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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 343 records · Page 19Linked to original sources
PubMed1990

Severe type III hyperlipoproteinemia in two patients maintained on chronic hemodialysis.

Two patients with severe hyperlipidemia receiving long-term hemodialysis were classified as type III hyperlipoproteinemic subjects. They are homozygous for apolipoprotein E2 and have an elevated VLDL-cholesterol/plasma-triglyceride ratio. The dyslipoproteinemia was severely aggravated by the renal failure, but careful treatment with bezafibrate was able to effectively lower elevated serum lipids. Accurate diagnosis of lipid abnormalities in patients with chronic renal failure seems to be necessary to plan appropriate therapeutic interventions and to lower the risk for accelerated atherosclerosis.

Apolipoproteins E↗
PubMed1990

Biological effects of synthetic AKH in Manduca sexta and estimates of the amount of AKH in corpora cardiaca.

Dose-response curves were measured with synthetic Manduca adipokinetic hormone (AKH) for glycogen phosphorylase activation in larvae and for lipid mobilization in adults. Both responses are known hormonal functions in Manduca sexta. In ligated larvae, full activation of glycogen phosphorylase was achieved with 0.1 pmol and half-maximal activation with 0.03-0.04 pmol. Maximal lipid mobilization in adults required 10 pmol and half-maximal mobilization 0.15 to 0.2 pmol, respectively. An estimate of AKH content of corpora cardiaca from M. sexta was gained by comparing the dose-response curves for synthetic Manduca AKH with curves from gland extracts. Corpora cardiaca extracts were also quantitated by high performance liquid chromatography. According to both estimates corpora cardiaca of adults contain 10-20 pmol AKH per pair, while a pair of larval corpora cardiaca contains 0.7-2 pmol.

Adipose Tissue↗
PubMed1990

In vitro detection of neutralizing antibodies after treatment of Paget's disease of bone with nasal salmon calcitonin.

To elucidate the biologic relevance of circulating sCT antibodies, an in vitro bioassay system for the detection of neutralizing antibodies was developed utilizing the human breast carcinoma cell line T47D. We reasoned that the inhibition of the dose-dependent cAMP response to sCT in the T47D assay system by anti-sCT antibodies could be used to determine the in vivo relevance of these antibodies. In this report the clinical course of nine patients with Paget's disease of bone treated with intranasal sCT was correlated with the presence of 125I-sCT binding and neutralizing antibodies. Of these seven patients, four were found to have neutralizing antibodies; the appearance of the antibodies coincided with the development of resistance. One of these patients was subsequently treated with human calcitonin and revealed a good response to the treatment. There was no clinical resistance observed in the three patients with 125I-sCT binding antibodies but no neutralizing antibodies; no resistance was observed in two patients without 125I-sCT binding or neutralizing antibodies. We conclude that this new technique to determine the biologic relevance of circulating anti-sCT antibodies may be an useful adjunct for determining the cause of resistance in patients treated with sCT.

Administration, Intranasal↗
PubMed1990

Chemotactic response of osteoblastlike cells to transforming growth factor beta.

Transforming growth factor beta (TGF-beta) has multiple effects on bone cell metabolism in vitro but its exact role in bone remodeling still needs to be defined. Here we demonstrate that TGF-beta is chemotactic for osteoblastlike cells from fetal rat calvariae and osteoblastlike ROS 17/2.8 osteosarcoma cells. Maximal chemotaxis occurred at 5-15 pg/ml of TGF-beta and was observed with TGF-beta 1 and TGF-beta 2 at equivalent concentrations. Conditioned medium from osteoblastlike cells containing latent TGF-beta failed to stimulate chemotactic migration. However, chemotactic activity was observed in conditioned medium that had been transiently acidified. Since acidification is known to activate TGF-beta, these results suggest that only active TGF-beta is capable of inducing a chemotactic response. Preincubation of osteoblastlike cells with TGF-beta in concentrations from 10 pg/ml to 1 ng/ml for 48 h abolished a subsequent chemotactic response of these cells to TGF-beta, indicating that TGF-beta-induced chemotaxis is a transient phenomenon. Since TGF-beta may be released from the bone matrix and/or activated during bone resorption, the chemotactic activity of TGF-beta for osteoblastlike cells may be important for the recruitment of osteoblastlike cells to sites of bone remodeling.

