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Biomedical subjects

G E Moore

Publications and source records attributed to G E Moore.

At least 37 records · Page 2Linked to original sources
PubMed2001

Maternal repression of the human GRB10 gene in the developing central nervous system; evaluation of the role for GRB10 in Silver-Russell syndrome.

The GRB10 gene encodes a growth suppressor and maps to human chromosome 7p11.2-p13. Maternal duplication (matdup) of this region has recently been associated with Silver-Russell syndrome (SRS), which is characterised by pre- and postnatal growth restriction, craniofacial dysmorphism and lateral asymmetry. Maternal uniparental disomy for chromosome 7 (mUPD7) occurs in approximately 7% of SRS patients. Exposure of a recessive allele due to isodisomy has been ruled out in five mUPD7 cases, suggesting genomic imprinting as the basis for disease. Assuming SRS patients with matdup of 7p11.2-p13 and mUPD7 share a common aetiology, this would implicate a maternally expressed gene from this interval, which is involved in growth inhibition. Murine Grb10 was identified as a maternally expressed gene by subtractive hybridisation using normal and androgenetic mouse embryos. Grb10 maps to the homologous region of proximal mouse chromosome 11, for which mUPD incurs reduced birthweight. A role for GRB10 in SRS was evaluated by determining its imprinting status in multiple human foetal tissues using expressed polymorphisms, and by screening the coding region for mutations in 18 classic non-mUPD7 SRS patients. Maternal repression of GRB10 was observed specifically in the developing central nervous system including brain and spinal cord, with biallelic expression in peripheral tissues. This is in contrast to mouse Grb10, and represents the first example of opposite imprinting in human and mouse homologues. While a role for GRB10 in mUPD7 SRS cases can not be ruled out on the basis of imprinting status, no mutations were identified in the patients screened.

Abnormalities, Multiple↗
PubMed2001

Moderate physical activity is associated with higher bone mineral density in postmenopausal women.

OBJECTIVES: To determine the associations between different levels of habitual physical activity, hormone replacement therapy (HRT), and bone mineral density (BMD) in postmenopausal women. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: Twenty sedentary women, 20 active nonathletic women, and 23 endurance-trained athletes, all of whom were postmenopausal, with half of each group on and half not on HRT. MEASUREMENTS: BMD and body composition determined by dual energy x-ray absorptiometry, maximal oxygen consumption (VO2max), dietary history by questionnaire, and vitamin D receptor (VDR) genotyping on deoxyribonucleic acid. RESULTS: Body weight was higher in the active nonathletic than in the sedentary and athletic women. Body fat was lower and VO2max higher in the athletic women than in the sedentary and the active nonathletic women. Physical activity level was significantly associated with BMD in three of the five measurements taken (L1-L4 lumbar spine, trochanter, total body; all P < .05). These differences were also generally significant after adjusting for body weight. The association between physical activity status and BMD at the neck of the femur and Ward's triangle bordered on significance (P = .07-.09). At most sites, the active nonathletic women had higher BMD than did the sedentary and athletic women. HRT was significantly associated only with total body BMD (P < .05). The groups were similar in terms of dietary habits (protein, calcium, sodium, phosphorus intake); VDR genotypes; and family, smoking, and nutritional histories. CONCLUSION: Given the similarity of the groups with respect to other factors that affect BMD, it appears that prolonged low-to-moderate-intensity physical activity, but not the same number of years of higher-intensity training for competitive events, was independently associated with higher BMD.

Aged↗
PubMed2001

FABP2 genotype is associated with insulin sensitivity in older women.

