Exposure of cultured beating rat heart cells to electromagnetic fields.
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Animals↗
Biomedical subjects
G E Moore
Publications and source records attributed to G E Moore.
Malignant melanoma: from subcutaneous nodule to brain metastasis.
A thirteen-year-old patient, diagnosed with melanoma was followed cytogenetically using short-term cultures of specimens from a subcutaneous nodule, lymph node, and brain metastases. Simple hypodiploid karyotypes with loss of heterozygosity for chromosomes 5, 9, 10, 16 and 17 and two structural changes in 3 and between 13 and 21 increased in complexity to near triploid in the lymph node. Two cell types of the lymph node showed a progression of structural rearrangements prior to metastasis to the brain. Translocation of 6p to chromosome 2, deletions of 8, and a translocation (2;19) preceded p and q arm deletions of both chromosomes 9 and 11 in the lymph node. Cells metastasizing to the brain showed the accumulation of all previous aberrations and had acquired a direct duplication of distal 17 long arm. Whether or not elevated levels of protein kinase C, located on chromosome 17q contribute to tumor adhesion and growth on the brain remains to be elucidated. Identification of most chromosomes undergoing rearrangement was carried out using whole chromosome painting probes in in situ hybridizations. Some of these rearrangements would have been impossible to identify by standard karyotyping.
Aneuploidy↗
The impact of recombinant human erythropoietin on exercise capacity in hemodialysis patients.
Peak oxygen uptake (VO2peak) of patients with end-stage renal failure treated with hemodialysis is very low. The improvement of anemia with recombinant human erythropoietin (rHuEPO) results in a very small change in VO2peak. This change is minimal compared with the magnitude of change in hematocrit, suggesting that other factors continue to limit exercise tolerance. This article reviews the physiology of oxygen transport and the determinants of VO2peak. Anemic hemodialysis patients are limited by a reduced cardiac output response to exercise and an inability to widen the arterio-venous oxygen difference. The lack of change in cardiac output and a remaining low arterio-venous oxygen difference following improvement of anemia with rHuEPO therapy suggest an underlying muscle limitation to exercise. Evidence for this muscle limitation is presented. Exercise training may improve the ability of muscle to use oxygen, thus optimizing the effect of the increased hematocrit resulting from rHuEPO therapy.
Anemia↗
Early embryonic failure associated with uniparental disomy for human chromosome 21.
As many as 16% of all recognized pregnancies may be anembryonic, with failure of the embryo at a very early stage of development leaving only the extraembryonic components of the conceptus to proliferate. Studies in the mouse have shown that the maternal and paternal contributions to the genome of the zygote are not functionally equivalent, due to parental genomic imprinting. Uniparental disomy can reveal imprinting effects, as in this phenomenon both members of a chromosome pair are inherited from the same parent. We have carried out a systematic search for uniparental disomy in tissues from 23 cases of early embryonic failure, using variable number tandem repeat (VNTR) analysis and PCR amplification of polymorphic short sequence repeats. Two cases of maternal uniparental heterodisomy for chromosome 21 were identified. One case occurred in conjunction with trisomy for chromosomes 7 and 9, but in the other case maternal uniparental heterodisomy for chromosome 21 was the only chromosomal abnormality found. We therefore postulate that there may be developmentally important genes on human chromosome 21 which are imprinted such that both parental copies are essential for normal embryogenesis.
Chromosome Aberrations↗
Linkage analysis of 62 X-chromosomal loci excludes the X chromosome in an Icelandic family showing apparent X-linked recessive inheritance of neural tube defects.
We report here the findings of a linkage analysis, involving numerous markers from the human X chromosome, in an attempt to localise a putative gene causing apparent X-linked spina bifida and anencephaly (SBA) in a large Icelandic pedigree. Two-point linkage analysis was performed using markers from 62 informative loci in this family. Although small positive lod scores were found at a number of these loci, none reached the significance level for linkage. Haplotypes were extensively analysed and found to exclude linkage to the X chromosome.
