Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 199 records · Page 11Linked to original sources

PubMed1995

Differential effects of glucocorticoids on human osteoblastic cell metabolism in vitro.

Clinical observations suggest that the onset and severity of glucocorticoid (GC) induced osteoporosis is dependent on the duration of the GC treatment and the applied GC compound. To test whether these in vivo observations are reflected by different in vitro effects of various synthetic GCs on human bone cell metabolism we isolated human osteoblast-like cells (HOC) from bone biopsies of healthy (no clinical symptoms of arthritis or arthrosis) adults who underwent selective orthopedic surgery. HOC were identified as bone cells by 1,25-vitamin D3-stimulated increase of specific alkaline phosphatase (ALP) activity, secretion of osteocalcin and type-I procollagen peptide, and the ability to form mineral in vitro. We investigated the effects of dexamethasone (dexa), methylprednisolone (mpred), prednisolone (pred), and deflazacort (defla) on DNA-synthesis, ALP, and osteocalcin (OC)- and type-I procollagen peptide secretion of HOC in vitro. In summary, (1) GC exposure stimulates DNA synthesis after 6-12 hour treatment periods; (2) dex and mpred strongly inhibit DNA (48-hour treatment) and collagen synthesis but stimulate ALP, whereas pred and defla exhibit smaller effects on DNA synthesis, ALP, and collagen production; and (3) all tested glucocorticoids inhibit OC secretion by HOC in vitro. Thus, the effect of GC on DNA synthesis of HOC varies with the duration of GC exposure, and dex and mpred more potently affect HOC metabolism in vitro than pred and defla.

Adult↗

PubMed1995

Virtual reality arthroscopy training simulator.

This paper describes the result of the interdisciplinary cooperation of traumatologists of the Berufsgenossenschaftliche Unfallklinik (BGU) in Frankfurt am Main and a team of computer graphics scientists of the Franunhofer Institute for Computer Graphics in Darmstadt. We have developed a highly interactive training simulator system by means of computer graphics and virtual reality techniques.

Arthroscopy↗

PubMed1995

Apolipophorin-III and adipokinetic hormone in lipid metabolism of larval Manduca sexta.

The hemolymph lipid levels were measured and the density of lipophorin was determined during late larval development in Manduca sexta. During the feeding phase of the 4th and 5th instar larvae the lipid level in hemolymph remained largely unchanged at less than 2 mg/ml. During the molt from 4th to 5th instar, the hemolymph lipid level increased, but decreased after feeding restarted in the 5th instar. In wandering larvae and prepupae the hemolymph lipid level increased from about 2 to nearly 10 mg/ml. The density of lipophorin from feeding larvae was found to be 1.148 g/ml with minor amounts of lipophorin having a lower density of about 1.128 g/ml and sometimes a small amount with a density of 1.174 g/ml. In molting larvae, however, the density was clearly lower, 1.116 g/ml. In wandering larvae of all ages, two predominant forms of lipophorin were observed; the density of these forms was 1.132 g/ml and 1.177 g/ml. Rarely, one or three different forms of lipophorin were observed. While the lipophorin of feeding larvae contains only apoLp-I and II (and lipids), the lipophorin of molting larvae contains in addition apoLp-III. ApoLp-III is seldom present in lipophorin from wandering larvae. According to our current models, lipophorin can take up only a certain amount of diacylglycerol before it needs apoLp-III for surface stabilization. Injection of 1 pmol of M. sexta AKH into feeding larvae increased the hemolymph lipid level, decreased the density of lipophorin to 1.125 g/ml and resulted in the association of apoLp-III with lipophorin. Cardiacectomy did not prevent feeding larvae from developing to wandering larvae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Biotin-containing proteins of the insect nervous system, a potential source of interference with immunocytochemical localization procedures.

