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Biomedical subjects

L Austin

Publications and source records attributed to L Austin.

At least 19 recordsLinked to original sources
PubMed1992

Effects of leukaemia inhibitory factor and other cytokines on murine and human myoblast proliferation.

It has been shown previously that leukaemia inhibitory factor (LIF) and transforming growth factor-alpha (TGF-alpha) stimulate proliferation of primary cultures of murine myoblasts. We now show that human myoblasts respond in a similar manner to LIF and TGF-alpha. These responses occur over a range of growth conditions. There are total additive effects in both human and murine myoblasts between LIF and TGF-alpha and LIF and fibroblast growth factor-beta (FGF-beta), but not between LIF and interleukin-6 (IL-6) or insulin-like growth factor 1 (IGF-1). The LIF response is initiated by a short exposure to the cytokine and is maintained for prolonged periods in its absence.

Animals↗
PubMed1992

Potential oxyradical damage and energy status in individual muscle fibres from degenerating muscle diseases.

Inherited degenerating muscle diseases result in disintegration of muscle fibres, which is initiated by a lack of or alteration to a muscle protein. In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) the protein is known to be dystrophin. The cellular function of dystrophin is not known in any detail but its absence appears to lead to a weakening of the sarcolemma. It has been proposed by Murphy and Kehrer that this leads ultimately to increased oxyradical production which may accelerate the degeneration. Studies have been carried out on individual muscle fibres derived from biopsy samples from patients with a number of degenerative muscle diseases. The glutathione cycling components, in particular glutathione and glutathione peroxidase, are significantly elevated in DMD, BMD and other diseases. Glutathione reductase is also elevated in some of these diseases. Energy producing systems are also affected particularly in intact fibres of muscle derived from muscle at an advanced stage of the disease. These results suggest that oxyradical damage may occur as a secondary consequence of muscle degenerating disease, leading to a breakdown in the glycogenolytic energy producing system.

Adenosine Diphosphate↗
PubMed1991

Duchenne muscular dystrophy and dystrophin: sequence homology observations.

Duchenne muscular dystrophy (DMD) is a genetically transmitted disease characterized by progressive muscle weakness and usually leads to death. DMD results from the absence, deficiency or dysfunction of the protein dystrophin. Analysis of protein data bases, including homology alignments and domain recognition patterns, have located highly significant correlations between dystrophin and other calcium regulating proteins. In particular, a major portion of the dystrophin sequence has been found to contain repeating units of approximately 100 amino acid residues. These repeating units were found to exhibit significant homology to troponin I. Troponin I has been found to bind to the calcium binding proteins calmodulin and troponin C. The regions of highest homology were characterized by patterns of high localization of charged amino acids and thus could represent a possible calmodulin or troponin C surface accessible binding site. Since subcellular localization studies have indicated that dystrophin is associated with the triadic junction, these findings imply that dystrophin could be involved in controlling intracellular calcium homeostasis.

Amino Acid Sequence↗
PubMed1991

Stimulation of myoblast proliferation in culture by leukaemia inhibitory factor and other cytokines.

Significant stimulation of growth of myoblasts in culture is achieved by leukemia inhibitory factor (LIF). The optimum activity of this cytokine occurs at about 6 pM LIF. Interleukin-6 (IL-6) also stimulates cultured myoblasts but to a lesser degree than LIF and the effect is not maintained for extended culture periods. In addition, transforming growth factor-alpha (TGF-alpha) also increases the growth rate of myoblasts but only after a considerable lag phase. All 3 cytokines may be of value in the large scale production of myoblasts for use in the potential treatment of primary myopathies by injection of cultured myoblasts into diseased muscle to form genetically complete muscle fibres after fusion of the myoblasts in situ. Their potential use is enhanced in that at least under the conditions used here they do not stimulate fibroblast proliferation.

Animals↗
PubMed1991

Rapid isolation of rat brain nuclei on percoll gradients.

A rapid isotonic method for fractionation of nuclei from rat brain is described. This procedure is based on the use of discontinuous colloidal silica gel (Percoll) gradients. We start from a 63,000-g purified nuclear pellet (fraction P3) isolated from gray matter and white matter separately. This is followed by fractionation of fraction P3 in an initial differential centrifugation step on five-step Percoll gradients producing six nuclear fractions designated 1, 2, 3 (gray matter) and 4, 5, 6 (white matter). Fractions 2, 4, and 5 obtained from this centrifugation are heterogeneous. These fractions are subfractionated further under isopycnic conditions using five-step Percoll gradients to yield subfractions 2b, 4b, and 5c. Three methods were used to characterize the nuclear types. First, light and electron microscopic examination was used to identify the nuclei in each preparation and to assess the purity of each preparation. Second, the activities of RNA polymerase I and II were monitored. Third, the protein/DNA ratios of the nuclear fractions were determined. Fraction 1 was enriched in neuronal nuclei; fractions 2b and 4b in astrocytic nuclei; and fractions 3, 5c, and 6 in nuclei of oligodendrocytes. RNA polymerase I and II activity was highest in fraction 1, which also displayed the highest protein/DNA ratio. Electron microscopy showed that the various classes of nuclei are congruent to 90% pure. Therefore, the procedure described here is suitable for obtaining highly purified neuronal and three types of glial nuclei from rat brain.