Adult↗
Reproducibility of the dose-response curve of steroid-induced cleft palate in mice.
Pregnant CD-1 mice were exposed to cortisone acetate at doses ranging from 20 to 100 mg/kg/day on days 10-13 by oral and intramuscular routes. Multiple replicate assays were conducted under identical conditions to assess the reproducibility of the dose-response curve for cleft palate. The data were fitted to the probit, logistic, multistage or Armitage-Doll, and Weibull dose-response model separately for each route of exposure. The curves were then tested for parallel slopes (probit and logistic models) or coincidence of model parameters (multistage and Weibull models). The 19 replicate experiments had a wide range of slope estimates, wider for the oral than for the intramuscular experiments. For all models and both routes of exposure the null hypothesis of equality of slopes was rejected at a significant level of p < 0.001. For the intramuscular group of replicates, rejection of slope equality could in part be explained by not maintaining a standard dosing regime. The rejection of equivalence of dose-response curves from replicate studies showed that it is difficult to reproduce dose-response data of a single study within the limits defined by the dose-response model. This has important consequences for quantitative risk assessment, public health measures, or development of mechanistic theories which are typically based on a single animal bioassay.
Animals↗
Pulmonary alveolar microlithiasis and ossification in a dog.
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Animals↗
Cytoreductive surgery and intraperitoneal chemotherapy.
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Antineoplastic Agents↗
Thyroxine-responsive unilateral forelimb lameness and generalized neuromuscular disease in four hypothyroid dogs.
Four dogs were examined because of unilateral forelimb lameness. For all dogs, results of physical examination, including complete neurologic examination, were unremarkable except for vague, intermittent signs of pain upon deep palpation of the affected limb. During electromyography, insertional activity, fibrillation potentials, and positive sharp waves were recorded symmetrically from all major muscle groups. Generalized neuromyopathy was diagnosed. All dogs were determined to be thyroid deficient, and L-thyroxine supplementation was initiated. The lameness resolved within 2 months in all dogs. During follow-up electromyography, abnormalities were not recorded from 3 of the dogs and were less severe in the fourth. Thyroxine supplementation was discontinued in 2 dogs, and lameness redeveloped. Lameness again resolved when supplementation was reinstituted.
Animals↗
Modified RPMI 1640 culture medium.
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Cell Division↗
Cytogenetic homogeneity in eight independent sites in a case of malignant melanoma.
Melanoma cell lines initiated from metastases excised at the same time from multiple sites in a patient reflect a single clone origin. The similarities of the karyotypes of these lines depend upon the site of excision, the selective survival in vitro, and the time span in vitro before study. In the present investigation, eight short-term cultures of malignant melanoma from the same patient were analyzed cytogenetically, six after the second passage in vitro, one from the third, and one from the fifth passage. Karyotypes were similar on all eight cultures, each having chromosome abnormalities der(1)t(1q;?), der(3)t(1;3), and t(7;9). Four cell lines had an isochromosome 4q, which was missing in four lines. Two cell lines were missing del(6). In five of eight cultures there was an occasional i(16q) or t(16q;21q). In the final culture, made 6 months after the first seven, three cell types present included a type corresponding to that of seven previous cultures, a similar cell type with an abnormal chromosome 11, and a third cell type with a 3;19 translocation. Comparisons are made with similar studies in the literature and a hypothesis has been formulated to explain melanoma metastases as revealed by the cytogenetics of multiple lesions excised simultaneously.
Adult↗
Uremic myopathy limits aerobic capacity in hemodialysis patients.