Animals↗
PubMed1990

Combination chemotherapy of advanced medullary and differentiated thyroid cancer. Phase II study.

A group of 20 patients with advanced medullary (MTC) or differentiated thyroid carcinoma (DTC) received a combination chemotherapy of doxorubicin (50 mg/m2), cisplatin (60 mg/m2) and vindesine (3 mg/m2). In the 18 (10 MTC, 8 DTC) evaluable patients only 1 partial remission (in a patient with MTC) and 3 minor responses (in 3 patients with DTC) were observed. These responses lasted for 15, 9, 13, and 22 months, respectively. Three MTC patients suffered from progressive disease and "no change" was seen in the other 11 patients. Toxicity, including 1 severe case of cardiomyopathy, was considerable. Thus, the combination chemotherapy of doxorubicin, cisplatin and vindesine has failed to prove superior to the commonly applied doxorubicin monotherapy in patients with advanced medullary or differentiated thyroid carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Alteration of plasma low density lipoprotein from smokers.

Thiobarbituric acid reactive substances (TBARS) in 38 low density lipoprotein (LDL) samples from 21 healthy male non-smokers and 17 smokers (greater than 20 cigarettes per day) were measured before and after oxidation. TBARS in the freshly isolated LDL from non-smokers and smokers were similar, however, oxidized LDL samples from smokers developed nearly twofold more TBARS than non-smoker LDL samples. 16 LDLs from 8 smokers and 8 non-smokers were conditioned in redox-metal containing F-10 medium and subsequently added to P 388 D.1 macrophage cultures. LDL dependent cholesteryl ester increase in the P 388 D.1 cells after an 18 h incubation with non-smoker LDL was significantly lower than in the cells incubated with smoker LDL (P less than 0.01). A higher reacylation rate of cholesterol in P 388 D.1 cells incubated with smoker LDL (P less than 0.05) suggests that LDL-cholesterol uptake is significantly higher in P 388 D.1 cells incubated with smoker-LDL than in P 388 D.1 cultures exposed to non-smoker LDL. This finding indicates that smoking might contribute to increased shunting of LDL into macrophages. The vitamin E content of 6 non-smoker LDL samples was significantly higher than that in 6 smoker-LDL samples (P less than 0.01). We conclude that the vitamin E/LDL ratio may differ significantly in heavy smokers and non-smokers.

Adult↗
PubMed1990

Type III hyperlipoproteinemia in a child with hemolytic uremic syndrome.

The case of a 6-year-old girl with severe hyperlipoproteinemia and chronic renal failure that developed after hemolytic uremic syndrome (HUS) is reported. The patient was homozygous for apolipoprotein (apo) E2, and her very-low-density lipoprotein (VLDL)-cholesterol/serum-triglyceride (TG) ratio of 0.63 was unusually high. She was consistently diagnosed to have type III hyperlipoproteinemia (HLP). This is the first report of type III HLP in a child with chronic renal disease.

Apolipoprotein E2↗
PubMed1990

A study of complaints and their relation to vertebral destruction in patients with osteoporosis.

Patients with spinal osteoporosis suffer from vertebral deformation, loss of height and back pain, as well as from functional limitations and alterations of mood. So far little is known about the extent of these clinical symptoms at all and whether they are related in a predictable manner to the fractures or damages of bone structure. In the present study we investigated the relation between vertebral deformation and clinical symptoms in 70 patients with osteoporosis. Clinical data like pain, functional limitations and parameters of mood were examined by a standardized questionnaire. The numbers of vertebral fractures were determined, and the vertebral destruction was quantified using the Spine Deformity Index (SDI). The symptoms and functional limitations were graded and correlated to the SDI and the number of fractures. Our results underline a relation between the extent of vertebral deformation and the reduction in quality of life by pain, functional limitations and alterations of mood. This relationship was absent or less evident, if the number of fractures was taken into account. Besides the difficulties concerning the grading and quantification of clinical symptoms and outcome of disease, our study revealed that there is a causal relation between the extent of vertebral destruction measured by the SDI and the extent of these clinical parameters.

