[Pyridinium cross-links in the urine. Specific markers of bone resorption in metabolic bone diseases].
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Biomedical subjects
Publications and source records attributed to R Ziegler.
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Larvae of two insects, a coccinellid beetle (Hyperaspis trifurcata) and a chamaemyiid fly (Leucopis sp.), feed on cochineal insects and appropriate their prey's defensive chemical, carminic acid, for protective purposes of their own. H. trifurcata discharges the chemical with droplets of blood (hemolymph) that it emits when disturbed; Leucopis sp. ejects the compound with rectal fluid. Ants are thwarted by these defenses, which are compared with the previously-described defense of a pyralid caterpillar (Laetilia coccidivora) that disgorges carminic acid-laden crop fluid. The defensive fluid of all three larvae contains carminic acid at concentrations spanning a range (0.2-6.2%) proven deterrent to ants. Many insects are known to appropriate defensive substances from plants. Insects that acquire defensive chemicals from animal sources may be relatively rare.
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A 72-year-old woman with Paget's disease of the femur (increasing curvature of the femur in the last 20 years, lately with ever more pain on walking) was at first treated with salmon calcitonin, daily 400 IU nasally, for 2 years. As a result, alkaline phosphatase (AP) concentration fell from initially 703 U/l, to 401 U/l after 7 months' treatment. An increase in AP concentration was first noted after 10 months of treatment, rising after 24 months to 688 U/l. The symptoms, initially having responded rather well to therapy, markedly progressed. In parallel, titres were recorded for binding (maximally 1:100) and neutralizing antibodies (neutralizing action maximally 75%) against salmon calcitonin. Because of the development of secondary resistance to salmon calcitonin the medication was changed to human calcitonin (100 IU daily, subcutaneously). This again resulted in a fall of the AP concentration (to 319 U/l), which remained essentially unchanged (401 U/l) over a period of 17 months on 100 IU human calcitonin three times weekly.
The urinary pyridinium crosslinks pyridinoline (PYD) and deoxypyridinoline (DPD) have been shown to provide valid indices of bone resorption. At present, both crosslink components are determined by reversed-phase HPLC, a time-consuming method precluding the use of these markers for routine purposes. Therefore, efforts have been made to develop simple immunoassays for the rapid measurement of urinary crosslinks, and their application to large-scale osteoporosis screening has been proposed. To evaluate the applicability and diagnostic validity of pyridinium crosslink measurements for screening purposes, urinary concentrations of total and free PYD and DPD were determined by HPLC and immunoassay technique (ELISA) in a sample of 269 individuals (male to female ratio = 130:139; age 50-81 years) recruited at random within a population survey of vertebral osteoporosis. On a molar basis, ELISA measures of crosslink-related epitopes were highly correlated with both total and free PYD and DPD as determined by HPLC (r > 0.82, p < 0.001). Age-specific means for creatinine-corrected total and free pyridinium crosslinks were significantly higher in females than in males (p < 0.001). In both sexes, neither age nor anthropometric variables (weight, height, and body mass index) showed a linear effect on the urinary crosslink/creatinine ratio. On average, 50% of the total amount of urinary crosslinks were present in free form. For both PYD and DPD, this proportion was significantly higher in women than in men (p < 0.05), but no change was observed with age or anthropometric measures. The excretion of pyridinium crosslinks was higher in osteoporotic (n = 18) than in nonosteoporotic individuals (n = 208) from the same population.(ABSTRACT TRUNCATED AT 250 WORDS)
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Serum amyloid A protein (SAA) concentrations were monitored in 12 consecutive liver transplant recipients until the 70th postoperative day. Fourteen rejection episodes were identified histologically in 42 liver biopsies of the grafts. Of 12 rejections 8 (66.7%) were characterized by pronounced simultaneous increases in SAA concentrations in plasma, the mean peak value being 16.94 +/- 8.82 mg/dl (range 4.58-28.55 mg/dl) compared with a mean normal value of 0.98 +/- 0.42 mg/dl in healthy controls. Of 42 biopsies 28 did not show histological evidence of graft rejection. Of 25 negative biopsies 24 (96.0%) were not accompanied by a parallel SAA increase in plasma. These findings demonstrate that measurements of SAA concentrations may provide a valuable noninvasive aid in identifying acute liver allograft rejection in humans.
