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Biomedical subjects

Suzanne Jan de Beur

Publications and source records attributed to Suzanne Jan de Beur.

5 recordsLinked to original sources
PubMed2005

Exercise effects on bone mineral density relationships to changes in fitness and fatness.

BACKGROUND: Weight loss typically reduces bone mineral density (BMD). Exercise may preserve or increase BMD even while reducing fatness. We examined the relationships among exercise-induced changes in fitness and fatness with BMD. DESIGN: Randomized controlled trial conducted between July 1999 and November 2003. PARTICIPANTS: Men and women (n =115) aged 55 to 75 years. INTERVENTION: Six months of exercise training. MAIN OUTCOME MEASURES: Fitness measured as peak oxygen uptake and muscle strength, body composition by anthropometry, dual-energy x-ray absorptiometry, and magnetic resonance imaging. RESULTS: A total of 51 men and 53 women completed the trial. Exercise increased aerobic and strength fitness and lean body mass, and reduced general and abdominal obesity. BMD did not change among men in either group. Among women exercisers, there were reductions in total skeleton BMD (p =0.02) and greater trochanter BMD (p =0.02). By bivariate correlation, among women, increased femoral neck BMD was associated with increased aerobic fitness (p =0.01) and with reduced body weight (p =0.02) and BMI (p =0.02). In the final regression model, 13% of the change in femoral neck BMD was explained by the change in aerobic fitness (p <0.01). Among the men, increased total hip BMD and femoral shaft BMD were associated with increased lean mass and lower-body strength. In the final regression models, the change in lean mass explained 9% of the variance in total hip BMD (p =0.04). The change in lean mass explained 20% of the change in femoral shaft BMD (p <0.01), and the change in lower-body strength explained an additional 6% (p <0.04). CONCLUSIONS: When examined by group assignment, 6 months of exercise had no effect on BMD among men, and reduced BMD among women. When examined by change in fitness and fatness, women who had the greatest increases in aerobic capacity and men who had the greatest increases in strength and lean mass were more likely to increase their BMD. Exercise-induced reductions in fatness did not lead to bone loss.

Absorptiometry, Photon↗
PubMed2003

Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal imprinting at GNAS1.

Although the molecular basis of pseudohypoparathyroidism type 1b (PHP type 1b) remains unknown, a defect in imprinting at the GNAS1 locus has been suggested by the consistent finding of paternal-specific patterns of DNA methylation on maternally inherited GNAS1 alleles. To characterize the relationship between the genetic and epigenetic defects in PHP type 1b, we analyzed allelic expression and methylation of CpG islands within exon 1A of GNAS1 in patients with sporadic PHP type 1b and in affected and unaffected individuals from five multigenerational kindreds with PHP type 1b. All subjects with resistance to parathyroid hormone (PTH) showed loss of methylation of the exon 1A region on the maternal GNAS1 allele and/or biallelic expression of exon 1A-containing transcripts, consistent with an imprinting defect. Paternal transmission of the disease-associated haplotype was associated with normal patterns of GNAS1 methylation and PTH responsiveness. We found that affected and unaffected siblings in one kindred had inherited the same GNAS1 allele from their affected mother, evidence for dissociation between the genetic and epigenetic GNAS1 defects. The absence of the epigenetic defect in subjects who have inherited a defective maternal GNAS1 allele suggests that the genetic mutation may be incompletely penetrant, and it indicates that the epigenetic defect, not the genetic mutation, leads to renal resistance to PTH in PHP type 1b.

Alleles↗
PubMed2003

Genetic basis for resistance to parathyroid hormone.

Pseudohypoparathyroidism (PHP) is associated with biochemical hypoparathyroidism (i.e. hypocalcemia and hyperphosphatemia) due to parathyroid hormone (PTH) resistance rather than to PTH deficiency. Patients with PHP type 1a have a generalized form of hormone resistance plus a constellation of developmental defects termed Albright hereditary osteodystrophy (AHO). Within PHP type 1a families some individuals will show AHO but have normal hormone responsiveness, a variant phenotype termed pseudo-PHP. By contrast, patients with PHP type 1b manifest only PTH resistance and lack features of AHO. These various forms of PHP are due to defects in the GNAS1 gene that lead to decreased expression or activity of the alpha-subunit of the stimulatory G protein (G(s)alpha). Tissue-specific genomic imprinting of GNAS1 accounts for the variable phenotypes of patients with GNAS1 defects.

Animals↗
PubMed2002

Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia.

BACKGROUND: Progressive osseous heteroplasia (POH), an autosomal dominant disorder, is characterized by extensive dermal ossification during childhood, followed by disabling and widespread heterotopic ossification of skeletal muscle and deep connective tissue. Occasional reports of mild heterotopic ossification in Albright's hereditary osteodystrophy (AHO) and a recent report of two patients with AHO who had atypically extensive heterotopic ossification suggested a common genetic basis for the two disorders. AHO is caused by heterozygous inactivating mutations in the GNAS1 gene that result in decreased expression or function of the alpha subunit of the stimulatory G protein (Gsalpha) of adenylyl cyclase. METHODS: We tested the hypothesis that GNAS1 mutations cause POH, using the polymerase chain reaction to amplify GNAS1 exons and exon-intron boundaries in 18 patients with sporadic or familial POH. RESULTS: Heterozygous inactivating GNAS1 mutations were identified in 13 of the 18 probands with POH. The defective allele in POH is inherited exclusively from fathers, a result consistent with a model of imprinting for GNAS1. Direct evidence that the same mutation can cause either POH or AHO was observed within a single family, in which the phenotype correlated with the parental origin of the mutant allele. CONCLUSIONS: Paternally inherited inactivating GNAS1 mutations cause POH. This finding extends the range of phenotypes derived from haplo insufficiency of GNAS1, provides evidence that imprinting is a regulatory mechanism for GNAS1 expression, and suggests that Gsalpha is a critical negative regulator of osteogenic commitment in nonosseous connective tissues.

Base Sequence↗