When the biotinylated Manduca sexta adipokinetic hormone gene was used as a probe for in situ hybridization, the intrinsic neurosecretory cells were stained with a biotin detection system that contained streptavidin or avidin. Further experiments showed that the DNA probe was not necessary for staining these cells by streptavidin-alkaline phosphatase, and that they were not stained by alkaline phosphatase alone. Similarly, the intrinsic neurosecretory cells were stained directly by streptavidin conjugated to a fluorescent dye. Other parts of the central nervous system could also be stained with streptavidin-alkaline phosphatase but not as readily as the intrinsic neurosecretory cells of the corpora cardiaca. Further analysis demonstrated three biotin-containing proteins in the intrinsic neurosecretory cells of the corpora cardiaca and in the brain. The most abundant of these proteins, when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was found to have a molecular weight of 130,000, which is the size of the subunits of pyruvate carboxylase, a biotin-containing enzyme. The same protein was recognized by an antiserum against an insect pyruvate carboxylase, indicating that this protein is probably pyruvate carboxylase. The results reported here indicate that the intrinsic neurosecretory cells of the corpora cardiaca may contain pyruvate carboxylase in a concentration higher that other cells of the central nervous system. We also note that caution is necessary to avoid false positive results if an avidin containing detection system is used for in situ hybridization or immunocytochemistry.

Animals↗

PubMed1995

Effects of fluoride on rat vertebral body biomechanical competence and bone mass.

For more than 30 years, sodium fluoride has been a commonly used therapeutic agent for established osteoporosis because of its repeatedly documented anabolic effect on trabecular bone mass. Recent clinical and experimental studies have, however, indicated a possible detrimental effect of fluoride on bone strength. Thus, the efficacy of fluoride therapy remains a controversial issue. The aim of this study was to investigate the effect of fluoride on both vertebral bone mass and quality in rats. Twenty-nine 3-month-old, female rats were randomized into three groups. One group served as a control group, and the other two groups received fluoridated water at different doses (100 ppm and 150 ppm). The rats were followed for 90 days. Three lumbar vertebrae were obtained from each rat, and changes in bone fluoride content, bone mass and biomechanical competence were assessed. The results revealed a significant increase in bone fluoride content, ash density and trabecular bone volume after fluoride treatment. Directly obtained load values and load corrected for cross-sectional area were constant. Load corrected for ash content, which is a measure of bone quality, decreased significantly after fluoride therapy. It is concluded that the increase in bone mass during fluoride treatment does not translate into an improved bone strength and that the bone quality declines. This investigation thereby supports the hypothesis of a possible negative effect of fluoride on bone quality.

Animals↗

PubMed1995

Clinical significance of antibodies against calcitonin.

Calcitonin (CT) inhibits osteoclast-mediated bone resorption and is being used to treat Paget's disease of bone, hypercalcemia of malignancy and postmenopausal osteoporosis. The formation of antibodies against heterologuous calcitonins like salmon calcitonin (sCT) is common and occurs in 40-70% of the patients treated for more than 4 months. Not all of these patients, however, develop a secondary resistance to sCT, therefore the clinical significance of sCT antibodies is discussed controversially. In vivo and in vitro approaches demonstrate a neutralizing effect in 35 to 60% of the patient sera with antibodies against sCT. These neutralizing antibodies appear to explain most cases of clinically relevant secondary resistance to sCT treatment, which occurs in 25-45% of the patients after treatment periods of 6 months and longer. A positive treatment response to human CT after development of secondary resistance to sCT proves the diagnosis of antibody related resistance. Few cases develop secondary resistance in the absence of sCT binding antibodies, the mechanism of this phenomenon is unclear. Antibody related resistance is a significant problem in long term treatment with sCT. Especially in conditions like postmenopausal osteoporosis, where no readily accessable marker of treatment response is available, the development of sCT antibodies and their possible neutralizing effect has to be considered.

Animals↗

PubMed1995

Evaluation of somatostatin as a plasma tumor marker in medullary thyroid carcinoma.