Within the European vertebral osteoporosis study four stratified systematic samples of German residents aged 50-79 in Lübeck, Heidelberg, Jena and East Berlin have been drawn. Overall 4628 subjects were included, of whom 4385 were contactable and 3106 (71%) responded to the postal questionnaire enquiring about rheumatic complaints "today". 2348 (54%) followed an invitation to a medical examination in which a specific gynaecological history was taken. The prevalence of current back-, neck- and joint-pain is consistently higher in females than in males in all age groups. Females show a peak prevalence in the age group 55-64. 104/1134 women were pre- or perimenopausal. 1030 women had not had their period for at least 13 months and were classified as "postmenopausal". Neither the menopausal status nor the duration of the postmenopause were statistically significantly associated with the frequency of the three rheumatic complaints.
There is no agreed definition for the assessment of vertebral fractures and deformities in patients with osteoporosis. Radiographs of 66 patients randomized for therapy with etidronate or placebo were analyzed at baseline and during follow-up (60/120/150 weeks) independently using two procedures. The first method of spinal deformity index (SDIG) and vertebral deformity score (VDSG) is based on a semiquantitative visual reading of each vertebra between T4 and L4. The second method of spine deformity index (SDIM) and vertebral deformity index (VDIM) is based on vertebral height measurements of T4 through L5 and each measurement from T5 to L5 (anterior, middle and posterior height) is related to T4 and compared with the respective T4-related normal range. There was good agreement between the mean vertebral deformation from T5 to L4 graded by VDSG and VDIM, with correlation coefficients between R = 0.52 (p < 0.0001) and R = 0.9 (p < 0.0001) respectively. Spinal deformation at baseline as measured by SDIM and SDIG was correlated with R = 0.76 (p < 0.0001). For diagnosing a vertebra as fractured or not, VDIM reached a sensitivity of 82% and a specificity of 85% using VDSG as a standard, and on the other hand VDSG reached a sensitivity of 78% and a specificity of 88% in relation to VDIM. The changes in spinal deformation from week 0 to 150 were correlated with R = 0.58 (p < 0.0002) between SDIM and SDIG. To detect vertebral fracture progression the sensitivity of VDIM was 74% and the specificity 86%, when changes in VDSG were used as a standard.(ABSTRACT TRUNCATED AT 250 WORDS)
Low bone mass as estimated by decreased bone mineral density (BMD) is an established predictor of osteoporotic fractures. One of the latest developments in bone densitometry is peripheral quantitative computed tomography (pQCT) of the forearm. In Germany, the CT bone scanner XCT 900 has already been widely used; however, interpretation of measurements with respect to osteoporosis risk assessment can be improved by better defined and validated reference data. In the present study, this device was used to measure BMD at the distal radius in a well-defined healthy population of 179 German adults (91 men, 88 women) aged 20-79 years. In vivo precision was 1.67% for trabecular and 0.81% for total BMD measurements. Peak values of trabecular and total BMD were observed at the ages 40-50 years in women and 30-40 years in men. Beyond these ages, both trabecular and total BMD showed a linear decline with age, decreasing by 0.85% and 1.08% per year in women and by 0.59% and 0.54% in men, respectively. Measures of BMD were not influenced by weight, height or body mass index (BMI). In both sexes, trabecular and total radial BMD showed a positive and significant correlation with femoral BMD measures obtained by dual X-ray absorptiometry (DXA). Weaker correlations were observed with DXA measures of the lumbar spine. Compared with the 95% reference range provided by the manufacturer, the distribution of age- and sex-specific values of trabecular BMD of the distal radius was shifted to lower values by up to 1 standard deviation.(ABSTRACT TRUNCATED AT 250 WORDS)
There is a definite hope to considerably reduce the number of osteoporotic fractures in the future. However, there are several reasons to assume that osteoporosis as a disease will remain a problem in the future: (1) the population is aging, and many people will live long enough to develop a bone mineral density lower than the fracture threshold; (2) the secular trend shows that more handicapped people reach the 'fracture age'; (3) osteoporosis may develop in spite of adequate treatment; (4) prophylaxis with HRT is limited by lower compliance at older age. Efficient treatment strategies should therefore be developed for osteoporosis with fractures also in the future.
