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S Erdmann

Publications and source records attributed to S Erdmann.

24 records · Page 2Linked to original sources
PubMed1998

Mapping of a carboxyl-terminal active site of parathyroid hormone by calcium-imaging.

We recently showed that the C-terminal fragment PTH (52-84) effectively increases intracellular free calcium ([Ca2+]i) in a subset of growth plate chondrocytes not activated by the N-terminal PTH fragment (1-34). Here we characterize the active site on C-terminal PTH (52-84) with respect to calcium (Ca2+)-signaling and the mechanism involved by using synthetic PTH-subfragments in digital CCD ratio-imaging experiments. Our results show amino acids 73-76 to be the core region for increasing [Ca2+]i. Ryanodine (1 microM), caffeine (10 mM), lithium (2 mM), or cyclopiazonic acid (2-5 microM), agents that interfere with intracellular Ca2+ release, all failed to block PTH (52-84) induced [Ca2+]i increases. Depletion of extracellular calcium ([Ca2+]o) blocked PTH (52-84) induced [Ca2+]i increases, indicating a transmembrane Ca2+ influx. In contrast to voltage-gated and Ca2+ release activated Ca2+ influx, PTH (52-84) evoked Ca2+ influx was not blocked by nickel (1 mM). We conclude that PTH amino acids 73-76 are essential for activation of a nickel-insensitive Ca2+ influx pathway in growth plate chondrocytes that is likely to be of relevance for matrix calcification, a key step in endochondral bone formation.

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PubMed1996

Differential effects of parathyroid hormone fragments on collagen gene expression in chondrocytes.

The effect of parathyroid hormone (PTH) in vivo after secretion by the parathyroid gland is mediated by bioactive fragments of the molecule. To elucidate their possible role in the regulation of cartilage matrix metabolism, the influence of the amino-terminal (NH2-terminal), the central, and the carboxyl-terminal (COOH-terminal) portion of the PTH on collagen gene expression was studied in a serum free cell culture system of fetal bovine and human chondrocytes. Expression of alpha1 (I), alpha1 (II), alpha1 (III), and alpha1 (X) mRNA was investigated by in situ hybridization and quantified by Northern blot analysis. NH2-terminal and mid-regional fragments containing a core sequence between amino acid residues 28-34 of PTH induced a significant rise in alpha1 (II) mRNA in proliferating chondrocytes. In addition, the COOH-terminal portion (aa 52-84) of the PTH molecule was shown to exert a stimulatory effect on alpha1 (II) and alpha1 (X) mRNA expression in chondrocytes from the hypertrophic zone of bovine epiphyseal cartilage. PTH peptides harboring either the functional domain in the central or COOH-terminal region of PTH can induce cAMP independent Ca2+ signaling in different subsets of chondrocytes as assessed by microfluorometry of Fura-2/AM loaded cells. These results support the hypothesis that different hormonal effects of PTH on cartilage matrix metabolism are exerted by distinct effector domains and depend on the differentiation stage of the target cell.

Animals↗
PubMed1994

Proliferating cell nuclear antigen (PCNA) expression of megakaryocytopoiesis in normal human bone marrow and reactive lesions with special emphasis on HIV-myelopathy.

A morphometric analysis was performed on bone marrow trephine biopsies using sequential double-immunostaining, to evaluate endoreduplicative activity of megakaryocytopoiesis. A total of 104 marrow specimens were studied with employment of monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen-PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa). In addition to the control group patients included non-specific inflammatory changes, HIV-myelopathy with normal or decreased platelet counts, idiopathic thrombocytopenic purpura (ITP), and finally reactive thrombocytosis (TH). To exclude an undue overexpression of PCNA, in a comparative pilot study we also applied MIB1 (Ki-67 antigen) on normal bone marrow specimens. In accordance with the various modalities of cell-cycle marker expression, no significantly different findings were disclosed. PCNA-labelling index was relatively low, ranging from 0.8 to 1.7% of the total megakaryocytopoiesis (promegakaryoblasts to mature platelet-shedding megakaryocytes). A significant relationship between megakaryocyte size and PCNA-expression was determinable. This implies that some of the cases with a prevalence of small megakaryocytes, like ITP, have the tendency to show a higher proportion of positively-stained cells. Moreover, this feature confirms a hypothesis postulating a decrease in the time for DNA-synthesis (S-phase) and a relative prolongation of the G1/G2-phases of the cell-cycle at higher ploidy levels (large-sized megakaryocytes). On the other hand, it may be speculated that some of the hyperpolyploid giant megakaryocytes may have reached their endstage of endoreduplication and enter into G0-phase. In comparison with the control group and the other entities under study, a significant reduction of PCNA-reactivity was recognizable in HIV-myelopathy accompanied by thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

An unusual polyanion from Physarum polycephalum that inhibits homologous DNA polymerase alpha in vitro.

From extracts of microplasmodia of Physarum polycephalum and their culture medium, an unusual substance was isolated which inhibited homologous DNA polymerase alpha of this slime mold but not beta-like DNA polymerase and not heterologous DNA polymerases. Analysis, especially NMR spectroscopy, revealed the major component to be an anionic polyester of L-malic acid and the inhibition to be due to poly(L-malate) in binding reversibly to DNA polymerase alpha. The mode of inhibition is competitive with substrate DNA and follows an inhibition constant Ki = 10 ng/mL. Inhibition is reversed in the presence of spermine, spermidine, poly(ethylene imine), and calf thymus histone H1. According to its ester nature, the inhibitor is slightly labile at neutral and instable at acid and alkaline conditions. Its largest size corresponds to a molecular mass of 40-50 kDa, but the bulk of the material after purification has lower molecular masses. The inhibitory activity depends on the polymer size and has a minimal size requirement.

Binding Sites↗
PubMedDate not supplied

[Multilocular erythema migrans in borreliosis].

BACKGROUND: Borreliosis is the most common vector transmitted disease in childhood. Although the disease manifests with an erythema migrans in 80 % of the patients, multilocular skin manifestations are only observed in 2-18 % of these. Differential diagnoses of erythema migrans include erysipelas, persistent insect bite reaction, and fixed drug eruption, in particular when the clinical history does not reveal a tick bite. PATIENT: We report on a 5-year-old boy showing nine erythemas with central pallor on his face, trunk, arms and legs. He recalled a tick bite 3 weeks before. RESULTS: Serological studies revealed an acute infection with Borrelia burgdorferi. After antibiotic treatment with orally administered amoxicillin skin manifestations resolved within three days. During a follow-up period of six months the patient revealed no signs of persistent borreliosis. CONCLUSION: Multilocular erythema migrans is a possible manifestation of borreliosis and is classified as disseminated early infection which is frequently associated with systemic reactions, including malaise, arthritis, carditis, headache and even meningeal signs. Treatment is based on antibiotics, which should preferably be given intravenously in case of systemic signs.

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