Search PubMed⌕ Search

Biomedical subjects

E Nägele

Publications and source records attributed to E Nägele.

At least 19 recordsLinked to original sources
PubMed1998

HIV type 1 V3 serotyping of Tanzanian samples: probable reasons for mismatching with genetic subtyping.

HIV-1 V3 serotyping is used to classify immunodeficiency viruses on the basis of antibody binding to V3 peptides derived from env genetic subtypes. Although it shows a reasonable overlap, it has been reported to be distinct from viral genetic subtypes. The aim of this study is to determine the feasibility of HIV-1 serotyping to predict genetic subtypes in an East African setting, where multiple HIV-1 subtypes have coexisted for many years. HIV-1 genetic subtypes of 86 AIDS patients in Mbeya Town, southwest Tanzania, were determined, using env nucleic acid sequencing as the basis for comparison. Those data were compared with V3 serotyping results obtained by four different methodologies. Four HIV-1 genetic subtypes were identified, including A (25, 29%), C (47, 55%), D (13, 15%), and G (1, 1%). The sensitivity and specificity of those serotyping assays varied considerably: sensitivity for genetic subtype A (40-48%), C (52-96%), and D (9-31%); and specificity for genetic subtype A (77-95%), C (46-63%), and D (97-100%). We further tried to identify reasons for the discrepancies between serotyping results and genetic subtypes. By means of logistic regression analysis three amino acid residues within the V3 loop (positions 12, 13, and 19; V, H, and A for serotype A, I, R, and T for serotype C) were found to be most important for antibody binding; a deviation from the subtype-specific amino acids was highly related to mismatched results. In addition, we have shown that phenetic analysis of V3 amino acid sequence data could be used to predict the majority of V3 serotypes (93-94%). Our data demonstrated that for the majority of specimens HIV-1 V3 serotyping results closely match the subtype of the analyzed sample as revealed by the V3 loop amino acid sequence. However, our data demonstrate that HIV-1 serotyping is not sufficiently accurate to predict genetic subtypes in Tanzania, where subtypes A, C, D, and G are circulating. This was due to highly similar amino acid sequences throughout the prevalent genetic subtypes, which caused the inability of HIV-1 V3 serotyping to differentiate subtype A from C as well as D from C. Instead, the serotyping results reflect the frequency distribution of V3 serotypes. To investigate HIV-1 genetic subtypes in population-based studies in this African setting additional or modified algorithms are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1997

S-Acylation and plasma membrane targeting of the farnesylated carboxyl-terminal peptide of N-ras in mammalian fibroblasts.

We have used a series of fluorescent lipid-modified peptides, based on the farnesylated C-terminal sequence of mature N-ras [-GCMGLPC(farnesyl)-OCH3], to investigate the membrane-anchoring properties of this region of the protein and its reversible modification by S-acylation in cultured mammalian fibroblasts. The farnesylated peptide associates with lipid bilayers (large unilamellar phospholipid vesicles) with high affinity but in a rapidly reversible manner. Additional S-palmitoylation of the peptide suppresses its ability to desorb from, and hence to diffuse between, lipid bilayers on physiologically significant time scales. NBD-labeled derivatives of the farnesylated N-ras C-terminal heptapeptide, when incubated with CV-1 cells in culture, are taken up by the cells and reversibly S-acylated in a manner similar to that observed previously for the parent protein. The S-acylation process is highly specific for modification of a cysteine rather than a serine residue but tolerates replacement of the peptide-linked farnesyl moiety by other hydrophobic groups. Fluorescence microscopy reveals that in CV-1 cells the S-acylated form of the peptide is localized preferentially to the plasma membrane, as has been observed for N-ras itself. This plasma membrane localization is unaffected by either reduced temperature (15 degrees C) or exposure to brefeldin A, treatments which inhibit various trafficking steps within the secretory pathway. These results suggest that in mammalian cells the plasma membrane localization of mature N-ras is maintained by a 'kinetic trapping' mechanism based on S-acylation of the protein at the level of the plasma membrane itself.

4-Chloro-7-nitrobenzofurazan↗
PubMed1997

Synthesis of characteristic lipopeptides of the human N-Ras protein and their evaluation as possible inhibitors of protein farnesyl transferase.

Lipopeptides carrying a farnesyl thioether or a palmitic acid thioester and a farnesyl thioether were prepared from S-farnesyl cysteine methyl ester by N-terminal extension of the peptide chain employing the base labile Fmoc blocking group of the palladium(0) sensitive Aloc urethane. By means of this technique a lipohexapeptide representing the completely functionalized, i.e. palmitoylated and farnesylated C-terminus of the human N-Ras protein, was prepared. If acid labile blocking functions like the Boc group were used, upon deprotection an undesired addition of the acid to the double bonds of the farnesyl residue occurred. Therefore, acid labile blocking groups should not be employed in the synthesis of farnesylated lipopeptides. The lipopeptide methyl esters which carry only a farnesyl group do not inhibit protein farnesyl transferase, whereas palmitoylated peptides are weak inhibitors of this enzyme.

Alkyl and Aryl Transferases↗
PubMed1981

[Intrapulmonary sarcoid, presenting as tumor or as multiple pulmonary nodules with and without cavities (author's transl)].

Eight cases of nodular, partially cavitary intrapulmonary--mainly acute--sarcoid mimicking metastatic disease or cavitary disease of other etiology are presented to point out the fact that sarcoid can occur in this form. Almost all these patients were young and asymptomatic with the lesions discovered incidentally on the chest films taken for other reasons. The pulmonary nodules and cavities present differential diagnostic problems; with the concomitant--or previous--presence of hilar or mediastinal lymph-adenopathy and the finding of unsharp borders of the nodules somewhat supporting the diagnosis of sarcoid.

Adult↗
PubMed1975

[Semi-deep radiotherapy under high-kilovoltage conditions].

The semi-deep radiotherapy, performed by high-kilovoltage technique, fills a gap between superficial and megavolttherapy, as it renders possible an irradiation in focal depth of 2--4 cm, while largely preserving the deep underlying tissue. Besides which, every form of radiotherapy can be used, as under conventinal conditions. A further advantage exists in the markedly greater skin tolerance and in the low bone absorption of high-kilovoltage radiation, so that much higher focal doses can be achieved. This means that--in superficial processes--the high-voltage technique can replace the much more expensive therapy with accelerated electrons. The RT 305 equipment for high-voltage technique can be especially recommended for the following indications: 1. Skin and limph node metastases as well as tumors and metastases which are not situated deeper than 5 cm below the skin surface. Hereby, thean be exposed up to 8000 R, by small or medium cone. At the same time, in comparison to conventional X-ray therapy, the deep tissue is largely preserved. 2. Postoperative radiotherapy of tumors situated right under the skin. 3. Radiotherapy of inoperable breast cancer. 4. Irradiation of relapses on pre-exposed skin. 5. We assume that the high-voltage technique is also suitable for primary radiotherapy of larynx carcinomas, although we have no personal experience of this. 6. The palliative irradiation of deep tumors with the RT 305, due to its preservation of the skin and the relatively low bone absorption, can be performed more easily than with conventional X-ray therapy. The method of choice, however, is the megavolt-therapy. 7. Degenerative diseases and arthroses.

Adult↗