Biomedical subjects
Publications and source records attributed to J M Walker.
Rapid microtiter plate-based colorimetric assays have been developed that allow the screening of large numbers of samples for the presence of inhibitors of alpha-glucosidase, alpha-amylase, and beta-galactosidase. The assays are particularly useful for screening large numbers of microbial culture filtrates.
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The demonstration of analgesia following in vivo administration of dynorphin A (Dyn A) has been difficult. In contrast, a number of electrophysiological and behavioral effects reported with in vivo injection of Dyn A can be produced by des-tyrosine dynorphin A (Dyn A 2-17). This suggested the extremely rapid amino terminal degradation of dynorphin A. To test this hypothesis, we examined the degradation of dynorphin A following in vivo injection into the periaqueductal gray (PAG) as well as in vitro using rat brain membranes under receptor binding conditions. In vivo, we observed the rapid amino terminal cleavage of tyrosine to yield the relatively more stable destyrosine dynorphin A. This same cleavage after tyrosine was observed in vitro. Inhibition of this aminopeptidase activity in vitro was observed by the addition of dynorphin A 2-17 or dynorphin A 7-17 but not after the addition of dynorphin A 1-13, dynorphin A 1-8, dynorphin B or alpha-neo-endorphin suggesting a specific enzyme may be responsible. The detection of the behaviorally active des-tyrosine dynorphin A following in vivo injection of dynorphin A suggests that this peptide may play an important physiological role.
Intracerebroventricular administration of the dynorphin analog, [D-Ala2,(F5)Phe4]-dynorphin 1-13-NH2 (DAFPHEDYN) in rats produced diuresis and profound analgesia. Both effects were antagonized by central administration of naltrexone or naloxone. Intravenous administration of 10, 25, and 50 mg/kg of DAFPHEDYN failed to induce diuresis. The increased potency of DAFPHEDYN was apparent from the failure of an equal dose of the parent compound (dynorphin 1-13) to produce diuresis and the failure of [D-Ala2]-dynorphin 1-13-NH2 to produce analgesia. Radioligand binding studies indicated the DAFPHEDYN retains the same degree of kappa selectivity as the parent compound (dynorphin 1-13) though a drop in affinity occurred. DAFPHEDYN may be of significant interest because it retains the essential pharmacology of the parent compound and exhibits marked in vivo potency.
Cell bodies in the head of the caudate nucleus that synthesize prodynorphin peptides form a substantial projection to the substantia nigra pars reticulata (SNR). The discovery of this pathway suggested an involvement of prodynorphin products in motor control. The effects of unilateral nigral microinjections of prodynorphin products were tested in an in vivo circling model. Dynorphin (1-8), dynorphin (1-7), dynorphin (1-6), dynorphin (2-17) (des-Tyr-dynorphin), and Leu-enkephalin induced spontaneous contralateral circling at 20 nmol doses. The effect of dynorphin (1-8) was dose dependent and was not blocked by pretreatment with naloxone or WIN 44,441-3. These findings clearly demonstrate the dynorphinergic involvement in nigral motor control which may consist of an opioid and a non-opioid component.
A series of cyclic conformationally restrained octapeptide analogs of somatostatin were examined for their ability to inhibit the binding of tritiated mu, kappa, and delta opiate receptor ligands. Several of these substances were found to have high affinity for mu opiate receptors while having very low affinity for both kappa and delta receptors. Previous suggestions that somatostatin analogs exhibit opiate antagonist activity led to a study of the ability of the two most potent compounds to inhibit morphine analgesia in rats after intracerebroventricular injection. One of the compounds significantly antagonized morphine analgesia although the other displayed severe toxicity. These two compounds differed in that the very toxic compound had previously been found to possess significant somatostatin activity. It thus appears that the structural requirements for toxicity and somatostatin activity can be differentiated from those for opiate activity.
Blockade of opiate receptors by naloxone (2 mg/kg) was found to produce a significant increase in pain sensitivity as measured by the tail-flick test. This finding supports the view that endogenous opiate systems may play a role in the modulation of pain sensitivity. Naloxone, however, was found to have no effect on pain responsiveness as measured by tail-pinch. These findings, together with additional reports, suggest that endogenous opiate systems may exert differential actions on different sensory modalities.