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Inflammatory bowel disease (Crohn's disease and ulcerative colitis) is associated with decreased bone mineral density and increased risk of osteoporosis. However, the pathogenesis of this bone loss is not yet fully understood. In the present study we measured lumbar bone mineral density (by dual photon absorptiometry), serum levels of parathyroid hormone (PTH) and vitamin D metabolites, and serum markers of bone turnover (alkaline phosphatase and osteocalcin) in 15 patients with Crohn's disease and in 4 patients with ulcerative colitis. The median duration of the disease was 4 years and the median lifetime steroid dose was 10g of prednisone. We compared our results to a control group of 19 normal persons, who were matched for age and sex to the patients. We found that lumbar bone density was reduced by 11% in patients compared with control persons (Z-score -0.6 +/- 0.6 versus -0.1 +/- 0.8; p < 0.05). In patients, the serum levels of PTH, 25-hydroxyvitamin D3, and calcitriol (1,25(OH)2D3) were significantly reduced compared with control persons. Serum alkaline phosphatase activity (AP) was significantly higher in the patients and was inversely related to lumbar bone density. Osteocalcin values were not different between patients and control persons. There was also no difference in serum levels of calcium between the two groups, whereas phosphorus levels were higher in patients. We conclude that malabsorption of calcium was not a primary cause of bone loss in our patients, because we did not find secondary hyperparathyroidism. Accordingly, we did not find a severe vitamin D deficiency, since 25-hydroxyvitamin D3 levels were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVES: The familial lipoprotein disorder type III hyperlipoproteinaemia (HLP) carries a marked increase in the risk of accelerated and premature atherosclerosis, but there is considerable variation amongst affected individuals in their susceptibility to cardiovascular disease (CVD). Therefore, it was the aim of our study to investigate the possible influence of lipoprotein (a) [Lp(a)] in the pathogenesis of type III HLP: DESIGN: Apolipoprotein (a) [apo(a)] phenotypes and Lp(a) concentrations were determined in patients with the disease and in an appropriate control group. SETTING: University out-patient lipid disorder clinic. SUBJECTS: Seventy-six apoE-2 homozygous patients with type III HLP and 76 normolipidaemic and healthy age- and sex-matched controls. MAIN OUTCOME MEASURES: The frequencies of different apo(a) phenotypes and their correlations with Lp(a) serum concentrations were determined in patients and controls. RESULTS: Lp(a) concentrations were not significantly different in type III HLP patients (14.1 +/- 19.1 mg dl-1) as compared with the controls (13.3 +/- 16.2 mg dl-1; P = 0.549, NS). In addition, there was no significant difference in apo(a) phenotype frequencies amongst both groups (0.2 > P > 0.1). CONCLUSIONS: We conclude that the apo(a) polymorphism does not participate (to a significant extent) in the phenotypical expression of type III HLP:
Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or underexpress (antisense construct) tissue factor. In vitro, there was no difference in plating efficiency or growth between these cell lines. In vivo, tumor cells transfected to overexpress tissue factor grew more rapidly, and established larger and more vascularized tumors than control transfectants. Antisense transfectants grew the slowest and were the least vascularized. Anticoagulation of mice with warfarin did not alter the difference between these tumor lines. Tumor cells over-expressing tissue factor released more (compared with control transfectants) mitogenic activity for endothelial cells in parallel with enhanced transcription of vascular permeability factor/vascular endothelial cell growth factor (VEGF/VPF), and diminished transcription of thrombospondin (TSP2), a molecule with anti-angiogenic properties. Antisense tissue factor transfectants, while releasing the lowest amount of mitogenic activity, had increased thrombospondin and decreased VEGF/VPF transcription compared with control transfectants or wild-type cells. Experiments with these sense, antisense, truncated sense, or vector tumor lines gave comparable results in complete medium, serum free medium or in the presence of hirudin, indicating that the activation of the coagulation mechanism was not likely to be responsible for changes in tumor cell properties. These results suggest that tissue factor regulates angiogenic properties of tumor cells by altering the production of growth regulatory molecules of endothelium by a mechanism distinct from tissue factor activation of the coagulation mechanism.
1,25-Dihydroxyvitamin D3 (1,25D3) inhibits cell growth and induces differentiation in many cell systems by inhibition of c-myc gene expression. In the human medullary thyroid carcinoma cell line (TT), c-myc gene expression appears to be closely related to cell proliferation and differentiation. TT cells are also a well known target system for 1,25D3, which inhibits calcitonin (CT) gene expression in these cells. So far, no direct cis-acting vitamin D-responsive element could be identified in the promoter region of the CT gene. We, therefore, investigated potential indirect mechanisms of 1,25D3-mediated CT gene expression by examining the hormone's effects on proliferation. In contrast to its well established antiproliferative action in other cell systems, addition of 1,25D3 to TT cells led to a 2.3-fold stimulation of DNA synthesis, which was maximal after 48 h and was preceded by a 4.8-fold increase in c-myc gene expression. c-Myc antisense DNA oligomers abolished the proliferative effect of 1,25D3, but not the latter's inhibition of CT gene expression. Here we present evidence that activation of c-myc gene expression mediates 1,25D3-stimulated TT cell proliferation, but not the 1,25D3-induced inhibition of CT gene expression.