Biomedical subjects

Kaisa K Ivaska

Publications and source records attributed to Kaisa K Ivaska.

7 recordsLinked to original sources

PubMed2004

Development of sensitive immunoassays for free and total human glandular kallikrein 2.

BACKGROUND: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity. METHODS: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2. The total hK2 assay used PSA-specific antibodies to block nonspecific signal. The capture antibody of the free hK2 assay did not cross-react with PSA. To determine the hK2 concentrations in the male bloodstream, total hK2 was measured in a control group consisting of 426 noncharacterized serum samples. Free and total hK2 were measured in plasma from 103 patients with confirmed prostate cancer. RESULTS: All 426 males in the control group had a total hK2 concentration above the detection limit of 0.0008 microg/L. The median total hK2 concentration was 0.022 microg/L (range, 0.0015-0.37 microg/L). hK2 concentrations were 0.1-58% of total PSA (median, 3.6%). hK2 concentrations were similar in men 41-50 and 51-60 years of age. The ratio of hK2 to PSA steadily decreased from 5-30% at PSA <1 microg/L to 1-2% at higher PSA concentrations. In 103 patients with prostate cancer, the median hK2 concentration in plasma was 0.079 microg/L (range, 0.0015-16.2 microg/L). The median free hK2 concentration was 0.070 (range, 0.005-12.2) microg/L. The proportion of free to total hK2 varied from 17% to 131% (mean, 85%). CONCLUSIONS: The wide variation in the free-to-total hK2 ratio suggests that hK2 in blood plasma is not consistently in the free, noncomplexed form in patients with prostate cancer. The new assay is sufficiently sensitive to be used to study the diagnostic accuracies of free and total hK2 for prostate cancer.

Adult↗

PubMed2004

Osteoclast-derived serum tartrate-resistant acid phosphatase 5b in Albers-Schonberg disease (type II autosomal dominant osteopetrosis).

BACKGROUND: Albers-Schönberg disease, or autosomal dominant osteopetrosis type II (ADO2), is caused by ineffective osteoclastic bone resorption resulting from mutations in the chloride channel 7 (ClCN7) gene. Individuals with ADO2 have increased numbers of large ineffective osteoclasts in addition to increased serum total tartrate-resistant acid phosphatase (TRACP) activity. METHODS: We investigated the serum activity of the osteoclast-derived 5b isoform of TRACP (TRACP 5b) and concentrations of the bone formation marker osteocalcin in clinically affected individuals, unaffected gene carriers, and healthy controls from 10 ADO2 families with known ClCN7 gene mutations. Bone fracture prevalence was studied in association with the serum markers. RESULTS: Similar to total TRACP, TRACP 5b was significantly increased in clinically affected individuals compared with age-matched controls. TRACP 5b correlated significantly with total TRACP (r = 0.833; P <0.001), suggesting that most of the TRACP in the serum of ADO2 patients is osteoclast-derived TRACP 5b. Osteocalcin was significantly increased in affected adults and slightly decreased in affected children. TRACP 5b and total TRACP were significantly increased in clinically affected individuals with severe fractures (P <0.05). CONCLUSIONS: The results indicate that in ADO2, serum TRACP 5b reflects the number of osteoclasts and that the extremely high serum TRACP 5b activity is a specific indicator of the disease. Similar to total TRACP, TRACP 5b appears to be a potentially useful marker to stratify individuals with ClCN7 gene mutations into clinically affected and unaffected gene carriers. It may also have a prognostic value in the prediction of fractures in patients with a ClCN7 gene mutation.

Acid Phosphatase↗

PubMed2004

Release of intact and fragmented osteocalcin molecules from bone matrix during bone resorption in vitro.

