The triply troubled teenager--chronic conditions associated with fewer protective factors and clustered risk behaviours.

AIM: This study aimed to measure protective factors and risk behaviour among adolescents with chronic conditions (CCs) and to evaluate the impact of protective factors on risk-taking. METHODS: A population-based study of 7262 students aged 15 and 17 years old was performed in Sörmland, Sweden 2008 (response rate 82%). The questionnaire explored background factors, CCs, risk behaviours and protective factors. CCs were reported by 8%, while 58% had no health problems. RESULTS: Girls with CCs encompassed less individual protective factors, while boys with CCs tended to over-report all individual risk behaviours compared with healthy peers. Both boys and girls with CCs were more likely to report few protective factors and co-occurrence of risk behaviours. The adjOR for clustered health risk behaviours was 1.6 (1.0-2.5) in youths with CCs and ≥4 protective factors and 6.3 (3.6-10.9) in youths with CCs and 0-3 protective factors, as compared to healthy peers with ≥4 protective factors. CONCLUSION: Adolescents with CCs reported fewer protective factors and more risk behaviours than their healthy peers. The vulnerability of adolescents with CCs and few protective factors is important to acknowledge. Professionals should provide stronger protection for these adolescents, to prevent risky behaviour.

Serglycin constitutively secreted by myeloma plasma cells is a potent inhibitor of bone mineralization in vitro.

Although the biological significance of proteoglycans (PGs) has previously been highlighted in multiple myeloma (MM), little is known about serglycin, which is a hematopoietic cell granule PG. In this study, we describe the expression and highly constitutive secretion of serglycin in several MM cell lines. Serglycin messenger RNA was detected in six MM cell lines. PGs were purified from conditioned medium of four MM cell lines, and serglycin substituted with 4-sulfated chondroitin sulfate was identified as the predominant PG. Flow cytometry and confocal microscopy showed that serglycin was also present intracellularly and on the cell surface, and attachment to the cell surface was at least in part dependent on intact glycosaminoglycan side chains. Immunohistochemical staining of bone marrow biopsies showed the presence of serglycin both in benign and malignant plasma cells. Immunoblotting in bone marrow aspirates from a limited number of patients with newly diagnosed MM revealed highly increased levels of serglycin in 30% of the cases. Serglycin isolated from myeloma plasma cells was found to influence the bone mineralization process through inhibition of the crystal growth rate of hydroxyapatite. This rate reduction was attributed to adsorption and further blocking of the active growth sites on the crystal surface. The apparent order of the crystallization reaction was found to be n=2, suggesting a surface diffusion-controlled spiral growth mechanism. Our findings suggest that serglycin release is a constitutive process, which may be of fundamental biological importance in the study of MM.

A sandwich ELISA for the estimation of human syndecan-2 and syndecan-4 in biological samples.

Syndecans are integral membrane proteoglycans containing both chondroitin and heparan sulphate side chains. Syndecans are shed from the cell surface, and may be detected in cellular supernatant or body fluids. In this study, we wished to design ELISA methods for syndecan-2 and syndecan-4, with the future aim of analyzing syndecans in large number of patient materials. Briefly, sandwich ELISAs for human syndecan-2 and syndecan-4 were designed employing monoclonal mouse antibodies as capture and commercially available polyclonal rabbit anti-syndecan as secondary antibodies. Although no quantified standard was available, relative estimation of syndecan-2 and syndecan-4 levels was possible in a small pilot material. The paper presents the ELISA method for these proteoglycans. We suggest that this may be a useful tool in the analysis of patient materials and in the detection of syndecans during proteoglycan purification.

Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma.