Eleven end-stage renal disease patients trained by stationary cycling during their hemodialysis treatments. After a 6-week control period, 12 weeks of training began and was increased to 30 to 60 minutes at > or = 70% of peak heart rate. Baseline, pretraining and, posttraining exercise tests were performed. Workload (WL), oxygen uptake (VO2peak), cardiac output (Q), heart rate (HR), and arterial oxygen content (CaO2) were measured. Stroke volume (SV), arteriovenous oxygen difference ((a-v)O2), and mixed-venous oxygen content (CvO2) were calculated. Rectus femoris biopsies were obtained pretraining and posttraining. At peak exercise, WL increased from 60 +/- 4 to 70 +/- 6 W (P < 0.05), VO2peak showed an upward trend from 14.8 +/- 0.9 to 16.8 +/- 1.3 mL/kg/min (P < 0.1), and Q, HR, SV, CaO2, CvO2, and (a-v)O2 were unchanged. Ten of the 11 patients increased WL, but only six increased VO2peak (five of 11 patients decreased VO2peak). The difference between groups (P < 0.02) was attributable to (a-v)O2, which increased in those who increased VO2peak (P < 0.02). There was an upward trend for succinate dehydrogenase activity (P < 0.06), and phosphofructokinase activity increased (P < 0.05). However, the rectus femoris capillary to fiber ratio, type I and II fiber areas, and fiber area variability were unchanged, and neither histomorphologic nor enzymatic activity changes were related to change in VO2peak. We conclude that not all dialysis patients increase VO2peak after training, but most can improve exercise capacity. Patients who improved VO2peak widened their (a-v)O2 difference, increasing oxygen extraction and showing that oxygen delivery is not always the limiting factor. Thus, the limitation of VO2peak in dialysis patients is a complex interaction of central and peripheral factors. Muscle therapies, such as exercise training, are needed in addition to increased oxygen delivery in rehabilitation of dialysis patients.
Adult↗
Changes in amniotic arachidonic acid metabolism associated with increased cyclo-oxygenase gene expression.
OBJECTIVES: To study the differences in the metabolism of arachidonic acid, to prostaglandins and other eicosanoids, between amnion cells before and after labour. To study the changes in the expression of the type 1 cyclo-oxygenase gene associated with the changes in arachidonic acid metabolism. DESIGN: Amnion cells collected before labour, at elective caesarean section, and following spontaneous labour and delivery were established in mono-layer culture. Intracellular arachidonic acid pools were radio-labelled and the metabolic fate of endogenous archidonic acid was then studied using high performance liquid chromatography. RNA was extracted from the cell cultures and expression of the cyclooxygenase gene was studied using northern hybridisation to a sheep cyclo-oxygenase cDNA. RESULTS: Metabolism of endogenous arachidonic acid in amnion cells established in culture prior to labour is principally via lipoxygenase and epoxygenase enzyme pathways to di- and mono-HETEs and EET with little cyclo-oxygenase metabolism to prostaglandins. Following labour there is a large increase in arachidonic acid metabolism with a change in the cyclo-oxygenase: lipoxygenase enzyme pathway ratio in favour synthesis of prostaglandin E2. Whilst synthesis of lipoxygenase metabolites doubles, the increase in prostaglandin E2 synthesis is ten fold. Expression of the cyclo-oxygenase gene is significantly greater in cell cultures established following spontaneous labour and delivery than in those established following elective caesarean section prior to labour. CONCLUSIONS: In association with labour there is an increase in arachidonic acid metabolism in amnion cells and a change in the ratio of metabolism via cyclo-oxygenase and lipoxygenase enzyme pathways to increase synthesis of prostaglandin E2. This change is associated with increased expression of the cyclooxygenase gene.
Amnion↗
Thyroxine and triiodothyronine distribution and metabolism in thyroxine-replaced athyreotic dogs and normal humans.
