Biomedical subjects

D L Andress

Publications and source records attributed to D L Andress.

At least 37 records · Page 2Linked to original sources

PubMed1995

IGF-binding proteins in human prostate tumor cells: expression and regulation by 1,25-dihydroxyvitamin D3.

The expression of the six known insulin-like growth factor binding proteins (IGFBPs) and their corresponding messenger RNAs has been examined in three cell lines established from surgical and biopsy specimens of human prostate carcinoma. All three cell lines produced both IGFBP-4 and IGFBP-6 and the respective mRNAs; expression of IGFBP-6 has not been previously demonstrated in human prostate tumor cells. No other binding proteins were detected. The levels of IGFBP mRNAs were not regulated by androgens or IGF-1, but the level of IGFBP-6 mRNA was sharply increased by 1,25-dihydroxyvitamin D3 (1,25(OH)D3). The stimulation was dose-dependent with a maximum effect at 10 nM 1,25(OH)D3 and a clearly discernible effect at 0.1 nM. The results support a role for vitamin D in the control of prostate tumor growth, mediated at least in part by interaction with IGFs and specific IGFBPs.

Biopsy↗

PubMed1995

Comparison studies of IGFBP-5 binding to osteoblasts and osteoblast-derived extracellular matrix.

Recent studies have identified a specific membrane protein in osteoblast-like cells which binds intact and carboxy-truncated IGFBP-5 with high affinity. The purpose of the present study was to evaluate the IGFBP-5 binding properties of osteoblast-derived extracellular matrix (ECM), with special interest in determining whether ECM proteoglycans were necessary for IGFBP-5 binding. Neonatal mouse osteoblasts and the ECM of these cells both bound intact [125I]IGFBP-5 and [125I] IGFBP-5(1-169), though the ECM bound both forms with lower affinity when compared to their cellular binding. Treatment of the ECM with heparinase or chondroitinase, to remove glycosaminoglycan (GAG) side-chains of proteoglycans, resulted in 20-34% enhanced binding of intact [125I]IGFBP-5 and a 92-100% enhancement of [125I]IGFBP-5(1-169) binding. Similar enzymatic treatment of osteoblast monolayers had no effect on the binding of either form of [125I]IGFBP-5. These results indicate that GAGs within ECM secreted by neonatal mouse osteoblasts do not mediate the binding of IGFBP-5. This study also shows that intact and carboxy-truncated IGFBP-5 preferentially bind to the osteoblast surface, but that removal of GAGs from osteoblast-derived ECM can increase IGFBP-5 localization to this pericellular space, particularly the carboxy-truncated form of IGFBP-5.

Animals↗

PubMed1995

IGFBP-3 and IGFBP-5 association with endothelial cells: role of C-terminal heparin binding domain.

IGFBP-3 and IGFBP-5, but not the other 4 IGF binding proteins, specifically bound to endothelial cell (EC) monolayers. Charged compounds, such as heparin and heparan sulfate, competed for this binding. Of the 6 IGFBPs, IGFBP-3 and IGFBP-5 had the greatest heparin affinity. Peptides of 18 amino acids were synthesized, corresponding to a common basic region of IGFBP-3 (P3), IGFBP-5 and IGFBP-6 (P6) which contained a heparin binding sequence. P3 and P6 inhibited IGFBP-3 and -5 binding to endothelial cell monolayers and the peptides bound directly to EC extracellular matrix. This suggested that the C-terminal basic segment of IGFBP-3/-5 is important for the association of the binding protein with the EC monolayer.

Amino Acid Sequence↗

PubMed1994

Identification and characterization of human neutrophil carbonic anhydrase.

Many functions of polymorphonuclear leukocytes (PMNs) appear to alter and be affected by changes in the intracellular and/or extracellular acid-base milieu, suggesting that carbonic anhydrase (CA) may be important. Although small amounts of CA activity in PMNs have been reported, it has not been characterized fully. We therefore studied isolated mature circulating human PMNs and cultured HL-60 cells, an undifferentiated myelopoietic cell line, and compared these to human red cells (RBCs) for CA activity. Activity and sulfonamide inhibition were measured by a modified micromethod assay. Isoenzyme and total CA concentrations were determined by radioimmunoassay for human isozyme CA I, differential inhibition by MK-927, inhibition by 0.2% sodium dodecyl sulfate (SDS), and quantitative sulfonamide binding. Total CA activity (units/10(6) cells) was 0.04 in PMNs, 0.06 in HL-60 cells, and 0.62 in RBCs. Human PMNs have a total CA concentration of 1.3 microM, of which 0.9 microM is CA I and the remainder is CA II. Total loss of CA activity with 100 microM ethoxzolamide and 0.2% SDS ruled out significant CA III or CA IV activity. Subcellular fractionation of PMNs revealed that all CA activity was cytosolic. The absence of CA activity in mitochondrial and microsomal membrane fractions argues against any mitochondrial CA V or membrane-bound CA IV contribution to total CA activity. Neutrophils contain both CA I and II isozymes in roughly the same proportion as RBCs but at much lower concentrations, suggesting that in the course of maturation the CA content of neutrophils is regulated differently from that in erythrocytes.