BACKGROUND AND OBJECTIVES: Osteopontin (OPN) is a non-collagenous matrix protein produced by various cells including osteoblasts, osteoclasts and several types of tumor cells. It is involved in a number of physiologic and pathologic events including adhesion, angiogenesis, apoptosis, inflammation, wound healing and tumor metastasis. We wanted to investigate the potential role of OPN in multiple myeloma. DESIGN AND METHODS: Myeloma cells and stromal cells from myeloma patients were investigated as potential OPN-producers. Furthermore, OPN was tested in proliferation, migration and adhesion assays with myeloma cells. Serum and plasma OPN in myeloma patients were measured by enzyme-linked immunosorbent assay (ELISA). OPN levels were correlated to disease variables at diagnosis and to disease outcome. RESULTS: Myeloma cells produce OPN, and stromal cells from myeloma patients express higher levels of OPN than stromal cells from healthy controls. The myeloma cell lines ANBL-6 and INA-6 adhered to OPN. NOD/SCID mice inoculated with OPN-producing ANBL-6 cells had elevated levels of murine OPN in serum, whereas human OPN was not detectable. Plasma and serum levels of OPN were significantly higher in myeloma patients than in healthy individuals. Interpretation and Conclusions. Myeloma cell lines adhere to OPN, indicating that elevated stromal expression of OPN may be one of the factors responsible for the retention of myeloma cells in the bone marrow. The elevated plasma OPN levels in myeloma patients could be due to both production of OPN by the tumor cells and tumor-induced production of OPN by non-tumor cells.

Increased levels of syndecan-1 in serum during acute graft-versus-host disease.

Acute graft-versus-host disease (GVHD) may affect several organs. Syndecan-1 is a heparan sulfate proteoglycan that can be shed from the surface of most epithelial cells (skin, liver, and gut among others), which are target organs for GVHD. Syndecan-1 was measured in serum samples from 60 patients after allogeneic stem-cell transplantation and was related to the degree of GVHD. Syndecan-1 levels increased in patients who developed acute GVHD but not in patients without GVHD. The difference between groups was significant 3 to 10 weeks after transplantation. The peak level of syndecan-1 in serum correlated with the degree of acute GVHD (r=0.46, P<0.001). Combined, the peak levels of syndecan-1 and soluble interleukin-2 receptor detected patients with acute GVHD (sensitivity 82%, specificity 89%). This study shows that syndecan-1 levels are increased during acute GVHD. Syndecan-1 may be a marker for acute GVHD, especially if combined with determination of soluble interleukin-2 receptor.

Hepatocyte growth factor in myeloma patients treated with high-dose chemotherapy.

Hepatocyte growth factor (HGF) is a cytokine produced by myeloma cells. We examined serum HGF levels in a population of young myeloma patients (median age 52 years) treated with high-dose chemotherapy. Sera from 128 myeloma patients at diagnosis and serial samples from 16 patients were analysed. Compared with 62 healthy controls, HGF was elevated at diagnosis in 25% of patients (median 0.48 and 1.08 ng/ml respectively; P < 0.0001). The 95 patients who completed therapy were analysed for the impact of HGF on survival. Median survival was not reached after 77 months in the patient group with normal HGF values (< 1.7 ng/ml, n = 69). In the group with elevated HGF (>/= 1.7 ng/ml, n = 26), median survival was 63 months (P = 0.08). In 16 patients, serum was drawn at diagnosis and at the time of expected disease remission (6 weeks to 3 months after chemotherapy). HGF values declined after treatment in 14 of these patients, from a median of 0.9 ng/ml (0.49-1.65) to 0.42 ng/ml (0.32-0.73) (P = 0.005). Our results show that in young myeloma patients HGF is elevated, and that patients with higher levels had a trend towards poorer prognosis. Treatment with high-dose chemotherapy reduced HGF in the serum of the majority of patients.

Serum insulinlike growth factor is not elevated in patients with multiple myeloma but is still a prognostic factor.

Insulinlike growth factor 1 (IGF-1) has growth-promoting effects on myeloma cells in vitro as well as in vivo. In this study, we measured the concentration of IGF-1 and its major binding protein, IGF- binding protein 3 (IGFBP-3), in serum from 127 patients with multiple myeloma. Serum had been drawn at the time of diagnosis, before treatment with high-dose melphalan. IGFBP-3 in myeloma patients (1.6 +/- 0.73 microg/mL; mean +/- SD) was significantly decreased compared to healthy age- and sex-matched controls (2.2 +/- 0.42 microg/mL). However, IGFBP-3 had no prognostic value in this study. The mean IGF-1 level did not differ between myeloma patients (17.8 +/- 7.7 nM) and controls (17.3 +/- 5.6 nM). Nevertheless, IGF-1 was a strong indicator of prognosis. After 80 months of follow-up, myeloma patients with low levels (< 13 nM) of serum IGF-1 had not reached median survival. In the patient group with IGF-1 levels above 13 nM, median survival was 62 months (P =.006). These findings support the hypothesis of a role for IGF-1 in myeloma disease progression.

Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells.

Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin-binding domain should be considered.