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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 181 records · Page 10Linked to original sources
PubMed1996

Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2-relevance of specific mutations in the RET proto-oncogene.

It has been suggested that specific mutations in the RET proto-oncogene correlate with clinical manifestation of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. We retrospectively analyzed 61 patients with MEN 2, 28 with associated pheochromocytoma, regarding the relevance of specific mutations in the RET proto-oncogene and the diagnostic sensitivity of catecholamine screening and localization procedures. The present study shows that the position of the RET mutation is related to disease phenotype; codon 634 mutations are predictive of families predisposed to pheochromocytoma. In 18% of our patients, the diagnosis of pheochromocytoma preceded detection of medullary thyroid carcinoma. Therefore, mutation analysis of the RET gene should be performed in apparently "sporadic" cases of pheochromocytoma to confirm or exclude MEN 2. The most sensitive biochemical marker for pheochromocytoma in MEN 2 is 24-h urinary epinephrine excretion. Computed tomography, magnetic resonance imaging and MIBG scintigraphy are all highly sensitive methods to localize pheochromocytoma. We conclude that, in all families with MEN 2, mutational analysis of the RET proto-oncogene should be performed, both to identify gene carriers for MEN 2 and to identify specific mutations that are more strongly associated with pheochromocytoma.

Adult↗
PubMed1996

Release of thrombomodulin from endothelial cells by concerted action of TNF-alpha and neutrophils: in vivo and in vitro studies.

Inflammatory cytokines decrease the expression of thrombomodulin (TM) on the endothelial cell surface by suppression of TM transcription and translation or internalization with subsequent degradation. Nevertheless, elevated serum TM levels are found in diseases associated with systemical or locally increased levels of inflammatory cytokines. To study directly the in vivo effects of tumour necrosis factor-alpha (TNF-alpha) we determined the course of serum TM after systemic recombinant human (rh)TNF-alpha therapy. The TM levels were determined by enzyme-linked immunosorbent assay (ELISA). Systemic rhTNF-alpha therapy resulted in a marked and significant increase of serum TM. Using a mouse model we studied whether increased serum TM is associated with a decreased expression of TM on the endothelial surface in vivo. The immunohistochemical staining of the vasculature of meth-A sarcoma transplanted in mice showed a loss of TM immunoreactivity 4 hr after intravenous TNF-alpha application. To study the mechanism of TNF-alpha mediated release of TM, cultured endothelial cells were incubated with neutrophils and TNF-alpha. Incubation with TNF-alpha alone did not lead to an increase of TM in vitro. However TM was released into the culture supernatant when endothelial cells pretreated with TNF-alpha were exposed to neutrophils. This was associated with morphological evidence of endothelial cell damage. Therefore, the concerted action of cytokine-stimulated endothelial cells and neutrophils results in release of TM from cultured endothelial cells after rhTNF-alpha therapy. This might explain the increased serum TM levels observed in diseases associated with increased systemic or local levels of inflammatory cytokines despite the induced internalization and the direct inhibitory effects of TNF-alpha on TM transcription and translation.

Adult↗
PubMed1996

Plasma thrombomodulin: a marker for microvascular complications in diabetes mellitus.

Thrombomodulin (TM), a marker of endothelial cell damage was studied in 183 patients with diabetes mellitus and different stages of complications. Thrombomodulin plasma levels correlated with duration of diabetes in patients with type I and type II diabetes. Thrombomodulin levels were higher in patients with increasing numbers of complications (nephropathy, retinopathy, arterio-occlusive disease, neuropathy). Neither the presence of retinopathy, nor neuropathy alone significantly increased plasma thrombomodulin in patients with similar urinary albumin concentration. The plasma level of thrombomodulin was more prominent in hypertensive than normotensive patients. Multivariate analysis showed that albuminuria is the factor which influences the most the increase of thrombomodulin in serum of diabetic patients.

Adult↗
PubMed1996

Comparison of total and bone-specific alkaline phosphatase in patients with nonskeletal disorder or metabolic bone diseases.