Osteocalcin detected from serum samples is considered a specific marker of osteoblast activity and bone formation rate. However, osteocalcin embedded in bone matrix must also be released during bone resorption. To understand the contribution of each type of bone cell in circulating osteocalcin levels, we used immunoassays detecting different molecular forms of osteocalcin to monitor bone resorption in vitro. Osteoclasts were obtained from rat long bones and cultured on bovine bone slices using osteocalcin-depleted fetal bovine serum. In addition, human osteoclasts differentiated from peripheral blood mononuclear cells were used. Both rat and human osteoclasts released osteocalcin from bovine bone into medium. The amount of osteocalcin increased in the presence of parathyroid hormone, a stimulator of resorption, and decreased in the presence of bafilomycin A1, an inhibitor of resorption. The amount of osteocalcin in the medium correlated with a well characterized marker of bone resorption, the C-terminal telopeptide of type I collagen (r > 0.9, p < 0.0001). The heterogeneity of released osteocalcin was determined using reverse phase high performance liquid chromatography, and several molecular forms of osteocalcin, including intact molecule, were identified in the culture medium. In conclusion, osteocalcin is released from the bone matrix during bone resorption as intact molecules and fragments. In addition to the conventional use as a marker of bone formation, osteocalcin can be used as a marker of bone resorption in vitro. Furthermore, bone matrix-derived osteocalcin may contribute to circulating osteocalcin levels, suggesting that serum osteocalcin should be considered as a marker of bone turnover rather than bone formation.

Animals↗

PubMed2004

Serum estradiol, testosterone, and sex hormone-binding globulin as regulators of peak bone mass and bone turnover rate in young Finnish men.

To study the role of serum testosterone (T), estradiol (E(2)), and SHBG as regulators of peak bone mass and bone turnover rate in males, a cross-sectional study with data on lifestyle factors collected retrospectively was performed in 204 young Finnish men, 18.3-20.6 yr old. One hundred fifty-four men were recruits of the Finnish Army, and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content, density, and scan area were measured in lumbar spine and upper femur by dual-energy x-ray absorptiometry. Blood was sampled for determination of serum total and free T, total and free E(2), SHBG, type I procollagen aminoterminal propeptide (PINP), total osteocalcin (TOC) and carboxylated osteocalcin (COC), and tartrate-resistant acid phosphatase 5b (TRACP5b); and urine was collected for determination of type I collagen aminoterminal telopeptide (NTX). Serum sex steroid concentrations did not associate with bone mineral content, scan area, or bone mineral density, adjusted for anthropometric and lifestyle factors at any measurement site. Instead, serum total (r = 0.23; P = 0.008) and free (r = 0.15; P = 0.023) T were positive predictors of serum TOC, whereas serum free E(2) correlated inversely with serum PINP (r = -0.20; P = 0.0039), TOC (r = -0.12; P = 0.086), COC (r = -0.14; P = 0.036), and urinary NTX (r = -0.15; P = 0.041). Interestingly, serum SHBG correlated positively with all the bone markers studied, the correlation coefficients being 0.18 for serum PINP (P = 0.012), 0.24 for TOC (P = 0.0006), 0.24 for COC (P = 0.0005), 0.27 for serum TRACP5b (P < 0.0001), and 0.21 for urine NTX (P = 0.0031). Serum SHBG was also a positive predictor of serum 25-hydroxyvitamin-D level (r = 0.20; P = 0.0036). The correlations of SHBG persisted after adjusting for weight, free E(2), and free T. We conclude that single measurements of serum E(2) and T were not determinants of peak bone mass in this population of young men. However, E(2) and T contributed to bone turnover rate, with serum T increasing bone formation, and serum E(2) suppressing both bone formation and resorption. Moreover, serum SHBG appeared to be an independent positive predictor of bone turnover rate, which also positively associated with serum 25-hydroxyvitamin-D levels.

Adult↗

PubMed2003

Biochemical markers of bone metabolism and prediction of fracture in elderly women.

