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Christian Timmann

Publications and source records attributed to Christian Timmann.

4 recordsLinked to original sources
PubMed2004

Genotyping of Plasmodium falciparum pyrimethamine resistance by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry.

Increasing resistance, recrudescences, and treatment failure have led to the replacement of chloroquine with the combination of pyrimethamine (PYR) and sulfadoxine (SDX) as the first-line antimalarial drugs for treatment of uncomplicated Plasmodium falciparum malaria in several areas where this disease is endemic. The development of resistance to PYR-SDX is favored by incomplete treatment courses or by subtherapeutic levels in plasma. PYR-SDX resistance has been associated with several single-nucleotide polymorphisms (SNPs) in the P. falciparum dihydrofolate reductase (pfdhfr) and the P. falciparum dihydropteroate synthetase (pfdhps) genes. We have established assays based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) that conveniently allow the identification of SNPs associated with PYR resistance. Variants occurring at codon positions 16, 51, 59, and 108 of the pfdhfr gene were analyzed by MALDI-TOF MS in synthetic oligonucleotides to determine the detection threshold. In addition, 63 blood samples from subjects with P. falciparum parasitemia of various degrees were analyzed. The results were compared to those obtained by DNA sequencing of the respective gene fragment. The results of MALDI-TOF MS and DNA sequencing were consistent in 40 samples. In 23 samples two or three pfdhfr variants were detected by MALDI-TOF assays, whereas DNA-sequencing revealed one variant only. Simultaneous detection of two different mutations by biplex assays was, in principle, feasible. As demonstrated by the example of PYR resistance, MALDI-TOF MS allows for rapid and automated high-throughput assessment of drug sensitivity in P. falciparum malaria.

Adult↗
PubMed2002

Onchocerca volvulus-exposed persons fail to produce interferon-gamma in response to O. volvulus antigen but mount proliferative responses with interleukin-5 and IL-13 production that decrease with increasing microfilarial density.

The cellular immune response to Onchocerca volvulus antigen (OvAg) was studied in 551 persons exposed to O. volvulus transmission in a hyperendemic area of Ghana, West Africa. A whole-blood assay showed that, in response to a soluble O. volvulus extract, cell proliferation, as well as interleukin (IL)-5 and IL-13 concentrations in the supernatants, were high in cultures of blood from microfilaria (mf)-negative persons and significantly decreased with increasing mf counts of the donors. Only background concentrations of interferon (IFN)-gamma were found, and these did not correlate with mf counts. In response to a mitogen, cells from all persons strongly reacted with proliferation and secretion of all 3 cytokines studied. These findings show that the response of human peripheral blood cells to OvAg does not include significant IFN-gamma production; that mf negativity is associated with IL-5 and IL-13 production but not, as previously suggested, with IFN-gamma production; and that IL-5 and IL-13 production decreases with increasing mf density.

Adolescent↗
PubMedDate not supplied

Familial Mediterranean fever with amyloidosis associated with novel exon 2 mutation (S1791) of the MEFV gene.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent attacks of fever, serositis, and a risk for AA amyloidosis. FMF is caused by mutations in the Mediterranean fever gene (MEFV), which is expressed in blood cells of the myelomonocytic differentiation pathway. We identified a novel mutation S1791 in exon 2 of MEFV in two members of a family of Turkish origin. In both cases, S1791 was in compound heterozygosity with MEFV mutation M694V, and the characteristic clinical syndrome of FMF including amyloidosis was found. The location of S1791 in exon 2 is of interest because (1) amyloidosis in FMF has previously been found to be strongly associated with compound exon 10 mutations and (2) it supports the notion that the mechanism causing FMF is connected to the cytoplasmic rather than nuclear function of the molecule.

Amyloidosis↗