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Biomedical subjects

A M Smith

Publications and source records attributed to A M Smith.

At least 217 records · Page 12Linked to original sources

Input-output properties of hand-related cells in the ventral cingulate cortex in the monkey.

1. Neurons with proprioceptive or cutaneous receptive fields associated with the hand were identified in the ventral bank of the cingulate sulcus in the monkey. Cells with proprioceptive fields outnumbered cells receiving cutaneous afferents by more than three to one. No cells were encountered that received convergent proprioceptive and cutaneous input. The high concentration of these neurons in the lateral depth of the cingulate sulcus establishes that a distinct hand representation exists within the rostral part of area 23c. 2. Hand-related neurons in area 23c exhibited strong activity modulations during grasping, lifting, and holding an object with the contralateral thumb and index finger. Force pulse perturbations applied to the object elicited excitatory responses at latencies of approximately 45 ms. The modulation of the cellular activity and the input-output properties of these cingulate neurons suggest that, like neurons of primary motor and sensory cortex, these cingulate neurons are also involved in the sensorimotor control of finger movements.

Afferent Pathways↗

Injuries in youth ice hockey: a pilot surveillance strategy.

OBJECTIVE: To determine the incidence and type of injuries in youth hockey players during practice and games as well as to test the applicability of the current methods to a national surveillance study of youth hockey injuries. DESIGN: During the 1993 to 1994 season, we undertook a prospective observational analysis of youth hockey players on four competitive teams at three levels of participation: Squirt, Peewee, and Bantam. MATERIAL AND METHODS: In a study group of 66 youth hockey players, types and anatomic sites of injury, mechanisms of injury, player position affected, and occurrence of injuries during practice or games were determined and analyzed statistically. An injury was strictly defined, standardized reporting strategies were used, and a single physician examined all injured athletes and made the diagnoses. RESULTS: A total of 14 injuries occurred during the season. The on-ice injury rate (per 1,000 player-hours) was 1.0 at the Squirt level (ages 9 and 10 years), 1.8 at the Peewee level (ages 11 and 12 years), and 4.3 at the Bantam level (ages 13 and 14 years). No game injuries and only one mild practice injury occurred in Squirt players (N = 16), and only two mild injuries occurred during practice sessions for Peewees (N = 17). No differences were noted between practice injury rates at the various levels; all recorded game injuries occurred only in Bantam players (N = 33). The most common types of injuries were contusions, fractures, strains, and sprains. The arm and shoulder were most frequently injured. CONCLUSION: Further research is necessary to determine whether injuries in youth ice hockey can be reduced by changes in playing rules, enforcement of existing rules, improvements in protective equipment, alteration in coaching techniques, and institution of educational programs.

Adolescent↗

Medical coverage for multievent sports competition: a comprehensive analysis of injuries in the 1994 Star of the North Summer Games.

OBJECTIVE: To determine the incidence and type of requests for medical assistance and the treatment required in 21 sports at the 1994 Star of the North Summer Games and to develop a plan, based on these findings, for efficient allocation of medical supplies and staff. DESIGN: We reviewed our experience with a large multisport amateur athletic event and analyzed the pattern of injuries for participants in the various sports. MATERIAL AND METHODS: Injury evaluation forms and medical supply kits were given to the health-care volunteers, who received preliminary instructions on classifications and definitions of injuries and on appropriate completion of the forms. When a medical contact occurred, an evaluation form was completed. The data from these forms were subsequently compiled and analyzed. RESULTS: Of 6,243 athletes who participated in the 1994 Star of the North Summer Games, 55 (0.88%) received medical attention (2 officials also required medical assistance). The sports with the greatest number of medical contacts were soccer and track and field--31 and 16 contacts for medical assistance, respectively. The lower extremities were the anatomic site most frequently involved in injury (62% of the medical contacts). The most common types of injury were contusions, strains, and sprains. CONCLUSION: Because few injuries were sustained and most were of minor severity, basic medical supplies (such as ice bags and compression wraps) were sufficient. For locations with a scarcity of medical personnel, a triage system can be established in which athletic trainers or registered nurses manage the initial assessments and refer cases, as needed, to physicians for specialized care. An effective communication system can also considerably reduce volunteer hours.

