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Biomedical subjects

K Davison

Publications and source records attributed to K Davison.

At least 37 records · Page 2Linked to original sources

Characterization of monoclonal antibodies to calpain 3 and protein expression in muscle from patients with limb-girdle muscular dystrophy type 2A.

Monoclonal antibodies were raised to two regions of calpain 3 (muscle-specific calcium-activated neutral protease), which is the product of the gene that is defective in limb-girdle muscular dystrophy type 2A. The antibodies produced characteristic patterns of bands on Western blots: normal calpain 3 protein was represented by bands at 94 kd, plus additional fragments at approximately 60 or 30 kd, according to the antibody used. Specificity was confirmed by the loss of all bands in patients with null gene mutations. The "normal" profile of bands was observed in muscle from 33 control subjects and 70 disease-control patients. Calpain 3 protein was found to be extremely stable in fresh human muscle, with full-size protein being detected 8 hours after the muscle had been removed. Blots of muscle from nine limb-girdle muscular dystrophy type 2A patients with defined mutations showed variation in protein expression, with seven showing a clear reduction in the abundance of protein detected. No simple relationship was found between the abundance and clinical severity. Two patients showed normal expression of the full-size 94 kd band accompanied by a clear reduction in the smaller fragments. This pattern was also observed in one patient with an undefined form of limb-girdle dystrophy. These results indicate that immunodiagnosis is feasible, but caution will need to be exercised with the interpretation of near-normal protein profiles.

Adult↗

Pharmacological modulation of human cardiac Na+ channels.

Pharmacological modulation of human sodium current was examined in Xenopus oocytes expressing human heart Na+ channels. Na+ currents activated near -50 mV with maximum current amplitudes observed at -20 mV. Steady-state inactivation was characterized by a V1/2 value of -57 +/- 0.5 mV and a slope factor (k) of 7.3 +/- 0.3 mV. Sodium currents were blocked by tetrodotoxin with an IC50 value of 1.8 microM. These properties are consistent with those of Na+ channels expressed in mammalian myocardial cells. We have investigated the effects of several pharmacological agents which, with the exception of lidocaine, have not been characterized against cRNA-derived Na+ channels expressed in Xenopus oocytes. Lidocaine, quinidine and flecainide blocked resting Na+ channels with IC50 values of 521 microM, 198 microM, and 41 microM, respectively. Use-dependent block was also observed for all three agents, but concentrations necessary to induce block were higher than expected for quinidine and flecainide. This may reflect differences arising due to expression in the Xenopus oocyte system or could be a true difference in the interaction between human cardiac Na+ channels and these drugs compared to other mammalian Na+ channels. Importantly, however, this result would not have been predicted based upon previous studies of mammalian cardiac Na+ channels. The effects of DPI 201-106, RWJ 24517, and BDF 9148 were also tested and all three agents slowed and/or removed Na+ current inactivation, reduced peak current amplitudes, and induced use-dependent block. These data suggest that the alpha-subunit is the site of interaction between cardiac Na+ channels and Class I antiarrhythmic drugs as well as inactivation modifiers such as DPI 201-106.

Animals↗

Effectiveness of two training methods to improve the quality of foodservice in small facilities for adult care.

OBJECTIVE: Community-based adult-care facilities (ACFs) with fewer than 25 beds provide homes for persons with disabilities who cannot live independently. The staff in these facilities are not required to have any formal foodservice training, yet they provide meals for the residents. The objective of this study was to evaluate the quality of foodservices before and after a foodservice training program. DESIGN: Forty-six ACFs from six health-unit areas throughout the province of British Columbia were enrolled in the study, which involved a pretest-posttest design over a 5-month period. The health units were randomly assigned to one of three programs. INTERVENTION: The ACFs received either a training workshop plus foodservice manual developed specifically for ACFs, the manual only, or no intervention. MAIN OUTCOME MEASURES: Facilities were audited on performance in food purchasing, menu planning, food safety, and food storage. These areas were rated according to established minimum government regulations and other foodservice standards. Differences between the two audit scores (postintervention score minus preintervention score) were analyzed for each program section. Group comparisons were done using analysis of covariance procedures, with the initial score being the covariable. RESULTS: No treatment effect was found on performance for food purchasing and food storage. Training via workshop plus manual resulted in a significant improvement in audit scores for menu planning and food safety compared with training via the manual alone. APPLICATION: Dietitians should consider providing foodservice training workshops for similar types of facilities. The benefits of providing a manual alone are negligible.

Adult↗

Dystrophin or a "related protein" in Duchenne muscular dystrophy?

Previously we have shown low levels of dystrophin immunoreactivity in muscle from patients with DMD. According to the "frame-shift hypothesis" DMD muscle should not synthesize any dystrophin through to the C-terminus and it has been suggested that the protein detected is not dystrophin, but a related autosomal homologue. We have labelled serial sections of DMD muscle with specific monoclonal antibodies to the amino, rod and C-terminal domains of dystrophin and find labelling on the same individual fibres, allowing us to conclude that the protein detected is Xp21-encoded dystrophin. This has an impact on the interpretation of myoblast transfer experiments. The abundance (on blots) of "C-terminal dystrophin" appears lower than "rod dystrophin" in both BMD and DMD.

