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Biomedical subjects

E L George

Publications and source records attributed to E L George.

At least 19 recordsLinked to original sources
PubMed2001

Requirement of CDC45 for postimplantation mouse development.

CDC45 is required for the initiation of DNA replication in Saccharomyces cerevisiae and functions as a DNA polymerase alpha loading factor in Xenopus, but its role in mammalian DNA replication is unknown. To investigate the genetic and physiological functions of CDC45, we used a gene targeting strategy to generate mice lacking a functional CDC45 gene. Homozygous mutant mice lacking a functional CDC45 gene underwent uterine implantation and induced uterine decidualization but did not develop substantially thereafter. Detailed analysis of CDC45 null embryos cultured in vitro revealed impaired proliferation of the inner cell mass. These findings make CDC45 the only putative replication factor experimentally proven to be essential for mammalian development. The CDC45 gene localizes to human chromosome 22q11.2 in the DiGeorge syndrome critical region (DGCR). Almost 90% of individuals with congenital cardiac and craniofacial defects have a monoallelic deletion in the DGCR that includes CDC45. We report here that heterozygous mutant mice develop into adulthood without any apparent abnormalities, so that it is unlikely that hemizygosity of CDC45 alone is responsible for the cardiac and craniofacial defects in the congenital syndromes.

Animals↗
PubMed2000

Family-focused treatment of bipolar disorder: 1-year effects of a psychoeducational program in conjunction with pharmacotherapy.

BACKGROUND: Few studies have examined the combined effects of psychosocial treatment and pharmacotherapy for bipolar disorder. This study used a randomized, controlled design to examine a 9-month, manual-based program of family-focused psychoeducational treatment (FFT). METHODS: Bipolar patients (N = 101) were recruited shortly after an illness episode and randomly assigned to 21 sessions of FFT (n = 31) or to a comparison treatment involving two family education sessions and follow-up crisis management (CM; n = 70). Both treatments were delivered over 9 months; patients were simultaneously maintained on mood stabilizing medications. Patients were evaluated every 3 months for 1 year as to relapse status, symptom severity, and medication compliance. RESULTS: Patients assigned to FFT had fewer relapses and longer delays before relapses during the study year than did patients in CM. Patients in FFT also showed greater improvements in depressive (but not manic) symptoms. The most dramatic improvements were among FFT patients whose families were high in expressed emotion. The efficacy of FFT could not be explained by differences among patients in medication regimes or compliance. CONCLUSIONS: Family-focused psychoeducational treatment appears to be an efficacious adjunct to pharmacotherapy for bipolar disorder. Future studies should evaluate family treatment against other forms of psychotherapy matched in amount of therapist-patient contact.

Adolescent↗
PubMed2000

Expressed emotion and attributions in the relatives of bipolar patients: an analysis of problem-solving interactions.

Among the relatives of schizophrenic and depressed patients, high expressed emotion (EE) attitudes are associated with "controllability attributions" about the causes of patients' symptoms and problem behaviors. However, previous studies have judged EE attitudes and causal attributions from the same assessment measure, the Camberwell Family Interview (CFI; C. E. Vaughn & J. P. Leff, 1976). The authors examined causal attributions among relatives of 47 bipolar patients, as spontaneously expressed to patients in family problem-solving interactions during a postillness period. Relatives rated high EE during the patients' acute episode (based on the CFI) were more likely than relatives rated low EE to spontaneously attribute patients' symptoms and negative behaviors to personal and controllable factors during the postillness interactional assessment. Thus, the EE-attribution linkage extends to the relatives of bipolar patients evaluated during a family interaction task.

Adolescent↗
PubMed1999

Bipolar disorder and family communication: effects of a psychoeducational treatment program.

Family psychoeducational programs are efficacious adjuncts to pharmacotherapy for patients with schizophrenic and bipolar disorders, but little is known about what these programs change about families. The authors assessed changes in face-to-face interactional behavior over 1 year among families of bipolar patients who received a 9-month family-focused psychoeducational therapy (FFT; n = 22) or crisis management with naturalistic follow-up (CMNF; n = 22), both administered with maintenance pharmacotherapy. Members of families who received FFT showed more positive nonverbal interactional behavior during a 1-year posttreatment problem-solving assessment than families who received CMNF, although no corresponding decreases were seen in negative interactional behaviors. The positive effect of family treatment on patients' symptom trajectories over 1 year was partially mediated by increases in patients' positive nonverbal interactional behaviors during this same interval.

