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Biomedical subjects

S Howell

Publications and source records attributed to S Howell.

125 records · Page 7Linked to original sources

Low-frequency fatigue in isolated skeletal muscles and the effects of methylxanthines.

1. A form of skeletal muscle fatigue was examined with isolated animal and human muscle preparations. The possibility that methylxanthines could overcome this was investigated. 2. Prolonged contractile activity resulted in a long-lasting impairment of force generation at low frequencies of stimulation at times when the force at higher frequencies had substantially recovered. This was seen with both fast-twitch and slow-twitch animal muscles and with samples of isolated human muscle. 3. The decrease in low-frequency force was due to a decrease in twitch amplitude, suggesting damage to the processes involved in excitation--contraction coupling. 4. Caffeine and theophylline at concentrations of 1 mmol/l rapidly and completely reversed the effects of this form of fatigue in both animal and human muscle preparations. 5. Agents that potentiate muscle force production could be an effective means of counteracting the effects of an important form of skeletal muscle fatigue, but a clinically useful compound would need to be more potent than the methylxanthines currently in use.

Animals↗

The effect of aminophylline on inspiratory muscle contractility.

The effects of aminophylline on diaphragmatic muscle contractility were studied in 8 dogs. The relationships of the electromyographic signal from the diaphragm and the pressures developed by this muscle were compared before and after the administration of aminophylline in doses of 6, 20, 40, 80, and 120 mg/kg. Measurements were made during occluded inspiratory efforts at functional residual capacity. In a second group of 4 dogs the relationships were compared while the rib cage expansion was limited by a plaster cast. Finally, in a third group of 4 dogs after the diaphragm had been paralyzed by phrenicotomy, the relationship of pleural pressure to the electromyographic signal of the intercostal muscles was assessed before and after administration of aminophylline. In all cases, aminophylline progressively shifted the electromyographic pressure relationship up and to the left. This effect became significant (p less than 0.01) at a dose of 20 mg/kg, reached a peak at 80 mg/kg, and then declined at a dose of 120 mg/kg. The amount producing blood concentrations closest to the human therapeutic blood concentration was 20 mg/kg. The peak increase in pressure compared with the control values were 58% in the first group, 27% in the second group, and 52% in the third group (p less than 0.01). We conclude that aminophylline increases respiratory muscle contractility in a dose-related manner. This may have important therapeutic and pathophysiologic implications.

Aminophylline↗

Assessment of palatal height in children.

In this study a palatal index (P.I.) was established for 121 randomly selected normal Australian children. Mean P.I. indices were compared in the primary, mixed and permanent dentitions. A subjective assessment of relative palatal height was also carried out by two independent examiners and an attempt was made to examine the reliability of the subjective assessment, and its validity compared with the P.I. Measurements were recorded on stone casts at Level 1 (distal to the primary second molars/second premolars) and Level 2 (between primary first and second molar/first and second premolars). At Level 1 the mean P.I. increased significantly from the primary to the mixed and permanent dentitions. At level 2 the P.I. remained stable. Findings indicate that subjective assessment of relative palatal height was fairly reliable: there was approximately 80% interexaminer and intraexaminer agreements. Subjective assessment of palatal height correlated reasonably well with the P.I.

Adolescent↗

Expression of the regulation of cAMP metabolism in somatic cell hybrids.

Normal rat liver cells (BRL-1) that respond to isoproterenol (beta+2), prostaglandin E1 (PGE+1) and adenosine (Ado+) with a rise in adenosine 3':5'-monophosphate (cAMP) content have been hybridized with rat hepatoma cells (H35) which do not respond to any of these agonists (beta-2, PGE-1 and Ado-). Both the initial hybrid line (BF5) and a subclone (BF5-1-1) expressed a beta+2, PGE+1, Ado- phenotype. However, full expression of the responsive phenotype in the BF5 line was apparent only if phosphodiesterase activity was blocked, for example, by methylisobutylxanthine (MIX). Direct measurements showed the rate of degradation of cAMP to be 7 times greater in intact BF5 cells than in the BRL-1 parent. In contrast to BF5 cells, the BF5-1-1 cells did not express maximal responsiveness to any of the agonists even in the presence of MIX. The differential accumulation of intracellular cAMP observed with BRL-1, BF5 and BF5-1-1 cells in response to isoproterenol was shown not to be as a result of differential rates of excretion of cAMP. Furthermore, no differences in the apparent affinities of the beta 2-catecholamine receptors for isoproterenol were observed. It is suggested that the increased degradative capacity of BF5 cells accounts for the difference in cAMP accumulation in these cells compared with the BRL-1 parent. The reduced responsiveness of BF5-1-1 cells, however, does not appear to be solely due to increased phosphodiesterase activity. It appears that the beta 2- phenotype may not always be dominant in hybrid crosses of this type as has been reported previously.

1-Methyl-3-isobutylxanthine↗

Chest physical therapy procedures in open heart surgery.

Chest physical therapy is now widely used after open heart surgery to prevent secondary pathology in the lungs and to improve the phhysical condition of the patient. A brief overview of cardiac surgery is presented. Factors occurring before, during, and after surgery that contribute to postoperative respiratory insufficiency are outlined, and a comprehensive three-phase treatment program is described. Also, treatment guidelines, precautions, and contraindications are discussed.

Cardiac Surgical Procedures↗

Post-translationally modified 14-3-3 isoforms and inhibition of protein kinase C.

This report compares the ability of individual members of the 14-3-3 protein family to inhibit particular protein kinase C (PKC) isoforms. We also show that two of these 14-3-3 isoforms (alpha and delta) specific to mammalian and avian brain are in vivo post-translationally modified forms of beta and zeta respectively. The presence of this modification enhances the activity of 14-3-3 as an inhibitor of protein kinase C nearly two fold. A method for analysing isoforms of 14-3-3 on acid-urea gels is also described. This permits the complete separation of all major isoforms and their unequivocal identification by a range of isoform specific antisera. The activity of recombinant 14-3-3 and isoforms renatured by a novel method after separation by reverse phase HPLC are compared. The effects of diacylglycerol and the phorbol ester, PMA (phorbol 1 2-myristate 13 acetate) on the inhibition suggest that one of the sites of interaction of 14-3-3 may be the cysteine-rich (C1) domain in PKC.

14-3-3 Proteins↗

Quality assurance in cytology. Rescreening of previously negative smears from high grade squamous intraepithelial lesions.

OBJECTIVE: To determine the problem areas in the cytologic diagnosis of high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia [CIN] 3). STUDY DESIGN: Previously negative smears from cases with histologically proven CIN 3 in 1988 and 1992 were reviewed for any discrepancies between the original and reviewed diagnoses. Such features as the presence of excessive inflammation, blood or bacteria, and atypical and dysplastic cellular changes were assessed. Original and reviewed reports for both years were compared, and the false negative rate was calculated. RESULTS: In the 1992 study, small numbers of abnormal cells, abnormal cells masked by inflammation and pale-staining HSIL were the common patterns when the diagnosis of HSIL was initially overlooked. In the 1988 study, the abnormal cells were overlooked mainly because of suboptimal smears. CONCLUSION: Determining cytologic patterns that pose problems in the diagnosis of HSIL is a valuable quality assurance procedure used in our laboratory. In performing these studies, we are able to pinpoint problem areas and educate our staff so as to minimize the number of false negative smears.

Cell Biology↗