UNLABELLED: We studied the ability of various markers of bone turnover to predict fracture in 1040 randomly recruited 75-year-old women. A total of 178 of the women sustained at least one fracture during follow-up (mean, 4.6 years). In elderly women, TRACP5b and urinary fragments of osteocalcin are promising new markers for prediction of fracture, in particular, vertebral fracture. INTRODUCTION: Biochemical markers reflecting bone turnover may improve the prediction of fractures. MATERIALS AND METHODS: The ability of 10 markers of bone turnover to predict fracture in 1040 elderly women in the Malmö OPRA study was studied. Serum bone-specific alkaline phosphatase and four different forms of serum osteocalcin (S-OC) were analyzed as markers of bone formation and serum C-terminal cross-linking telopeptides of type I collagen (S-CTX), serum TRACP isoform 5b (S-TRACP5b) and urinary free deoxypyridinoline (U-DPD) as markers of bone resorption. Two novel assays for osteocalcin fragments in urine (U-OC) were analyzed. Areal BMD (aBMD) was measured by DXA in the femoral neck and lumbar spine. RESULTS: In total, 231 fractures were sustained by 178 of the women during a 3- to 6.5-year (mean, 4.6 years) follow-up period. When women with prospective fractures were compared with women without fractures, S-TRACP5b, S-CTX, one S-OC, and one U-OC were higher in women with a fracture of any type (all p < 0.05), and all bone markers were higher in women with clinical vertebral fracture (all p < 0.05). Markers were not significantly elevated in women with hip fracture. When women within the highest quartile of a bone marker were compared with all others, S-TRACP5b and one U-OC predicted the occurrence of a fracture of any type (odds ratio [OR]), 1.55 and 1.53; p < 0.05). S-TRACP5b, the two U-OCs, and S-CTX predicted vertebral fracture (OR, 2.28, 2.75, 2.71, and 1.94, respectively; all p < 0.05), and the predictive value remained significant for S-TRACP5b and the two U-OCs after adjusting for aBMD (OR, 2.02-2.25; p < 0.05). Bone markers were not able to predict hip fracture. CONCLUSION: These results show that biochemical markers of bone turnover can predict fracture, and in particular, fractures that engage trabecular bone. S-TRACP5b and U-OC are promising new markers for prediction of fracture.

Aged↗

PubMed2003

Osteoblast recruitment from stem cells does not decrease by age at late adulthood.

This study was aimed to characterize the ability of human bone marrow mesenchymal stem cells (MSC) to differentiate into osteoblasts in vitro. Twenty-three women and 20 men at late adulthood (52-92 years of age) were selected for the study. MSCs were isolated and cultured in vitro and alkaline phosphatase (ALP) activity, secretion of amino-terminal propeptide of type I procollagen (PINP), type III procollagen (PIIINP) and osteocalcin were analyzed. Matrix mineralization was analyzed by the von Kossa staining and by calcium quantification. We found that the ALP and PINP levels compared with control increased to 2.8- and 2.9-fold, respectively, when cells were cultured for three weeks. ALP activity, PINP and calcium deposition in response to dexamethasone treatment increased by age in women and was unchanged in men. Overall our data suggests that the osteogenic potential of MSCs does not decrease by age in either women or men at late adulthood.

Age Factors↗

PubMed2003

Identification of novel proteolytic forms of osteocalcin in human urine.

In this study, we report the isolation and characterization of osteocalcin in human urine using mass spectrometry and N-terminal sequencing. Multiple proteolytic forms of osteocalcin were found, which consisted of 16-27 residues from the middle region of the molecule. Several fragments had residue Gly7 at the N-terminus and the most predominant was fragment 7-31. Additional fragments starting from residue Asp14 were detected in the samples of children and young adults. Immunochemical detection of urine osteocalcin fragments had a statistically significant negative correlation to bone mineral density in evaluation of urine samples from 75-year-old women. Thus, the measurement of osteocalcin fragments in urine may have potential applications in diagnostics related to disorders of bone metabolism.

Aged↗