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Biomedical subjects

M R Mann

Publications and source records attributed to M R Mann.

6 recordsLinked to original sources
PubMed2001

Tibiotalocalcaneal arthrodesis: a biomechanical analysis of the rotational stability of the Biomet Ankle Arthrodesis Nail.

We hypothesized that the posterior-to-anterior (PA) calcaneal interlocking screw of the Biomet Ankle Arthrodesis Nail would increase rotational stability secondary to increased bone purchase compared with the standard lateral-to-medial (transverse) screw. Each of 10 fresh human cadaver lower limbs (five matched pairs) were stabilized with a nail inserted retrograde through the calcaneus, talus, and tibia according to standard technique. One limb of each pair was fixed with a transverse calcaneal screw; the contralateral limb, with a PA calcaneal screw. Each limb was then subjected to torsional testing on an MTS Mini Bionix load frame. The PA screw construct was significantly stiffer than the transverse screw construct: 1.96 and 1.41 Nm/E, respectively (P < 0.036).

Ankle Joint↗
PubMed2000

Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo.

The H19 gene is imprinted with preferential expression from the maternal allele. The putative imprinting control region for this locus is hypermethylated on the repressed paternal allele. Although maternal-specific expression of H19 is observed in mouse blastocysts that develop in vivo, biallelic expression has been documented in embryos and embryonic stem cells experimentally manipulated by in vitro culture conditions. In this study the effect of culture on imprinted H19 expression and methylation was determined. After culture of 2-cell embryos to the blastocyst stage in Whitten's medium, the normally silent paternal H19 allele was aberrantly expressed, whereas little paternal expression was observed following culture in KSOM containing amino acids (KSOM+AA). Analysis of the methylation status of a CpG dinucleotide located in the upstream imprinting control region revealed a loss in methylation in embryos cultured in Whitten's medium but not in embryos cultured in KSOM+AA. Thus, H19 expression and methylation were adversely affected by culture in Whitten's medium, while the response of H19 to culture in KSOM+AA approximated more closely the in vivo situation. It is unlikely that biallelic expression of H19 following culture in Whitten's medium is a generalized effect of lower methylation levels, since the amount of DNA methyltransferase activity and the spatial distribution of Dnmt1 protein were similar in in vivo-derived and cultured embryos. Moreover, imprinted expression of Snrpn was maintained following culture in either medium, indicating that not all imprinted genes are under the same stringent imprinting controls. The finding that culture conditions can dramatically, but selectively, affect the expression of imprinted genes provides a model system for further study of the linkage between DNA methylation and gene expression.

Animals↗
PubMed1999

Towards a molecular understanding of Prader-Willi and Angelman syndromes.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct neurological disorders that map to human chromosome 15q11-q13 and involve perturbations of imprinted gene expression. PWS is caused by a deficiency of paternal gene expression and AS is caused by a deficiency of maternal gene expression. Experiments in the last year have focused on molecular analysis of the human chromosomal region as well as the homologous region on central mouse chromosome 7. New transcripts and exons have been identified and the epigenetic status of the PWS/AS region in mice and humans has been examined. The imprinting center that is hypothesized to control the switch between the maternal and paternal epigenotypes has also been characterized in greater detail and a mouse model that deletes the homologous element demonstrates a conservation in imprinting center function between mice and humans. In addition, analysis of non-deletion AS patients has revealed that UBE3A intragenic mutations are found in a significant number of cases. However, both human patients and mouse model systems indicate that other genes may also contribute to the AS phenotype. Thus, although much has been learned in the last year, considerable information is still required before these complex syndromes are fully understood.

Angelman Syndrome↗
PubMed1975

Aromatizing activity of placental microsomal fractions from ewes in late gestation.

Placental microsomes from eight domestic sheep at 136-146 days of gestation were incubated with radioactive androstenedione, testosterone and dehydroepiandrosterone. Aromatizing activity was examined in the presence and absence of cortisol and the rates of both oestrone and oestradiol synthesis were measured. Oestrone predominated in preference to oestradiol in most of the incubations, a result opposite to that found with human placentae. The sharp increase in the rate of oestradiol production found in the 144- to 146-day-old placentae incubated with testosterone may indicate a more rapid increase of aromatizing than of 17beta-hydroxysteriod dehydrogenase activity. The presence of cortisol in the mixtures did not significantly affect the placental aromatizing activity, indicating that there is no direct effect of cortisol on the enzyme system as measured in vitro. The dramatic rise of overall mean aromatizing activity from 4.86 plus or minus 0.22 (S.E.M.) at 138-141 days of gestation to 12.96 plus or minus 0.38 pmol/mg protein/min at 144-146 days (with a greater relative increase in the rate of oestradiol formation), suggests that changes in placental aromatizing activity may play an important role in maternal and foetal plasma oestrogen surges before ovine parturition.

Androstenedione↗