Adolescent↗

Hysterectomy experience among mid-aged Australian women.

OBJECTIVES: To determine the rate of oophorectomy in, use of hormone replacement therapy by, and health, social and lifestyle factors of, mid-aged Australian women who have undergone hysterectomy. DESIGN AND PARTICIPANTS: A community-based cross-sectional survey by telephone interview of a random sample of 2001 Australian-born Melbourne women aged between 45 and 55 years. MAIN OUTCOME MEASURES: The health status, sociodemographic and lifestyle correlates of women who had undergone hysterectomy compared with women in the natural menopause transition. RESULTS: Twenty-two per cent of the women had undergone hysterectomy. Of these, 21% had had one ovary removed, and 20% both. Mean age at hysterectomy was 40.4 years. There was no trend in the bilateral oophorectomy rate over the last two decades. Current hormone replacement therapy use increased significantly with surgery, from 17% of non-hysterectomised women to 31% of hysterectomised women, and 49% for women who had undergone hysterectomy and bilateral oophorectomy. Hysterectomised women were significantly more likely to be of lower educational level, and to report a history of troublesome premenstrual complaints, more dilatation and curettage procedures and nongynaecological operations, and use of prescription medications. CONCLUSIONS: Social and pre-existing health problems influence hysterectomy rates. Many women undergo oophorectomy at hysterectomy despite limited evidence of benefit.

Australia↗

Euthanasia.

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Advisory Committees↗

Purification and characterisation of a second cathepsin L proteinase secreted by the parasitic trematode Fasciola hepatica.

A 29.5-kDa cysteine proteinase was purified from medium in which mature Fasciola hepatica parasites were maintained. The N-terminal sequence (14 residues) of the purified protein is similar to known cathepsin L proteinases, including a 27-kDa cathepsin L proteinase, also secreted by this parasite, which had been isolated previously in our laboratory [Smith, A. M., Dowd, A. J., Mc Gonigle, S., Keegan, P.S., Brennan, G., Trudgett, A. & Dalton, J.P. (1993) Mol. Biochem. Parasitol. 62, 1-8]. The N-terminal sequences of the 29.5-kDa and 27-kDa cathepsin L proteinases differ only in residue number seven (arginine and proline, respectively). Immunoblot studies, using antiserum that reacts with both cathepsin L proteinases, rule out the possibility of both enzymes arising from a higher molecular sized parent molecule. The reaction kinetics of the two F. hepatica cathepsin L proteinases on a variety of peptide substrates revealed that the two enzymes differ in their substrate specificity. Five peptide substrates that are cleaved with high affinity by the 29.5-kDa cathepsin L isolated in this study are not cleaved by the previously purified 27-kDa cathepsin L. The protein-modifying reagent, tetranitromethane, affected the 29.5-kDa cathepsin L proteinase only, causing inactivation of the enzyme and changing its migration in polyacrylamide gel electrophoresis. Our studies suggest that the two F. hepatica cysteine proteinases represent two distinct subclasses within the cathepsin L class.

Amino Acid Sequence↗

Search for a schizophrenia susceptibility locus on human chromosome 22.

We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected pedigree member analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three different weighting functions.

Chromosome Mapping↗

The development of cyclic sulfolanes as novel and high-affinity P2 ligands for HIV-1 protease inhibitors.

Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the S2-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as P2 ligands for HIV-1 protease inhibitors. Subsequently, we have found that the urethane of 3(S)-hydroxysulfolane further increased the in vitro potency of these inhibitors. Furthermore, introduction of a small 2-alkyl group cis to the 3-hydroxyl group of either heterocyclic system further enhanced enzyme affinity. The cis-2-isopropyl group thus far offered optimum enhancement of the inhibitory properties. This led to the discovery of inhibitor 43 (IC50 3.5 nM, CIC95 50 +/- 14 nM) of comparable in vitro antiviral potency to the current clinical candidate 1 (Ro 31-8959) but of reduced molecular weight due to the exclusion of the P3 quinoline ligand. Also, it has been demonstrated that the octahydropyrindene derivative 34 is an effective replacement of the P1' decahydroisoquinoline derivative.

