Biallelic expression of IGFBP1 and IGFBP3, two candidate genes for the Silver-Russell syndrome.
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3' Untranslated Regions↗
Biomedical subjects
G E Moore
Publications and source records attributed to G E Moore.
Silver-Russell syndrome and ring chromosome 7.
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Abnormalities, Multiple↗
Insulin sensitivity in postmenopausal women: independent and combined associations with hormone replacement, cardiovascular fitness, and body composition.
OBJECTIVE: The effects of combined physical activity and hormone replacement therapy (HRT) on insulin sensitivity in postmenopausal (PM) women are unclear. The purpose of the study was to test the following hypotheses: 1) PM women who have undergone vigorous exercise training have greater insulin sensitivity than PM women who are physically active and PM women who are sedentary, and 2) PM women using HRT have greater insulin sensitivity than PM women not using HRT. We also sought to determine whether body composition or cardiovascular fitness was the stronger predictor of insulin sensitivity in these women. RESEARCH DESIGN AND METHODS: Three groups of PM women classified as sedentary (n = 18), physically active (n = 19), and athletic (n = 23) underwent an insulin-modified frequently sampled intravenous glucose tolerance test to determine the insulin sensitivity index (SI) and dual-energy X-ray absorptiometry to determine body composition. RESULTS: There was a significant association between both physical activity (P = 0.036) and HRT (P = 0.007) and fasting plasma insulin levels. The athletic PM women had the lowest plasma insulin levels and the highest SI. Across all physical activity levels, PM women using HRT (n = 29) had significantly lower fasting plasma insulin levels and a lower SI than PM women not using HRT (n = 31). HRT was significantly (P = 0.025) associated with intravenous glucose tolerance (KG); the women not using HRT had a higher K(G); than the PM women using HRT (0.83 +/- 0.08 vs. 0.60 +/- 0.05% per minute). Percent body fat (r = -0.37, P = 0.004) and VO2max (r = 0.35, P = 0.007) were similar predictors of SI. CONCLUSIONS: We conclude that, although overall HRT was associated with an attenuated SI, vigorous exercise training was independently associated with the greatest SI. In addition, PM women using HRT may benefit from having lower plasma insulin levels, but they may also have a lower SI.
Adipose Tissue↗
The search for the gene for Silver-Russell syndrome.
Patients with Silver-Russell syndrome display intrauterine growth restriction and other dysmorphic features. No single genetic cause for this syndrome has been found, although there are a small number of familial cases and some patients with chromosomal rearrangements. Maternal uniparental disomy of chromosome 7 has been found in approximately 7% of patients with Silver-Russell syndrome. In five of these patients exhibiting maternal uniparental disomy, no common regions of isodisomy were found, thereby ruling out the expression of a recessive allele. It is most likely that one or more imprinted genes are responsible for the phenotype of Silver-Russell syndrome. Human chromosome 7 demonstrates homology with two imprinted regions on mouse chromosomes 6 and 11, which are equivalent to human chromosome regions 7q32 and 7p11-p13, respectively. We directly analysed the imprinting status of candidate genes from chromosome 7 that mapped to homologous imprinted regions in the mouse and also had a potential role in growth. The candidates were the genes that encode the epidermal growth factor receptor and the insulin-like growth factor binding proteins-1 and -3. All three of these candidate genes are localized to chromosome region 7p11-p13. Using intragenic polymorphisms as markers, we found that all three genes showed biallelic expression in different fetal tissues. Therefore, it is unlikely that these candidate genes are directly involved in producing the phenotype of Silver-Russell syndrome. Other candidates are under analysis, including two newly identified genes that are known to be imprinted.
Abnormalities, Multiple↗
Cardiovascular hemodynamics with increasing exercise intensities in postmenopausal women.
We sought to determine the cardiovascular responses to increasing exercise intensities in postmenopausal women with different physical activity levels and hormone replacement therapy (HRT) status. Forty-four women (11 sedentary, 19 physically active, 14 master athletes; 24 not on HRT, 20 on HRT) completed treadmill exercise at 40, 60, 80, and 100% of maximal oxygen consumption. Oxygen consumption, heart rate, blood pressure, and cardiac output, determined via acetylene rebreathing, were measured at each exercise intensity. HRT did not affect cardiovascular hemodynamics. Stroke volume (SV) decreased significantly between 40 and 100% of maximal oxygen consumption in all groups, and the decrease did not differ among groups. The greater oxygen consumption of the athletes at each intensity was due to their significantly greater cardiac output, which was the result of a significantly greater SV, compared with both of the less active groups. The athletes had significantly lower total peripheral resistance at each exercise intensity than did the two less active groups. There were no consistent significant hemodynamic differences between the physically active and sedentary women. These results indicate that SV decreases in postmenopausal women as exercise intensity increases to maximum, regardless of their habitual physical activity levels or HRT status.