Adult↗
PubMed1990

Multiple target antigens in pre-type I diabetes: implications for prediction.

The prodromal phase of type I diabetes is characterized by the presence of a series of autoantibodies reacting with distinct autoantigens [anti-insulin, anti-64 kDa, islet cell antibodies ('antiganglioside')]. Anti-insulin autoantibodies appear to be unique in that the levels of such antibodies correlate with both the rate of progression to diabetes and age at which type I diabetes develops. With a combination of assays it is now possible to predict type I diabetes, allowing the design of research trials for diabetes prevention.

Animals↗
PubMed1990

[Combination therapy with adriamycin, cisplatin and vindesine in C cell carcinoma of the thyroid].

Ten patients with advanced medullary thyroid carcinoma were treated with the combination of adriamycin (50 mg/m2), cisplatin (60 mg/m2) and vindesine (3 mg/m2). Only one partial remission (PR) was seen. There were six "no changes" and three "progressive diseases (PD)". Comparing with data from the literature the polychemotherapy of adriamycin, cisplatin and vindesine seems not to be superior to the mostly employed adriamycin-monotherapy. The tumor-markers calcitonin (CT) and carcinoembryonic antigen (CEA) were pathologically elevated in any case. During chemotherapy they proved to be valuable parameters of the course of the disease. In the patient with PR the CT- and CEA-serum levels reflected the clinical remission. In the patients with PD, however, they rose continuously.

Adolescent↗
PubMed1990

Differential regulation of plasminogen activator and plasminogen activator inhibitor by osteotropic factors in primary cultures of mature osteoblasts and osteoblast precursors.

Plasminogen activators (PA) and plasminogen activator inhibitors (PAI) have been implicated in the process of extracellular matrix degradation. To study their role in bone matrix turnover, we examined the activity and regulation of PA and PAI in cultures of periosteal osteoblast-like precursor cells and mature osteoblast-like cells from fetal rat calvariae. Both cell populations released PA activity of the tissue type and a 50K PAI species into the culture medium. However, mature osteoblasts had a strikingly lower PA activity and higher PAI activity than periosteal precursor cells, indicating that osteoblast differentiation is associated with a marked decrease in the PA/PAI ratio. PTH and prostaglandin E2 transiently increased PA activity and decreased PAI activity. In contrast, transforming growth factor-beta decreased PA activity and increased PAI activity. Differential effects of these factors on PA and PAI activity may be involved in the regulation of extracellular matrix deposition by osteoblasts.

Animals↗
PubMed1990

Stimulation of bone matrix apposition in vitro by local growth factors: a comparison between insulin-like growth factor I, platelet-derived growth factor, and transforming growth factor beta.

Many recent in vitro studies have shown effects of insulin-like growth factor I (IGF I), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF beta) on the proliferation and differential functions of bone-forming osteoblasts; however, the question whether these factors might ultimately lead to a net increase or decrease in bone formation has been difficult to assess. In this study, we have used an autoradiographic method based on the incorporation of [3H]proline into freshly synthesized bone matrix to determine the overall effects of these factors on bone matrix apposition in 21-day-old fetal rat calvariae. IGF I, PDGF, and TGF beta increased bone matrix apposition in a dose-dependent manner up to 2-fold within 48 h. In addition, they partially or completely reversed the inhibition of bone matrix apposition observed with PTH. Exogenously added TGF beta was significantly more potent than equimolar concentrations of PDGF or IGF I in stimulating bone formation. Matrix apposition was greatest when IGF I, PDGF, and TGF beta were added simultaneously to the culture medium, indicating that these factors can enhance each other in stimulating bone formation. In conclusion, our results provide direct evidence that IGF I, PDGF, and TGF beta are capable of stimulating bone formation in vitro.

Animals↗
PubMed1990

Bone mass reduction after estrogen deprivation by long-acting gonadotropin-releasing hormone agonists and its relation to pretreatment serum concentrations of 1,25-dihydroxyvitamin D3.