To evaluate the diagnostic validity of new assays for bone-specific alkaline phosphatase (BAP), we compared measurements of total alkaline phosphatase (TAP) in serum with results for three different assays of serum BAP in healthy adults (n = 119), patients with chronic nonskeletal disorders (n = 123), and patients with metabolic bone diseases (n = 113). Serum TAP was determined by a standard colorimetric assay, BAP by the methods of lectin precipitation (L-BAP), enzyme immunoassay (E-BAP), and immunoradiometric assay (I-BAP). Impairment of liver function resulted in significant increases of all alkaline phosphatase (AP) measurements, with the smallest changes being exhibited by E-BAP. Compared with the results by TAP, diagnostic sensitivity (i.e., of values exceeding the reference interval) was not improved by BAP, but receiver-operating characteristic (ROC) curve analyses revealed improved discrimination for primary hyperparathyroidism by E-BAP. These results indicate that, in the presence of liver disease, the specificity of AP measurements is improved by measuring BAP. In most other clinical situations, serum TAP appears to provide sufficient clinical information; however, the cross-sectional study design used here allows no statement about the usefulness of BAP in serial measurements.

Adult↗
PubMed1995

Crucial role of c-myc in 1,25(OH)2D3 control of C-cell-carcinoma proliferation.

1,25(OH)2D3 (1,25D3) enhances DNA synthesis and cell proliferation in the human C-cell carcinoma cell line (TT). These effects are dependent on previous stimulation of c-myc gene expression. Since the TT cell line has lost some characteristic C-cell features, we investigated the rat rMTC 6-23 line to assess whether the 1,25D3 effects on TT cells are representative of C-cell carcinoma cells. Addition of 1,25D3 (10(-7)M) led to a 2.5-fold stimulation of 3H-thymidine incorporation (3H-T) in TT cells, which was preceded by a 2-fold increase in c-myc mRNA. In contrast, in proliferating nonstimulated rMTC 6-23 cells, c-myc mRNA was undetectable. Upon addition of 1,25D3 to these cells, 3-HT decreased to 70% of control, with no change in c-myc expression. Thus, the stimulatory effect of 1,25D3 in TT cells seems to depend, at least in part, on a c-myc-dependent pathway.

Calcitriol↗
PubMed1995

Characterization of the adipokinetic hormone receptor form the fat body of Manduca sexta.

A tritium labeled Manduca sexta adipokinetic hormone (M-AKH) was synthesized (pE-L-T-[p3H]F-T-S-S-W-G-NH2) (specific activity 27 Ci/mmol) which was fully active in a bioassay. It was used in a filtration based binding assay to characterize the M-AKH receptor from the fat body of M. sexta. Membrane fractions were prepared from fat body and optimal binding conditions were determined. A Kd of 7.10(-10) M was determined and the receptor concentration estimated to be 0.5 pmol/mg membrane protein. No receptor binding was found when membranes were prepared from brain, heart or flight muscle of M. sexta or from fat body of the cockroach Blaberus discoidalis. However, specific binding was found with membrane preparations from the pterothoracic ganglion of M. sexta. The membranes from the ganglion had a much smaller number of binding sites than the fat body membranes, however, the binding was specific and observed in each experiment.

Amino Acid Sequence↗
PubMed1995

[Therapy of metastatic medullary thyroid gland carcinoma with the somatostatin analog octreotide].

AIM OF THE STUDY: Medullary thyroid carcinoma like other neuroendocrine tumors express somatostatin receptors. PATIENTS AND METHODS: Antisecretory and antiproliferative effects of the long-acting somatostatin analog octreotide should be evaluated in a prospective study in 7 patients with metastasizing medullary thyroid carcinoma. RESULTS: Treatment with octreotide in daily doses between 100 and 1000 micrograms resulted in a remission lasting up to 12 months in 2 of 7 patients. A decrease of tumor marker levels was observed in 2 patients, improvement of diarrhea and a remission of a lymph node metastasis in one of these. CONCLUSION: This minor therapeutic effect may be due to the relatively low density of receptors or with a low affinity of the receptors expressed in medullary thyroid carcinoma to octreotide.

Adolescent↗
PubMed1995

Virtual reality in surgical arthroscopic training.

