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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 307 records · Page 17Linked to original sources
PubMed1991

[Therapy of Paget's disease with bisphosphonate pamidronate (AHPrBP, formerly APD)].

We studied the effect of the intravenous administration of the bisphosphonate pamidronate (AHPrBP) in 7 patients with Paget's bone disease. The medication was given in a daily dose of 20 mg for 9 days in 0.9% saline infusion over 4 hours (total dose 180 mg). Thereafter the patients received no therapy. At the end of treatment a slight but significant fall of plasma calcium (p less than or equal to 0.01) was observed, but no patient displayed hypocalcemia. The urinary excretion of hydroxyproline fell below 45% of initial within 6 days of treatment. Only 3 out of 7 patients showed a decline in alkaline phosphatase activity (AP) already at the end of treatment, but after 3 to 6 months AP was below 30% of the initial value in all observed patients. After 9 months no relapse of AP was observed. Roentgenograms demonstrated dramatic improvement of bone lesions in one case. Hyperthermia occurred in 2 patients as side effect; one patient developed headache. However, treatment could be continued in all cases. The short-term intravenous administration of pamidronate is a useful means to suppress the activity of Paget's disease and no further treatment is necessary at least for several months.

Aged↗
PubMed1991

Structure-activity studies on adipokinetic hormones in Manduca sexta.

Structure-activity studies were performed for adipokinetic hormone (AKH) in Manduca sexta. Seven naturally occurring and four synthetic peptides of the red pigment concentrating hormone (RPCH)/AKH family were tested in larvae of M. sexta for activation of glycogen phosphorylase in fat body. pGlu at the N-terminal was found to be important for activity of peptides; however, Manduca AcGly1AKH is partially active. The amino acids at all positions appear to be of importance for activity, with the possible exception of the two serine residues in positions six and seven. Generally, the more amino acids are exchanged, the less the peptide will bind to the receptor. In M. sexta a beta-bend appears not to be important for the binding of peptides. Peptides ten amino acids long appear to be more active than shorter ones.

Amino Acid Sequence↗
PubMed1991

Serum amyloid A protein in very low density--and high density lipoproteins during the course of acute myocardial infarction.

In a preceding paper we reported on the detection and characterization of human serum amyloid A protein (SAA) in very low density lipoproteins (VLDL) and high density lipoproteins (HDL) of patients after acute myocardial infarction. Here we describe the time course of the occurrence of SAA in VLDL and HDL in the postinfarction period. SAA reached its maximum in VLDL and HDL approximately 53 h after the acute event. At the peak of the acute-phase response, SAA comprised as much as 38% of the total apoproteins of VLDL and HDL. SAA appeared at the same points in time and with nearly the same concentrations in VLDL and HDL. We conclude that SAA is not exchanged in plasma between lipoproteins of different densities and that this protein is secreted on its own by hepatocytes and not as a part of an already constituted lipoprotein particle.

Adult↗
PubMed1991

Spine deformity index (SDI) versus other objective procedures of vertebral fracture identification in patients with osteoporosis: a comparative study.

Radiologic identification of vertebral fractures is most important in the diagnosis and monitoring of patients with spinal osteoporosis. Different methods, using vertebral height measurements for fracture identification, have therefore been developed. We compared four methods for fracture identification in spinal x-rays of 62 female patients with primary osteoporosis. The methods of Hedlund and Gallagher, Melton et al., and Davies et al. are based on the ratio of heights within one vertebra or of the height ratios of adjacent vertebrae; all three methods result in counting the number of vertebral fractures. The fourth method of Minne et al. relates anterior, middle and posterior heights of the vertebrae between T5 and L5 to the respective heights of T4. The relative vertebral heights of patients with osteoporosis are compared to the respective relative heights (anterior, middle, and posterior) of normal subjects (T5-L5). This allows the identification of fractured vertebrae, as well as a quantification of the extent of deformation due to these fractures (spine deformity index, SDI). The same measurement data of 62 spinal x-rays of anterior, middle, and posterior heights between T4 and L5 were used to detect vertebral fractures by the four different methods. Correlation between the number of identified fractures by the different methods ranged between r = 0.56 and 0.83. On the other hand, we found a remarkable difference in the mean number of identified fractures and a discrepancy in the identification of single vertebrae as fractured or not. All four methods revealed an accumulation of fractures in the midthoracic area and in the region of transition from thoracic to lumbar spine. Vertebral fractures as identified by SDI were not detected by the other three methods in 12-29% of the cases, even if vertebral height reduction was more than 6 mm. The reliability of each method was examined by the determination of "decreasing" number of fractures during follow-up. A decrease in the number of fractures was found in about 25% patients, if using the three methods that count only the number of fractures. We obtained a 3.6% decrease in the number of fractures using the fourth method. Furthermore, the decrease in SDI values in follow-up was within the range of variance. We therefore believe that SDI and related procedures are reliable in quantifying spinal osteoporosis and monitoring during follow-up.

