Modulation of cell surface glycocalyx: studies on large, external, transformation-sensitive protein.
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Biomedical subjects
Publications and source records attributed to A Murray.
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The immediate heart-rate response to standing was measured in 22 normal controls and 25 patients with diabetes, 15 of whom had autonomic neuropathy. The response in the controls and patients without autonomic neuropathy was characteristic and consistent, with tachycardia maximal at around the 15th beat and relative bradycardia maximal at around the 30th beat. The diabetics with autonomic neuropathy, however, showed a flat response. In three controls the response was abolished with intravenous atropine but not with propranolol, showing that it is mediated through the vagus. A simplified test using routine ECGs and measuring the R-R interval at beats 15 and 30 with a ruler is easily performed as an outpatient procedure and may be used as a measure of autonomic function in diabetes.
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Intercellular matrices secreted by chick embryo fibroblasts in culture were studied by scanning electron microscopy. Cell-cell contact is a prerequisite for the expression of such matrices. The smallest fiber detected by transmission electron microscopy is 5--10 nm in diameter. These matrix fibers tend to cluster to form bundles. Immunofluorescence and immunoferritin procedures reveal that LETS protein is one of the components of the matrices. The matrices are isolated from other cellular organelles by detergent treatment. More than 90% of the proteins in cell-free matrices are LETS protein, suggesting that the matrices are probably made of only one component--LETS protein. Since the solubilization of matrices requires beta-mercaptoethanol, LETS protein matrices may be the first known polymer system in nature to use disulfide linkage as an intermolecular polymerization vehicle. Collagen does not appear to be involved in such matrices. The LETS protein matrix supports the morphological conversion of rounded cells into spindle-shaped, and also promotes myoblast fusion. It does not, however, exert an effect upon cell growth, the rate of glucose uptake or protease production.
The interrelationship of malaria and severe ascariasis was studied in Anjouan children with a previously described syndrome of enlarged parotids, localized forehead edema, heavy infestation with Ascaris lumbricoides, and unusual freedom from malaria. After treatment of 37 such children with the ascaricide piperazine, 35 had resolution of parotid enlargement and forehead edema, but 19 developed attacks of malaria. Children treated with placebo had neither resolution of clinical findings nor attacks of malaria. We propose that suppression of the malaria in these children is a nutritional consequence of severe ascariasis and may represent an ecological balance for optimum co-survival of the host and the two parasites.
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The measurement of praecordial ST segment elevation after myocardial infarction is of value in assessing the natural history of ischaemic injury and the effectiveness of intervention. Hand analysis is, however, time consuming and inaccurate. A technique for continuous recording from 35 praecordial leads and subsequent computer analysis is presented, together with illustrative case studies. Changes in body posture and in heart rate are of importance in subsequent data interpretation.
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Peripheral and autonomic nerve function was assessed in 10 newly diagnosed male diabetics (six insulin-treated and four sulfonylurea-treated) with repeated observations over the subsequent six months. There was significant impairment of motor-conduction velocity in the common peroneal nerve at diagnosis in both treatment groups, with improvement following treatment in only the insulin-treated patients. In contrast, although the blood glucose level fell in both groups, the mean level was significantly lower in the sulfonylurea-treated patients at two months and at each subsequent visit. In the autonomic function tests significant abnormality was found in the electrocardiographic R-R-interval (beat-to-beat) variation in resting heart rate in two of the insulin-treated patients and all of the sulfonylurea-treated group, with improvement in only one of the latter. One patient in the sulfonylurea-treated group also showed an abnormal response to the Valsalva maneuver (expressed as the Valsalva ratio), and this remained abnormal throughout the period of study. All other patients had normal responses to the Valsalva maneuver and sustained handgrip test. None of the patients had postural hypotension. Abnormalities in autonomic nerve function in diabetics at diagnosis have not been previously reported.
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Phleomycin has devastating effects on regeneration of skeletal muscle when applied during an early wave of replication in the pre-myotube (new fibre) period of the reaction. The effect cannot be explained from the contribution of dividing cells to myotubes. Phleomycin's effects on regeneration are much less severe when the challenge coincides with a later wave of pre-myotube proliferation, effects that can be explained from the contribution of such cells to new muscle. An attempt has been made, by means of electron microscopy, to explain how phleomycin distributes early versus late wave cells, using a mercury substitution stain to detect the antibiotic. Cells of the two periods showed conspicuous differences in the staining characteristics of their chromatin. Positive staining reactions outside the nucleus were confined mainly to ribosomes. Exceptions included materials in transit across nuclear and cytoplasmic membranes.
In a controlled study using mexiletine and placebo, the incidence of ventricular arrhythmias after acute myocardial infarction (AMI) has been compared. The study covered 40 male patients who had sustained AMI and who in the first 48 h after onset of infarction had exhibited ventricular tachycardia, R on T-, multiform or close-coupled ventricular ectopic beats. Half of the patients were given either mexiletine (250 mg 8-hourly) or placebo. On the 4th and 10th day after onset of infarction a continuous 24-hour ECG was performed. 76% of the patients receiving placebo showed serious ventricular arrhythmias compared with 32% receiving mexiletine (p less than 0.05). These results demonstrate (1) the frequency of ventricular arrhythmias in a group of patients already at risk, and (2) the efficacy of an oral antiarrhythmic agent like mexiletine in the management of these rhythm disorders.
Peripheral and autonomic nerve function was assessed at intervals over a 3-month period in seven diabetics after ketoacidosis. There was marked improvement in motor conduction velocity and terminal latency of both ulnar and common peroneal nerves in all patients. Five had one or more abnormal autonomic function tests but there were no consistent changes during the same period. It is postulated that peripheral nerves may be more susceptible to acute metabolic damage than autonomic fibres.