Biomedical subjects
M Burke
Publications and source records attributed to M Burke.
Trypsinolysis promotes disulfide formation between 21- and 50-kilodalton segments of myosin subfragment 1 during reaction with 5,5'-dithiobis(2-nitrobenzoic acid).
The reaction of 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) with S1 and tryptic S1 has been examined to identify the sites of mixed and intramolecular disulfides formed in the initial and final stages of the reaction in these two forms of S1. With undigested S1, the two mixed disulfide bonds initially formed were found to be in the 21-kDa segment. The intramolecular disulfide bond, formed in the subsequent slow phase of the reaction, was also found to be mainly confined to the 21-kDa segment although a small fraction arose from disulfide formation between the 21-kDa and 50-kDa segments. Only 35% of the light chain was modified in undigested S1 after 24 h. For tryptic S1, the initial reaction also led to the formation of mixed disulfides in the 21-kDa segment. However, in the second slower phase, the formation of the intramolecular disulfide occurred primarily between thiols in the 21-kDa and 50-kDa fragments, and in this case, the light chain was labeled to about 60% after 24 h. The enhanced formation of disulfide links between 21-kDa and 50-kDa domains in tryptic S1 points to an increase in flexibility between the thiol-containing regions of these segments.
Studies of ligand-induced conformational perturbations in myosin subfragment 1. An examination of the environment about the SH2 and SH1 thiols using a photoprobe.
The effect of ligand binding on the environment near the SH2 and SH1 thiols in myosin subfragment 1 has been investigated by photocross-linking after specific labeling of these thiols individually with 4-(N-maleimido)benzophenone (MBP). On photolysis, cross-linking occurred from SH2-MBP to the middle 50-kDa segment, and subsequent immunopeptide mapping revealed that the cross-link was made to a peptide stretch 31-32 kDa from the N terminus in the absence of MgADP, whereas in its presence the cross-link occurred at about 60-61 kDa from the N terminus. Photolysis of SH1-MBP in the absence of MgADP resulted in a major cross-link to the 27-kDa N-terminal segment and minor cross-links to the 50-kDa middle segment. In the presence of MgADP, no new cross-link occurred but the amount of cross-linking to the 50-kDa segment increased at the expense of the other. Immunopeptide mapping indicated that the regions in the 27- and 50-kDa peptides that were cross-linked to SH1-MBP are at about 14-16 and 55-56 kDa from the N terminus respectively. These results indicate that when nucleotide binds to S1, SH2 is displaced relative to the 50-kDa segment, whereas the local environment around SH1 does not change significantly because photolysis in the presence of MgADP resulted in a change at the site of cross-linking for SH2-MBP but caused only a redistribution of the relative amounts of the cross-links formed from SH1-MBP.
Tuberculous and granulomatous mastitis.
Granulomatous breast diseases are rare and may be indistinguishable clinically from carcinoma. Four cases illustrating the various modes of presentation and diagnostic difficulties are presented. Guidelines for management are suggested.
Mammography and the primary care management of breast lumps.
Breast cancer is the commonest cause of death from malignancy in women in the Western world. Although advances have been made in treatment, 11,000 women a year continue to die from the disease in Britain. Prognosis is undoubtedly better with early diagnosis, and this may best be achieved by prompt referral to a breast unit if a persistent mass is suspected clinically.
Body wall ecchymosis.
Explore the source record for details and available documents.
Structural changes in myosin subfragment 1 by mild denaturation and proteolysis probed by antibodies.
The perturbations in the structure of myosin subfragment 1 (S1) by mild denaturation or proteolysis were investigated by measuring the inhibition of the binding of antibodies to immobilized S1 by treated S1 in a solution-phase competitive immunochemical assay. The structural changes in S1 were probed by using anti-50-kDa segment, anti-N-terminus, anti-27-kDa segment, and anti-A1 light chain monoclonal antibodies (MAbs). Methanol and heat denaturation increased MAb binding to the 50-kDa segment. MAb binding to regions in the 27-kDa segment was also promoted, slightly by methanol and more drastically by heat. Proteolysis also induced structural alterations in 50- and 27-kDa segments as shown by increased MAb binding to these regions in cleaved S1. These results indicate that mild denaturation and proteolysis induce structural perturbations which alter the epitope accessibility in 50- and 27-kDa segments of S1 and that antibody binding studies afford a sensitive probe to such perturbations.
Characteristics of established group practices in Ontario.
Established group practices in Ontario were surveyed to determine their structure, characteristics and attitudes toward government assistance in the development of group practice. The degree of organization of the groups surveyed was related to size and less than that reported in surveys of United States group practices. Group size and years of operation were strongly associated. Night, weekend and vacation coverage, the use of a unit patient record and the employment of non-physician administrators were reported frequently, and were more common in older and larger groups. As well, fringe benefits, except for professional organization dues, were not commonly provided.
Marital quality, depression, and inconsistent parenting: relationship with observed mother-child conflict.
In a study of 47 intact families with two same-sex children, associations among parental depression, marital satisfaction, family conflict, and inconsistent child rearing practices were examined, both between parents and within individual parents. Results are discussed in terms of gender-related differences in family process. The need for further research on father-child interactions is highlighted.