Adult↗
PubMed1991

A systemic acceleratory phenomenon (SAP) accompanies the regional acceleratory phenomenon (RAP) during healing of a bone defect in the rat.

The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as a regional acceleratory phenomenon (RAP). We investigated the local healing process with rats with a burr hole defect (1.2 mm in diameter) in the left tibia. We differentiated an initial phase of bone formation followed by a phase of predominant resorption. To determine whether this regional enhancement of bone formation would result in a systemic impact on bone metabolism, we analyzed both tibiae and femora and the fourth lumbar vertebra. On day 7 both femora of rats with the tibial defect showed a significant increase in computerized x-ray density, dry weight, ash weight, and Ca2+ content. Both tibiae and the fourth lumbar vertebra showed a significant increase in mineralizing surface, mineral apposition rate, and bone formation rate. Because of these results we conclude that a systemic acceleratory phenomenon (SAP) accompanies the RAP. SAP affects only the cancellous, but not the cortical bone compartment. SAP is associated closely with the occurrence of woven bone during the formation phase of the healing process. Thus we assume that woven bone formation plays a pivotal role in the mediation of SAP.

Absorptiometry, Photon↗
PubMed1991

Effects of 17 beta-estradiol on calcitonin secretion and content in a human medullary thyroid carcinoma cell line.

The presence of a direct estrogen effect on calcitonin secretion is controversial. Because most of the data available were obtained from complex in vivo systems, we chose an in vitro approach to assess the problem. Using a human C cell carcinoma cell line (TT cells) with well-documented estrogen receptors, we investigated the effect of 17 beta-estradiol (E2) on basal and stimulated calcitonin secretion, on calcitonin content, and on total cellular protein. After short (30 and 180 minutes) and long-term (24 h to 6 days) incubation of the cells with different concentrations of E2 (from 0.01 to 100 nM) we observed no stimulatory but a transient dose-dependent inhibitory effect on CT secretion and content. The nadir of the effect on CT secretion appeared at 24 h, demonstrating a reduction to 80.5 +/- 7.8% of control at 1 nM and to 59.1 +/- 15% of control at 100 nM E2. After 72 h, the CT levels of the E2-exposed groups returned to control levels. The acute stimulation of the cells with TPA plus forskolin after preincubation with E2 up to 6 days showed no difference in the increment of CT release compared to the control groups. Additionally, E2 had a dose-dependent stimulatory effect on cell protein content. The data demonstrate the absence of a direct stimulatory effect of E2 on CT secretion, revealing a dose-dependent inhibitory effect on CT secretion and content.

Calcitonin↗
PubMed1991

Changes in lipid and carbohydrate metabolism during starvation in adult Manduca sexta.

Adult Manduca sexta feed very irregularly in the laboratory, and many adult males never feed. Feeding adults live longer and feeding females lay many more eggs; however, in both feeding (sugar water) and starving adults a decrease of metabolic reserves is observed. Carbohydrates disappear from hemolymph and from fat body. Fat body lipid also decreases, while hemolymph lipid concentration increases strongly in starving adults. The activity of fat body glycogen phosphorylase increases strongly in starving adult M. sexta. The activity of glycogen phosphorylase is correlated inversely with hemolymph sugar concentration. Injected trehalose inactivates glycogen phosphorylase within 2 h. and lowers the hemolymph lipid level within 6 h. In starving adult M. sexta, neither the activation of glycogen phosphorylase nor the increase of hemolymph lipid concentration depends on adipokinetic hormone, since cardiacectomy does not prevent the activation of glycogen phosphorylase nor the increase of hemolymph lipid level.

Adaptation, Biological↗
PubMed1991

Superior local tolerability of human versus salmon calcitonin preparations in young healthy volunteers.

Possible local and systemic adverse effects following administration of salmon (sCT) and human (hCT) calcitonin (CT) have been evaluated in a double-blind, within-subject, comparative trial in 30 young, healthy volunteers. Each subject received 0.25 and 0.5 mg hCT and 100 IU sCT s.c.. Adverse effects and hypocalcaemia were recorded 1, 3 and 6 h after each injection. Significantly fewer local adverse reactions were observed after hCT (20 or 33%) than after sCT (80%), possibly due to the different vehicles employed (mannitol solution and acetic acid). The most frequent systemic adverse effects were gastrointestinal (nausea, vomiting), which occurred in 80% after 1 h, independently of the CT--preparation used. Hypocalcaemic changes were generally small and lasted longer after sCT. It is concluded that the hCT preparations were better tolerated locally than sCT in young, healthy volunteers, and that there were no differences in the systemic side effects or hypocalcaemic activity.