Reported parenteral L-thyroxine (T4) replacement doses (10-20 micrograms.kg-1 x day-1) are larger than T4 production rates (2.5 micrograms.kg-1 x day-1) in athyreotic dogs but not humans. Furthermore, initial volumes of 3,5,3'-triiodothyronine (T3) tracer distribution exceed those for T4 in both species. To evaluate these discrepancies, serum T4 and T3 tracer kinetic studies from T4-replaced athyreotic dogs (5 micrograms.kg-1 x day-1 sc) and euthyroid humans were analyzed in a three-pool model (rapidly and slowly equilibrating pools with serum). Dogs had lower total T4 (41%) and T3 (31%) and higher free fractions of T4 (432%) and T3 (456%) than humans. Initial T3 distribution volumes were 454% those for T4 in dogs and 149% in humans, 498% of predicted plasma volumes in dogs and 121-138% in humans. Thus plasma volumes were used as time 0 estimates for T3 data analysis. Dogs had higher fractional T4 and T3 transfer rates from serum to the rapid pools (440-451%), total T4 clearance (353%) and production rates (147%), similar total T3 clearance, but lower free T3 clearance (32%) and production rates (45%) than humans. These findings suggest: 1) higher fractional transfer rates of T4 and T3 from serum to tissues and total serum T4 clearance rates in dogs than humans relate to lower canine serum T4 and T3 binding, and 2) parenteral L-T4 replacement doses required to achieve upper-normal serum total T4 concentrations in athyreotic dogs (5 micrograms.kg-1 x day-1) correspond to T4 production rates (6.8 micrograms.kg-1 x day-1).
Adult↗
31P-magnetic resonance spectroscopy assessment of subnormal oxidative metabolism in skeletal muscle of renal failure patients.
In hemodialysis patients, erythropoietin increases hemoglobin, but often the corresponding increase in peak oxygen uptake is low. The disproportionality may be caused by impaired energy metabolism. 31P-magnetic resonance spectroscopy was used to study muscle energy metabolism in 11 hemodialysis patients, 11 renal transplant recipients, and 9 controls. Measurements were obtained during rest, static hand-grip, and rhythmic hand-grip; recoveries were followed to baseline. During static hand-grip, there were no between-group differences in phosphocreatine (PCr), inorganic phosphate (Pi), or PCr/(PCr + Pi), although intracellular pH was higher in hemodialysis patients than transplant recipients. During rhythmic hand-grip, hemodialysis patients exhibited greater fatigue than transplant recipients or controls, and more reduction in PCr/(PCr + Pi) than transplant recipients. Intracellular pH was higher in controls than either hemodialysis patients or transplant recipients. Recoveries from both exercises were similar in all groups, indicating that subnormal oxidative metabolism was not caused by inability to make ATP. The rhythmic data suggest transplantation normalizes PCr/(PCr + Pi), but not pH. In hemodialysis patients, subnormal oxidative metabolism is apparently caused by limited exchange of metabolites between blood and muscle, rather than intrinsic oxidative defects in skeletal muscle.
Adenosine Triphosphate↗
Determinants of VO2peak in patients with end-stage renal disease: on and off dialysis.
Peak oxygen uptake (VO2peak) of patients on maintenance hemodialysis is very low. Exercise training performed during, or "on" dialysis, and at other times, "off" dialysis, both improve VO2peak. Equivalence of these approaches has not been shown, nor have the physiologic factors limiting VO2peak been clarified in these patients. We hypothesized that hemodialysis does not acutely alter the cardiovascular response to peak exercise, and further that anemia and a low peak heart rate limit VO2peak. Ten patients with end-stage renal disease (ESRD) performed cycle ergometry to peak exercise. Peak oxygen uptake measured immediately prior to dialysis was compared with predicted values, and with measurements obtained during the second 30 min of dialysis. The determinants of VO2peak were compared with previously reported norms. "Off" dialysis, VO2peak for nine of 10 patients was below the 95% confidence limit for normals. Their cardiovascular response to peak exercise was unchanged by 30-60 min of hemodialysis. Stroke volume was similar to that of normals; however, peak heart rate was 77% of predicted, and hematocrit was 27% (at rest). Peak exercise mixed-venous oxygen content was 3.6 ml O2 ml.dl-1 blood, similar to values reported for athletes. These findings show that up to 1 h of dialysis minimally effects VO2peak, and imply that low oxygen delivery limited VO2peak in these patients.
Adult↗