This study determined whether sequence variations in genes related to glucose and insulin metabolism are associated with insulin sensitivity in postmenopausal women after accounting for habitual physical activity levels, body composition, and hormone-replacement therapy (HRT). Eighteen sedentary, 19 physically active, and 23 athletic postmenopausal white women underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (S(I)) and dual-energy x-ray absorptiometry to determine body composition. After accounting for the effects of body composition, habitual physical activity levels, and HRT status, S(I) was 26% lower in subjects with the Thr54 fatty acid-binding protein 2 (FABP2) allele compared with Ala54 homozygotes (4.3 +/- 0.5 v 5.8 +/- 0.6 microU x 10(-4)/min/mL; P <.05). Angiotensin-converting enzyme genotype was not significantly associated with S(I). There were no significant associations between Gln27Glu beta(2)-adrenergic receptor or Pro12Ala peroxisome proliferator-activated receptor gamma variants and glucose or insulin kinetic parameters. It was concluded that FABP2 genotype influences insulin sensitivity independent of body composition, habitual physical activity levels, and HRT status in postmenopausal white women.

Absorptiometry, Photon↗
PubMed2001

Obesity gene variant and elite endurance performance.

beta2-adrenergic receptor (ADRB2) Gln27Glu genotype was determined in sedentary (n = 19), active (n = 20), and elite endurance athletic (n = 24) Caucasian postmenopausal women. Age was similar in all physical activity and ADRB2 genotype groups. ADRB2 genotypes were in Hardy-Weinberg equilibrium in sedentary and active women, but not in the athletes (chi(2) = 4.28, P <.05), due to the near absence of ADRB2 Glu27Glu homozygotes among the athletes. Weight tended to be higher in ADRB2 Glu27Glu women (63.5 +/- 1.8 v 57.7 +/- 1.7 and 60.0 +/- 1.8, P =.08), as did body mass index (BMI) (25.0 +/- 0.4 v 22.9 +/- 0.6 and 23.4 +/- 0.5 kg/m(2), P =.05), due to a higher fat mass in Glu27Glu women (24.1 +/- 1.0 v 18.1 +/- 1.4 and 20.1 +/- 1.4 kg, P <.05). Maximal O2 consumption was lower in ADRB2 Glu27Glu than in ADRB2 Glu27Gln and Gln27Gln genotype women (25.4 +/- 1.1 v 32.4 +/- 1.5 and 29.1 +/- 1.7 mL/kg/min, P <.05). We conclude that the Glu27Glu ADRB2 genotype may dissociate from and the Gln27Gln and Gln27Glu genotypes may associate with elite endurance performance in older women.

Aged↗
PubMed2001

Specific genetic markers of endurance performance and VO2max.

Specific genetic markers of endurance performance and VO2max. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 15-19, 2001. Recent advances have revolutionized genetic studies of quantitative traits. Mitochondrial DNA and creatine kinase variations may influence VO2max. Other data strongly suggest that angiotensin-converting enzyme genotype affects VO2max and endurance performance capacity, but the mechanisms are unclear. A recent genome-wide scan study also has provided candidate loci requiring further study.

Creatine Kinase↗
PubMed2001

Silver-Russell syndrome: a dissection of the genetic aetiology and candidate chromosomal regions.

The main features of Silver-Russell syndrome (SRS) are pre- and postnatal growth restriction and a characteristic small, triangular face. SRS is also accompanied by other dysmorphic features including fifth finger clinodactyly and skeletal asymmetry. The disorder is clinically and genetically heterogeneous, and various modes of inheritance and abnormalities involving chromosomes 7, 8, 15, 17, and 18 have been associated with SRS and SRS-like cases. However, only chromosomes 7 and 17 have been consistently implicated in patients with a strict clinical diagnosis of SRS. Two cases of balanced translocations with breakpoints in 17q23.3-q25 and two cases with a hemizygous deletion of the chorionic somatomammatropin gene (CSH1) on 17q24.1 have been associated with SRS, strongly implicating this region. Maternal uniparental disomy for chromosome 7 (mUPD(7)) occurs in up to 10% of SRS patients, with disruption of genomic imprinting underlying the disease status in these cases. Recently, two SRS patients with a maternal duplication of 7p11.2-p13, and a single proband with segmental mUPD for the region 7q31-qter, were described. These key patients define two separate candidate regions for SRS on both the p and q arms of chromosome 7. Both the 7p11.2-p13 and 7q31-qter regions are subject to genomic imprinting and the homologous regions in the mouse are associated with imprinted growth phenotypes. This review provides an overview of the genetics of SRS, and focuses on the newly defined candidate regions on chromosome 7. The analyses of imprinted candidate genes within 7p11.2-p13 and 7q31-qter, and gene candidates on distal 17q, are discussed.