Aged↗
An analysis of common isodisomic regions in five mUPD 16 probands.
Intrauterine growth retardation (IUGR) with or without additional abnormalities is recognised as a common feature of maternal uniparental disomy for chromosome 16 (mUPD 16) and is usually associated with confined placental mosaicism (CPM). Although it is likely that the CPM largely contributes to the IUGR, postnatal growth retardation and other common abnormalities may also be attributed to the mUPD. Five cases with mUPD 16 and CPM were analysed for common regions of isodisomy using polymorphic markers distributed along the length of the chromosome. In each case the aberration was consistent with a maternal meiosis I error. Complete isodisomy was not detected in any of the patients although two patients were found to be mixed with both iso- and heterodisomy. Interestingly, the patient with the greater region of isodisomy was the most severely affected. The fact that there were no common regions of isodisomy in any of the patients supports the hypothesis that imprinted genes, rather than recessive mutations, may play a role in the shared phenotypes.
Blotting, Southern↗
An analysis of the distribution of hetero- and isodisomic regions of chromosome 7 in five mUPD7 Silver-Russell syndrome probands.
Silver-Russell syndrome (SRS) shares common features of intrauterine growth retardation (IUGR) and a number of dysmorphic features including lateral asymmetry in about 50% of subjects. Its genetic aetiology is complex and most probably heterogeneous. Approximately 7% of patients with SRS have been found to have maternal uniparental disomy of chromosome 7 (mUPD7). Genomic DNA samples from five SRS patients with mUPD7 have been analysed for common regions of isodisomy using 40 polymorphic markers distributed along the length of chromosome 7. No regions of common isodisomy were found among the five patients. It is most likely that imprinted gene(s) rather than recessive mutations cause the common phenotype. Heterodisomy of markers around the centromere indicated that the underlying cause of the mUPD7 is a maternal meiosis I non-disjunction error in these five subjects.
Abnormalities, Multiple↗
Molecular cloning and characterization of a highly conserved human 67-kDa laminin receptor pseudogene mapping to Xq21.3.
A highly conserved laminin receptor processed pseudogene (LAMRL5) that has been isolated from a fetal brain cDNA library is described. The pseudogene is a complete copy (97.9% identical) of the transcribed laminin receptor (LAMR1) with all the introns precisely removed. The sequence has direct repeats of 18 bp at either end. It has an 885 nucleotide open reading frame from the start methionine codon to the stop codon that contains no deletions, additions or premature stop codons relative to the expressed LAMR1 gene and has the coding potential for a protein of 295 amino acids. Although TATA and CAAT boxes exist in the region 5' to the open reading frame and a polyadenylation signal is present in the 3' region, no evidence could be obtained either by reverse transcriptase-polymerase chain reaction (RT-PCR) or in the expressed sequence tag (EST) database that LAMRL5 is expressed in vivo. If not expressed, it is estimated that this LAMRL5 pseudogene was incorporated into the human genome approximately 3.5-5 million years ago.
Amino Acid Sequence↗
Expression of the insulin-like growth factors and their receptors in term placentas: a comparison between normal and IUGR births.
Intrauterine growth retardation (IUGR) is defined as growth retarded to be below the tenth centile. The insulin-like growth factors and their receptors are implicated in pre- and postnatal growth and development, and it is believed that alteration in their activity may contribute to IUGR. In this study nine normal and nine intrauterine growth retarded births were followed and term placentas examined for expression of the insulin-like growth factors and their receptors. It was found that the expression of insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2), and the insulin, IGF1 and IGF2 receptor transcripts (IGF1R and IGF2R, respectively) was present in all term placentas examined. Expression of insulin was not detected. Quantitative polymerase chain reaction (PCR) was used to compare transcription levels in term placentas from normal with IUGR births. There was no significant difference in the levels of transcripts for IGF1, insulin receptor, or IGF2R between normal and IUGR term placentas. However, the IUGR term placentas had significantly higher levels of IGF2 and IGF1R expression compared with the normal term placentas. The increase in the transcription of IGF2 and IGF1R in IUGR term placentas may represent a counter regulatory mechanism in response to the growth retardation.
Adult↗
Tumors. Abstract from 1970.
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History, 20th Century↗
Cardiovascular response to submaximal stationary cycling during hemodialysis.