Animals↗
PubMed1991

Dynamic cardiomyoplasty: clinical follow-up results.

From 1985 to April 1990, 78 clinical dynamic cardiomyoplasty procedures were performed using the latissimus dorsi muscle stimulated with the Medtronic Cardiomyoplasty System. Indications for surgery were mostly ischemic and idiopathic dilated cardiomyopathies with patients in severe cardiac insufficiency (NYHA Class III and IV). Results of this multicenter study (11 centers) indicate that the dynamic cardiomyoplasty procedure can be transferred and reproduced in many centers with low perioperative mortality and that it improves the functional status of patients who survive the procedure. The survival rate suggests a long-term benefit (average implant time: 11.7 months). Although clinical functional improvement was reported, actual hemodynamic augmentations could not be clearly demonstrated under the protocol. Further studies of functional and hemodynamic parameters are necessary to determine if dynamic cardiomyoplasty is efficacious for a well-defined group of congestive heart failure patients. These points will be addressed in forthcoming studies.

Adolescent↗
PubMed1979

Depression simulating organic brain disease.

The authors report four cases of depression manifesting as organic brain syndrome in adult nongeriatric patients. The correct diagnoses in three cases were made by a psychiatrist's or resident's empathic response to the patient, and in the fourth by the patient's history of depression. The authors state that only by maintaining a high degree of suspicion and trusting one's empathic response to the patient will unusual presentation of depression be recognized.

Adult↗
PubMed1978

Phospholipid composition and metabolism in mouse muscular dystrophy.

1. The composition and metabolism of phospholipids were studied in various tissues from both normal and dystrophic mice of the 129 ReJ strain. Phospholipids extracted from forebrain, spinal cord, sciatic nerve and plasma were fractionated by t.l.c. and measured. 2. Very significant alterations were found in the choline phospholipids from these tissues, except forebrain. Plasma phosphatidylcholine in the dystrophic mouse was increased by 38%. There was a 2-fold increase in lysophosphatidylcholine in the spinal cord of dystrophic mice. The sciatic nerve showed a marked decrease in sphingomyelin content, which is approximately half of that in the controls. 3. Five enzymes involved in phosphatidylcholine metabolism [namely cholinephosphotransferase (EC 2.7.8.2); phospholipases A (EC 3.1.1.4, EC 3.1.1.32); lysophospholipase (EC 3.1.1.5); lysophosphatidylcholine acyltransferase (EC 2.3.1.23); phospholipase C (EC 3.1.4.3)] were studied in tissue preparations from forebrain, spinal cord, sciatic nerves, gastrocnemius muscles and liver. 4. Activities of phospholipases A and C were significantly increased, about 5-fold and 60% respectively, in gastrocnemius muscle of dystrophic mice compared with controls. Phospholipases A also showed 50% higher activity in the sciatic nerves of dystrophic than of normal mice. Lysophosphatidylcholine acyltransferase activities were significantly increased in the sciatic nerves and spinal cord, by 50-100% over that of the controls. The forebrain and spinal cord from dystrophic mice, however, had only 60% of lysophospholipase activities of that of the normal control. Cholinephosphotransferase activity was unchanged in these tissues from both normal and dystrophic mice. 5. It is suggested that are number of features of mouse muscular dystrophy related to altered membrane structure and function can be rationalized in terms of changes in lipid composition and metabolism.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1978

Axonal transport of 4S RNA in the chick optic system.

The axonal transport of tRNA has been investigated in the chick optic system. Chicks were injected with [3H]uridine intraocularly or intracranially and the RNA of the retina, nerve complex, and tecta separated by polyacrylamide gel electrophoresis and then counted. The ratio of tRNA to rRNA specific activities increased with time in both the nerve complex and contralateral tectum. The ratio increased more rapidly in the nerve complex than the tectum. However, no increase was observed in the case of intracranially injected animals. This is consistent with the axonal flow of tRNA. When [methyl-3H]methionine was used as precursor, the preferential labeling of 4S RNA to rRNA which resulted more clearly showed a transport of 4S RNA from the retinal cells to the tectum. In conclusion, it was found that about 40% of the radioactive RNA observed within the optic tectum 4 days after an intraocular injection of [3H]uridine was accounted for by 4S RNA which has flowed from the retina. However, the migration of a methylated RNA molecule of size 4S, but unrelated to rRNA, cannot be entirely eliminated.

Animals↗