/day. The final resorption depth was 76 microns. The diameter of osteoclast containing cutting cones was significantly smaller (P less than 0.05) than cutting cones containing mononuclear cells, indicating an initial osteoclastic resorption phase preceding a mononuclear resorption phase. The average mineralization lag-time was 8 days and the formative period 89 days. Osteoid thickness during this period averaged 5.8 microns. The seam thickness varied with the underlying uncompleted wall thickness, i.e., during the course of the formative period, with matrix deposition initially exceeding, later equalling and finally lower than the rate of mineralization. The mineral appositional rate (MAR) was 1.2 microns/day and the adjusted mineral appositional rate (Aj.AR) 0.9 micron/day. Both MAR and Aj.AR decreased during the formative period. A completed wall thickness of 62 microns left a Haversian canal with a diameter of 29 microns. After a quiescent period of 438 days the osteon (or parts of it) was reactivated. The average activation frequency was 0.93 per year.

Adult↗
PubMed1991

Hypercalcemia of malignancy: pathophysiology, diagnosis and treatment.

Malignancy is the most frequent cause of hypercalcemia in hospitalized patients. The pathophysiology of hypercalcemia of malignancy (HM) is complex. Increased bone resorption is involved in most cases caused either by extensive local bone destruction or by humoral factors. Tumor extracts from patients with humoral hypercalcemia of malignancy (HHM) often contain PTH-like bioactivity. Recently, cDNAs coding for a PTH-related protein (PTH-rP) has been cloned. The N-terminal amino acid sequence of this protein shows a considerable homology with human PTH. However, other bone resorbing factors including prostaglandins, transforming growth factors, colony stimulating factors, leucocyte cytokines and 1,25-dihydroxyvitamin D may be involved in different types of malignancy. HM is usually progressive with troublesome symptoms and a high mortality. Several treatment alternatives are available including rehydration, bisphosphonates, calcitonin, plicamycin, phosphate, and glucocorticoids. Others are under investigation. Treatment should be individualized taking into account the pathophysiological mechanisms involved, the extent of hypercalcemia and renal failure, and the prognosis related to the malignant disease.

Amino Acid Sequence↗