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Biomedical subjects

M Dorsey

Publications and source records attributed to M Dorsey.

6 recordsLinked to original sources
PubMed2000

Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to erythropoietic protoporphyria.

Ferrochelatase (FECH; EC 4.99.1.1) catalyzes the terminal step of the heme biosynthetic pathway. Defects in the human FECH gene may lead to erythropoietic protoporphyria (EPP), a rare inherited disorder characterized by diminished FECH activity with protoporphyrin overproduction and subsequent skin photosensitivity and in rare cases liver failure. Inheritance of EPP appeared to be autosomal dominant with possible modulation by low expression of the wild-type FECH allele. Animal FECHs have been demonstrated to be [2Fe-2S] cluster-containing proteins. Although enzymatic activity and stability of the protein appear to be dependent on the presence of the [2Fe-2S] cluster, the physiologic role of the iron-sulfur center remains to be unequivocally established. Three of the 4 [2Fe-2S] cluster-coordinating cysteines (ie, C403, C406, and C411 in the human enzyme) are located within the C-terminal domain. In this study 5 new mutations are identified in patients with EPP. Three of the point mutations, in 3 patients, resulted in FECH variants with 2 of the [2Fe-2S] cluster cysteines substituted with tyrosine, serine, and glycine (ie, C406Y, C406S, and C411G) and with undetectable enzymatic activity. Further, one of the patients exhibited a triple point mutation (T(1224)-->A, C(1225)-->T, and T(1231)-->G) leading to the N408K/P409S/C411G variant. This finding is entirely novel and has not been reported in EPP. The mutations of the codons for 2 of the [2Fe-2S] cluster ligands in patients with EPP supports the importance of the iron-sulfur center for the proper functioning of mammalian FECH and, in at least humans, its absence has a direct clinical impact. (Blood. 2000;96:1545-1549)

Female↗
PubMed1992

A spontaneous chromosomal amplification of the ADH2 gene in Saccharomyces cerevisiae.

A spontaneous antimycin A-resistant mutant carrying approximately four extra copies of ADH2 on chromosome XII was isolated from yeast strain 315-1D which lacks a functional copy of ADH1 and thus is antimycin A-sensitive. The additional copies of the normally glucose-repressed ADH2 are expressed during growth on glucose accounting for the antimycin A resistance. These extra copies are inserted into nonadjacent ribosomal DNA sequences (rDNA) near the recombination stimulating sequence HOT1. Each extra copy of the ADH2 gene (1548 bp) replaces most of the 37S transcript (approximately 7400 bp) in one of the approximately 200 copies of the rDNA present in the yeast genome. All four extra copies of ADH2 are lost at a rate of approximately 1 x 10(-5) deletions per cell per generation. One of the joints between the rDNA and ADH2 DNA is located 7 nucleotides downstream from 20 adenine residues in the normal copy of ADH2. This joint occurs at the end of a stretch of 16-29 thymidines in the rDNA which has been expanded to 57-59 thymidines. The other novel joint is located in a short region of sequence similarity between ADH2 and the rDNA. These observations suggest that amplification of ADH2 was a two step process: first the ADH2 gene was inserted into the rDNA, then multiple copies were generated by unequal crossing over or gene conversion within the rDNA.

Alcohol Dehydrogenase↗
PubMed1992

Spontaneous amplification of the ADH4 gene in Saccharomyces cerevisiae.

Five spontaneous amplifications of the ADH4 gene were identified among 1,894 antimycin A-resistant mutants isolated from a diploid strain after growth at 15 degrees. Four of these amplifications are approximately 40-kb linear extrachromosomal palindromes carrying telomere homologous sequences at each end similar to a previously isolated amplification. ADH4 is located at the extreme left end of chromosome VII, and the extrachromosomal fragments appear to be the fusion of two copies of the end of this chromosome. The fifth amplification is a chromosomal amplification carrying an extra copy of ADH4 on both homologs of chromosome VII. These results suggest that the ADH system can be used to study amplification in Saccharomyces cerevisiae.

Alcohol Dehydrogenase↗
PubMed1991

Relationships among and demographic predictors of dentists' self-reported adherence to national guidelines.

How dentists learn about and integrate new procedures and techniques into dental practice are major concerns in innovation research in dentistry. The purposes of this study were to: (1) develop reliable measures of self-reported adherence to different national guidelines; (2) to examine the relationships among the different measures; and (3) to determine if predictors of these adherence behaviours exist. One thousand U.S. general dentists were asked to complete a survey of adherence behaviours to established guidelines in infection control, radiation protection, and antibiotic prophylaxis. Thirty-five percent responded to the mailed survey. Reliable scales were developed in infection control and antibiotic prophylaxis behaviors. Step-wise multiple regression analysis produced several weak predictors of adherence to guidelines in these two areas. Characteristics of early adopters such as office complexity, membership in professional associations, and year of graduation, were consistent with other dental innovation literature. Significant correlations were found between adherence behaviors in infection control and antibiotic prophylaxis. These correlations do support the findings that practitioners who are early adopters of innovation are likely to do so in more than one area.

Anti-Bacterial Agents↗