Somatostatin (SRIF) immunoreactivity has been frequently reported in tumor tissues of cell types, belonging to the APUD system, including medullary thyroid carcinoma (MTC). However, the value of SRIF as a plasma tumor marker for MTC is controversial. We have measured SRIF plasma levels in 35 patients with different stages of MTC to evaluate the use of SRIF as a plasma tumor marker compared to the current "gold standard" calcitonin (CT). The median SRIF value in healthy controls was 36.5 pg/mL, the upper limit of normal was defined at the controls. The median value was 28 pg/mL (p = 0.37, Mann-Whitney U test). Five patients in the control group and three in the MTC group had SRIF levels that exceed the 95th percentile. SRIF and CT levels correlated only weakly (0.38), as determined by the Spearman rank order correlation test. Pentagastrin stimulation led to a diagnostic increase in SRIF levels in only one of five MTC patients. During selective venous catheterization, diagnostic gradients for CT, allowing tumor localization, could be demonstrated, whereas measurement of SRIF levels did not aid in tumor detection. Although SRIF immunostaining may be valuable as an additional marker in the histochemical diagnosis of MTC, SRIF has no value as a plasma tumor marker in the diagnosis of this disease.

Adult↗

PubMed1995

Pathophysiology of osteoporosis: unresolved problems and new insights.

Optimal bone mass depends on sufficient sex hormones, building materials, and loading. Sex hormones add to bone mass the amount that is needed for reproduction. Healthy males keep their testosterone until death, but the female sex loses estrogens at menopause, connected with high bone turnover and bone loss. It is not known why and which women lose more bone than others and develop osteoporosis. One factor could be latent hypoandrogenism. Even in men the levels of bioavailable plasma testosterone correlate with bone mineral density. With respect to nutrition, calcium and vitamin D are most important contributors to bone mass. Osteoporotics absorb less calcium from the gut than controls, perhaps because of unfavorable gene alleles for the vitamin D receptor. Furthermore, the general supply with calcium and vitamin D in the normal population could be of greater significance than assumed. The combination of a receptor defect and a latent deficiency could be deleterious. Finally, bones need loading. Mechanoreceptors that transform physical stress into biochemical signals are postulated to exist and to be upregulated by the sex hormones. As a result, bone mass increases more after exercise when it has been exposed to sex hormones. The amount of bone mass due to spontaneous activity is likely to be genetically determined. Current efforts are devoted to the better identification of risk factors and behavior that impair bone mass and density. The discovery of genetic risks and their early diagnosis in humans would greatly facilitate a preventive regimen.

Animals↗

PubMed1995

Somatostatin receptor imaging in persistent medullary thyroid carcinoma.

OBJECTIVE: Somatostatin is secreted from thyroid C-cells and seems to play an important part in the regulation of calcitonin secretion. We therefore evaluated the usefulness of somatostatin receptor scintigraphy in the localization of tumour tissue in patients with persistent medullary thyroid carcinoma. DESIGN: A prospective clinical study. PATIENTS: The series consisted of 26 patients with elevated calcitonin levels after total thyroidectomy for histologically proven medullary thyroid carcinoma. METHODS: Somatostatin receptor scintigraphy using 111In-pentetreotide (Octreoscan) was performed in all patients and the results correlated with histology, ultrasonography, computerized tomography, magnetic resonance imaging, plain radiography, bone scintigraphy and selective venous catheterization. Calcitonin and carcinoembryonic antigen levels were measured. RESULTS: The sensitivity of somatostatin receptor scintigraphy for localization of persistent medullary thyroid carcinoma was 57% in patients with histologically proven disease. The results depended on tumour mass (low sensitivity (33%) in minimal residual disease) and on the location of metastases (insensitive in detecting liver metastases). CONCLUSIONS: Somatostatin receptor scintigraphy is of value as an additional diagnostic tool in localizing medullary thyroid carcinoma, especially pulmonary metastases. It is of minor importance in detecting minimal residual disease.

