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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 325 records · Page 18Linked to original sources
PubMed1991

Specific association of HLA-DR4 with increased prevalence and level of insulin autoantibodies in first-degree relatives of patients with type I diabetes.

First-degree relatives of patients with insulin-dependent (type I) diabetes (n = 264 from 106 families) were evaluated with HLA typing and determination of competitive insulin autoantibodies (CIAAs) and islet cell autoantibodies (ICAs). The levels of CIAAs in 30 relatives exceeded our upper limit of normal (greater than or equal to 39 nU/ml), and 30 had high-titer ICAs (greater than or equal to 40 Juvenile Diabetes Foundation units [JDF U]). Eleven of the HLA-typed relatives developed diabetes during follow-up. Twenty-three percent (28 of 123) of the relatives with at least one HLA-DR4 allele were CIAA+ (CIAA greater than or equal to 39 nU/ml) versus 4% (6 of 141) among DR4- relatives (P less than 0.0001). Twenty-one of 22 of the highest CIAA values were all in the DR4+ group (DR4+ vs. DR4-, P = 0.003, Wilcoxon's rank-sum test). HLA-DR3 did not correlate with the level of CIAAs, and neither DR3 nor DR4 correlated with titer of ICAs measured in JDF U. We conclude that, in first-degree relatives of patients with type I diabetes, there is a striking association with HLA-DR4 in both the prevalence of relatives exceeding the normal CIAA range and in the level of CIAAs. These data suggest that a gene on HLA-DR4 haplotypes contributes to the level of anti-insulin autoimmunity, and we hypothesize that DR4-associated diabetes susceptibility, distinct from DR3-associated susceptibility, may be secondary to this influence.

Autoantibodies↗
PubMed1991

A new role for the low density lipoprotein receptor.

It is well established that the low density lipoprotein (LDL) pathway functions to maintain a constant concentration of cellular cholesterol, but LDL effects that are unrelated to cholesterol metabolism have not been studied in great detail. In the present investigation we demonstrate that the LDL receptor pathway regulates cellular levels of free arachidonic acid (AA) and hence prostaglandin (PG) synthesis. We used platelet-derived growth factor (PDGF)-stimulated fibroblasts as a model system to investigate mechanism of LDL-dependent PG synthesis. PDGF-stimulated but not quiescent cells formed radiolabelled prostacyclin (PGI2) and PGE2 upon incubation with LDL that had been reconstituted with cholesteryl-(1-14C)-arachidonate (rec-LDL), while fibroblasts from patients that are afflicted with the LDL receptor negative phenotype of familial hypercholesterolaemia (FH) failed to synthesize significant amounts of PGs. Furthermore cells that had been preincubated with chloroquine or an anti LDL receptor antibody, that prevents binding of LDL to its receptor, did not produce significant amounts of PGs upon incubation with rec-LDL. Moreover incubation of PDGF-stimulated cells with LDL or AA led to a time and concentration-dependent inactivation of PGH synthase, the rate limiting enzyme of PG synthesis. When taken together our results establish a new role of the classical LDL receptor pathway of Brown and Goldstein by demonstrating that LDL provides AA to fibroblasts for eicosanoid formation and that LDL has a profound inhibitory effect on the key enzyme of PG synthesis, the PGH synthase.

Arachidonic Acid↗
PubMed1991

Parkinson's syndrome: cranial computed-tomography findings. Their dependence on sex and age.

Cranial Computed Tomography (CCT) findings in 123 patients suffering from Parkinson's syndrome were compared with a sex- and age-matched normal control group. Signs of supratentorial atrophy--cortical and subcortical--were more significantly marked in the Parkinson group. In both groups, signs of atrophy were more prevalent in men than in women. Parkinsonian women also more frequently showed limited features, such as lacunar lesions, around the lateral ventricles. Moreover, in these patients atrophy was marked in the frontal cortex.

Age Factors↗
PubMed1991

Type III hyperlipoproteinemia in a patient with idiopathic hemochromatosis.

A 60-year-old man is reported with idiopathic hemochromatosis and type III hyperlipoproteinemia. Regular phlebotomy therapy and fenofibrate treatment favorably influenced the disorder of iron metabolism and the lipid disease. Evidence is given that both errors of metabolism are independently inherited diseases, although the symptoms of the first (idiopathic hemochromatosis) may aggravate the expression of the second (type III hyperlipoproteinemia).

Adult↗
PubMed1991

[Fluoride therapy of osteoporosis].

The effects of fluoride on bone seem to be dose- and time dependent: The optimized exposition to fluorides over decades might serve the bone as a trace element in a similar manner like in the case of caries prophylaxis of the teeth. This infers the potential that lifelong optimized fluoride supply (e.g. via drinking water) could serve as a general osteoporosis prophylaxis. This is to be differentiated from the use of much higher doses of fluoride as a pharmacological stimulus of the osteoblasts. In fact, such fluoride treatment increases the mass of trabecular bones, as demonstrated by histological and osteodensitometric techniques. In parallel during the last more than 20 years many retrospective studies yielded results indicating a decrease in osteoporotic fractures during fluoride treatment. However, the first two randomized double blind studies from the USA do not show this decrease in vertebral fracture incidence. The reasons for this could be due to the study design (unchanged high dosage over four years in contrast to the commonly used individual adaptation of dosage and time); however, also the earlier positive results could be an error. Therefore, new studies are mandatory, but until their results are available, the continuation of fluoride treatment of established osteoporosis is justified, competent surveillance being a prerequisite.