Exercise intolerance is a problem in renal failure. Stationary cycle training during hemodialysis treatment is recommended as safe, effective, and practical, but requires compensations for both exercise and acute changes in uremia. Eight patients pedalled for 5 minutes, at 60% of VO2peak, at 0, 1, 2, and 3 hours of a hemodialysis treatment. Fluid removed, blood pressure, cardiac output, heart rate, O2 uptake, hematocrit, and arterial O2 content were measured. Mean arterial blood pressure, systemic vascular resistance, stroke volume, (a-v)O2 difference, and mixed-venous O2 content were calculated. Fluid removed was 1,356 mL/hr (P < 0.002 for each hour), but with no significant cardiovascular effects during the first 2 hours. At 3 hours, decreasing cardiac output, stroke volume, and mean arterial pressure all reached significance at rest (P < 0.05), and five of eight patients could not exercise. We conclude that the cardiovascular exercise response is superimposed on hemodynamic effects of dialysis and is adequately stable during the first 2 hours of treatment. After 2 hours, cardiovascular decompensation may preclude exercise.
Analysis of Variance↗
Routine addition of human insulin-like growth factor-I ligand could benefit clinical in-vitro fertilization culture.
Animal studies suggest that the insulin-like growth factors play an important role in preimplantation embryo development. Human preimplantation embryos express mRNA for insulin-like growth factor-I receptor (IGF-IR) but the ligand, insulin-like growth factor-I (IGF-I), is not expressed by the embryo until after implantation. We tested the hypothesis that IGF-I produced by the female reproductive tract may bind to these receptors, augmenting embryo survival, growth and development. Transcripts of mRNA for IGF1 were detected using reverse transcription-polymerase chain reaction in midcycle human Fallopian tube. Immunohistochemistry localized immunoreactive IGF-I to the cytoplasm of all the major structures of the Fallopian tube, with the most intense staining seen in the tubal epithelial lining. Maternally produced IGF-I was present in the fluid found in the human tube and uterus at concentrations of 8.0 and 10.9 nM respectively. Supplementation of culture medium with IGF-I increased the proportion of embryos developing to the blastocyst stage from 35% in controls to 60% in the presence of IGF-I. In addition the total number of cells in day 6 blastocysts was increased by 19% (64.44 versus 54.08% in control, not significant), due entirely to a statistically significant 59% increase (25 versus 15.75%, P = 0.020) in the number of cells in the inner cell mass. The effect of IGF-I was mediated through the IGF-I receptor. Immunocytochemistry using an alphaIR3 antibody confirmed the presence of IGF-I receptor in human blastocysts and the same antibody completely inhibited the stimulation of blastocyst formation by IGF-I. These data suggest that human preimplantation development is enhanced by maternal IGF-I. Mimicking this in-vivo paracrine relationship may improve clinical in-vitro embryo culture and IVF pregnancy rates.
Blastocyst↗
VO2 max is associated with ACE genotype in postmenopausal women.
Relationships have frequently been found between angiotensin-converting enzyme (ACE) genotype and various pathological and physiological cardiovascular outcomes and functions. Thus we sought to determine whether ACE genotype affected maximal O2 consumption (VO2 max) and maximal exercise hemodynamics in postmenopausal women with different habitual physical activity levels. Age, body composition, and habitual physical activity levels did not differ among ACE genotype groups. However, ACE insertion/insertion (II) genotype carriers had a 6.3 ml . kg-1 . min-1 higher VO2 max (P < 0.05) than the ACE deletion/deletion (DD) genotype group after accounting for the effect of physical activity levels. The ACE II genotype group also had a 3.3 ml . kg-1 . min-1 higher VO2 max (P < 0.05) than the ACE insertion/deletion (ID) genotype group. The ACE ID group tended to have a higher VO2 max than the DD genotype group, but the difference was not significant. ACE genotype accounted for 12% of the variation in VO2 max among women after accounting for the effect of habitual physical activity levels. The entire difference in VO2 max among ACE genotype groups was the result of differences in maximal arteriovenous O2 difference (a-vDO2). ACE genotype accounted for 17% of the variation in maximal a-vDO2 in these women. Maximal cardiac output index did not differ whatsoever among ACE genotype groups. Thus it appears that ACE genotype accounts for a significant portion of the interindividual differences in VO2 max among these women. However, this difference is the result of genotype-dependent differences in maximal a-vDO2 and not of maximal stroke volume and maximal cardiac output.
Body Composition↗
Genetics of Silver-Russell syndrome.