Adult↗
PubMed1991

Influence of parathyroidectomy, 1,25-dihydroxyvitamin D3 and high dietary calcium intake on demineralized bone matrix powder-induced bone formation in the rat.

Demineralized bone matrix induces ectopic endochondral bone formation. We used this model to study the effect of parathyroidectomy (PTX), 1,25-dihydroxyvitamin D3 treatment, and calcium enriched diet on bone formation in the rat. Hypocalcemia and hyperphosphatemia in PTX rats were corrected by 1,25-dihydroxyvitamin D3 treatment (2 x 12.5 ng/day) or by calcium enriched diet (3% calcium). Serum 1,25-dihydroxyvitamin D3 concentration was decreased in PTX rats and in intact rats with high dietary calcium intake. Calcium content of ectopic new bones (42 days after bone matrix implantation) was reduced in PTX rats compared with intact control rats. This could be prevented by 1,25-dihydroxyvitamin D3 treatment. In contrast, calcium enriched diet led to diminished mineralization of ectopic bones both in intact and PTX rats. We conclude that the effect of parathyroidectomy on bone formation may be mediated by 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 directly stimulates bone formation in this model and this effect is not simply the result of increasing serum calcium concentration.

Animals↗
PubMed1991

Osteolytic activity of Walker carcinosarcoma 256 is due to parathyroid hormone-related protein (PTHrP).

The hypercalcemic Walker carcinosarcoma 256 of the rat is an animal model for humoral hypercalcemia of malignancy. Previous in vivo studies suggested the production of a parathyroid hormone-related protein (PTHrP) by the Walker tumor. Therefore, we have measured immunoreactive PTHrP in serum-free conditioned medium from cells derived from this tumor using an antibody raised against human PTHrP(1-34). Walker tumor cell conditioned medium (WCM) displaced 125I-hPTHrP(1-34) from the antibody in a dose dependent manner, whereas control medium contained no immunoreactive PTHrP. In contrast, we detected no secretion of immunoreactive rat parathyroid hormone (rat PTH) by the Walker tumor cells using a midregional radioimmunoassay for rat PTH. WCM stimulated adenylate cyclase in osteoblast like cells, the dose-response curve paralleling that of hPTHrP(1-34). This effect could be inhibited by the PTH antagonist (8Nle, 18Nle, 34Tyr)bPTH(3-34) and by the addition of anti-hPTHrP(1-34) antibody. Bone resorbing activity of WCM in organ culture (calvaria of fetal rats) was not inhibited by indomethacin and glucocorticoids, suggesting a prostaglandin independent mechanism of osteoclast activation in this model.

Adenylyl Cyclases↗
PubMed1991

Increased incidence of euthyroid and hyperthyroid goiters independently of thyrotropin in patients with acromegaly.

The incidence of palpable goiters, the thyroid functional state and thyroid radioisotope uptake was analyzed retrospectively in 80 patients with acromegaly and 80 patients with prolactinomas. 71% of all patients with acromegaly had an enlargement of the thyroid (goiter); 49% of them had diffuse and 39% nodular goiters. The incidence of goiters in patients with prolactinomas from the same iodine deficient geographic region was only 35% (82% diffuse and 18% nodular). 17.5% of acromegalic patients underwent thyroid surgery before diagnosis of growth hormone excess. 17.5% of acromegalic patients with goiters had autonomous areas in their thyroids and 5% were clearly hyperthyroid. Goiters developed slightly more often in females (74%) than in males (67%). The mean preoperative growth hormone level was higher in acromegalic patients with goiter. The incidence of goiters was positively correlated with the documented time of elevated growth hormone concentration in serum. Two patients with exaggerated response of thyrotropin (TSH) (delta TSH greater than 20 mU/l) to the application of thyrotropin-releasing hormone (TRH) had no goiters. On the other hand most patients (61%) with goiters had a low TSH-response to TRH (delta TSH less than 10 mU/l) representing in part occult autonomy of thyroid function. No patient with prolactinoma has had previous thyroid surgery nor thyroid autonomy. One patient with prolactinoma suffered from Graves' disease and none of the acromegalic patients had this disease. We finally conclude that the elevation of growth hormone leads to increased incidence of euthyroid and hyperthyroid (autonomous) goiters independently of the influence of TSH.