Adolescent↗
PubMed1998

Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia.

The thrombospondins are a family of extracellular calcium-binding proteins that modulate cellular phenotype. Thrombospondin-1 (TSP-1) reportedly regulates cellular attachment, proliferation, migration, and differentiation in vitro. To explore its function in vivo, we have disrupted the TSP-1 gene by homologous recombination in the mouse genome. Platelets from these mice are completely deficient in TSP-1 protein; however, thrombin-induced platelet aggregation is not diminished. TSP-1-deficient mice display a mild and variable lordotic curvature of the spine that is apparent from birth. These mice also display an increase in the number of circulating white blood cells, with monocytes and eosinophils having the largest percent increases. The brain, heart, kidney, spleen, stomach, intestines, aorta, and liver of TSP-1-deficient mice showed no major abnormalities. However, consistent with high levels of expression of TSP-1 in lung, we observe abnormalities in the lungs of mice that lack the protein. Although normal at birth, histopathological analysis of lungs from 4-wk-old TSP-1-deficient mice reveals extensive acute and organizing pneumonia, with neutrophils and macrophages. The macrophages stain for hemosiderin, indicating that diffuse alveolar hemorrhage is occurring. At later times, the number of neutrophils decreases and a striking increase in the number of hemosiderin-containing macrophages is observed associated with multiple-lineage epithelial hyperplasia and the deposition of collagen and elastin. A thickening and ruffling of the epithelium of the airways results from increasing cell proliferation in TSP-1-deficient mice. These results indicate that TSP-1 is involved in normal lung homeostasis.

Animals↗
PubMed1997

Fibronectins are essential for heart and blood vessel morphogenesis but are dispensable for initial specification of precursor cells.

The underlying mechanisms of lethal cardiovascular defects associated with the fibronectin-null (FN.null) mutation in mouse embryos were investigated by lineage analysis of myocardial, endocardial, and endothelial cells. A wide variation in phenotype was observed on two genetic backgrounds. In the less severe class (C57/BL6 background), FN.null embryos display a defective heart. Myocardial cells express the specific marker MF-20 and are correctly localized in the anterior trunk region, but myocardial organization is disrupted, resulting in a bulbous heart tube. Endocardial cells express the specific marker platelet-endothelial cell adhesion molecule-1 (PECAM-1) and are localized within the myocardium, but the endocardium appears collapsed. Endothelial cells of two vascular beds are specified, but the aortae are distended and lack contact with the surrounding mesenchyme, while no vessels form in the yolk sac. Defects in the more severe class suggest that FNs are essential earlier in development on the 129/Sv background. Myocardial and endocardial cells are specified, but morphogenesis of the myocardium and endocardium does not occur. Aortic endothelial cells are specified and localized normally, but remain scattered. Yolk sac endothelial cells resemble those of the less severe class. We conclude that FNs are essential for organization of heart and blood vessels, but are dispensable for cellular specification in the appropriate regions within the embryo.

Animals↗
PubMed1997

A brief scale for assessing parental child-rearing practice: psychometric properties and psychosocial correlates.

The development and initial validation of the 20-item Colorado Parental Child-Rearing Scale (CPCRS) is described, based on three studies of college students, including one study that obtained data from students and their parents. The scale comprises four 5-item subscales that are largely uncorrelated and that reliably assess parental affection, punitiveness, control, and lax discipline. The first three of these subscales have been repeatedly found in previous studies of parental child-rearing, while the fourth subscale has been found somewhat less commonly. Many previously identified relationships linking parental child-rearing practice and respondent personality and demographic characteristics were confirmed in the present study. Data obtained from parents and siblings yielded descriptions of parental child-rearing practice that were generally significantly correlated with those obtained from index students. Suggestions for additional investigation of parental child-rearing practice are proposed.

Adolescent↗
PubMed1996

Mesodermal development in mouse embryos mutant for fibronectin.

Three independent mutations were made by homologous recombination in two different regions of the fibronectin (FN) gene; all three appeared to be functional null mutations. The embryonic lethal phenotypes of these mutations were indistinguishable; all three FN mutant strains show mesodermal defects and fail to develop notochord or somites. Nevertheless analysis with lineage markers (Brachyury, sonic hedgehog, Notch-1, and mox-1) showed that both the notochord and the somite lineages were induced at the correct times and places. Furthermore, notochord precursor cells showed extensive cell migration in the absence of FN. However, neither notochord nor somites condensed properly in the absence of FN. These results show that specification of notochordal and somitic mesodermal lineages and significant cell migration are independent of fibronectin but that correct morphogenesis of these structures is FN-dependent.