Antiviral Agents↗

Parallel costimulatory pathways promote myelin basic protein-stimulated proliferation of encephalitogenic rat T cells.

Activation pathways responsible for myelin basic protein (MBP)-stimulated proliferation of encephalitogenic T cells were studied by derivation of new monoclonal antibodies against rat T cell surface proteins. These monoclonal antibodies were derived by immunization of Balb/c mice with THYB-2 T cell hybrids or with the GP2.E5 line of encephalitogenic T-helper cells. The LRTC1 mAb inhibited MBP-stimulated IL-2 production by THYB-2 hybrids but not by THYB-1 hybrids and did not inhibit the alternative response of MBP-induced growth inhibition by either hybrid subset. Although LRTC1 labeled virtually all rat leukocytes, it selectively inhibited proliferative responses to T cell mitogens but not to B cell mitogens. LRTC1 inhibited MBP-stimulated IL-2 production by GP2.E5 T cells but did not effectively block MBP-stimulated proliferation. Rather, LRTC1 acted in synergy with a second mAb (LRTC2) to effectively inhibit MBP-stimulated proliferation by GP2.E5 T cells. The observation that LRTC1 did not exhibit synergy with a third biologically active mAb (LRTC3) supported the hypothesis that LRTC1 and LRTC2 represented a specific combination of synergistic mAb. In contrast to the inhibitory activity on GP2.E5 T cells, LRTC1 and LRTC2 synergistically stimulated antigen-independent IL-2 production by the THYB-1 hybrid LSS-A1. These results support the hypothesis that GP2.E5 T cells respond to parallel costimulatory pathways that are respectively inhibited by LRTC1 and LRTC2 mAb. Furthermore, these synergistic mAb exhibited inhibitory or stimulatory activities that may be diagnostic of distinct T-helper cell subsets. These novel mAb may thereby facilitate studies of costimulatory pathways and T-helper cell subsets in the pathogenesis of autoimmune disease.

Animals↗

Adult Schistosoma mansoni express cathepsin L proteinase activity.

This report presents the deduced amino acid sequence of a novel cathepsin L proteinase from Schistosoma mansoni, and describes cathepsin L-like activity in extracts of adult schistosomes. Using consensus primers specific for cysteine proteinases, gene fragments were amplified from adult S. mansoni cDNA by PCR and cloned. One of these fragments showed marked identity to Sm31, the cathepsin B cysteine proteinase of adult S. mansoni, whereas another differed from Sm31 and was employed as a probe to isolate two cDNAs from an adult S. mansoni gene library. Together these cDNAs encoded a novel preprocathepsin L of 319 amino acids; this zymogen is predicted to be processed in vivo into a mature, active cathepsin L proteinase of 215 amino acids. Closest homologies were with cathepsins L from rat, mouse, and chicken (46-47% identity). Southern hybridization analysis suggested that only one or a few copies of the gene was present per genome, demonstrated that its locus was distinct from that of Sm31, and that a homologous sequence was present in Schistosoma japonicum. Because these results indicated that schistosomes expressed a cathepsin L proteinase, extracts of adult S. mansoni were examined for acidic, cysteine proteinase activity. Based on rates of cleavage of peptidyl substrates employed to discriminate between classes of cysteine proteinases, namely cathepsin L (Z-phe-arg-AMC), cathepsin B (Z-arg-arg-AMC) and cathepsin H (Bz-arg-AMC), the extracts were found to contain vigorous cathepsin L-like activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Self-rated health: biological continuum or social discontinuity?