Abnormalities, Multiple↗
PubMed2001

Evidence that insulin is imprinted in the human yolk sac.

Allelic variation in the size of the insulin (INS) variable number tandem repeat (VNTR) correlates with the expression of both INS in the pancreas and thymus and IGF2 (the gene downstream of INS) in the placenta. In addition, the shorter, class I alleles are associated with type 1 diabetes, whereas the longer, class III alleles are associated with type 2 diabetes, polycystic ovary syndrome (PCOS), and size at birth. Parent-of-origin effects have been reported for type 2 diabetes and PCOS, thus implicating a role for genomic imprinting in these phenotypes. In mice, Ins2 is imprinted and paternally expressed in the yolk sac. In humans, evidence for the imprinting of INS is circumstantial, with occasional monoallelic expression in the thymus. In the present study, we found evidence for the imprinted paternal expression of INS in the human yolk sac. Two other imprinted genes from the same cluster are also expressed monoallelically in the human yolk sac. IGF2 was expressed solely from the paternal allele, and H19 was expressed solely from the maternal allele. These data suggest not only further functional roles for the human yolk sac in early fetal growth, but also evidence for a potential causal link between the control of insulin expression during development and insulin/growth-related diseases in later life.

Alleles↗
PubMed2001

Incidence of zoonotic diseases in military working dogs serving in Operations Desert Shield and Desert Storm.

The United States deployed 118 military working dogs (MWDs) to the Persian Gulf theater during Operations Desert Shield and Desert Storm. This study is a retrospective descriptive study of medical records of these deployed dogs, with the objective to determine whether there were infectious or parasitic diseases with a zoonotic potential in a sentinel population of MWDs that may be of concern to Persian Gulf veterans. Fifty-one percent of visits to veterinary treatment facilities during deployment were for illness or injury. Potential zoonotic conditions accounted for 21% of the total visits, 41% of the "sick-call" visits, and 63% of presentations for illness to veterinary treatment facilities. This study did not determine whether the diseases treated were transmitted between MWDs and the troops. Although the etiologic agents were not determined in these cases, no evidence was found supporting new or reemerging illnesses in this population of dogs.

Absenteeism↗
PubMed2000

Osteosarcoma in adjacent lumbar vertebrae in a dog.

An 8-year-old male Belgian Malinois was referred for evaluation of progressive caudal paresis of 2 to 3 weeks' duration. Radiography revealed a mottled appearance to the body of L4 and misshapen intervertebral foramen at L4-L5. Myelography revealed that the dye column terminated within the body of L4. Computed tomography revealed a soft tissue mass adjacent to or involving the spinal cord and L4, with complete destruction of a portion of the floor of the vertebral foramen. Small circular lesions were also noticed within the body of L3 and L5. A left-sided hemilaminectomy was performed. Histologic examination of a biopsy specimen revealed a high-grade sarcoma. Because of the poor prognosis, the dog was euthanatized. Necropsy examination revealed osteosarcoma, with lesions in L3 to L7, the sacrum, and the lungs. Metastatic lesions in adjacent bones have been termed skip metastases and the primary tumor is typically in long bones. Prognosis associated with skip metastases is similar to or even graver than that associated with pulmonary metastases. In the dog of the present report, the unusual finding of distinct foci of osteosarcoma within 5 adjacent lumbar vertebrae and the sacrum was consistent with skip metastases, potentially spread via the vertebral venous plexus.

Animals↗
PubMed2000

Evaluation of a commercial enzyme-linked immunosorbent assay for detection of Borrelia burgdorferi exposure in dogs.

