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Biomedical subjects

G Morgan

Publications and source records attributed to G Morgan.

At least 253 records · Page 14Linked to original sources

Breast cancer: the role of postoperative radiotherapy.

Although the role of radiotherapy in breast cancer is controversial, there are clearly defined indications for its use. The probability of local relapse can be determined by careful evaluation of the histological features of the primary tumour, the absolute number of involved axillary nodes and the type and and extent of the surgery performed. Using these data, patients can be divided into a relatively low risk group who probably do not require radiotherapy and a group at significant risk of relapse who, even with adjuvant systemic therapy, are likely to benefit from postoperative radiotherapy. Despite the often-repeated view to the contrary, radiotherapy is more effective in the locoregional control of breast cancer if given postoperatively than if withheld until tumour relapse occurs. Radiotherapy at the time of relapse provides long-term control in only 40-55% of patients. This results in significant morbidity from uncontrolled local disease in the one-third of patients who survive 5 years and the one-quarter of patients who survive 10 years from the time of local relapse. This paper outlines the rationale and indications for the use of radiotherapy in improving locoregional control in breast cancer.

Axilla↗

An immunological cryo-ultrastructural study of a sequential appearance of proteins in placental binucleate cells in early pregnancy in the cow.

Using the most sensitive immunocytochemical method available, on ultrathin frozen sections, the results in this paper demonstrate that bovine placental lactogen (bPL) is present in the earliest fetal binucleate cells found at 21 days post coitum in the trophectoderm. A second protein, the SBU-3 antigen, which is absent in the early stages of pregnancy appears abruptly in the binucleate cell granules at 30 days post coitum coincident with the start of villus development. Subsequently, the granules contain both bPL and the SBU-3 antigen. This sequential production of unlike proteins indicates that the binucleate cell has different functions depending on the stage of pregnancy and has important roles to play both at implantation and in villus development.

Animals↗

The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion.

About 60% of both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) is due to deletions of the dystrophin gene. For cases with a deletion mutation, the "reading frame" hypothesis predicts that BMD patients produce a semifunctional, internally deleted dystrophin protein, whereas DMD patients produce a severely truncated protein that would be unstable. To test the validity of this theory, we analyzed 258 independent deletions at the DMD/BMD locus. The correlation between phenotype and type of deletion mutation is in agreement with the "reading frame" theory in 92% of cases and is of diagnostic and prognostic significance. The distribution and frequency of deletions spanning the entire locus suggests that many "in-frame" deletions of the dystrophin gene are not detected because the individuals bearing them are either asymptomatic or exhibit non-DMD/non-BMD clinical features.

Adolescent↗

Binding of monoclonal antibody to CD16 causes calcium mobilization in large granular lymphocytes but inhibits NK killing.

A monoclonal antibody (mAb), CLB/FcR gran I, reactive with the CD16 Fc receptor (FcRlo/FcRIII) of human cells, leads to calcium mobilization in large granular lymphocytes (LGL) but not in granulocytes. Identical responses are obtained with F(ab')2 fragments of this antibody, indicating that the response is independent of Fc-FcR binding, and that bivalent cross-linking of this receptor is adequate for optimal calcium mobilization. The calcium response was greater in CD3- LGL compared to CD3+ LGL, although the response was augmented in the latter cells by prior rosetting with sheep red blood cells (SRBC). Calcium mobilization in CD3- LGL induced by CLB/FcR gran I is associated with inhibition of natural killer cell (NK) killing, and inhibition of the enhanced NK killing induced by the anti-CD2 low-density monoclonal antibody, 9.1. This supports the view that the NK-enhancing activity of 9.1 is due to simultaneous binding to CD2 and CD16, and may in fact be transduced through the CD16 molecule. The variable reported effects of anti-CD16 antibodies on NK killing are likely to reflect the epitope bound rather than the isotype of antibody used, since F(ab')2 fragments of CLB/FcR gran I also inhibit NK killing.

Antibodies, Monoclonal↗

Molecular analysis of Philadelphia positive essential thrombocythemia.

Seven patients with Philadelphia (Ph) chromosome positive essential thrombocythemia (ET) were investigated for the presence of a rearrangement within the major breakpoint cluster region (M-bcr) using the Southern blot technique and, in six cases, for the presence of the hybrid bcr-abl mRNA using the polymerase chain reaction (PCR). The molecular studies showed rearrangement of M-bcr in all cases; there was evidence of the b2a2 mRNA junction in one case and of b3a2 junction in five cases. These findings are identical to what might have been expected in Ph-positive chronic myeloid leukemia. These features may explain the poor prognosis of Ph-positive ET in comparison with cytogenetically normal cases. Conversely, the differences in clinical presentation may be due to other genetic changes.

Adult↗

Platelet number and size in relation to serum orosomucoid concentration in Crohn's disease.

The relationship between platelet size and platelet count was investigated in 41 patients with Crohn's disease. A high platelet count was associated with a decrease in platelet size, but an overall increase in the platelet crit. There was also a significant correlation between the patient's platelet count and serum orosomucoids, which have traditionally been used to assess disease activity.

Adolescent↗

Effect of uncouplers of oxidative phosphorylation on transmitter release in dystrophic mice.

Intracellular recording was used to study the effect of uncouplers of oxidative phosphorylation on miniature endplate potentials (m.e.p.p.s) in skeletal muscles from dystrophic mice and their clinically normal littermates. Control m.e.p.p. frequency in muscles from dystrophic mice was not significantly different from normal. In the presence of the inhibitors 2,4-dinitrophenol (10(-4) M) or guanidine (5 X 10(-3) M) m.e.p.p. frequency was increased less in muscles from dystrophic mice than that in muscles from normal littermates. In contrast, raising the extracellular calcium concentration, depolarising nerve terminals with potassium or motor nerve stimulation all caused a similar increase in m.e.p.p. frequency in normal and dystrophic muscles. It is suggested that there is a difference in the way in which calcium is stored in dystrophic nerve terminals but that their ability to regulate free calcium is normal.