Adolescent↗

PubMed1995

Parathyroid hormone increases the concentration of insulin-like growth factor-I and transforming growth factor beta 1 in rat bone.

Intermittent treatment with parathyroid hormone (PTH) increases bone mass in experimental animals and humans. In vitro studies have suggested that the anabolic effect of PTH may be mediated by local growth factors. However, the relevance of these findings to in vivo situations remains unclear. In this study, we examined a time course of daily s.c. injections of hPTH (1-34) on the skeletal concentration of insulin-like growth factor (IGF)-I, IGF-II, and transforming growth factor beta (TGF-beta) in the proximal tail vertebrae of male rats. PTH caused a time and dose-dependent increase in the bone mineral density of the lumbar spine. This anabolic effect on bone mass was accompanied by progressive increases in bone matrix-associated IGF-I and TGF-beta 1. Increases in IGF-I and TGF-beta 1 became apparent after four and eight weeks of PTH treatment respectively and persisted through week 12. PTH had no effect on circulating IGF-I, suggesting that the increase of bone matrix IGF-I was due to the local effect of PTH on bone tissue directly rather than to an increase of circulating IGF-I. These data are consistent with the hypothesis that IGF-I and TGF-beta 1 may play a role as local mediators of the anabolic effects of PTH on bone metabolism.

Age Factors↗

PubMed1995

Increased cytokine secretion by human bone marrow cells after menopause or discontinuation of estrogen replacement.

Studies on circulating human mononuclear cells and rodents have suggested that cytokines such as interleukin-1 (IL-1) and IL-6 may be paracrine mediators of postmenopausal bone loss. However, the assumption that the concentration of these cytokines is increased in the local bone microenvironment of postmenopausal women is still unproved. To address this question, we aspirated bone marrow from the iliac crest of 40 women during surgery for localized breast cancer and analyzed cytokine release in short term cultures. Cytokine levels in the cell supernatants from premenopausal (n = 12) and late postmenopausal (n = 18) subjects were not significantly different. Bone marrow cells from women who had discontinued estrogen replacement within 1 month before aspiration (n = 5) secreted significantly more IL-1 alpha, tumor necrosis factor-alpha, IL-6, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor than bone marrow cells from either premenopausal or late postmenopausal subjects. Increased levels of IL-6, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor were also observed in cultures from women who were within 5 yr of natural menopause (n = 5). Our data show that estrogen withdrawal is associated with an increased potential of human bone marrow cells to release bone-resorbing cytokines and strengthen the hypothesis that these cytokines may play a role in the accelerated bone resorption after menopause.

Adult↗

PubMed1995

Human bone cell phenotypes differ depending on their skeletal site of origin.

This report describes skeletal site-related differences in human osteoblastic cell metabolism in studies of four patients. Northern analyses of the constitutive growth factor messenger ribonucleic acid (mRNA) expression pattern in mandibular and iliac crest-derived human osteoblastic cells (based on within-patient comparisons) revealed higher mRNA levels for strong mitogenic growth factors such as basic fibroblast growth factor (bFGF) and insulin-like growth factor II (IGF-II) in the rapidly proliferating and less alkaline phosphatase (ALP)-expressing mandibular osteoblastic cells compared to those in the lower bFGF and IGF-II mRNA levels in slowly proliferating iliac human osteoblastic cells exhibiting a higher ALP expression level. In contrast, transforming growth factor-beta (TGF beta) mRNA was more abundant in iliac human osteoblastic cells than in mandibular osteoblastic cells. Furthermore, we found that there was a proportionality, based on data from both sites, between the level of constitutive TGF beta mRNA and the response to exogenously administered bFGF or IGF-II. A comparable pattern of growth characteristics and mRNA expression was also observed in transformed human osteoblastic cells that had been subcloned in sublines expressing high and low levels of the human osteoblastic differentiation marker ALP. These findings are consistent with 1) skeletal site-related differences in human bone cell phenotypes, and 2) decreased IGF-II and bFGF expression and increased TGF beta expression and responsiveness to bFGF and IGF-II in human bone cells exhibiting a high ALP expression.