Antibodies, Monoclonal↗

Handedness and epileptic schizophrenia.

Thirty-two epileptic patients with RDC diagnoses of schizophrenia were tested for handedness on the Annett Handedness Schedule, and handedness was assigned on the basis of Annett-Maudsley criteria. They were compared with three other groups of patients. Five (15.6%) of the epileptic schizophrenic patients were mixed or left handed. The prevalence of mixed and left handedness did not differ between the samples studied. However, there was a significant reduction of mixed and left handedness in male epileptics with schizophrenia. Mixed or left handedness in male epileptics appears to be protective against the development of psychiatric illness in general.

Adult↗

Dystrophin in skeletal muscle. I. Western blot analysis using a monoclonal antibody.

The value of analysing dystrophin on Western blots of skeletal muscle for the differential diagnosis of Xp21 muscular dystrophies is now fairly well established. Here we describe a sensitive system based on monoclonal antibodies to dystrophin. The specificity of the antibodies was established and experiments were undertaken to identify the source of dystrophin-related protein bands which were detected on blots of normal skeletal muscle. These investigations formed a necessary preliminary study to the application of the assay to samples of muscle obtained at biopsy from patients with Duchenne and Becker muscular dystrophy.

Antibodies, Monoclonal↗

Dystrophin in skeletal muscle. II. Immunoreactivity in patients with Xp21 muscular dystrophy.

In the preceding paper a sensitive Western blotting analysis system based on the use of a monoclonal antibody to dystrophin was described. Here we report the immunoreactivity on blots and on unfixed frozen sections of muscle from patients with Duchenne (DMD) and Becker (BMD) muscular dystrophy. Muscle from 3 BMD patients showed variation both in the band pattern observed on blots and in the immunocytochemical labelling of dystrophin on frozen sections. In contrast to previous reports, we were able to detect some minor dystrophin bands on blots from 6 of 9 DMD biopsy samples. Tissue sections from 8 of the 9 contained isolated fibres with dystrophin-positive labelling. We conclude that the majority of DMD patients have muscle fibres which can synthesize dystrophin in a limited manner.

Adolescent↗

Epileptic schizophrenia: clinical features and outcome.

The aim of this study was to investigate the clinical characteristics and outcome of epileptic schizophrenia. A total of 106 patients with combined diagnoses of epilepsy and psychiatric disorder were identified; 20 were excluded and 70 agreed to participate. They were interviewed using the Schizophrenia and Affective Disorders Schedule - Lifetime Version and psychiatric diagnoses were assigned based on Research Diagnostic Criteria. Thirty-two subjects with additional diagnosis of schizophrenia were identified and compared with 31 functional schizophrenic patients matched for age. Both groups shared third person auditory hallucinations most in common, and delusions of passivity least; delusions of passivity occurred significantly more in functional schizophrenia. The global outcome was worse in epileptic schizophrenia and there was also evidence of significantly worse performance on the Mini-Mental State Examination by the same group.

Adult↗

Mania following head injury. A report of two cases and a review of the literature.

Secondary mania has been described in association with a variety of physical conditions. While there have been a number of reports of mania occurring in individuals with intracranial cerebral lesions, there have been few reporting its occurrence in association with non-penetrating cerebral trauma. Two further cases of mania following non-penetrating head injury and the efficacy of ECT in its management are reported, and a brief review of the literature relating to the subject is given.

Aged↗

Psychiatric sequelae of subarachnoid haemorrhage.

Twenty cases with psychiatric disorder occurring after subarachnoid haemorrhage were studied. Seventy per cent had a research diagnostic criteria diagnosis of major depressive disorder, most of whom also had signs of persisting organic brain damage. Ten per cent of the cases committed suicide, and only 10% had made a full recovery from the psychiatric disorder. There was no significant association between the laterality of damage and the subsequent development of major depressive disorder, however, middle cerebral artery haemorrhage was over-represented in the sample.

Adult↗

Specificity of neuropeptide degradation by two calcium-activated neutral proteases from human skeletal muscle.

Two calcium-activated neutral proteases (CAPI & II) were purified from human skeletal muscle by anion exchange, gel filtration and affinity (antipain-Sepharose and Blue Ultrogel A4R) chromatography. The enzymes were homogenous as judged by polyacrylamide gel electrophoresis, and have similar properties with the exception of the Ca2+ concentration required for optimum activity (CAP I = 0.1 mM; CAP II = 1 mM). Both enzymes hydrolysed a wide variety of neuropeptides. In six cases, the products were separated and identified by hplc and amino acid analysis. Neurotensin was hydrolysed at Tyr3-Glu4; dynorphin1-13 at Arg8-Arg9; LH-RH at Gly6-Leu7; CCK-8 at Phe8-NH2, substance-P at Met10-NH2; somatostatin at Thr10-Phe11. Although differences in the rates of neuropeptide degradation were noted for the two CAP's the specificity was the same for these six peptides. It is suggested that conformational requirements may be more important than side chains adjacent to the cleavage site in directing the specificity of CAP.

Amino Acids↗