Use of gene replacement to construct Escherichia coli strains carrying mutations in two genes required for stability of multicopy plasmids.
Escherichia coli mutants completely defective in ColE1 cer-mediated site-specific recombination have been mapped to two genes, xerA and xerB. In this study, xerA xerB double mutants were constructed by gene replacement with a lambda dv plasmid and were shown to be both viable and defective in ColE1 site-specific recombination.
Malignant primary pulmonary paraganglioma.
The histological, immunocytochemical, and electron microscopic findings in a case of malignant primary pulmonary paraganglioma are reported. The existence of this rare tumour is evidence for the presence of pulmonary chemoreceptors.
Muscle plasticity: comparison of a 30-Hz burst with 10-Hz continuous stimulation.
The changes in the contractile properties induced by a 30-Hz phasic stimulation paradigm were measured and compared with the changes induced by a 10-Hz continuous stimulation paradigm. The study was performed on the tibialis anterior muscles of cats with one paradigm applied to one hindlimb muscle and the other to the contralateral limb. Both hindlimb muscles received the same number of stimuli in a day, making the average stimulation frequency 10 Hz. Two periods of daily stimulation were studied, 8 and 24 h/day. Muscles stimulated at 30 Hz produced greater overall tetanic tension and, during a prolonged stimulation test, exerted a greater mean tension than muscles stimulated at 10 Hz (50 and 32% increase for animals stimulated for 8 and 24 h/day, respectively). Muscle mass was least reduced and fewer pathological abnormalities were observed in the muscles stimulated at 30 Hz. There were no apparent differences in the histochemistry or biochemistry between muscles stimulated at 10 and 30 Hz, which could account for these differences in muscle properties. These results indicate the 30-Hz paradigm may be better suited than 10 Hz continuous stimulation for applications requiring sustained muscle tension such as correction of scoliosis or muscle conditioning for motor prostheses.
Effects of captopril on locomotor activity, passive avoidance behaviour and spatial memory tasks in the trimethyltin-treated rat.
The potential neuroprotective/cognitive enhancing actions of captopril were investigated in the trimethyltin (TMT)-induced neurotoxicity rat model. Acute exposure to TMT produces alterations in locomotor activity, passive avoidance behaviour and spatial memory tasks. Captopril treatment given in combination with the single acute injection of TMT reversed the deficits in spatial memory tasks in 8 out of 25 trials. While post-treatment of TMT-treated rats with captopril brought about a significant improvement in 3 out of 25 trials, pre-treatment of rats for 3 weeks with captopril did not reverse the behavioural deficits produced by TMT in the Morris maze test. Captopril treatment did not block the characteristic hyperactivity or the deficits in passive avoidance behaviour of TMT-treated animals.
Intravenous lignocaine for migraine headache.
One per cent lignocaine injected intravenously over 90 seconds at a dose not exceeding 1 mg per kg is a good alternative to existing treatment regimens for classic and common migraine.
Bilateral brachial artery emboli presenting as aortic dissection.
Loss of peripheral pulses in a patient with chest pain suggests the diagnosis of aortic dissection. An 80-year-old woman presented with an episode of chest pain and acute bilateral loss of upper extremity pulses that was initially treated as aortic dissection. Findings of physical examination and echocardiography were consistent with mitral stenosis. Angiography revealed bilateral brachial artery emboli, which were treated by embolectomy. To our knowledge, this case represents the first report of simultaneous brachial artery emboli in association with mitral stenosis.
Temperature and ionic strength dependence of the subunit interactions in vertebrate skeletal myosin. A comparison of the interaction between the alkali light and heavy chains of mammalian and avian myosin.
The stability of the interaction of A1 in myosin and subfragment 1 isolated from fast-twitch mammalian and avian muscles with respect to temperature and ionic strength has been examined. This was done by determining the extent of exchange of the endogenous free A1 light chain into these proteins from the two species. Whereas the extent of exchange at 37 degrees C into mammalian S1, occurring after 60 min, is about 80% of the theoretically expected amount at physiological ionic conditions, the level of exchange observed with the avian S1 is significantly lower. However, close to the theoretical limit is observed for the avian S1 when exchange is done at 43 degrees C which is close to average avian body temperature. A similar dependence with temperature is observed in the case of exchanges into avian myosin. In the case of mammalian myosin, 50% of the theoretical exchange is observed at 37 degrees C under physiological ionic strength, whereas the level of exchange observed under these conditions with the avian protein is much lower in agreement with recent observations (Waller, G. S., and Lowey, S. (1985) J. Biol. Chem. 260, 14368-14373; Pastra-Landis, S. C., and Lowey, S. (1986) J. Biol. Chem. 261, 14811-14816). If, however, the exchanges are done at 43 degrees C in physiological ionic strength, significant extents of exchange can be observed in avian myosin. These results suggest that at physiological ionic and temperature conditions relevant for the source of myosin and S1 being investigated, the alkali light chains are in dynamic equilibrium between free and heavy chain associated states. Therefore, the failure to observe alkali light chain exchange in avian myosin at 37 degrees C appears to be related to the higher temperature stability of its interaction with the heavy chain.