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Biomedical subjects

D J Soares

Publications and source records attributed to D J Soares.

5 recordsLinked to original sources

Archaeal histones: structures, stability and DNA binding.

Structures, stability and DNA-binding properties have been established for archaeal histones from mesophiles, thermophiles and hyperthermophiles. Most archaeal histones are simply histone folds that are stabilized by dimer formation. Archaeal histones and the histone folds of the eukaryotic nucleosome core histones share a common ancestry and bind and wrap DNA similarly using conserved residues. The histone-fold residues that stabilize dimer-dimer interactions within an archaeal histone core contribute to determining archaeal histone-DNA affinity.

Amino Acid Sequence↗

Mutational analysis of archaeal histone-DNA interactions.

Site-specific mutagenesis of the hmfB gene cloned from the archaeon Methanothermus fervidus, followed by expression in Escherichia coli, has been used to generate approximately 90 recombinant (r) variants of the archaeal histone HMfB. The abilities of these variants to form stable archaeal nucleosome-containing complexes with linear pBR322 DNA, and with an 89 bp restriction fragment of this DNA have been determined. Variants that failed to form such complexes, based on negative gel-shift assays, had substitutions at the N terminus or within the alpha1, L1 and L2 regions of the rHMfB histone fold, at sites predicted to be homologous to eucaryal histone fold residues that contact the DNA in the eucaryal nucleosome. Variants that failed to give gel shifts were further assayed for their abilities to facilitate ligase-catalyzed circularization of a linear 88 bp DNA molecule, and to reduce the ellipticity of a DNA solution at 275 nm (theta(275)). Consistent with cooperative but independent sites of DNA binding, a combination of three residue substitutions, one each in alpha1, L1 and L2, was required to generate a rHMfB variant with no detectable DNA binding based on gel shift, circularization and theta(275) reduction assays.

Allosteric Site↗

Relapse with multibacillary leprosy caused by rifampicin sensitive organisms following paucibacillary multidrug therapy.

Many leprosy patients treated with multidrug therapy (MDT) had previously received dapsone (DDS) monotherapy for many years. We report here 2 such patients treated with modified paucibacillary MDT composed of rifampicin and DDS who subsequently relapsed with multibacillary leprosy 5 and 6 years after release from treatment. Isolates of Mycobacterium leprae from both patients were resistant to DDS but sensitive to rifampicin, suggesting that the relapses were caused by rifampicin sensitive 'persister' organisms. The implications of this for surveillance of patients released from treatment (RFT) and the management of relapsed patients is discussed.

Adult↗

The role of IgM antiphenolic glycolipid-1 antibodies in assessing household contacts of leprosy patients in a low endemic area.

This study was carried out to assess the role PGL-1 antibodies may have to play in assisting with early diagnosis in close contacts of leprosy patients. Blood samples were collected from patients and contacts. It was found that 6.9% of index cases and 1% of healthy contacts were positive for PGL-1 antibody. None of the healthy contacts developed clinical leprosy and all had become seronegative at follow-up. We conclude that screening for PGL-1 antibodies has a limited role in the screening of healthy contacts and may not be of use in low endemic areas.

Adult↗