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Biomedical subjects

M Parker

Publications and source records attributed to M Parker.

At least 109 records · Page 6Linked to original sources
PubMed1997

Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo.

A replicon vaccine vector system was developed from an attenuated strain of Venezuelan equine encephalitis virus (VEE). The replicon RNA consists of the cis-acting 5' and 3' ends of the VEE genome, the complete nonstructural protein gene region, and the subgenomic 26S promoter. The genes encoding the VEE structural proteins were replaced with the influenza virus hemagglutinin (HA) or the Lassa virus nucleocapsid (N) gene, and upon transfection into eukaryotic cells by electroporation, these replicon RNAs directed the efficient, high-level synthesis of the HA or N proteins. For packaging of replicon RNAs into VEE replicon particles (VRP), the VEE capsid and glycoproteins were supplied in trans by expression from helper RNA(s) coelectroporated with the replicon. A number of different helper constructs, expressing the VEE structural proteins from a single or two separate helper RNAs, were derived from attenuated VEE strains Regeneration of infectious virus was not detected when replicons were packaged using a bipartite helper system encoding the VEE capsid protein and glycoproteins on two separate RNAs. Subcutaneous immunization of BALB/c mice with VRP expressing the influenza HA or Lassa virus N gene (HA-VRP or N-VRP, respectively) induced antibody responses to the expressed protein. After two inoculations of HA-VRP, complete protection against intranasal challenge with influenza was observed. Furthermore, sequential immunization of mice with two inoculations of N-VRP prior to two inoculations of HA-VRP induced an immune response to both HA and N equivalent to immunization with either VRP construct alone. Protection against influenza challenge was unaffected by previous N-VRP immunization. Therefore, the VEE replicon system was characterized by high-level expression of heterologous genes in cultured cells, little or no regeneration of plaque-forming virus particles, the capability for sequential immunization to multiple pathogens in the same host, and induction of protective immunity against a mucosal pathogen.

Animals↗
PubMed1997

Refractive errors in young children with Down syndrome.

Significant refractive errors are common among older children and adults with Down syndrome. We examined infants and children with Down syndrome to determine the prevalence of these errors at younger ages. Noncycloplegic retinoscopy was used to determine the refractive state of 92 infants and children with Down syndrome, aged 4 months to 12 years. The results for infants show a similar distribution of refractive errors in patients with Down syndrome and an age-matched control group. However, rather than a narrower distribution for the older age groups, as is the case with the controls, the distribution is wider, and the prevalence of refractive errors (including astigmatism) is higher among young children with Down syndrome than among controls. This high prevalence of refractive defects cannot be explained by the presence of strabismus or other pathologies.

Child↗
PubMed1996

An integrated approach to team assessment in head injury.

The development of multidisciplinary teams for the assessment and treatment of traumatic brain injury has not seen a parallel development in methods of coordinating and collating the information gathered by different professions. The team at the Head Injury Rehabilitation Centre (HIRC), Sheffield uses a process of assessment that encourages the coordination of such information, particularly across the areas that do not fall neatly into the remit of specific disciplines. The framework of the assessment is presented, together with discussion of methods of gathering information and of sharing that information. The advantages of this approach are discussed in terms of benefits for the client, for the professionals involved in the assessment and for other services that might be involved with the client.

Activities of Daily Living↗
PubMed1996

Visual acuity and accommodation in infants and young children with Down's syndrome.

Accommodation and visual acuity were measured in 53 children with Down's syndrome aged between 12 weeks and 57 months. Results were compared with data for 136 control (typically developing) children aged between 4 weeks and 48 months. Whereas the control children accommodated accurately on near targets, accommodation was defective in 92% of the children with Down's syndrome, and there was no change in accommodative ability with age. On the other hand, visual acuity lay within normal limits for the younger children. Children over the age of 2 years showed a below-normal visual acuity, which is not explained either by refractive error or by the effect of poor accommodation. The data suggest a sudden change in the rate of development of visual acuity which may be associated with physiological changes in the visual cortex. Previously reported defects of accommodation and visual acuity in older children and adults with Down's syndrome are confirmed by our findings in infants and young children.

Accommodation, Ocular↗
PubMed1996

Creating an integrated health care system: the health and human risk management model.

This article critiques the current health care system and presents a new conceptual model that offers the potential for an integrated health care system in the future. Health care currently consists of parallel care systems based on the competing conceptual frameworks of the medical model and the psychosocial model. It is argued that psychosocial factors must be included in an integrated system. Research literature is reviewed that documents the need for, the therapeutic effectiveness of, and the medical cost-offset benefits of mental and behavioral health interventions. The Health and Human Risk Management Model is described and illustrated with a case example as well as research outcomes from its implementation at United HealthCare Corporation.

Delivery of Health Care, Integrated↗
PubMed1995

Circadian variation in human ventricular refractoriness.