Carbonic Anhydrase Inhibitors↗

PubMed1993

Carboxy-truncated insulin-like growth factor binding protein-5 stimulates mitogenesis in osteoblast-like cells.

Recently we demonstrated that a 23 kDa form of IGFBP-5, derived from osteoblast-like cells, stimulates osteoblast mitogenesis and enhances IGF-I action. Because osteoblast-derived IGFBP-5 is smaller than recombinant intact IGFBP-5 (23 vs 30 kDa) and has decreased binding affinity for IGF-I, we proposed that the native 23 kDa form of IGFBP-5 was truncated at a carboxy-terminal position. We now show that a recombinant form of carboxy-truncated IGFBP-5 binds IGF-I with reduced affinity and stimulates mitogenesis in mouse osteoblasts. We also show that 125I-truncated IGFBP-5 specifically binds to osteoblast monolayers with low binding affinity, similar to that seen with native 23 kDa IGFBP-5. These data indicate that carboxy-truncated IGFBP-5 stimulates osteoblast mitogenesis and suggest that reduced IGF-binding and cell-surface attachment are local mediators of this response.

Animals↗

PubMed1992

Human osteoblast-derived insulin-like growth factor (IGF) binding protein-5 stimulates osteoblast mitogenesis and potentiates IGF action.

Insulin-like growth factor (IGF)-binding proteins (IGFBPs) either inhibit or enhance IGF-stimulated cellular effects. While inhibition occurs by sequestration of IGF from cell-surface receptors, the exact mechanism of IGF-enhancement remains undefined. Human osteoblast-like bone cells in culture secrete several IGF-binding proteins, one of which we have previously identified as IGFBP-5. In this study we purified a 23-kDa IGFBP-5 from cultures of human osteoblast-like cells using ligand affinity chromatography and reversed-phase high performance liquid chromatography and tested its bioactivity in serum-free cultures of normal mouse osteoblast-like cells. Binding studies with radioiodinated IGF showed similar and relatively low affinities for IGF-I and IGF-II consistent with a carboxyl truncated IGF-binding protein. Mitogenic assays demonstrated that the binding protein, when coincubated with IGF-I or -II, enhanced mitogenesis. This enhancement was unique from other binding proteins in not requiring a preincubation period or serum co-factors. Furthermore, the osteoblast-derived IGFBP-5 stimulated mitogenesis in the absence of exogenous or endogenous IGF. Using radioiodinated IGFBP-5 we found that the binding protein could associate with the osteoblast surface, an effect which did not require IGF nor an interaction with IGF receptors. We suggest that osteoblast-derived IGFBP-5 may stimulate osteoblast mitogenesis in at least two ways, by association with IGF and by a second pathway that is independent of IGF receptor activation.

Animals↗

PubMed1991

A novel human insulin-like growth factor binding protein secreted by osteoblast-like cells.

Insulin-like growth factor binding proteins (IGFBPs) modulate the cellular action of the insulin-like growth factors. Inhibition or enhancement of IGF effects by these cell-secreted binding proteins have been described. We have purified two IGFBPs (23 and 29 kDa) from media conditioned by U-2 human osteosarcoma cells using ligand-affinity chromatography and reversed phase HPLC. N-terminal amino acid analysis of the 23 kDa protein revealed a unique sequence with variable homology to IGFBPs 1-4. The 29 kDa IGFBP was found to be nearly identical to a recently reported IGFBP. Because the affinity purified U-2 IGFBPs enhanced IGF-I-stimulated osteoblast mitogenesis, we suggest that one or both of these binding proteins enhance IGF action in bone.

Amino Acid Sequence↗

PubMed1991

Identification of a low molecular weight inhibitor of osteoblast mitogenesis in uremic plasma.

