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Biomedical subjects

G Morley

Publications and source records attributed to G Morley.

15 recordsLinked to original sources
PubMed1998

Conditional lineage ablation to model human diseases.

Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

Action Potentials↗
PubMed1997

Cloning and sequencing of the mouse Gli2 gene: localization to the Dominant hemimelia critical region.

The GLI family of zinc finger genes has been implicated in both neoplastic and developmental disorders. We have cloned and sequenced the mouse homolog of the zinc finger gene Gli2 and demonstrated significant similarity to the human GLI3 gene. We have also localized Gli2 to mouse chromosome 1, in the vicinity of the morphogenetic mutation Dominant hemimelia (Dh), which is characterized by tibial hemimelia, poly/oligodactyly, and a number of visceral abnormalities, most strikingly absence of the spleen. Using a Gli2-associated microsatellite, we demonstrated no recombination between Dh and Gli2 in a Dh intraspecific backcross. Gli2 is expressed in Dh heterozygotes and homozygotes. However, using a combination of mismatch analysis and direct sequencing, we have failed to identify any mutations in the coding sequence of Gli2 from Dh. We have also demonstrated that it is unlikely that there are any Gli genes in the mouse genome in addition to the previously described Gli, Gli2, and Gli3.

Amino Acid Sequence↗
PubMed1995

Expression of a B-cell marker, CD24, on nasopharyngeal carcinoma cells.

Random sequencing of clones from a lambda gt10 cDNA library, made from mRNA expressed in an Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) has revealed the gene transcript of human CD24. The CD24 antigen, a glycosylphosphatidylinositol-anchored cell surface molecule, has been identified as a B-cell marker that is lost during cell maturation. We show here that it is expressed on 3 NPC xenografts, previously defined as consisting of poorly differentiated epithelial cells, and on an NPC biopsy. In the case of the former, the level of expression of CD24 corresponds to the EBV load. A B-lymphoblastoid cell line carrying the same EBV genome as one of the tumours, C15, and an EBV-negative Burkitt's lymphoma cell line do not display the antigen, but epithelial-like cells of a laryngeal tumour cell line (Hep2) do express it. Our data suggest that CD24 may be a marker of cell differentiation not only for B cells but also for epithelial cells and may have an indirect association with EBV gene expression.

Animals↗
PubMed1978

Relationship between maternal anti-D levels, fetal phenotype and haemolytic disease of the newborn.

It has been demonstrated that a lower level of maternal anti-D is required to produce the same symptoms of haemolytic disease of the newborn in R2r infants than in R1r infants. This difference could be explained by postulating that the higher site density of R2r cells is associated with an increased association constant and thus will bind sufficiently more anti-D. The level at which amniocentesis should be considered has been calculated to be 1.44 microgram anti-D/cm3 of maternal serum for R1r infants and 0.73 for R2r infants.

Erythroblastosis, Fetal↗
PubMed1978

A study of different rhesus phenotypes and their binding characteristics.

A method has been developed using the Auto Analyzer to study the binding characteristics of anti-D with cells of various rhesus phenotypes. A positive association has been demonstrated between site density and association constant. A hypothesis is proposed for the presence of two types of antigenic sites on the cell surface recognised only by affinity difference. The high affinity site binds both arms of an IgG anti-D molecule, whereas the low affinity site binds only one.

Binding Sites, Antibody↗
PubMed1977

Use of discriminant analysis in relating maternal anti-D levels to the severity of haemolytic disease of the Newborn.

The automated assay of maternal anit-D levels has been compared with manual methods and correlated with the severity of haemolytic disease of the newborn using discriminant analysis. The automated assay of anti-D proved to be marginally better than manual techniques in predicting the need for amniocentesis. The level at which amniocentesis should be considered has been calculated to be 4IU/ml of maternal serum.

Animals↗
PubMed1977

Androgens in the anaemia of chronic renal failure.

Plasma levels of testosterone-like substances (TLS) were depressed in seven patients with chronic renal failure. Intramuscular testosterone (as Sustanon 250 once a week) elevated plasma TLS levels to above normal throughout the week with an initial high peak. Sublingual testosterone produced a high but brief peak in TLS. Results were similar in renal failure patients and normal controls. A controlled trial of weekly Sustanon 250 in 24 regular dialysis patients produced a significant increase in haemoglobin from 6.8 to 8.2 g/dl. Side effects were mainly mild and acceptable but one patient developed priapism and another a large haematoma. The discriminate use of androgens is recommended for anaemic male patients on regular haemodialysis.

Adult↗
PubMedDate not supplied

Hydergine treatment and psychophysiological measures in primary degenerative dementia.

Changes in smooth pursuit eye movements and the P300 component of the auditory evoked potential were studied in patients with primary degenerative dementia during a double-blind, placebo-controlled study of ergoloid mesylates (Hydergine). After 18 weeks of treatment, P300 latency and amplitude, recorded at three scalp electrode sites, had not changed significantly. Smooth pursuit gain was elevated for the drug group under some stimulus conditions, suggesting a normalization of pursuit eye movement functioning. However, the results of several other measures of the quality of pursuit eye movements failed to corroborate this finding.

Aged↗