Biomedical subjects

M F Shuler

Publications and source records attributed to M F Shuler.

3 recordsLinked to original sources

PubMed2001

Photodynamic therapy update.

Photodynamic therapy uses a photoactivating agent to selectively treat choroidal neovascularization. In April 2000, the United States Food and Drug Administration approved verteporfin photodynamic therapy for the treatment of subfoveal, predominately classic, choroidal neovascularization caused by age-related macular degeneration. The treatment of choroidal neovascularization from other causes such as myopia, angioid streaks, and idiopathy, and presumed ocular histoplasmosis syndrome is still under investigation. Other photoactivating agents are being evaluated. Photodynamic therapy has been shown to halt the progression of visual loss in patients with age-related macular degeneration who have subfoveal predominately classic choroidal neovascularization. The socio-economic impact of verteporfin approval has yet to be determined.

Choroidal Neovascularization↗

PubMed1995

Sequence-specific interactions between promoter DNA and the RNA polymerase sigma factor E.

In order to determine which amino acyl residues in a secondary sigma factor govern its specificity of recognition at the -35 region of promoters, we examined the effects of amino acid substitutions in sigma E in Bacillus subtilis that made the sequence of its putative -35 recognition region more similar to another sigma factor in B. subtilis, sigma K. We found that a single amino acid substitution at position 217 of sigma E resulted in a sigma factor that could direct transcription from sigma K-dependent promoters. Furthermore, we tested whether this amino acid substitution in sigma E had changed the specificity of interactions of the sigma with -35 region sequences by examining the activity of the mutant sigma E on derivatives of sigma E-dependent promoters that contained single base-pair substitutions. We found that this substitution in sigma E specifically suppressed the effect of a single base-pair substitution at position -31 in a sigma E-dependent promoter spoIIID. The amino acyl residue at another position (219) on sigma E affected the specificity of interaction with position -33 in spoIIID promoter. The amino acyl residues at the two positions in sigma E, 217 and 219, that determine the specificity of interactions between the sigma and base-pairs in the -35 region of its cognate promoters (positions -33 and -31, respectively, in the spoIIID promoter) probably closely contact these base-pairs.

Amino Acid Sequence↗

PubMed1995

A single amino acid substitution in sigma E affects its ability to bind core RNA polymerase.

We have examined the role of the most highly conserved region of bacterial RNA polymerase sigma factors by analyzing the effect of amino acid substitutions and small deletions in sigma E from Bacillus subtilis. sigma E is required for the production of endospores in B. subtilis but not for vegetative growth. Strains expressing each of several mutant forms of sigE were found to be deficient in their ability to form endospores. Single amino acid substitutions at positions 68 and 94 resulted in sigma factors that bind with less affinity to the core subunits of RNA polymerase. The substitution at position 68 did not affect the stability of the protein in B. subtilis; therefore, this substitution probably did not have large effects on the overall structure of the sigma factor. The substitution at position 68 probably defines a position in sigma E that closely contacts a subunit of RNA polymerase, while the substitution at position 94 may define a position that is important for protein stability or for binding to core RNA polymerase.

Amino Acid Sequence↗