BACKGROUND: The incidence of sudden cardiac death is highest in the morning hours. Although a circadian variation in myocardial ischemia may be responsible in part for this observation, other factors also may be contributory. It is not known whether a circadian variation in ventricular refractoriness exists that may be related to the increased morning incidence of sudden cardiac death. METHODS AND RESULTS: Nine subjects with primary conduction system disease, no evidence of structural heart disease, and permanent pacemakers were studied. Autonomic nervous system function as assessed by tilt table and baroreflex sensitivity testing was normal in all subjects. Using noninvasive programmed stimulation, ventricular effective refractory periods were measured hourly for 24 hours. Potassium, epinephrine, and norepinephrine levels also were measured hourly. In a subset of five subjects, ventricular refractory periods were again measured hourly over 24 hours during beta-blockade. A significant circadian variation in ventricular refractoriness was noted, with a mean difference between the shortest and longest refractory periods in individual subjects of 23 ms and 21 ms at drive cycle lengths of 600 ms and 400 ms, respectively. In eight subjects, the shortest refractory periods observed over 24 hours occurred within 2 hours of waking (random probability < 10(-8)). Adjustment of refractory period data according to the hour of waking resulted in a better correlation between ventricular refractory periods and time. Although a significant circadian variation was observed in potassium and catecholamine levels, neither was an independent predictor of refractory periods after adjustment for the hour of waking. The adjusted time of day was the only significant (P < .0001) independent predictor of refractory periods. beta-Blockade abolished the circadian variation in ventricular refractory periods. CONCLUSIONS: A significant circadian variation in ventricular refractory periods exists. Maximal shortening between hourly refractory periods as well as the shortest refractory periods occur in the early morning hours when the incidence of sudden cardiac death is greatest. Fluctuations in beta-adrenergic tone appear to be largely responsible for this phenomenon.

Adult↗
PubMed1995

Comparison of an oral rice-based electrolyte solution and a glucose-based electrolyte solution in hospitalized infants with diarrheal dehydration.

This randomized trial compared the efficacy of a rice-based (50 g/L) oral rehydration solution with the standard glucose-based WHO/UNICEF solution in the treatment of 100 hospitalized infants, ages 3-18 months, with acute dehydrating diarrhea. The main outcomes examined were stool output and duration of diarrhea. Patients were placed on a "metabolic" bed so that intake and losses could be measured accurately throughout the study. Overall, 89% of patients were successfully rehydrated orally; the rehydration failure rate was similar in the two groups and it was significantly associated with infection by specific E. coli serotypes. Stool output in the first 24 h was 11% lower in the rice group (112 versus 126 ml/kg), but this difference was not significant. Neither stool output in the second 24 h nor total stool output were different between groups. The median duration of diarrhea was 3.8 days in the rice group and 3.9 days in the glucose group (p = NS). Other (secondary) outcomes, such as fluid intake, urine output, emesis losses, weight change, and electrolyte balance were also similar between the two groups. Some evidence of carbohydrate malabsorption was detected in 61% of the rice group versus 45% of the glucose group (p = NS) and was not associated with any particular treatment outcome. These results show that a rice-based oral rehydration solution is as efficacious as, but not better than the standard glucose-based solution in the treatment of infants with acute dehydrating diarrhea not associated with cholera.

Acute Disease↗
PubMed1995

Autonomy, problem-based learning, and the teaching of medical ethics.

Autonomy has been the central principle underpinning changes which have affected the practice of medicine in recent years. Medical education is undergoing changes as well, many of which are underpinned, at least implicitly, by increasing concern for autonomy. Some universities have embarked on graduate courses which utilize problem-based learning (PBL) techniques to teach all areas, including medical ethics. I argue that PBL is a desirable method for teaching and learning in medical ethics. It is desirable because the nature of ethical enquiry is highly compatible with the learning processes which characterize PBL. But it is also desirable because it should help keep open the question of what autonomy really is, and how it should operate within the sphere of medical practice and medical education.

Curriculum↗
PubMed1995

Use of adventure experiences in traditional counseling interventions.

Use of adventure as an intervention in traditional counseling was explored with 84 adolescent clients from two community-based counseling agencies and residents from two boys' homes. The adolescents were assigned to conditions of counseling plus adventure experiences, counseling only, adventure only, or a control. Analysis indicated limited support for increasing self-esteem and social skills by adding adventure experiences to on-going counseling.

Adolescent↗
PubMed1994

T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and enhance their costimulatory activity.

Activation-induced cell surface molecules are involved in mediating bidirectional T-B lymphocyte signaling that is important in the induction of T or B lymphocyte effector functions. In this regard, T-BAM/CD40-L is an activation-induced CD4+ T cell surface molecule known to be important in inducing B cell effector functions. This report demonstrates that T-BAM/CD40-L molecules on a Jurkat T cell leukemia subclone (D1.1) or nonlymphoid 293 kidney cell transfectants induce B cells or B-CLL cells to express CD80 (B7/BB-1) in a manner that is specifically inhibited by anti-T-BAM/CD40-L mAb 5C8. Because activation-induced B cell surface molecules, such as CD80, deliver costimulatory signals to T cells that augment T cell proliferation, the functional costimulatory capacity of T-BAM/CD40-L-primed B cells and B-CLL cells was studied. T-BAM/CD40-L-primed B cells or B-CLL cells augment the proliferative responses of allogenic T cells. Furthermore, T-BAM/CD40-L priming is specifically inhibited by mAb 5C8. Together, these studies demonstrate that T-BAM/CD40-L induces CD80 expression on resting B cells or B-CLL cells. Moreover, T-BAM/CD40-L signaling enhances B cell costimulatory capacity. These studies suggest that T-BAM/CD40-L molecules not only induce B cell differentiative processes that result in Ab secretion, but also enable B cells to prime Ag-specific T cells for subsequent clonal expansion.

B-Lymphocytes↗
PubMed1994

The cytolytic toxin aerolysin: from the soluble form to the transmembrane channel.

Aerolysin is a cytolytic toxin which forms channels in the plasma membranes of eucaryotic cells. The protein is secreted by Aeromonas hydrophila as an inactive protoxin. Its stability and water solubility are conferred by its ability to dimerize. Maturation of the protein occurs through proteolytic removal of a C-terminal peptide outside the secreting cell. Although the aerolysin which is so produced is still a dimer, it then has the ability to oligomerize. The oligomer is the active form of the toxin, capable of forming the transmembrane channels that disrupt cells. We review here the present knowledge about the structure of aerolysin in relation to the various steps in channel formation.

Aeromonas hydrophila↗