A low molecular weight inhibitor of cartilage sulfation has been detected in the plasma of dialysis patients. Preliminary studies of this inhibitor have suggested that it may have a role in decreasing bone mass, possibly by suppressing bone cell proliferation. Since the in vitro bioassay of crude sulfation inhibitor preparations is relatively nonspecific, we investigated whether there might also be an inhibitor of osteoblast mitogenesis in uremic plasma. We fractionated plasma and plasma ultrafiltrates from dialysis patients by gel filtration chromatography and looked for inhibition of mitogenesis in cultured osteoblasts. Material from fractions with a molecular weight range of 750 to 900 inhibited osteoblast mitogenesis. The inhibitory effect, however, could be overcome with serum or insulin-like growth factor-I, suggesting that the mechanism of inhibition was not growth factor dependent. Further characterization of the inhibitor revealed that it was not a peptide or a polar lipid. We conclude that uremic plasma contains a bone cell mitogenic inhibitor which may have a role in regulating bone remodeling in adults and bone growth in children.

Cell Division↗

PubMed1991

Beta 2-microglobulin deposition in bone in chronic renal failure.

Recently, there have been reports of beta 2-microglobulin (beta 2 m) related amyloid deposition in perineural and periarticular tissues in patients receiving long-term hemodialysis, but it has been rarely described in bone. We, therefore, examined previously obtained bone biopsy specimens in patients receiving long-term hemodialysis to determine the prevalence of beta 2 m deposition in bone and to assess the relationship between beta 2 m deposits and bone histomorphometry. We found beta 2 m deposits in bone in 8% of 224 patients examined. Bone deposition of beta 2 m was absent in patients who were on dialysis for less than six years, but was present in 19% who dialyzed longer than 10 years. beta 2 m deposits were found in specimens from the iliac crest, femoral bone, tibia, vertebra and rib. In the iliac crest beta 2 m deposition was localized predominantly to the periosteum. Among these patients with beta 2 m in iliac crest periosteum, 62% had suffered a femoral neck fracture compared to only 4% of matched patients who had negative staining for beta 2 m in the iliac crest (P less than 0.001). Histologically, osteitis fibrosa seemed more common in patients positive for beta 2m than in patients negative for beta 2m deposition. We conclude that beta 2m deposition in bone is common in uremic patients who have received hemodialysis longer than 10 years. The high prevalence of femoral neck fracture in patients with beta 2m localized to the periosteum of the iliac crest suggests that this involvement may be useful to predict susceptibility to femoral fracture.

Adolescent↗

PubMed1990

Low-molecular-weight peptides in bone extracts that stimulate osteoblast mitogenesis.

Although a majority of regulatory peptides elaborated by neuroendocrine cells are small, i.e., less than 50-60 residues, no low-molecular-weight, bone-derived mitogenic peptides have been described. We have size-fractionated extracts of neonatal mouse calvaria, a rapidly forming bone, and assayed for osteoblast proliferation. Mitogenic peptides with estimated sizes of 1,600, 1,050, and 770 daltons were detected. Their protein nature was demonstrated by the reduction in mitogenic activity following protease treatment. Fibroblast mitogenesis was not stimulated by any of the peptides. These data indicate that there are mitogenic peptides in bone smaller than any previously described locally-derived bone cell growth factor.

Animals↗

PubMed1989

Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure.

Osteitis fibrosa, a frequent complication of chronic renal failure, is characterized by increased rates of bone formation and bone resorption due to increased secretion of parathyroid hormone (PTH). Effective treatment with oral calcitriol is often impossible in patients with osteitis fibrosa, because low doses may cause hypercalcemia. Because short-term infusions of intravenous calcitriol are capable of suppressing the secretion of parathyroid hormone in patients with uremia without causing hypercalcemia, we evaluated the effectiveness of long-term intermittent calcitriol infusions (1.0 to 2.5 micrograms three times weekly, during dialysis) in treating severe osteitis fibrosa in 12 consecutive patients on hemodialysis whose disease was refractory to conventional therapy. After a mean (+/- SE) treatment period of 11.5 +/- 1.4 months, the mean bone-formation rate declined from 1642 +/- 277 to 676 +/- 106 microns 2 per square millimeter per day (P less than 0.01) in the 11 patients who successfully completed the study. Similar reductions occurred in the osteoblastic osteoid (18 +/- 3 to 9 +/- 2 percent; P less than 0.01) and the degree of marrow fibrosis (6.2 +/- 1.7 to 3.5 +/- 1.3 percent; P = 0.01). Concomitant serum biochemical changes included increased calcium levels (2.55 +/- 0.03 to 2.67 +/- 0.05 mmol per liter; P less than 0.01), decreased alkaline phosphatase levels (489 +/- 77 to 184 +/- 32 U per liter; P less than 0.001), and decreased levels of PTH (amino-terminal, 172 +/- 34 to 69 +/- 16 ng per liter in five patients, P less than 0.03; and carboxy-terminal, 1468 +/- 467 to 1083 +/- 402 ml-eq per liter in six patients, P not significant). Although the majority of the patients had transient episodes of asymptomatic hypercalcemia, this complication could be quickly reversed by temporarily halting treatment or decreasing the dose of calcitriol. We conclude that long-term intermittent infusions of intravenous calcitriol are effective in ameliorating osteitis fibrosa in patients on dialysis. Patients whose osteitis fibrosa is refractory to oral calcitriol and who are candidates for parathyroidectomy should be considered first for intravenous calcitriol therapy.