Arthroscopy has become an irreplaceble method in diagnostics. The arthroscope, with optics and light source, and the exploratory probe are inserted into the knee joint through two small incisions underneath the patella. Currently, the skills required for arthroscopy are taught through hands-on clinical experience. Therefore, the Fraunhofer-Institut fuer Graphische Datenverarbeitung in Darmstadt, in cooperation with the Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, developed a highly interactive medical training system for arthroscopy through computer graphics and virtual reality (VR) techniques. Two main issues are addressed: the three-dimensional (3-D) reconstruction process and the 3-D interaction. The goal of the reconstruction process is to obtain a realistic representation of the knee joint derived from a magnetic resonance image sequence suitable for computer simulation. Moreover, the 3-D interaction of the training system must stimulate real arthroscopy, providing an intuitive handling of the instruments.

Arthroscopy↗
PubMed1995

Effects of passive immunization against parathyroid hormone-related protein: PTHrP is the responsible factor in mediating hypercalcemia in the Walker carcinosarcoma 256 rat model.

The Walker carcinosarcoma (WCS) 256 is a well-characterized rat model of humoral hypercalcemia of malignancy (HHM). We addressed the question of whether parathyroid hormone-related protein (PTHrP) is the factor responsible for mediating HHM in this model. WCS 256 cells were subcutaneously implanted in female rats. We examined the plasma at days 0, 2, 4, 6, and 8. The midregional PTHrP measured by radioimmunoassay (RIA) and the plasma calcium increased significantly. Measuring PTHrP by a two-site immunoradiometric assay (IRMA) showed comparable results. There was a strong positive correlation between plasma calcium and midregional PTHrP (r = 0.85, p < 0.0001). A strong positive correlation between tumor weight and both midregional PTHrP (r = 0.83, p < 0.0001) and plasma calcium (r = 0.87, p < 0.0001) was also found. After surgical removal of the tumor at day 5, both plasma calcium and plasma PTHrP levels fell to within the normal range. Ip administration of native polyclonal antiserum against PTHrP(53-84) led to a significant decrease of plasma calcium. Extracted WCS 256 tumor showed 5-fold increased levels of midregional PTHrP compared with liver. Immunohistochemistry and Western blot were positive for PTHrP. RNA from the WCS 256 tumor was positive for PTHrP whereas liver tissue RNA was negative. WCS 256 cells grown in vitro also secreted PTHrP into the medium. We conclude that PTHrP is synthesized and secreted by WCS 256 and that PTHrP is the factor responsible for mediating hypercalcemia in the WCS 256 rat model.

Analysis of Variance↗
PubMed1995

Apolipophorin III is dramatically up-regulated during the programmed death of insect skeletal muscle and neurons.

The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta, participate in the emergence behavior of the adult moth and then die during the subsequent 30 hours. In addition, several populations of interneurons and uniquely identified motor neurons also die after adult emergence. The trigger for all of these deaths is a decline in the circulating titer of the insect molting hormone 20-hydroxyecdysone. The ability of the muscles and neurons to die requires de novo gene expression. A differential hybridization screen of a "condemned" ISM cDNA library permitted the isolation of clones encoding four new up-regulated mRNAs. On sequencing, one of these recombinants was found to encode apolipophorin III (apoLp-III), a component of lipophorin, the major hemolymph lipoprotein of insects, previously shown to be synthesized in fat body. Although apoLp-III mRNA and protein were expressed at all stages of ISM development, levels of both molecules were dramatically elevated with the commitment of the cells to die. When ISM cell death was delayed by injection of 20-hydroxyecdysone, expression of apoLp-III at both the RNA and protein levels was markedly reduced at the normal time of cell death. Immunocytochemistry demonstrated that apoLp-III protein was abundantly expressed in the cytoplasm of dying muscles, interneurons, and identified motor neurons at the time of cell death. Apolipoproteins I and II, required components of lipophorin, were not expressed at detectable levels in the muscles or neurons. Furthermore, Western blots of native gels suggest that apoLp-III was not associated with any other proteins. These data suggest that apoLp-III has activities independent of lipid transport that may play a role in programmed cell death. ApoLp-III joins apolipoproteins E and J (clusterin, sulfated glycoprotein-2) as a group of proteins that function in both lipid transfer and cell death.

Animals↗