Acromegaly↗
PubMed1991

Expression of type III hyperlipoproteinaemia in a subject with secondary hypothyroidism bearing the apolipoprotein E2/2 phenotype.

Post-surgical hypothyroidism developed in a now 43-year-old woman with complete insufficiency of the anterior pituitary gland who discontinued levothyroxine replacement therapy. Serum cholesterol and serum triglyceride levels increased in parallel, and classical type III hyperlipoproteinaemia (HLP) with xanthoma striata palmaris developed. The patient is homozygous for apolipoprotein (apo) E2. The case reported here represents the first example of manifestation of type III hyperlipoproteinaemia in a subject with secondary hypothyroidism bearing the apo E2/2 phenotype.

Adult↗
PubMed1991

Papillary carcinoma in an ectopic thyroid.

Ectopic thyroid tissue can be seen anywhere from the foramen caecum to the lower neck. Most frequently it presents as a thyroglossal duct cyst associated with a normal thyroid gland. Less common is total ectopia, which can occur as a lingual thyroid or occasionally in non-lingual locations. Malignant transformation of such ectopic tissue is extremely uncommon. Only 21 cases of lingual thyroid carcinomas have been reported until 1971. We present, to our knowledge, the first case of a papillary carcinoma in a non-lingual ectopic thyroid in the absence of an orthotopic thyroid.

Adolescent↗
PubMed1991

Implication of specific DQB1 alleles in genetic susceptibility and resistance by identification of IDDM siblings with novel HLA-DQB1 allele and unusual DR2 and DR1 haplotypes.

Genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) is associated with the HLA-DR3 and DR4 haplotypes. The HLA-DR2 haplotype is negatively associated with IDDM, an association that has been interpreted as dominant protection. Here, we describe the molecular analysis of the HLA class II genes in an unusual family with three HLA-DR1/2 siblings, all of whom have IDDM. With polymerase chain reaction amplification and sequence analysis to characterize the class II alleles, we identified a novel DQB1 allele on the DR1 haplotype and an unusual DQB1 allele on the DR2 haplotype. However, the DRB1 alleles on these DR1 and DR2 haplotypes are the conventional alleles (*0101 and *1501, respectively). These results suggest that it is the conventional DQB1 allele (*0602) not the DRB1 allele (*1501) on the protective DR2 haplotype that confers protection in the general population and, furthermore, that these unusual DQB1 alleles may confer susceptibility to IDDM in this family. The unusual DQB1 allele on this DR2 haplotype encodes Asp at position 57, indicating that it is the allele DQB1*0602 and not simply the presence of this residue that is responsible for the protective effect.

Adolescent↗
PubMed1991

T-lymphocyte changes linked to autoantibodies. Association of insulin autoantibodies with CD4+CD45R+ lymphocyte subpopulation in prediabetic subjects.

The onset of insulin-dependent (type I) diabetes is predictable before hyperglycemia by the presence of islet cell autoantibodies (ICAs) and competitive insulin autoantibodies (CIAAs). CIAA+ICA+ first-degree relatives of individuals with type I diabetes have increased numbers of CD4 cells bearing the CD45R antigen and reciprocal depressions of the CD4 cells bearing the CD29 determinant. In addition, depressed CD4/CD8 ratios are present. In this study, we investigated the correlation between autoantibody levels and T-lymphocyte changes in the prediabetic state. The data demonstrate a clear linear relationship between rising CIAA levels, a marker of disease rate, and rising elevations in the CD4+CD45R+/CD4+CD29+ ratio in 37 CIAA+ICA+ and CIAA+ICA- relatives (r = 0.93). In marked contrast, the degree of CD4/CD8 depression found in individuals with prediabetes or long-term diabetes failed to correlate with either CIAA (r = 0.32) or ICA (r = 0.29) levels. The investigation of T-lymphocyte changes in siblings of individuals with type I diabetes with different stable autoantibody patterns (CIAAs and/or ICAs), and thus varying risks for diabetes, revealed differences in the prediabetic groups. Fifteen CIAA+ICA- relatives with high CIAA levels (greater than 80 nU/ml) had high CD4+CD45R+/CD4+CD29+ ratios (P = 0.03) and depressed CD4/CD8 ratios (P = 0.008). In contrast, CIAA+ICA- relatives with low CIAA levels (39-80 nU/ml), and thus low risk of diabetes, had no alteration in their CD4/CD8 ratio (P = 0.75) or CD4+CD45R+/CD4+CD29+ ratio (P = 0.33). Nineteen CIAA-ICA+ siblings with a predicted intermediate risk for diabetes showed heterogeneity in the presence of T-lymphocyte abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