The Silver-Russell syndrome (SRS) is generally sporadic, but with sufficient reported cases of dominant and recessive patterns of inheritance to suggest a genetic cause in some cases, at least. No consistent cytogenetic abnormalities have been found although some features of the syndrome have been reported to be associated with structural abnormalities of distal 15q. More recently it has been shown that about 10% of SRS patients have maternal uniparental disomy of chromosome 7 which suggests the presence of a maternally imprinted gene on chromosome 7 that is associated with SRS. In the majority of patients with normal biparental inheritance of chromosome 7 the same gene could be involved if the paternal copy were deleted or mutated so that it is disabled and the maternal copy is silent because of the imprinting.
Chromosome Aberrations↗
Health-related fitness and quality of life in organ transplant recipients.
BACKGROUND: The purpose of this study was to describe the levels of health-related fitness and quality of life in a group of organ transplant recipients who participated in the 1996 U.S. Transplant Games. METHODS: A total of 128 transplant recipients were selected on a first reply basis for testing. Subjects with the following organ types were tested: kidney (n=76), liver (n=16), heart (n=19), lung (n=6), pancreas/kidney (n=7), and bone marrow (n=4). Cardiorespiratory fitness (peak oxygen uptake) was measured using symptom-limited treadmill exercise tests with expired gas analysis. The percentage of body fat was measured using skinfold measurements, and the Medical Outcomes Short Form questionnaire (SF-36) was used to evaluate health-related quality of life. RESULTS: Participants achieved near age-predicted cardiorespiratory fitness (94.7+/-32.5% of age-predicted levels). Scores on the SF-36 were near normal. The active subjects (76% of total sample) had significantly higher levels of peak VO2 and quality of life and a lower percentage of body fat compared with inactive subjects (P<0.01). CONCLUSIONS: Although this is a highly select group which is not representative of the general transplant population, the data suggest that near-normal levels of physical functioning and quality of life are possible after transplantation and that those who participate in regular physical activity may achieve even higher levels.
Adult↗
The Food and Drug Administration's regulation of tobacco products.
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Humans↗
Expression of mRNA for the insulin-like growth factors and their receptors in human preimplantation embryos.
Insulin, insulin-like growth factor-I (Igf-I), and insulin-like growth factor-II (Igf-II) are known to enhance growth in mouse preimplantation embryos. The addition of insulin, Igf-I, and Igf-II to mouse embryos in culture results in an increase in protein synthesis, cell number, and the proportion of embryos developing to the blastocyst stage. To study the role of the insulin-like growth factors in early human development, the timing of gene expression of insulin, IGF1, IGF2, and their receptors was analysed. Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the presence of transcripts in preimplantation embryos. Following reverse transcription, strategically designed nested primers were used for amplification from cDNA. Transcripts for all three receptors (insulin receptor, IGF1R, IGF2R) were present in human oocytes and preimplantation embryos. However, of the ligands, only IGF2 transcripts were detected. This is consistent with expressed patterns seen in the mouse. As in the human, mouse Igf2 is the only ligand in the family expressed and has been shown to have an autocrine effect on preimplantation development. It has previously been shown that insulin and Igf-I are produced by the mouse maternal reproductive tract and have a paracrine effect on the preimplantation embryo. We speculate that a similar relationship exists in the human and that preimplantation development may be regulated by IGFs from both embryonic (IGF-II) and maternal (insulin and IGF-I) sources.
Animals↗
The incidence of uniparental disomy associated with intrauterine growth retardation in a cohort of thirty-five severely affected babies.
OBJECTIVE: Our purpose was to screen for uniparental disomy 35 babies with idiopathic intrauterine growth retardation < 5th percentile. STUDY DESIGN: The placenta and the baby's blood were conventionally karyotyped. Deoxyribonucleic acid from the parents, the baby's blood, and the placenta were then screened for uniparental disomy for 12 candidate chromosomes with use of chromosome-specific polymorphic deoxyribonucleic acid markers. RESULTS: Two cases of maternal uniparental disomy for chromosome 16 were found associated with confined placental mosaicism for chromosome 16. No other uniparental disomy was found for any of the 12 chromosomes tested. Four structural chromosome abnormalities were also found in this cohort through standard karyotyping. CONCLUSION: Uniparental disomy for the chromosomes tested does not explain the etiology of the majority of cases of intrauterine growth retardation < 5th percentile. Maternal uniparental disomy for chromosome 16 accounts for 5% of this cohort. Structural chromosomal abnormalities are also much higher than expected at 11%.
Chromosome Aberrations↗