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Biomedical subjects

G Morgan

Publications and source records attributed to G Morgan.

At least 289 records · Page 16Linked to original sources

Changes in cross-bridge properties of sensitized airway smooth muscle.

We have reported previously that in ovalbumin-sensitized canine tracheal smooth muscle (TSM) the maximum ability to shorten is increased. This could account for the increased airway narrowing seen in vivo in allergic bronchoconstriction. It was associated with increased velocity of shortening. We now report that, by using an electromagnetic muscle lever system, quick releases were applied to control and sensitized TSM at 0.5-s intervals throughout the course of a lightly preloaded 10-s isotonic contraction. From the records obtained it is possible to determine that, early in contraction, shortening is brought about by relatively rapidly cycling [0.35 optimal muscle length units +/- 0.033/s (SE)] cross bridges. We also report that in the sensitized TSM it is the early bridges that increase their velocity by 26.6% (P less than 0.05) compared with similar bridges in muscles from control animals. Since 70% of the maximum shortening of the muscle occurs when early bridges are operative, it is likely that these bridges are responsible for the major part of the shortening. It is thus probable that increased allergic bronchoconstriction is produced by increased activity of early, rapidly cycling bridges. The bridges that are active late in the shortening show no difference between control and sensitized airway smooth muscles.

Animals↗

Control of binucleate cell migration in the placenta of sheep and goats.

In the ruminant placenta 15-20% of the trophectodermal epithelium consists of granulated binucleate cells (BNC). In the sheep the granules contain ovine placental lactogen (oPL). These cells migrate from the trophectoderm to form fetomaternal hybrid tissue from implantation to term. The number of BNC, their percentage migration and the potential secretory activity of the syncytium they form were estimated by semiquantitative transmission electron-microscopical techniques after several surgical techniques and hormone or drug infusions. BNC numbers decrease normally just before parturition, and this fall could be eliminated by fetal hypophysectomy or induced early by administration of tetracosactrin to intact or hypophysectomized fetuses. If only one twin was treated with tetracosactrin the placenta of the untreated twin did not show the fall in BNC numbers found in the other unless it died in utero some time before sampling. This indicates fetal control of BNC number and migration. However, fetal catheterization, hypophysectomy, stalk section, adrenalectomy, infusion of mouse epidermal growth factor or bromocriptine had little or no effect on binucleate cell numbers or migration percentages. Maternal carunclectomy, ovariectomy, or epostane or bromocriptine administration also had no consistent significant effect. Previous reports of degeneration of BNC structure plus a decrease in their number (with bromocriptine) or an increase in migration frequency (after adrenalectomy or stalk section) have not been confirmed by this study. The BNC migration delivers the oPL-containing BNC granules close to the maternal circulation but the variation in migration seems only loosely correlated with the reported maternal oPL concentrations. The results indicate that BNC migration is independent of the hormonal milieu, but that BNC production is greatly modified by the hormonal changes just before parturition, with cortisol production by the fetus a possible primary cause.

Adrenalectomy↗

A family study of the X-linked lymphoproliferative syndrome: evidence for a B cell defect contributing to the immunodeficiency.

The X-linked lymphoproliferative syndrome (XLPS) is an immunodeficiency characterized by severe primary infection with the Epstein Barr (EB) virus, which is often fatal. This has been attributed to failure to generate T lymphocytes which are specifically cytotoxic for EB virus-infected B lymphocytes, and which develop in all normal individuals following primary infection. We have studied a kindred which carried the defective gene for XLPS and have confirmed that the pattern of serum antibody responses to EB viral antigens can be used to detect affected males and female carriers. Furthermore, an EB virus genome-carrying B cell line which grew spontaneously from a culture of bone marrow cells from a male child with XLPS at the time of primary infection showed a decreased sensitivity to MHC-restricted, EB virus-specific killing by a T cell clone when compared to its in vitro EB virus-transformed counterpart. From these results we suggest that a subset of EB virus-infected B lymphocytes which were resistant to EB virus-specific killing existed in this child, and may have contributed to the overwhelming EB virus infection and its fatal outcome.

Antibodies, Viral↗

Regional vasorelaxant selectivity of atrial natriuretic factor in isolated rabbit vessels.

Synthetic atrial natriuretic factor (ANF) exhibited a marked selectivity in its ability to relax isolated rabbit arteries and veins. The aorta, renal and mesenteric arteries and the facial vein were the most sensitive vessels with the more distal arteries and most veins being relatively unresponsive to ANF. All preparations were effectively relaxed by sodium nitroprusside. ANF (up to 10(-7) M) failed to elicit any effect on isolated rabbit right atria or papillary muscles. The profound regional vasorelaxant selectivity of ANF may help to explain the hemodynamic effects of this substance in vivo.