Iontophoretic application of the sigma ligands, 1,3-di-o-tolylguanidine (DTG), dextrallorphan, and (+)-pentazocine reliably inhibited the firing rate of rubral neurons. Dextrallorphan inhibited 87% of the neurons tested, DTG inhibited 76%, and (+)-pentazocine inhibited 50%. These inhibitions were current dependent and occurred without significant changes in spike amplitude or duration, suggesting that local anesthetic effects were not involved. In contrast to the other sigma ligands, iontophoretic application of (+)-3-PPP in the rat red nucleus resulted in very few inhibitions and tended to elicit weak excitations instead. Only 14% of rubral neurons were inhibited by (+)-3PPP, while 36% were excited. Although unusual, (+)-3-PPP has atypical effects when compared to other sigma ligands in numerous functional assays for sigma receptor activity. (+)-3-PPP, therefore, appears to have complex effects and may act through nonsigma mechanisms or through a different type of sigma binding site than the other compounds. The inhibition of firing rate produced by the more typical sigma ligands may contribute to the postural changes produced by microinjection of sigma ligands into the rat red nucleus.
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Five major approaches have been employed to determine the role of endocannabinoids in pain modulation: (1) studies of various markers of endocannabinoid action aimed at determining whether the necessary cannabinoid biochemical machinery is present in those brain areas that control pain sensitivity; (2) administration of exogenous cannabinoids to determine whether endocannabinoid action at appropriate sites would lead to a loss of pain sensitivity; (3) administration of compounds that would affect endocannabinoid action such as antagonists and transport inhibitors to determine whether drug-induced preterbation of cannabinoid action would alter pain sensitivity; (4) studies of genetically altered animals aimed at determining whether pain responses or responses to cannabinergic drugs are altered; and (5) studies that measure the release of endocannabinoids. Converging evidence from each of these research areas indicates that endocannabinods function to control pain in parallel with endogenous opioids but via different mechanisms.
The purpose of this study was to identify factors that influence enrollment in Dalhousie University's BSc (PT) degree-completion program. A geographically stratified, random sample of 100 nondegree physiotherapists practising in Atlantic Canada was surveyed by mail. The questionnaire solicited information on demographic data, program awareness and attitudes towards degree-completion programs. The response rate was 63 percent. More than 65 percent of respondents were trained in Canada, were older than 30 years, and had at least one child. Ninety percent of respondents were aware of the Dalhousie program; seven were currently enrolled. Ninety-three percent of respondents were confident they could continue to practise without a degree and 70 percent were confident they could meet academic standards required to complete a degree. Respondents were least certain on whether employers valued experience over a degree. Family responsibilities, age over 50, and job security were deterrents to enrollment. Nondegree physiotherapists in Atlantic Canada may not choose to upgrade to a degree because of the regional manpower shortage and job security. A strong pool of degree-completion students was not identified.
This study was designed to gather information and opinion on the impact and role of auxiliary personnel in physiotherapy, in Nova Scotia (NS). The physiotherapist/auxiliary ratio and present and future levels of education, supervision, and activities of auxiliary personnel were investigated. All NS physiotherapists registered with the Nova Scotia College of Physiotherapists (NSCP) were surveyed by mailed questionnaire; one follow-up was sent. Two questionnaires were developed. Potential levels of the terms assistant and technician were defined to facilitate interpretation of the opinion statements. Questionnaire A was mailed to all registered physiotherapists (n = 279, response rate 83%). Questionnaire B was mailed with Questionnaire A to directors and clinic owners (n = 73, 79% response rate). Results showed a physiotherapist/auxiliary personnel ratio (excluding clerical) of 3.75:1. The majority of personnel were trained in-house. There was a trend toward less frequent supervision with more extensively trained auxiliary personnel. More respondents considered that formally trained assistants would best serve the profession of physiotherapy in the future. To conclude, this study adds to the body of knowledge of the Canadian Physiotherapy Association and the NSCP. It should assist the NS Department of Health and Fitness in analyzing needs for training of auxiliary personnel in Physiotherapy, and provide data for future studies.