Adult↗

PubMed1989

Plasma insulin-like growth factors and bone formation in uremic hyperparathyroidism.

Bone formation in uremia is considered to be regulated in part by parathyroid hormone (PTH). However, while low levels of immunoreactive PTH are usually associated with low rates of bone formation in uremia, elevated PTH levels do not always correlate with increased bone formation. In an attempt to identify other factors that may regulate bone formation in uremic patients, we measured plasma immunoreactive insulin-like growth factors (IGF-I and IGF-II) in 15 patients who did not have aluminum-associated reductions in bone formation. Plasma levels of IGF-I but not PTH, were significantly higher in patients with high rates of bone formation when compared to patients with low or normal bone formation (P less than 0.02). While the bone formation rate at the tissue level correlated significantly with plasma PTH (r = 0.53, P less than 0.05) and IGF-I (r = 0.67, P less than 0.01), only for plasma IGF-I were there significant correlations with bone apposition (r = 0.57, P less than 0.05) and bone formation rate at the BMU level (r = 0.62, P less than 0.02), parameters which reflect mineralization activity at the cellular level. Among the static histologic parameters, osteoblastic osteoid correlated only with plasma PTH (r = 0.76, P less than 0.001), while osteoclast number correlated with both PTH (r = 0.56, P less than 0.05) and IGF-I (r = 0.67, P less than 0.01). There were no correlations between IGF-II levels and bone histology. From these data we suggest that IGF-I may promote bone formation in uremic patients with hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Aluminum-related osteodystrophy.

In this review, we have discussed the history, clinical course, and what is known about the epidemiology and pathology of aluminum-related bone disease in patients with renal failure. In addition, we have reviewed current thoughts about prevention and treatment. This disorder of medical progress, along with the other forms of renal osteodystrophy, has provided us important new information about calcium regulation and bone. These insights may well permit better understanding and management of much more common skeletal disorders.

Aluminum↗

PubMed1988

Bone aluminum accumulation in hemodialysis patients: a longitudinal perspective.

Serial bone biopsies obtained from 19 chronic hemodialysis patients asymptomatic for bone disease were examined retrospectively. We found only modest amounts of stainable bone aluminum after the first few years of hemodialysis therapy. Over the ensuing 5 to 15 years, there was a progressive increase in stainable bone aluminum (% of total bone surface): 0 to 4.9 years, 19.9 +/- 3.8% (mean +/- SEM); 5.0 to 9.9 years, 28.4 +/- 5.3%; and greater than or equal to 10.0 years, 58.0 +/- 7.7%. At final biopsy, the extent of bone surface aluminum was significantly correlated with duration of hemodialysis therapy (r = 0.54) and with bone formation rate (BFR) (r = -0.54). Patients who developed aluminum-associated bone disease did not differ from other patients in duration of hemodialysis, intake of 1-hydroxylated vitamin D3 compounds, or the findings on early bone biopsy. High-turnover renal osteodystrophy remains the dominant bone lesion throughout the course of hemodialysis in patients with intact parathyroid glands. In individual patients, bone histology frequently changes over time and in some patients, aluminum-associated bone disease may improve spontaneously. Bone biopsy in an asymptomatic patient who has received hemodialysis therapy for less than 5 years does not appear to be useful in predicting the subsequent appearance of aluminum-associated bone disease.

Adult↗

PubMed1988

Reversal of aluminum-related bone disease after substituting calcium carbonate for aluminum hydroxide.