Animals↗

Interactions of DPI 201-106, a novel cardiotonic agent, with cardiac calcium channels.

The interaction of DPI 201-106, a novel cardiotonic agent, with the calcium entry blocker receptor complex was studied using porcine cardiac sarcolemmal membranes. DPI 201-106 and the chemically-related calcium antagonist, cinnarizine, produce concentration-dependent inhibition of nitrendipine, gallopamil and diltiazem binding to their respective sites in these vesicles. This effect of DPI 201-106 is not stereoselective since resolved stereoisomers of this compound display equal potency in inhibiting each of the binding reactions. Equilibrium ligand binding studies revealed that DPI 201-106 and cinnarizine cause mixed inhibitory patterns at the aralkylamine and benzothiazepine sites (i.e. both Kd and Bmax values were affected) while mainly increasing Kd at the dihydropyridine site. The kinetics of ligand dissociation from the three calcium entry blocker receptors, together with measurements of dihydropyridine association kinetics, further demonstrate that DPI 201-106 interacts at a unique site in the receptor complex and allosterically modulates binding of nitrendipine, gallopamil and diltiazem. The functional consequences of the above interactions with the calcium channel were studied in isolated cardiac preparations. In guinea-pig atria, DPI 201-106 increased force of contraction. This inotropic effect is seen only with the S(-) enantiomer and is unaltered by nitrendipine-, verapamil- or diltiazem-pretreatment, indicating DPI 201-106 does not act as a stimulant of this channel. Furthermore, DPI 201-106 did not alter the inotropic action of Bay K 8644, a calcium channel stimulant. Spontaneous rate of guinea-pig right atria is decreased by both DPI 201-106 and cinnarizine. In addition, potassium-induced contractures in cat papillary muscles are reduced by both agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A device for measurement of radius of curvature of obstetric forceps.

Details of the design of obstetric forceps are important to ensure that they can be used safely for mother and baby. One of the most important measurements is the radius of the cephalic curve of the blades since if this is inappropriate there will be a poor grip on the baby's head and risk of slippage, superficial injury or even intracranial haemorrhage and brain damage because of undue compression. Because of the complex design of the forceps blades, which have a pelvic curve as well as a cephalic curve and a fenestra, the radius of the cephalic curve is difficult to measure. A device was designed to facilitate this measurement and was found to be accurate and reliable in use. This was the first stage in the study to assess the suitability for modern practice of instruments designed many years ago.

Equipment Design↗

Prenatal diagnosis and carrier detection by DNA studies in a Duchenne muscular dystrophy family with no living affected male.

Restriction fragment length polymorphism studies and gene dosage analysis using the intragenic probes pERT87 were used to detect deletions in potential carriers in a family with Duchenne muscular dystrophy in which the only affected male was deceased. Two females were found to have inherited the paternal pERT87 alleles but not the maternal alleles, suggesting that they have inherited the pERT87 deletion from their mothers. The hybridization signals of pERT87 from these two females upon gene dosage analysis also suggested that they had a single copy of pERT87. The chorionic villi of a male fetus from one of these two females was found to be deleted for pERT87, suggesting that it was affected. This result confirmed the carrier status of the mother.

Alleles↗

Alterations in uterine epithelial tight junction structure during the oestrous cycle and implantation in the pig.

The structure of the pig uterine epithelium tight junction has been studied using freeze-fracture methods during oestrus and implantation. Compared with non-pregnant non-cyclic pigs, in both pregnancy and during the cycle the number of intersections per unit area of the tight junction ridges increases to a maximum 16 days after ovulation. There was no significant alteration in the depth or number of ridges in the tight junction band. The only significant difference between tight junctions in cyclic and pregnant pigs was a brief increase in the depth during the cycle (12-15 days after ovulation). The number of intersections is thought to be a far more important measure than depth in determining the permeability of the tight junction. It therefore seems unlikely that changes in tight junction structure play any direct role in the rescue of the corpus luteum or in establishing pregnancy but merely reflect the alterations in progesterone concentrations. However, the decrease in uterine permeability indicated by the increase in intersection frequency has been reported for other species and may reflect an important change in the uterine milieu in preparation for a possible pregnancy, apparently induced by alterations in progesterone concentration.

Animals↗

Experience with DNA analysis in Duchenne and Becker muscular dystrophy families in NSW.

Results of the use of recombinant DNA techniques for the diagnosis of both forms of X-linked muscular dystrophy, Duchenne (DMD) and Becker (BMD), over an 18 month period, are reviewed. In all, 97 families with DMD were investigated and four with BMD. In 90 families the propositi were examined for deletions, in 21 families the maximum number of meioses was examined (in order to generate recombination fraction data) and in 45 families the study was undertaken to provide carrier and prenatal diagnosis.

Chromosome Deletion↗

The use of field-inversion gel electrophoresis for deletion detection in Duchenne muscular dystrophy.

Deletion is a common cause of Duchenne muscular dystrophy (DMD). Field-inversion gel electrophoresis, in conjunction with Southern blot hybridization, was used to detect large SfiI DNA fragments in the DMD locus. Two unrelated boys with DMD were found to have abnormal sized DNA fragments resulting from deletions. Some of the female relatives of these patients were also shown by this method to have deletions in the DMD locus.

Chromosome Deletion↗