OBJECTIVE: To evaluate the effectiveness of a commercially available ELISA kit for detecting antibodies against Borrelia burgdorferi in dogs. SAMPLE POPULATION: Banked sera from 440 military working dogs were used for serologic analyses. PROCEDURE: Serum samples were analyzed for antibodies against B burgdorferi by use of a commercially available ELISA and subsequently by western blot analysis as a confirmatory test. RESULTS: Results from the ELISA indicated that 89 (20%) samples were positive for exposure to B burgdorferi or canine Lyme disease vaccine, and 351 (80%) were negative. Follow-up testing by western blot analysis indicated that results for 109 (25%) samples were positive and 331 (75%) were negative for exposure. All samples that had positive results on the ELISA also had positive results on western blot analysis (true positives). Of the 351 samples that had negative results on the ELISA, only 331 had negative results on western blot analysis (true negatives). The remaining 20 samples had positive results on western blot analysis. By use of a standard 2 x 2 table, it was determined that the ELISA had a sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 94%. CONCLUSIONS AND CLINICAL RELEVANCE: The commercial ELISA kit evaluated in this study appeared to lack adequate sensitivity for detecting all potential cases of borreliosis in dogs. The ELISA was also unable to discriminate natural exposure from exposure attributable to vaccination, which could complicate interpretation of positive results and treatment of dogs with clinical signs.

Animals↗
PubMed2000

Apparent confined placental mosaicism of trisomy 16 and multiple fetal anomalies: case report.

Trisomy 16 is frequently found confined to the placenta (confined placental mosaicism (CPM)), with a structurally normal fetus. In some cases of trisomy 16, the fetus has uniparental disomy for chromosome 16 (UPD16) which is associated with intrauterine growth restriction (IUGR) and fetal anomalies. We report a case of apparent confined placental mosaicism for trisomy 16, using standard cytogenetic techniques, but with multiple fetal abnormalities including congenital diaphragmatic hernia in which there was no evidence of UPD in the disomic tissues examined. Subsequent examination of fetal tissues using fluorescent in situ hybridization (FISH) demonstrated low levels of mosaicism for trisomy 16 in all the tissues examined. The use of FISH permits identification of mosaicism which conventional techniques may not identify.

Abnormalities, Multiple↗
PubMed2000

Genomic imprinting, uniparental disomy and foetal growth.

Genomic imprinting is an epigenetic phenomenon identified in the past 15 years. Thus, maternally imprinted genes are only expressed from the paternal allele and vice versa. The mechanism of imprinting is still far from certain, but most probably it involves differential methylation of specific sites in or near imprinted genes. Disrupted imprinting can lead to phenotypic changes, and an increasing number of resultant clinical disorders are being identified. Many of these conditions involve disordered growth and/or development, particularly prenatal.

Animals↗
PubMed2000

Examination of trisomy 13, 18 and 21 foetal tissues at different gestational ages using FISH.

In man high levels of aneuploidy are seen in spontaneous abortions. Very few autosomal trisomies survive to birth, the three most common being those for chromosome 13, 18 and 21 giving rise to the syndromes named Patau, Edwards and Down respectively. Since the majority of these spontaneously abort, what makes the survivors different from the aborters? Could it be that they have tissue specific mosaicism with the additional normal cell line supporting survival? In this study fluorescence in situ hybridisation was used as a convenient way to detect trisomy in interphase cells. To study the level of mosaicism across gestation, different tissues from 21 trisomic foetuses were analysed using probes for chromosome 13, 18, 21, X and Y. Two trisomy 18 foetuses exhibited mosaicism. Two others, one trisomy 13 and one trisomy 18 had mosaic placentas. There was no clear association between the limited mosaicism seen and severity of the phenotype. We conclude that at least for this sample set, tissue-specific mosaicism was not likely to be responsible for potential survival to birth.

Adult↗
PubMed2000

Duplication of 7p11.2-p13, including GRB10, in Silver-Russell syndrome.