Electronic parameters for a series of amino-, chloro-, and nitro-substituted anilines relative to their potential for activation to hydroxylamines, aryl-nitrenium ions, and ring epoxides, and to their potential deactivation to phenols were calculated using semi-empirical molecular orbital methods. The relative mutagenic activities of aminoanilines could be explained by parameters reflecting potential for N-hydroxylation and stability of the arylnitrenium ions. Both chloro and nitro groups deactivate the amine group to N-hydroxylation and the ring to epoxidation, and no active products from cytochrome P-450 would be predicted. This result is consistent with lack of mutagenic activity observed for chloro derivatives, but does not account for activity of the nitro derivatives, which is presumed to be due to transformation of the nitro group itself to an active mutagenic species by other enzyme systems.
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Seventy-four acetabula from a total of 140 normal human fetuses, obtained from abortions and deaths in the prenatal period, were used. The fetuses ranged from 9.1 to 40 cm in crown-rump length and are believed to be between 12 weeks and term. Acetabula were decalcified embedded in paraffin or celloidin, sectioned, and stained using conventional histologic techniques. Sections from the superior one-quarter of the acetabulum were examined for the initial appearance and later spread of osseous tissue. Throughout the fetal period bone was present only in the floor of the acetabulum and did not extend into the socket walls. Ossification was detected initially more posteriorly in the socket floor, and at all ages, ossification was more prominent on the ischial side of the socket. Despite the lack of osseous tissue a well-formed hyaline cartilage socket was present. The fetal labrum was composed of fibrous tissue with the density of fibers increasing with age. Typical-appearing chondrocytes were detected at only the inner articular margin of the labrum. Contributing from one-fifth to one-half of the socket depth, the labrum may play a greater role in containing the femoral head at birth than it does in the mature joint. In seven acetabula, from joints that were neither subluxated nor dislocated, an area of areolar tissue with capillaries was detected at the hyaline cartilage-labrum junction. Such defects may weaken the labrum and contribute to neonatal hip instability.
Hip joints (280) from 140 human fetuses, obtained from abortions and deaths in the perinatal period, were studied. The fetuses ranged from 8.7 to 40 cm in crown-rump length and are believed to be between 12 and 42 weeks in age. The joints were dissected, morphology inspected, and measurements taken of the depth and diameter of the acetabulum, the diameter of the femoral head, length and width of the ligament of the head, the neck-shaft, and torsion angles of the proximal femur. Regression models were fitted to determine which would best predict the growth pattern. Multivariate analysis of variance showed no significant differences between males and females or between the right and left sides. Acetabular depth was shown to be the slowest-growing hip variable, increasing less than fourfold in the period studied. Acetabular indices less than 50 percent indicate a shallow socket at term. Femoral head and acetabular diameter demonstrated a strong relationship (r = 0.860) and in many joints the femoral head diameter exceeded that of the acetabulum. Considerable variability was demonstrated in both femoral angles. The femoral angles showed only low correlation with the other hip variables. These observations indicate that soft tissue structures about the joint must play an important role in neonatal joint stability. The explanation of greater female and left side involvement in congenital hip disease must lie in factors other than growth changes of hip dimensions. Neither angle appears to be a useful indicator of normal joint development.
The question of decreasing sphericity of the human femoral head during fetal growth was investigated with a Talyrond roundness-measuring machine. In 58 pairs of randomly selected femore, from 12 weeks to term, there was a trend for the femoral head to become less round with age and more oval or ellipsoidal in shape. At term a position of best "fit" may exist. No significant laterality or sex differences were found. Restriction of joint motion towards the end of pregnancy may decrease congruency, decrease joint stability, and become a factor in neonatal hip instability.
Measurement of the length and width of the ligament of the head of femur (ligamentum teres) in 140 normal human fetuses between 12 weeks and term provides limits for growth changes in this structure. These observations provide no morphological evidence of a significant difference between males and females, or between the right and left sides, to explain the female and left hip preponderance reported in congenital hip disease. The ligament is shown to be variable in length, width, and shape, and it is not a distinctly linear structure through linearity may increase with age. Tests of femoral head mobility support the opinion that this ligament must play a role in fetal and neonatal hip joint stability. Weak correlation only was demonstrated between the ligament variables and acetabular depth, which suggests that ligament shape and socket shape are not closely related. Comparison of measurements from normal and 12 dysplastic or subluxated joints provides no evidence to support previous observations that this structure is unusually long in abnormal hip joints which are not frankly dislocated.