Animals↗

The attitudes of the Australian community to treatment of infertility by in vitro fertilization and associated procedures.

Sequential surveys of public opinion within the Australian community have consistently demonstrated very significant support for in vitro fertilization (IVF) to enable infertile couples to have children. Embryo freezing and the use of donor gametes have lower approval rates, but those who approve significantly outnumber those who disapprove. There was no community concensus about the use of surrogacy as an extension of IVF treatment.

Australia↗

The creatine kinase reference interval. An assessment of intra- and inter-individual variation.

Serum creatine kinase (CK) values in reference populations generally vary by greater than one order of magnitude. This large range of variation overlaps the range of values found in female carriers of Duchenne muscular dystrophy and limits the clinical usefulness of serum CK testing. In order to examine whether the source of this variation is intrinsic variability of individual CK values, or whether the variation is due to day-to-day variation in each individual's CK activities, we tested 15 female medical students at weekly and 22 female medical students on at least 3 occasions. Each venesection followed a 3-day exercise free interval, according to a standard protocol, designed to minimise the effects of exercise. Each individual tended to have consistent CK activities. The range of variation in the same individuals on different occasions was small (the mean coefficient of variation, CV was 19%). There was a much greater range of serum CK activities between individuals (CV 47%). Even when sporting activities were excluded slightly higher values were found after minor exercise was recorded in the three days prior to venesection. The conclusion that individuals have consistent serum CK activities was supported by the results from a larger population tested under standardised resting conditions on three different occasions which yielded similar frequency distributions on each occasion.

Adult↗

Variable distributions of serum creatine kinase reference values. Relationship to exercise activity.

Although the effect of exercise on serum creatine kinase (CK: EC 2.7.3.2) activity is well known, no standard protocol for blood collection conditions has been developed. Variable frequency distributions of CK activities have been reported for reference range samples from different laboratories and have been attributed to laboratory differences. In this study the frequency distributions of creatine kinase activities (CK: EC 2.7.3.2) in serum samples obtained from the same groups of volunteers varied from a normal Gaussian distribution, to skewed distributions, on different occasions. In one collection extremely high CK values followed the performance of an eccentric exercise step test 5-8 days previously. In 2 students serum CK activities had not returned to resting values 12 and 15 days later. Peak serum CK values occurred within 24 h of other types of exercise. Serum CK frequency distributions in blood samples obtained from a group of nurses was skewed, whereas the distribution in mothers of school children was Gaussian. When repeat samples were obtained from the nurses after instruction to avoid exercise, the distribution became Gaussian. In view of the increasing levels of physical activity in the community, a standard protocol for serum CK analysis is required, in which exercise activity over the previous three weeks should be documented. Test subjects should be counselled to avoid unusual eccentric exercise and sampling should include 3 tests at least 1 week apart.

Adolescent↗

Lung cancer and pregnancy.

Two pregnant patients presenting with bronchogenic carcinoma are described. A retrospective study of patients with bronchogenic carcinoma as well as a review of the literature attest to the rarity of this combination. If current smoking patterns continue, the association of pregnancy and bronchogenic carcinoma will increase in frequency.

Adult↗

Smooth muscle contractility. Effects of hypoxia.

Mechanical perturbation of smooth muscle provides information about the mechanical properties of its crossbridges. We have developed a method for identifying: (1) that normally cycling and very slowly cycling are sequentially activated, (2) the moment of this transition, and (3) the proportions of the two types of bridges recruited. Hypoxia decreases muscle shortening ability before isometric force. The former is due to depression of activity of both types of bridges.

Animals↗

Absence of gap junctional complexes in two established renal epithelial cell lines (LLC-PK1 and MDCK).

The type of junctions present in the membranes of the two renal epithelial cell lines, LLC-PK1 and MDCK, and of subcultured porcine aortic endothelial (PAE) cells have been studied by freeze-fracture. No gap junctions were observed in the two renal cell lines, while they were numerous in the endothelial cells. Tight junctions were abundant in LLC-PK1 and MDCK cells and varied in numbers of ridges from one to ten. ONly a few simple tight junctions unconnected with gap junctions were observed in PAE cells. The occurrence of gap junctions in these cells correlates with their ability to form intercellular communicating channels.

Animals↗

Childhood lymphoblastic leukaemia: sex difference in 6-mercaptopurine utilization.

Twelve boys and 10 girls on similar long term remission maintenance treatment for lymphoblastic leukaemia had 79 random assays of their red cell 6 thioguanine nucleotide ( 6TGN ) concentrations performed as an index of cytotoxic activity generated by oral 6-mercaptopurine ( 6MP ). Correlation between the dose of 6MP and 6TGN was statistically significant in the girls (r = 0.58, P less than 0.001) but not in the boys (r = 0.15). Additionally, as a group the boys tolerated more 6MP (P less than 0.05), despite similar prescribing criteria, but this did not result in a higher mean 6TGN concentration or increased myelotoxicity. It appears that girls develop 6MP cytotoxicity at lower doses and more predictably than boys. If so, this may be relevant to the as yet unexplained but marked sex difference in prognosis apparent in some studies.