Silver-Russell syndrome (SRS) is characterized by pre- and postnatal growth failure and other dysmorphic features. The syndrome is genetically heterogeneous, but maternal uniparental disomy of chromosome 7 has been demonstrated in approximately 7% of cases. This suggests that at least one gene on chromosome 7 is imprinted and involved in the pathogenesis of SRS. We have identified a de novo duplication of 7p11.2-p13 in a proband with features characteristic of SRS. FISH confirmed the presence of a tandem duplication encompassing the genes for growth factor receptor-binding protein 10 (GRB10) and insulin-like growth factor-binding proteins 1 and 3 (IGFBP1 and -3) but not that for epidermal growth factor-receptor (EGFR). Microsatellite markers showed that the duplication was of maternal origin. These findings provide the first evidence that SRS may result from overexpression of a maternally expressed imprinted gene, rather than from absent expression of a paternally expressed gene. GRB10 lies within the duplicated region and is a strong candidate, since it is a known growth suppressor. Furthermore, the mouse homologue (Grb10/Meg1) is reported to be maternally expressed and maps to the imprinted region of proximal mouse chromosome 11 that demonstrates prenatal growth failure when it is maternally disomic. We have demonstrated that the GRB10 genomic interval replicates asynchronously in human lymphocytes, suggestive of imprinting. An additional 36 SRS probands were investigated for duplication of GRB10, but none were found. However, it remains possible that GRB10 and/or other genes within 7p11.2-p13 are responsible for some cases of SRS.

Abnormalities, Multiple↗
PubMed2000

Determinants of body composition in postmenopausal women.

BACKGROUND: Little is known about the effects of different levels of long-term physical activity on total body and regional fat and whether hormone replacement therapy interacts with physical activity level to affect body composition in postmenopausal women. METHODS: We determined the associations between different levels of habitual physical activity, hormone replacement therapy (HRT), and total and regional body composition in postmenopausal women. Twenty sedentary, 20 active nonathletic, and 23 endurance-trained women (approximately half on HRT) had total and regional body composition assessed by dual-energy x-ray absorptiometry. The athletes and active nonathletic women had been active for the same number of years and the same number of hours per week. RESULTS: The athletes and sedentary women weighed the same, but the active nonathletic groups on and not on HRT weighed 3-12 kg more (p < .05). Athletes had less trunk, arm, leg, and total body fat than sedentary and active nonathletic women (p < .05). Women on HRT tended to have lower total body (p = .07), but not regional, fat values. Linear regression analyses indicated that VO2max in ml/kg/min was the major independent determinant of total and regional body fat accounting for 52% to 70% of their variances. Athletes had greater caloric and carbohydrate intake than their less active peers, but all groups had similar protein, fat, saturated fat, monounsaturated fat, and polyunsaturated fat intakes. CONCLUSIONS: Intense training, but not low- to moderate-intensity physical activity, is associated with markedly lower levels of total and regional body fat in postmenopausal women. HRT has less of an effect on body composition than intense exercise training in postmenopausal women.

Adipose Tissue↗
PubMed2000

Enhanced cardiovascular hemodynamics in endurance-trained postmenopausal women athletes.

PURPOSE: We sought to determine whether older women athletes who had habitually performed vigorous endurance exercise training had higher stroke volumes and cardiac outputs than sedentary postmenopausal women during maximal exercise. METHODS: Seventeen endurance-trained, postmenopausal women athletes (age 65 +/- 4 yr; VO2max 2.11 +/- 0.31 L x min(-1), 38.3 mL x kg(-1) x min(-1)) and 14 sedentary, postmenopausal women (age 63 +/- 5 yr; VO2max 1.41 +/- 0.22 L x min(-1), 23.7 +/- 3.5 mL x kg(-1) x min(-1)) performed maximal treadmill exercise while cardiac output (via acetylene rebreathing) and other cardiovascular hemodynamics were measured. Approximately half of the subjects in each group were on hormone replacement therapy (HRT). RESULTS: The greater VO2max of the athletes was the result of a greater cardiac output (12.8 +/- 1.6 vs. 9.3 +/- 1.4 L x min(-1)) resulting from their significantly larger stroke volume (80 +/- 10 vs 57 +/- 10 mL) at maximal exercise. There were no significant differences in maximal cardiac output or maximal stroke volume related to HRT status in the sedentary women or athletes. CONCLUSIONS: These data indicate that endurance-trained, competitive, postmenopausal women have higher stroke volumes and cardiac outputs during maximal exercise, than their sedentary peers. However, these data suggest that HRT may not affect maximal CV function in sedentary or endurance-trained postmenopausal women.

Aged↗