Alkaline Phosphatase↗

PubMed1995

Adipokinetic hormone stimulates neurones in the insect central nervous system.

A simple preparation designed to screen and compare the central action of putative neuroactive agents in the moth Manduca sexta is described. This approach combines microinjections into the central nervous system with myograms recorded from a pair of spontaneously active mesothoracic muscles. Pressure injection of either octopamine or Manduca adipokinetic hormone (M-AKH) into the mesothoracic neuropile increases the monitored motor activity. Under the conditions used, the excitatory effects of M-AKH exceed those of the potent neuromodulator octopamine. This suggests that M-AKH plays a role in the central nervous system in addition to its known metabolic functions and supports recent evidence that neuropeptides in insects can be multifunctional.

Amino Acid Sequence↗

PubMed1995

[Successful use of a heparinoid (danaparoid sodium) for heparin-induced thrombocytopenia type II in aortic valve reoperation].

The 29-year-old, heroin-addicted patient received an aortic valve prosthesis (SJM) 10 years ago because of aortic valve stenosis III. One year after surgical treatment he refused to take Phenprocoumon and thus received no anticoagulation for 9 years. The patient was hospitalized due to cardial decompensation and thrombosis of the aortic valve prosthesis was diagnosed. Under heparinization, he developed heparin-induced thrombocytopenia type II, which disappeared after changing the medication to Danaparoid-Sodium. In order to avoid any further heparin exposure, we also carried out the surgical replacement of the aortic valve prosthesis under anticoagulation with Danaparoid-Sodium.

Adult↗

PubMed1995

Antiparasitic treatment of patients with P. falciparum malaria reduces the ability of patient serum to induce tissue factor by decreasing NF-kappa B activation.

Serum from patients with P. falciparum malaria at day 1 (pretherapy) induces tissue factor (TF) in cultured endothelial cells. TF induction depends on de novo transcription as shown in Nuclear Run On assays. Electrophoretic mobility shift assays demonstrated binding of AP-1 and NF-kappa B/Rel proteins to their recognition sites in the TF promotor. After therapy (day 28), stimulation of TF antigen by patient serum is reduced by 70%. When serum obtained before and after therapy was compared, a decrease of NF-kappa B activation was evident. Activation of NF-kappa B-like proteins was in part dependent on TNF alpha in patient serum, since a TNF alpha neutralizing antibody reduced induction of TF transcription and translation and induction of NF-kappa B-like proteins. Induction of TF activity was suppressed by pDTC, an inhibitor of NF-kappa B activation. When different promotor constructs of the TF gene were tested, induction was dependent upon the presence of the intact NF-kappa B-like binding site in the TF promotor. A mutant with deleted NF-kappa B, but intact AP-1 sites was not inducible. Mutation of the AP-1 sites did not prevent induction, but reduced inducibility by pretherapy serum. Therefore, NF-kappa B/Rel proteins are responsible for induction of TF transcription by pretherapy serum, but AP-1 is needed for highest inducibility. The effect of antiparasitic therapy on the induction of TF by serum from patients with complicated P. falciparum malaria is dependent on a therapy-mediated loss of activation of NF-kappa B-like proteins in post-treatment patient serum.

Antimalarials↗

PubMed1995

[Thrombomodulin is a marker of microvascular, but not for macrovascular endothelial cell damage].