Adolescent↗

Thyroid hormone binding in rat liver cytosol.

Binding of 3,5,3'-tri-iodothyronine (T3) and thyroxine (T4) to components of perfused rat liver supernatant fraction and isolated liver cell cytosol was studied. Of the four binding fractions in supernatant (X, A, Y and Z) separable by gel chromatography, both T3 and T4 bound preferentially to the A-fraction, which was shown to contain albumin as the major binding protein. When cytosol prepared from isolated cells was examined, T4 was again bound mainly in the A-fraction; however, T3 was observed to bind predominantly in the Y-region. Hormone binding to soluble protein in the latter system is thought to reflect the pattern in vivo, better than does binding in supernatant, although the possibility exists that the concentration of albumin observed in cytosol may be artificially high due to transfer of membrane-bound albumin during cell disruption. Nevertheless, albumin (possibly derived from more than one intracellular source) is capable of binding T4 in vivo. The presence of this protein within the hepatocyte may thus contribute to the high T4 binding capacity of the liver compared to other tissues.

Albumins↗

Bachelor grandpa.

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Community-Institutional Relations↗

Calcium entry blocker activity of cyproheptadine in isolated cardiovascular preparations.

Cyproheptadine was compared with nifedipine, verapamil and diltiazem for calcium entry blocker activity in isolated cardiovascular preparations. Using rat aortic strips, all compounds (10(-7) M) inhibited both the contraction caused by the readdition of calcium (1.0 mM) into regular buffer or buffer containing potassium (130 mM) or norepinephrine (10(-5) M) and the potassium-stimulated uptake of 45Ca. The rank order of potency for these experiments was in general nifedipine greater than cyproheptadine greater than or equal to verapamil greater than diltiazem. The same order of potency also was found for the four compounds in relaxing potassium (40 mM)-contracted aortic strips (IC50 values: nifedipine, 2.6 X 10(-9) M; cyproheptadine, 6.3 X 10(-8) M; verapamil, 7.6 X 10(-8) M; and diltiazem, 2.1 X 10(-7) M), but cyproheptadine was the least potent agent in antagonizing the spontaneous contractions of the rat portal vein (IC50 values: nifedipine, 6.6 X 10(-9) M; verapamil 7.7 X 10(-8) M; diltiazem 9.6 X 10(-8) M; and cyproheptadine 3.9 X 10(-7)M). None of the compounds (10(-7) M) inhibited the contraction to norepinephrine (10(-5) M) in rabbit aortic strips bathed in calcium-free buffer (1 mM ethylene glycol bis(beta-aminoethyl ether)-N, N'-tetraacetic acid). Nifedipine, verapamil and diltiazem were more potent in inhibiting the restoration of contractility by isoproterenol in potassium-depolarized rabbit papillary muscles than decreasing force in normally polarized muscles; cyproheptadine was equipotent when tested in these two preparations. Cyproheptadine was the least potent of the four compounds in lowering perfusion pressure in the perfused canine hindlimb.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antigens of the erythrocytes stages of the human malaria parasite Plasmodium falciparum detected by monoclonal antibodies.

A range of 22 mouse anti-P. falciparum monoclonal antibodies have been characterized by indirect immunofluorescence and immunoprecipitation. On the basis of these studies, 5 groups of antibodies and 6 classes of antigen were defined. Group I antibodies give, bright, uniform, generalised staining of all blood stages including gametocytes. Three of these antibodies precipitate a metabolically labelled molecule(s) of 35 kDa. One precipitates a 50 kDa antigen. Group II antibodies, which give strong localised immunofluorescence in merozoites, and a weak diffuse pattern in earlier stages, precipitate biosynthetically labelled molecules of 160 kDa. Group III antibodies react with all asexual stages. With merozoites they produce intense staining around the perimeter, both in fixed and unfixed preparations. They precipitate biosynthetic molecules of 190 kDa. Group IV antibodies are identical to Group III except they are stage restricted to schizonts and merozoites. They also precipitate 190 kDa antigens. These, however, in contrast to group III, are readily accessible to 125I-lactoperoxidase labelling. One antibody also precipitates a set of smaller peptides. Finally, Group V antibodies produce very bright ill-defined staining of pigment-containing parasites, as well as of inclusions in the red cell. They precipitate a series of molecules of 160, 60 and 35 kDa which are readily accessible to 125I. The 160 kDa molecule is also labelled by [35S]methionine. These results are discussed in the context of the development of a malaria vaccine and immunodiagnostic tests.

Animals↗