Correlates of self-rated health among a randomly selected sample of 1863 Australian-born women 45-55 years of age were examined in two logistic regression analyses: one comparing a self-rated health of worse than one's peers with a self-rated health the same as one's peers; and, one comparing a self-rated health of better than one's peers with a self-rated health the same as one's peers. The final model for worse health was largely a reflection of the physical experience of ill health while that for better health was a more complex construct including not only the absence of illness but also markers of sociodemographic advantage and self-image. The two models had only three variables in common. Notably, the relationship between the outcome measures and one common variable, body mass index, differed markedly. It is suggested that previous analyses of self-rated health have had their power to adequately describe correlates and determinants of health status constrained. By assuming that the various self-rated health states are part of a continuum and employing statistical methods consistent with that assumption, previous studies have been unable to demonstrate the discontinuity among such states. In particular, it is suggested that self-rated health is at least in part a reflection of social role and as there is no basis for assuming that such roles form a continuum as the use of correlation-based analyses imply, then such analyses are inappropriate.

Body Mass Index↗

A single injection of either flupenthixol decanoate or haloperidol decanoate produces long-term changes in cocaine self-administration in rats.

The effect of decanoate forms of flupenthixol and haloperidol on cocaine self-administration was evaluated. Forty-two male Wistar rats were implanted with chronically indwelling jugular cannulae and trained to self-administer cocaine (0.6 mg/inj) either on a fixed ratio (FR) 1 schedule or a progressive ratio (PR) schedule. After a stable response pattern was established, animals received a single i.m. injection of either flupenthixol (2.0 mg), haloperidol (2.5 mg) or vehicle (0.1 ml oil). Both neuroleptics produced a long lasting increase in cocaine intake on a FR 1 schedule which reached a peak on post-injection day three and diminished slowly over the next seven days. All animals maintained on a PR schedule showed a long lasting decline in breaking points. These data suggest that the decanoate forms of flupenthixol and haloperidol may attenuate the reinforcing effects of cocaine and indicate that the therapeutic value of depot neuroleptics as anti-cocaine treatments would depend on the economics of cocaine availability.

Animals↗

Physical activity and the menopause experience: a cross-sectional study.

A randomly selected community cohort of 2000 Australian born women aged 45 to 55 were interviewed on the telephone and information obtained on their health and well-being. These women were divided into pre-, peri-, natural and surgical menopausal groups on their menstrual history. A physical activity questionnaire was sent to 1181 women in the first three of these groups. These questionnaires were completed and returned by 61.6% of the women. The response rate in all groups was significantly associated with the years of education, employment status, body mass index (BMI) and self-rated health of the participants. The aim of the study was to test the hypothesis that physical activity is a major contributor to health and well-being by establishing the relationships between physical activity and certain health outcomes, such as menopausal symptoms, psychological well-being, self-rated health and BMI in this cohort of mid-life women. The inter-relationship between physical activity and other variables, including menopausal status, interpersonal stress, health related and preventive health behaviours was examined. Levels of physical activity were significantly associated with better self-rated health, lower BMI measurements, moderate alcohol intake and self-breast examination. There was no significant association between levels of physical activity, psychological well-being and women's experience of symptoms during the natural menopause transition.

Attitude to Health↗

Psychological well-being, mid-life and the menopause.

Few studies of women's health in the menopausal years have formally assessed well being. The present study aimed to determine whether well-being during mid-life related to menopausal status, social circumstance, health status, interpersonal stress, attitudes and lifestyle behaviours. A random sample of 2000 Melbourne women aged 45-55 years were sought by random digital telephone dialling. A response rate of 70.6% was achieved. Interviews conducted on the telephone included a well-being scale--the Affectometer 2. The final data set, comprising 1503 individuals, was subjected to analyses of variance. Menopausal status did not significantly affect well-being. Well-being was found to be significantly related to current health status variables of general psychosomatic symptoms, general respiratory symptoms, history of premenstrual complaints, overall health assessment and interpersonal stress. Attitudes to ageing and to menopause were also significantly related to well-being scores. Lifestyle behaviors of smoking, exercise and marital status were also significantly related to well-being. Thus well-being of urban Australian-born, mid-aged women was related to current health status, psychosocial and lifestyle variables rather than to endocrine changes of the menopause.

Affect↗