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Biomedical subjects

Helen Simpson

Publications and source records attributed to Helen Simpson.

5 recordsLinked to original sources
PubMed2006

Non-DNA binding, dominant-negative, human PPARgamma mutations cause lipodystrophic insulin resistance.

PPARgamma is essential for adipogenesis and metabolic homeostasis. We describe mutations in the DNA and ligand binding domains of human PPARgamma in lipodystrophic, severe insulin resistance. These receptor mutants lack DNA binding and transcriptional activity but can translocate to the nucleus, interact with PPARgamma coactivators and inhibit coexpressed wild-type receptor. Expression of PPARgamma target genes is markedly attenuated in mutation-containing versus receptor haploinsufficent primary cells, indicating that such dominant-negative inhibition operates in vivo. Our observations suggest that these mutants restrict wild-type PPARgamma action via a non-DNA binding, transcriptional interference mechanism, which may involve sequestration of functionally limiting coactivators.

DNA↗
PubMed2005

GH secretion in acute exercise may result in post-exercise lipolysis.

Exercise is a potent stimulator of growth hormone (GH) secretion. We hypothesised that after a short bout of intense exercise GH may increase lipolysis during recovery. In 7 moderately trained young male subjects (21.8 +/- 0.5 years) and 7 moderately trained older male subjects (56.0 +/- 1.0 years) [(2)H(5)] glycerol was infused for 370min to measure glycerol production rate (R(a)), a measure of lipolysis. At 130 min subjects exercised on a cycle ergonometer for 20 min at 70% V(O2 max), followed by rest for 220 min. On a separate occasion the study was repeated in the young subjects with a 1h GH infusion (4microgkg(-1)h(-1)) at 130 min instead of exercise. In response to exercise, catecholamines (p < 0.02) and glycerol R(a) (p < 0.01) increased, peaking during exercise. GH concentration increased in response to exercise (p < 0.01), peaking after exercise (150-160 min) in both groups with no significant difference in peak response between groups. A post-exercise rise in glycerol R(a) was demonstrated in both groups peaking at 265-295 min in the older group (p < 0.002, peak vs. basal) and continuing to rise until 370 min in the young group (p < 0.01, peak vs. basal). The timing and magnitude of this was reproduced with the GH infusion. There was a significant correlation between the peak GH response to exercise and the post-exercise rise in glycerol R(a) measured as area under the curve (r=0.57, p < 0.04). In conclusion, this study provides evidence that the GH response to acute exercise may increase lipolysis during recovery.

Adult↗
PubMed2002

Punch biopsy of the human placental bed.

OBJECTIVE: The purpose of this study was to report our experience with placental bed biopsy with the use of forceps. STUDY DESIGN: Placental bed biopsies were undertaken transcervically under ultrasound guidance in 313 women who underwent termination of pregnancy between 7 and 20 weeks of gestation, in 104 women with a missed abortion who underwent evacuation of retained products of conception between 7 and 21 weeks of gestation, and in 13 women after vaginal delivery. Placental bed biopsies were also undertaken in 139 women who underwent caesarean delivery. Frozen sections were immunostained with monoclonal antibodies to cytokeratin, factor VIII-related antigen, and desmin. RESULTS: Of the 417 cases attempted at <22 weeks, the placental bed was successfully sampled 281 women (67%); in 229 women (55%), at least one of the biopsy specimens contained a uterine spiral artery. Success was correlated with gestational age. Figures for the late cases that were sampled during caesarean delivery were 108 of 139 cases (78%) and 66 of 139 cases (47%) and after vaginal delivery were 11 of 13 cases (84%) and 6 of 13 cases (46%), respectively. The sampling procedure did not result in any significant morbidity. CONCLUSION: With the use of forceps, uterine spiral arteries can be sampled successfully throughout pregnancy in approximately 50 % of cases.

Arteries↗