UNLABELLED: Plasma levels of thrombomodulin are increased in diseases associated with microangiopathia. The target of this study was to examine whether plasma thrombomodulin is also influenced by macroangiopathia. There was no variation of plasma thrombomodulin in a sample of 183 diabetic patients with or without peripheral arterio-occlusive disease of the lower limbs. In a second sample of 33 patients with peripheral arteriosclerosis of the lower limbs, without any indication of diabetes, plasma levels of thrombomodulin were not significantly increased compared to a control group. Since thrombomodulin is also found in thrombocytes, we analysed whether plasma thrombomodulin levels were influenced by platelet activation. Neither platelet activation after hyperthermal limb perfusion not the PGE1-treatment showed any effect on plasma thrombomodulin level. CONCLUSION: Thrombomodulin is a marker for microvascular but not for macrovascular endothelial cell damage.

Adult↗

PubMed1995

1,25-Dihydroxyvitamin D3 stimulates growth and inhibits calcitonin secretion in a human C cell carcinoma cell line.

1,25-Dihydroxyvitamin D3 (1,25D3), calcitonin (CT) and parathyroid hormone are the major calcium-regulating hormones. In addition, 1,25D3 has been reported to be a modulator of cell growth and differentiation in many tissues. Recently, a suppressive effect of 1,25D3 on CT secretion and synthesis in C cells was demonstrated in vivo and also in vitro, but there are no data about its effects on thyroid C cell growth. We investigated the effects of 1,25D3 on basal and stimulated CT secretion and on [3H]thymidine incorporation, using a human medullary thyroid carcinoma cell line (TT cells). After a 4-day exposure to 1,25D3, TT cells showed a dose-dependent inhibition of basal CT secretion (64% of the value for the control group at 100 nM 1,25D3). Calcium (3 mM) plus K+ (50 mM) greatly increased CT secretion in both the control and vitamin D-treated groups. However, in the cells preincubated with 1,25D3 the stimulated CT levels were less than observed in controls. A dose-dependent increase in [3H]thymidine incorporation (200% of the value for the control group at 100 nM 1,25D3) and in cell number (150% of the value for the control group at 100 nM 1,25D3 after 72 h) was observed in the groups treated with 1,25D3. 24,25D3 had no effect on CT secretion or cell growth compared to the control group. These data show that 1,25D3 decreased basal and Ca(2+)-stimulated CT secretion, a specialized function of these cells, and stimulated their growth. Hence, in contrast to its effects on other cell lines, 1,25D3 appears to induce a dedifferentiation on TT cells.

Calcitonin↗

PubMed1994

[Osteoporosis].

Liver cirrhosis may be accompanied by osteoporosis and, rarely, osteomalacia. Normal liver function is required for normal digestion and absorption of calcium-containing nutrients. The liver plays an important role for the metabolisation of vitamin D: the 25-hydroxylation takes place in the liver. However, the respective enzymatic capacity is not limited by liver diseases except for almost complete liver insufficiency. Therefore, true hypovitaminosis D only rarely plays a role in hepatic osteopenia, but direct toxic effects on bone forming cells (osteoblasts) are discussed: e.g. by bile salts. Coexisting hypogonadism leads to further bone loss. Patients with primary biliary cirrhosis in part present with osteoporosis and fractures. Bone histology reveals normal resorption, but decreased formation. Calcitropic hormones are generally normal. Chronic alcoholism induces the same histologic picture in bone, i.e. normal resorption and diminished formation. These changes are reversible after abstinence and as long as of cirrhosis has not yet developed. Patients undergoing liver transplantation due to end stage liver insufficiency including cirrhosis present with diminished bone mass before receiving a new liver, and they show further bone loss after the transplantation due to immunosuppressive treatment including glucocorticoids. There is no specific treatment of bone loss or osteoporosis due to liver cirrhosis. Preventive efforts should be devoted to the avoidance of suboptimal calcium and vitamin D supply, immobilization, and hypogonadism. Fluorides may increase bone mass after liver transplantation--perhaps they are also useful in liver cirrhosis. Antiresorption agents like calcitonins or bisphosphonates may be cautiously tried.

Calcitonin↗