Animals↗
PubMed1996

Respiratory care of the postoperative lung transplantation patient.

The management of patients receiving lung transplantation has been evolving during the last thirty years. Transplant programs have continued to develop both in United States and internationally. Patient evaluations and experiences with procedures help guide the decision as to which type of transplant would best benefit the patient. To care for lung transplantation patients, nurses need an understanding of the alterations in physiology from the procedure. An understanding of the clinical experiences in the areas of immunosuppression, preoperative conditioning, surgical techniques, preservation techniques, ventilatory management, and nursing care have made significant contributions to patient survival.

Critical Care↗
PubMed1996

New psychosocial treatments for the outpatient management of bipolar disorder.

The psychosocial treatment of bipolar disorder has the potential to augment the efficacy of outpatient pharmacotherapy if it succeeds in enhancing the protective effects of the social and familial environment and the patient's adherence to drug regimes. We describe two manual-based psychotherapies under evaluation in controlled clinical trials: a family-focused psychoeducational treatment and an individual, interpersonally-oriented psychotherapy. Both target recently ill patients and are delivered in combination with standard pharmacotherapies on an outpatient basis. Results from the ongoing clinical trials suggest high patient retention rates for both models over the first year of treatment. Future research should focus on the appropriate sequencing of pharmacologic and psychosocial treatments, and the conditions under which psychosocial treatment will be most effective.

Adult↗
PubMed1995

Reducing length of stay in patients undergoing open heart surgery: the University of Pittsburgh experience.

The clinical pathway, one component of the case management model, was implemented at one university medical center in the coronary artery bypass surgical group. In this article, the authors describe the development, use, and evaluation of the clinical pathway. The role of the advanced nurse practitioner as the case manager is discussed. The initial data base created by the case manager includes patient demographics, daily progress, length of stay, charges, discharge disposition, and readmissions within 15 days. Data collected on all patients undergoing coronary artery bypass graft surgery from July 94 to October 94 are reported and compared with the benchmark set with the development of the clinical pathway. Strategies developed for future improvement in the clinical pathway process and data management are identified.

Coronary Artery Bypass↗
PubMed1993

Perinatal toxicity associated with nickel chloride exposure.

Several reports have suggested that soluble nickel salts may affect development. In this study female Long-Evans rats drank nickel chloride solutions (0, 10, 50, or 250 ppm Ni) for 11 weeks prior to mating and then during two successive gestation (G1, G2) and lactation (L1, L2) periods. Pups were observed until weaning; breeder males were unexposed. Dams drinking 250 ppm consumed less liquid and more food per kilogram body weight than did controls (liquid: prebreeding, G1, and G2; food: prebreeding, G2 and L2). Maternal weight gain was reduced during G1 in the high- and middle-dose groups; indices of reproductive performance were comparable across groups. Pup birth weight was unaltered by treatment and weight gain was reduced only in male pups exposed to 50 ppm Ni during L1. The frequency of perinatal death is the most significant toxicologic finding of the study. The proportion of dead pups per litter was significantly elevated at the high dose in L1 and at 10 and 250 ppm in L2 (50 ppm, P = 0.076), with a dose-related response in both experimental segments. The number of dead pups per litter was significantly increased at each dose in L2. Prolactin levels in pups were unchanged by treatment and were reduced in dams at the high dose. We conclude that 10 ppm Ni represents the lowest observed adverse effect level (LOAEL) in this study.

Animals↗
PubMed1993

Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin.

To examine the role of fibronectin in vivo, we have generated mice in which the fibronectin gene is inactivated. Heterozygotes have one half normal levels of plasma fibronectin, yet appear normal. When homozygous, the mutant allele causes early embryonic lethality, proving that fibronectin is required for embryogenesis. However, homozygous mutant embryos implant and initiate gastrulation normally including extensive mesodermal movement. Neural folds also form but the mutant embryos subsequently display shortened anterior-posterior axes, deformed neural tubes and severe defects in mesodermally derived tissues. Notochord and somites are absent; the heart and embryonic vessels are variable and deformed, and the yolk sac, extraembryonic vasculature and amnion are also defective. These abnormalities can be interpreted as arising from fundamental deficits in mesodermal migration, adhesion, proliferation or differentiation as a result of the absence of fibronectin. The nature of these embryonic defects leads to reevaluation of suggested roles for fibronectin during early development based on results obtained in vitro and in embryos of other species.

