Biomedical subjects

A Lode

Publications and source records attributed to A Lode.

5 recordsLinked to original sources

PubMed2007

Calcium phosphate bone cements, functionalized with VEGF: release kinetics and biological activity.

Calcium phosphate bone cements are of great interest for bone replacement since the nanocrystalline structure allows their remodelling into native bone tissue. A strategy to accelerate vascularization of the implant region is the functionalization with vascular endothelial growth factor (VEGF), which is known to mediate angiogenesis in vivo. In this study, the release of recombinant human VEGF (rhVEGF(165)) following physical adsorption to Biocement D (BioD) and several modifications were investigated. Our data demonstrate a high VEGF binding capacity of BioD and a sustained release with a moderate initial burst. A proliferation assay using endothelial cells revealed maintenance of biological activity of VEGF after release from BioD. Release behavior of BioD was not improved by modification with mineralized collagen type I, as well as with a combination of mineralized collagen with O-phospho-L-serine and sodium citrate, respectively. In contrast, a positive impact of these modifications on the activity of released VEGF was observed; in case of the phosphoserine- and sodium citrate-modified cements, the biological efficacy of released VEGF was even higher than that of nonreleased control VEGF. We conclude that the bone implant material BioD and, especially, the phosphoserine modification may support activation of angiogenesis by delivery of VEGF in a local and sustained manner.

Animals↗

PubMed2001

Plastidic (Pho1-type) phosphorylase isoforms in potato (Solanum tuberosum L.) plants: expression analysis and immunochemical characterization.

Higher plants contain two types of phosphorylase (EC 2.4.1.1). One type is plastidic (Phol) and the other resides in the cytosol (Pho2). For Solanum tuberosum L., two highly homologous Pho1-type sequences (designated as Pho1a and Pho1b, respectively) have been described that occur both in a homodimeric, (Pho1a)2, and a heterodimeric, Pho1a-Pho1b, state [U. Sonnewald et al. (1995) Plant Mol Biol 27:567 576; T. Albrecht et al. (1998) Eur J Biochem 251:981-991]. We present a spatial and temporal analysis of the expression patterns of the Pho1-type phosphorylases in S. tuberosum. Expression was analyzed at transcript, protein and activity levels. The specificity of both the probes and the antibodies used was carefully determined to ensure selectivity of detection. For both the Pho1a and Pho1b probes the degree of cross-hybridization was estimated. Peptide scanning identified the epitopes of the anti-Pho 1a and anti-Pho 1b antibodies. Expression of the two Pho1-type genes was analyzed in various organs of the potato plant. In all organs studied the Pho1a transcript levels exceeded those of Pho1b. Furthermore, leaves of a given developmental stage were sampled during the light period and were analyzed for transcript and protein levels and for various carbohydrate pools as well. The data show that in leaves the Pho1a gene expression closely corresponds to starch accumulation, suggesting that the enzyme fulfils a metabolic function within the process of starch biosynthesis. In tubers, Pho1a is constitutively expressed in the parenchyma cells whereas expression of the Pho1b, gene is restricted to cells in close vicinity of the vascular tissue.

Amino Acid Sequence↗

PubMed2000

The P(174)L mutation in the human hSCO1 gene affects the assembly of cytochrome c oxidase.

Mutations of the yeast SCO1 gene result in impaired COX assembly. Recently, heterozygous mutations in the human homologue hSCO1 have been reported in infants suffering from neonatal ketoacidotic coma and isolated COX deficiency (Valnot et al., 2000). One of the hSCO1 alleles harboured a frame shift mutation resulting in a premature stop codon, the other a missense mutation leading to a substitution of proline(174) by leucine. This position is next to the essential CXXXC motif, which is conserved in all Sco1p homologues. We used chimeric proteins with the amino-terminal portion derived from yeast Sco1p and carboxy-terminal portion including the CXXXC motif from the human hSco1p to provide experimental evidence for the pathogenic nature of the P(174)L mutation. These chimeras are able to complement yeast sco1 null mutants. Introduction of the P(174)L mutation affects the function of these chimeric proteins severely, as shown by impaired COX assembly and loss of COX activity.

Amino Acid Sequence↗

PubMed2000

Mitochondrial copper metabolism in yeast: interaction between Sco1p and Cox2p.

Yeast mitochondrial Sco1p is required for the formation of a functional cytochrome c oxidase (COX). It was suggested that Sco1p aids copper delivery to the catalytic center of COX. Here we show by affinity chromatography and coimmunoprecipitation that Sco1p interacts with subunit Cox2p. In addition we provide evidence that Sco1p can form homomeric complexes. Both homomer formation and binding of Cox2p are neither dependent on the presence of copper nor affected by mutations of His-239, Cys-148 or Cys-152. These amino acids, which are conserved among the members of the Sco1p family, have been suggested to act in the reduction of the cysteines in the copper binding center of Cox2p and are discussed as ligands for copper.

Binding Sites↗

PubMed2000

What to do with targeted IL-2.

A common strategy in immunotherapy of cancer is the induction of an increased immunogenicity of syngeneic malignancies. A novel approach to achieve this goal is the targeting of cytokines into the tumor microenvironment with antibody-cytokine fusion proteins, called immunocytokines. This report summarizes therapeutic efficacy and immune mechanisms involved in targeting IL-2 to syngeneic tumors and describes their extended use as a synergistic treatment modality for cancer vaccines and antiangiogenesis. Treatment of established melanoma and colon carcinoma metastases with IL-2 immunocytokines resulted in eradication of disease, followed by a vaccination effect protecting mice from lethal challenges with wild-type tumor cells. In a syngeneic neuroblastoma model, targeted IL-2 elicited effective antitumor responses mediated by NK cells in the absence of a T-cell memory. Interestingly, targeted IL-2 was effective in amplification of memory immune responses previously induced by cancer vaccines. Furthermore, a synergistic effect achieved by combining targeted IL-2-immunotherapy with an antiangiogenic inhibitor of integrin alpha(v)beta(3) extends the potential of this immunotherapeutic strategy in combination with antiangiogenesis as demonstrated in three syngeneic tumor models. Based on these findings, targeted IL-2 may provide an effective tool for the adjuvant treatment of cancer either applied as a single strategy or in combination with cancer vaccines and antiangiogenic strategies.

Journal Article↗