Fluoridation↗
PubMed1990

[Epidemiology of hypercalcemia. Significance of the determination of intact parathyroid hormone for differential diagnosis].

Serum-calcium levels were determined in 9666 hospital inpatients during one year. Hypercalcaemia was present in 101 patients (51 women, 50 men, mean age 57 years). In 46 patients, hypercalcaemia was caused by malignancy. The second commonest cause was primary hyperparathyroidism (pHPT) in 35 cases. In the other 20 patients, hypercalcaemia was related to thiazid medication (8 patients), elevated 25-hydroxy-vitamin-D3-levels (six patients) or immobilisation (two patients). In four patients, no cause was found. Intact parathyroid hormone levels reliably distinguished patients with pHPT (values greater than 60 ng/l) from patients with hypercalcaemia of other causes (values less than 40 ng/l). Other laboratory tests were less useful. Serum-calcium levels greater than 2.9 mmol/l were found only in pHPT and hypercalcaemia of malignancy. In pHPT, the medical history frequently revealed nephrolithiasis (12 patients) and gastrointestinal ulcers (8 patients), whereas weight loss was far more common in hypercalcaemia of malignancy (28 patients).

Adult↗
PubMed1990

[Clinical aspects of osteoporosis].

The development of osteoporosis is a multifactorial process. Part of contributing factors are not to be influenced, others may be avoided or prevented. The achievement of an optimal peak bone mass as well as its maintenance require sufficient sex hormones in connection with optimal calcium supply with the nourishment and sufficient physical exercise. During the preclinical phase of osteoporosis only the analysis of risk factors is possible. There are no clinical symptoms of the condition itself. Manifestation of osteoporosis is documented by crush fractures or discontinuing fractures. In osteoporosis type I the vertebral column is involved. Back pains and loss of body height are the consequences leading to diminished quality of life. The pain syndrome is unspecific and may be caused by other diseases, too. In osteoporosis type II in addition peripheral fractures at disposed sites show up (neck of femur, distal radius = Colle's fracture). During aging the diminished bone mass presumably becomes less decisive for the fracture risk whereas the significance of impaired eye sight, loss of hearing, delayed reflexes and diminished muscle strength increases. For evaluating clinics of osteoporosis systems for grading are mandatory.

Bone Density↗
PubMed1990

Effects of helodermin on fetal rat bone metabolism in vitro.

Helodermin belongs to the VIP family of polypeptides. Recent in vivo data suggest that helodermin-like peptides might be involved in the regulation of calcium metabolism. We show that helodermin specifically binds to a secretin-type receptor in osteoblast-like cells from fetal rat calvaria and increases the basal and PTH-stimulated cAMP concentration of these cells. In organ cultures of fetal rat calvaria, helodermin strongly inhibits bone matrix apposition and augments PTH-induced bone resorption. Helodermin-like peptides may thus be capable of enhancing the direct effects of PTH on bone metabolism.

Animals↗
PubMed1990

1,25-Dihydroxyvitamin D3 suppresses dexamethasone effects on calcitonin secretion.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and dexamethasone (DEX) influence synthesis and secretion of various hormones. Recent reports concerning the interaction of the two steroids revealed opposite--agonistic as well as antagonistic--effects in different biological systems. As calcitonin (CT) gene expression is affected by both agents, inhibited by 1,25(OH)2D3 and stimulated by DEX, we utilized CT secretion and storage as a model to study the combined effects of the two hormones. A human C cell carcinoma cell line (TT) was used, incubating the cells for a period of 4 days with 1,25(OH)2D3 and DEX alone and in combination. 1,25(OH)2D3 resulted in a decrease, whereas DEX resulted in a increase of CT secretion and content. Combining the two steroids, 1,25(OH)2D3 surprisingly abolished the stimulation of DEX on CT secretion and content. The underlying mechanism is yet unclear and could be envisioned to include steroid receptor regulation or gene transcription.

Animals↗
PubMed1990

[Therapy of hirsutism in females with adrenal enzyme defects of steroid hormone biosynthesis: comparison of dexamethasone with cyproterone acetate].