Aluminum-related osteodystrophy, a crippling disease in patients with renal failure, can develop from the long-term ingestion of aluminum hydroxide gels. We present a diabetic patient treated with continuous ambulatory peritoneal dialysis (CAPD) who developed markedly elevated plasma aluminum levels but no musculoskeletal symptoms. Bone biopsy revealed features of the aplastic form of aluminum-related disease with significant aluminum staining, decreased osteoblastic osteoid, and decreased bone formation by double tetracycline labeling, but no excess accumulation of unmineralized osteoid. Aluminum hydroxide gels were discontinued and the patient received calcium carbonate to control hyperphosphatemia; 9 months later, a bone biopsy showed marked improvement of the aluminum-related bone disease, and at 2 to 10 months, plasma aluminum had decreased from 208.7 +/- 10.3 (SE) to 55.7 +/- 3.9 micrograms/L.

Aged↗

PubMed1987

Early deposition of aluminum in bone in diabetic patients on hemodialysis.

Aluminum-associated bone disease is a special problem in uremic patients on hemodialysis. We have observed this disorder in uremic patients with insulin-dependent diabetes soon after the start of dialysis treatments. We therefore studied bone biopsy specimens from 18 diabetic patients on hemodialysis to determine whether aluminum accumulates on bone surfaces at an accelerated rate in diabetes. We also measured the rates of bone formation, because lower rates may enhance the accumulation of aluminum on bone surfaces. As compared with 18 nondiabetic controls with uremia who were matched for age and duration of dialysis, the patients with diabetes had a higher rate of aluminum accumulation on bone surfaces (2.1 +/- 0.7 vs. 0.4 +/- 0.2 percent per month, P less than 0.01) and a lower rate of bone formation (117 +/- 50 vs. 396 +/- 81 microns 2 per square millimeter per day, P less than 0.01). Also, the patients with diabetes whose cumulative aluminum intake exceeded 0.5 kg had higher serum aluminum levels after an infusion of deferoxamine, as compared with controls matched for aluminum intake (P less than 0.01). These measurements reflected a higher aluminum content in the whole body in patients with diabetes. We suggest that the enhanced rate of aluminum accumulation on bone surfaces in uremic patients with diabetes occurs as a result of a low rate of bone formation and an increased accumulation of aluminum in the whole body.

Aluminum↗

PubMed1987

Bone histomorphometry of renal osteodystrophy in diabetic patients.

Bone biopsies and plasma parathyroid hormone (PTH) from 27 diabetic dialysis patients were compared to biopsies and PTH levels from matched patients without diabetes to determine if PTH has a role in preserving bone mass in diabetic renal osteodystrophy. Significantly lower values were present in the diabetic group for mineralized bone area (p less than 0.003), osteoblastic osteoid (p less than 0.01), resorptive surface (p less than 0.001), fibrosis (p less than 0.005), bone apposition rate (p less than 0.01), bone formation rate (BMU level) (p less than 0.04), and plasma PTH (p less than 0.05). Bone-surface aluminum was higher in the diabetic group (44 +/- 5% vs. 20 +/- 5%, p less than 0.005). Linear regression analysis revealed significant positive correlations of mineralized bone area with time on dialysis, bone formation rate, bone resorption, and PTH only in the group without diabetes. While both groups had significant positive correlations of PTH with osteoblastic osteoid and bone resorption, only in the nondiabetic group was there a positive correlation of PTH with bone apposition and bone formation rate (BMU level), observations suggesting that the lower bone formation in the diabetic patients may have arisen in part from a failure of PTH to promote bone mineralization. We conclude that relatively low PTH levels and high bone aluminum in diabetic patients with chronic renal failure may be responsible in part for low bone mass when compared to uremic patients without diabetes.

Adult↗

PubMed1987

Bone histologic response to deferoxamine in aluminum-related bone disease.

We have examined the changes in bone histology in 28 uremic patients after long-term treatment with the aluminum chelator, deferoxamine. Marked declines in stainable bone-surface aluminum were associated with increases in bone formation rate and osteoblastic osteoid following deferoxamine. The increased bone formation resulted from increases in bone apposition and length of double-tetracycline labels, the latter being highly correlated with the increase in osteoblastic osteoid (r = 0.85). While bone surface aluminum was highly correlated with bone formation rate (r = .69, p less than .001), bone aluminum content did not correlate with bone formation (r = 0.13) and was often elevated after treatment despite an improvement in bone histology. Patients who had undergone prior parathyroidectomy were less likely to have improved bone histology than those with intact parathyroid glands. We conclude that aluminum chelation therapy with deferoxamine is effective in ameliorating the bone histology of patients with chronic renal failure and bone aluminum accumulation, and that the change in stainable bone-surface aluminum is a more sensitive indicator than the change in bone aluminum content in assessing adequacy of chelation therapy. Patients who need deferoxamine treatment but have undergone a prior parathyroidectomy will probably require a more intensive treatment schedule than those who have intact parathyroid glands.

Aluminum↗