Biomedical subjects

Stefan Marklund

Publications and source records attributed to Stefan Marklund.

3 recordsLinked to original sources

PubMed2003

Sustained decrease in superoxide dismutase activity underlies constrictive remodeling after balloon injury in rabbits.

OBJECTIVE: The redox pathophysiology of vascular repair is incompletely understood. We assessed the role of vascular superoxide dismutase (SOD) activity in oxidative/nitrative stress and caliber loss postinjury (PI). METHODS AND RESULTS: Rabbits submitted to iliac artery balloon overdistension were followed for 14 days PI. Significant decrease in vascular SOD activity occurred at 7 and 14 days PI (by 45% and 34%, respectively, versus control, 96+/-1 U/mg, P<0.05). Separation in concanavalin-A column showed that both extracellular SOD (ecSOD) and CuZn SOD activities were reduced, whereas Western analysis showed normal or augmented protein expression. Immunoreactivity to nitrotyrosine, neuronal NO synthase (NOS), and inducible NOS (iNOS) increased in media and neointima PI; iNOS mRNA also augmented. Administration of ecSOD from days 7 to 14 PI corrected the SOD activity decrease and minimized caliber loss by 59% (P=0.007) despite unaltered neointima. Nitrate levels markedly increased with ecSOD in injured artery homogenates (26+/-5 versus 4+/-0.3 micromol/L per mg, P=0.001). Such increase was 70% inhibited by specific iNOS antagonist 1400w. Nitrotyrosine and neuronal NOS expression decreased after ecSOD. CONCLUSIONS: Sustained low vascular SOD activity has a key role in constrictive remodeling after injury, promoting oxidative/nitrative stress and impairment of iNOS-derived NO bioavailability. SOD function may critically determine whether iNOS induction is beneficial or deleterious in vivo.

Animals↗

PubMed2002

A large duplication associated with dominant white color in pigs originated by homologous recombination between LINE elements flanking KIT.

The Dominant White (I/KIT) locus is one of the major coat color loci in the pig. Previous studies showed that the Dominant White (I) and Patch (IP) alleles are both associated with a duplication including the entire KIT coding sequence. We have now constructed a BAC contig spanning the three closely linked tyrosine kinase receptor genes PDGFRA-KIT-KDR. The size of the duplication was estimated at about 450 kb and includes KIT, but not PDGFRA and KDR. Sequence analysis revealed that the duplication arose by unequal homologous recombination between two LINE elements flanking KIT. The same unique duplication breakpoint was identified in animals carrying the I and IP alleles across breeds, implying that Dominant White and Patch alleles are descendants of a single duplication event. An unexpected finding was that Piétrain pigs carry the KIT duplication, since this breed was previously assumed to be wild type at this locus. Comparative sequence analysis indicated that the distinct phenotypic effect of the duplication occurs because the duplicated copy lacks some regulatory elements located more than 150 kb upstream of KIT exon 1 and necessary for normal KIT expression.

Alleles↗

PubMed2002

A nonsense mutation in the FMO3 gene underlies fishy off-flavor in cow's milk.

Fish-odor syndrome or Trimethylaminuria (OMIM #602079) in humans is an inborn error of metabolism associated with a characteristic fishy body odor due to elevated levels of trimethylamine (TMA) in body fluids. It is caused by loss-of-function mutations in FMO3 encoding flavin-containing mono-oxygenase 3. A fishy off-flavor is occasionally observed in cow's milk and it has been established recently that this phenotype is due to elevated TMA levels. Here, we report that fishy off-flavor in cow's milk is caused by a nonsense mutation (R238X) in the bovine FMO3 ortholog. RT-PCR analysis indicated that the mutant transcript is present in a very low amount. The mutation was found to be surprisingly common (q = 0.155) in one breed of cattle.

Amino Acid Substitution↗