Animals↗
PubMed1992

Adverse male reproductive effects following subchronic exposure of rats to sodium dichloroacetate.

Dichloroacetate (DCA) activates the pyruvate dehydrogenase complex enhancing carbohydrate and lactate utilization in animals. As a result it is used clinically in the treatment of acute lactic acidosis and has therapeutic potential in the treatment of stroke. Adverse effects of chronic DCA treatment include polyneuropathy and testicular degeneration. Since DCA is a principal product of the aqueous chlorination of fulvic acids concern has arisen regarding the agent's impact on environmental health. We treated male Long-Evans rats with 0, 31.25, 62.5, or 125 mg DCA/kg/day by oral gavage for 10 weeks. Compared to controls, preputial gland and epididymis weights were reduced at 31.25 mg/kg, body and liver weights at 62.5 mg/kg, and accessory organ weights at 125 mg/kg. Epididymal sperm counts were reduced and sperm morphology was impacted at the 62.5 and 125 mg/kg doses levels. Histologic examination of the testis and epididymis revealed inhibited spermiation in testes at the 125 mg/kg dose level. Computer-assisted sperm motion analysis revealed reductions in percentage motile sperm, curvilinear and straight-line velocity, linearity, and amplitude of lateral head displacement at both the 62.5 and the 125 mg/kg dose levels. In the assessment of fertility after an overnight mating, the number of viable implants on Day 14 of gestation was decreased only in the highest dose group. These studies demonstrate adverse effects of NaDCA treatment on the rat male reproductive system, primarily on the accessory organs and sperm within them at lower doses (31.25 and 62.5 mg/kg), and on the testis at the highest dose (125 mg/kg).

Animals↗
PubMed1991

Sources of variation in the computer-assisted motion analysis of rat epididymal sperm.

Random and nonrandom factors associated with sample preparation and the automated analysis (CellSoft) of rat cauda epididymal sperm motion were studied. Random factors included inherent system variation at both the individual cell level and at the multiple cell level. Repeated analyses of identical tracks across grey level revealed a statistical interaction between grey settings and curvilinear velocity. However, in multiple track analyses, grey level was seen to be a factor only at higher settings. Nonrandom factors included time after sample preparation, dilution medium, and sample preparation procedures. Using a nicked preparation of the entire cauda epididymis from Long-Evans rats, the effects of time were studied on sperm suspended in 1) phosphate-buffered saline + 10 mg BSA/mL, 2) TEST yolk buffer, and 3) Medium 199. In PBS/BSA, the percent motile sperm estimate decreased (50% to 30%) over an hour, while the curvilinear velocity increased (127 to 142 microns/sec). Both sperm motion parameters were maintained in the TEST yolk buffer and in the Medium 199, although at lower values for the latter. Evaluation of the relative contribution of several factors, nested within sample, to the overall variance of three separate motion endpoints revealed that there was a large variation from field to field, negligible variation between overall CellSoft analyses of 200 cells or more, low variation at the preparation aliquot level, and moderate variation at the animal level. In planning experiments to test for effects on sperm motion endpoints, consideration of the relative contribution of the individual study factors to the overall variance of the parameter estimates will result in more sensitive experimental designs.

Animals↗
PubMed1991

Reproductive effects in Long-Evans rats exposed to chlorine dioxide.

Long-Evans rats, 4-6 weeks of age, were dosed with 0.0, 2.5, 5.0, or 10.0 ml/kg chlorine dioxide (ClO2) in deionized water for up to 73 days. Males were exposed for 56 days and females for 14 days prior to breeding, and throughout the 10-day breeding period. Males were killed and evaluated for sperm parameters and reproductive tract histopathology following the breeding period. Females continued to be dosed throughout gestation and lactation until weaning on lactation day 21, when both dams and selected pups were necropsied. Neither clinical signs of toxicity nor adverse effects on any reproductive parameter examined were observed in the parental animals. Litter size, pup viability, and pup weight were unaltered by chlorine dioxide exposure. F0 reproductive tract organ weights and F1 organ weights for testis, epididymis, uterus, and ovaries were not different between groups, but vaginal weight was significantly decreased (P less than 0.03) for female weanlings in the high dose (10.0 mg/kg) group relative to controls. There were no changes in thyroid hormone parameters that appeared to be attributable to chlorine dioxide treatment.

Animals↗