In patients with adrenal hirsutism or enzyme deficiencies in steroidogenesis, elevated adrenal androgens could be normalized by dexamethasone. We were interested to see if dexamethasone would be as effective as cyproterone acetate in treating hirsutism in selected patients with adrenal pathogenesis. Therefore 28 patients with hirsutism of adrenal origin or enzyme deficiency were treated cyclically either with cyproterone acetate and ethinylestradiol (2 mg cyproterone acetate + 0.035 mg ethinyl-estradiol days 1-21, +10 mg cyproterone acetate days 1-15) (n = 15) or with 0.25-0.5 mg dexamethasone daily at 10 pm (n = 13). In the dexamethasone group there was a significant drop in dehydroepiandrosterone and dehydroepiandrosterone sulfate levels within 9 months, but there was a diminution in hirsutism in only four women (31%); in four out of seven menstrual irregularities decreased. In the cyproterone acetate group hirsutism diminished significantly in 66% (n = 10) without suppression of adrenal androgens. Weight gain occurred in a few cases in both groups; other side effects developed in 33% in the cyproterone acetate group. Preselection of patients with hirsutism is useful with respect to diagnosis; adrenal pathogenesis should not generally indicate dexamethasone treatment of hirsutism unless there is a desire for pregnancy, because cyproterone acetate is a more powerful agent in reducing hair growth.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

Atypical type III hyperlipoproteinemia in a patient with Ig A myelomatosis.

We studied a 58-year-old woman with severe therapy-refractory hyperlipidemia, xanthomatosis, and multiple myeloma (immunoglobulin A, lambda light chain). The lipid disorder became evident about half a year prior to the expression of myelomatosis. Clinical symptoms were similar to those found in classical type III hyperlipoproteinemia but the underlying metabolic defect was different from the one described in this primary dyslipoproteinemia. The patient has the heterozygous apolipoprotein E3/2 phenotype and her VLDL-cholesterol/serum-triglyceride ratio is unusually low at 0.05. Evidence is given that the hyperlipoproteinemia is due to an impaired catabolism of intermediate density lipoproteins probably because of a reduced hepatic triglyceride lipase activity.

Cholesterol, VLDL↗
PubMed1990

[Terguride in hyperprolactinemia--experiences with 5 patients].

Hyperprolactinemia can successfully be treated by dopaminagonists such as bromocriptin or lisuride. About 10% of patients complain about side effects like orthostatic hypotension, nausea or vomiting, which may lead to discontinuation of treatment. We therefore conducted a study using terguride--a new dopaminagonist--in 5 patients with hyperprolactinemia and intolerable side effects under conventional treatment. Terguride is the transdihydroderivative of lisuride (Dopergin). We treated 5 patients, 2 men with macroprolactinoma and 3 women with microprolactinoma with terguride. The mean duration of treatment was 15.6 months (7-37 months). Patients were treated with up to 5 mg terguride daily. All 5 patients had a marked initial decrease of elevated prolactin levels 8 h after administration of 0.25 mg terguride orally. Three patients became normoprolactinemic after sufficient increase of the dose of terguride, 2 female patients with a microprolactinoma got eumenorrhoeic thereafter. The treatment with terguride was tolerated without side effects by all patients. There were no significant changes of the examined parameters of clinical chemistry nor the other pituitary hormones. Results of cranial computertomography did not change in 4 patients, one patient had tumor progression. Tergurid as a dopaminagonist is an effective inhibitor of prolactin with little side effects and thus a useful drug in the treatment of hyperprolactinemia.

Adult↗
PubMed1990

Binding characteristics of reduced hepatic receptors for acetylated low-density lipoprotein and maleylated bovine serum albumin.

The binding characteristics of reduced hepatic membrane proteins for acetylated low-density lipoprotein (acetyl-LDL) and maleylated bovine serum albumin (Mal-BSA) have been examined. Two receptor activities were extracted from hepatic membranes in the presence of octyl beta-D-glucoside and beta-mercaptoethanol, and were separated by chromatography on Mal-BSA-Sepharose 4B. The receptors were revealed by ligand blotting. The active binding proteins had apparent molecular masses of 35 and 15 kDa in SDS/polyacrylamide gels. Equilibrium studies with protein-phosphatidylcholine complexes indicated that the reduced 35 kDa protein expresses two binding sites for Mal-BSA and one for acetyl-LDL, whereas the 15 kDa protein-phosphatidylcholine complex binds 131I-Mal-BSA and 131I-acetyl-LDL with a 4:1 stoichiometry. 131I-Mal-BSA binding was linear with both proteins, with a Kd of 4.8 nM at the 35 kDa protein and a Kd of 5.6 nM at the 15 kDa protein. The 35 kDa protein displayed saturable binding of 131I-acetyl-LDL with a Kd of 5 nM; the 15 kDa binding protein bound 131I-acetyl-LDL with a Kd of 2.3 nM. A 85 kDa protein was obtained by Mal-BSA-Sepharose chromatography when the hepatic membranes had been solubilized with Triton X-100 in presence of GSH/GSSG. This protein displayed saturable 131I-Mal-BSA binding with a Kd of 30 nM and 131I-acetyl-LDL binding with a Kd of 6.5 nM. The 131I-Mal-BSA binding capacity was four times higher than that of 131I-acetyl-LDL. Competition studies with the 35 kDa, 15 kDa and 85 kDa proteins binding Mal-BSA, acetyl-LDL, formylated albumin and polyanionic competitors provide evidence for the existence of more than one class of binding sites at the reduced binding proteins.

Acetylation↗