Estrogen deficiency results in bone mass reduction of largely varying extent in postmenopausal females, indicating that additional mechanisms influence the response of bone. They are by no ways identified in either the animal experiment or under clinical conditions. In search for factors, conditioning the response of bone to estrogen deficiency, we have conducted a study in females under treatment with the GnRH agonist decapeptyl (D-Trp6-LHRH). This drug blocks ovarian function and was administered for treatment of endometriosis or uterine leiomyoma. We determined spinal (dual photon absorptiometry) and forearm (single photon absorptiometry) bone mineral density before and 3 and 6 months after the onset of therapy and measured biochemical parameters of bone metabolism. Our results showed an increase in bone turnover after initiation of estrogen deficiency, as indicated by the elevation of alkaline phosphatase and osteocalcin. This resulted in a secondary decrease in serum intact PTH and 1,25-dihydroxy-vitamin D3. Furthermore, we found a positive correlation between pretreatment values of serum 1,25-dihydroxyvitamin D3 as well as its decrease and the reduction in bone mass during GnRH agonist treatment. This demonstrates that the patients' metabolic conditions predict their response to estrogen deficiency.

Adult↗
PubMed1990

Internalization of calcitonin receptors in primary rat kidney cell cultures.

Cultured rat kidney cells possess specific calcitonin receptors and a calcitonin-responsive adenylate cyclase. At 37 degrees C bound 125I-salmon calcitonin becomes increasingly resistant to acid washing. If 125I-salmon calcitonin is removed from the medium after binding, bound hormone decreases over the next 5 h. Monensin, which blocks lysosomal processing, inhibits the decrease of bound hormone. These data indicate that calcitonin receptors are internalized after binding of hormone in kidney cells. Cycloheximide prevents internalization, when it is administered 4 h before 125I-salmon calcitonin binding is studied. Pre-incubation of the cells with 10(-7) mol/l unlabelled salmon calcitonin decreases specific binding; recovery of binding needs 48 h to occur. The long time interval for recovery makes it unlikely that calcitonin receptors recycle. This is the first demonstration that normal rat kidney cells internalize calcitonin after binding. It might contribute to the loss of calcitonin bioactivity which is seen after continuous administration.

Adenosine Triphosphate↗
PubMed1990

17 beta-estradiol inhibits LDL oxidation and cholesteryl ester formation in cultured macrophages.

The effects of 17 beta estradiol, testosterone, the estradiol benzoate, and probucol on the oxidation kinetics of low density lipoprotein (LDL) in vitro in absorption presence of 10 microM Cu (II) are examined. Changes in the absorption at 234 nm (A234) and fluorescence (Ex340/Em420) are monitored. The kinetics of the changes observed let us suggest a precursor-product relationship between dienes and fluorochromes in the oxidized LDL. The addition of 17 beta estradiol and probucol to LDL results in a prolongation of the lag phase characterized by only insignificant formation of dienes and fluorochromes. The addition of testosterone and estradiol benzoate used as control compounds has no effect on the lag phase and thus no LDL stabilizing effect. Conditioned LDL which was incubated in F-10 medium before exposure to cultured P388D.1 macrophages increases the formation of cytoplasmic lipid droplets and of cellular cholesteryl esters. The LDL stabilizing compounds beta estradiol and probucol (but not testosterone) causes a reduction of the cholesteryl ester content of the cultured macrophages. Protection of LDL particles against oxidative damage apparently results also in lowering of cytoplasmic cholesteryl ester in cultured P388D.1 cells. We conclude that the known antiatherosclerotic potency of 17 beta estradiol may in part result from its LDL stabilizing activity.

Animals↗
PubMed1990

[Type III hyperlipoproteinemia in idiopathic hemochromatosis].

We studied a 60-year-old male with idiopathic (primary) hemochromatosis and type III hyperlipoproteinemia. Periodical phlebotomy therapy could favourably influence the disease of iron metabolism as well as the familial lipoprotein disorder in addition to fenofibrate treatment. Idiopathic hemochromatosis as aggravating cause of type III hyperlipoproteinemia has not been reported yet.

Bloodletting↗