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Biomedical subjects

L Wright

Publications and source records attributed to L Wright.

At least 19 recordsLinked to original sources
PubMed1995

Regulation of the complement cascade by soluble complement receptor type 1. Protective effect in experimental liver ischemia and reperfusion.

The complement cascade was inactivated in a model of rat liver ischemia with the purpose of studying the role of complement in tissue injury after ischemia and reperfusion. Soluble human complement receptor type 1 (sCR1) was administered either in a single dose of 25 mg/kg or in 2 doses of 50 mg/kg i.v. over 24 hr after vascular occlusion. Sham-operated rats, nontreated rats submitted to liver ischemia, and rats pretreated with cobra venom factor and submitted to liver ischemia were used as controls. This experiment consists of the temporary interruption of arterial and portal blood flow to the left lateral and medial lobes of the liver for 45 min, followed by a 24-hr period of follow-up after reperfusion. Liver blood flow and hemoglobin saturation were recorded for 1 hr after declamping, with statistically significant differences between the experimental groups and the untreated control group, which received liver ischemia (P < 0.001). At 24 hr, galactose elimination was assayed as a liver function test; it was significantly better in the sCR1-treated rats when compared with control rats submitted to ischemia (P < 0.01). Alanine aminotransferase levels were also significantly lower in the sCR1-treated rats at 6 and 24 hr (P < 0.05). Complement activity was reduced to 25% and 12.5% of normal rats with the respective doses of sCR1. Immunoperoxidase stainings for C3 and C9 were performed on liver sections; they showed endothelial deposits of C3 and C9 in the control group subjected to ischemia. Few C3 deposits were present in the sCR1 (25 mg/kg)-treated rats, but not in the cobra venom factor or sCR1 (50 mg/kg) groups. These results confirm that complement is inactivated by sCR1 with amelioration of reperfusion injury in the rat liver.

Animals↗
PubMed1995

The control of hyperacute rejection by genetic engineering of the donor species.

Activation of endogenous complement is inhibited both in the soluble phase and at the membrane surface by a group of structurally similar proteins. A possible solution to hyperacute rejection is to produce donor animals transgenic for human complement regulators. Mouse cells expressing the human complement regulatory proteins decay accelerating factor (DAF) or membrane cofactor protein (MCP) were produced both by hybridoma technology and by transfection with the appropriate cDNAs. The expression of either or both of these products protected the mouse cell from lysis by human (though not rabbit) complement in the presence of naturally occurring human anti-mouse antibody. This effect could be abrogated by the addition of monoclonal antibody against DAF or MCP. Hyperacute rejection of discordant organ xenografts is mediated by human complement. A 6.5 kilobase minigene for DAF has been microinjected into porcine fertilised ova. Forty-five pigs transgenic for human DAF have been produced. Of these, 65% transcribe message. The amount of message produced varied substantially from animal to animal and was independent of copy number integrated. Expression of human DAF on the porcine lymphocyte surface could be detected and this was able to downregulate human complement activation. Amounts of protein expressed on different tissues varied both from pig to pig and within animals from tissue to tissue. The pigs grow and develop normally with no evidence of ill effects due to possession of the transgene.

Animals↗
PubMed1994

Cytokine activity after allogeneic bone marrow transplantation. V. Analysis of IL-2 and IFN production by isolated CD4+ and CD8+ cells.

Previous studies from this laboratory have shown that PBMC from recipients of an HLA-identical sibling bone marrow transplant produce levels of IL-2 which are 10-100-fold lower than those produced by the same number of PBMC from healthy controls, whereas production of IFN-gamma is normal. The present study examined IL-2 and IFN production over a range of cell numbers for PBMC and for isolated CD4+ and CD8+ cells for controls and marrow transplant recipients. There was a 5-fold lower IL-2 production in marrow transplant recipient CD8+ cells compared with equivalent numbers of control cells, whereas no difference was found in IL-2 production by CD4+ cells. In contrast, IFN production by CD4+ cells from marrow transplant recipients was 4-fold higher than in controls, whereas CD8+ cells from both populations produced similar amounts of IFN. When the observed production of cytokine by PBMC was compared with the expected production based on the CD4+ and CD8+ content of the PBMC, control values were similar, but the expected values for both cytokines were approximately 2-fold higher than the observed values for marrow transplant recipients. The results suggest that the capacity of T cells from marrow transplant recipients to produce IL-2 and IFN is not impaired, but that the frequency of cytokine-producing cells may be reduced, and that a negative interaction present in recipient PBMC, eliminated by isolating T-cell subsets, is responsible for the observed low levels of cytokine production.

Adult↗
PubMed1994

Validation of a single point flow cytometric assay for determining P-glycoprotein activity in multidrug resistant cell lines.

P-glycoprotein, a transmembrane protein which acts as an energy dependent efflux pump, has been implicated as one mechanism of multidrug resistance (MDR) in human tumours. Commonly employed assays measure P-glycoprotein immunohistochemically or mdr1 messenger RNA. In this study we compared a single point flow cytometric assay for determining activity of P-glycoprotein with cellular expression of P-glycoprotein determined by Western blot. Five cell lines, with varying levels of multiple drug resistance, were incubated with daunorubicin (DNR) in the presence (treated) and absence (control) of cyclosporine or verapamil, agents known to inhibit the activity of P-glycoprotein. The treated cell lines, along with non-treated controls were examined for intracellular concentrations of DNR measured by fluorescence intensity using a flow cytometer. The ratio of fluorescence intensity expressed in the treated/control was used as an index of functional activity of P-glycoprotein. Functional activity of the P-glycoprotein as determined by flow cytometry correlates highly with cellular content of P-glycoprotein measured by western blot (correlation coefficients of r = 0.90-0.98 for the various cell line combinations). This method represents a rapid single point flow cytometric assay which may be suitable for screening clinical samples for P-glycoprotein activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Stuttering therapy with British-Asian children. I: A survey of service delivery in the United Kingdom.

The results of a UK survey of speech and language therapy services offered to Asian children and adolescents who stutter are set in the context of current therapy approaches favoured in the UK. Eighty-seven speech and language therapists from the major centres of Asian population in the UK completed a postal questionnaire. This yielded data on: service delivery to stuttering children in general; the size and nature of the Asian populations served; therapists' own cultural backgrounds; steps taken by therapists to increase their skill in this area; interpreter services available; changes made to usual working practices aimed at accommodating the cultural needs of Asian clients. The results revealed a service mostly provided by non-specialist therapists, who treated small numbers of both stuttering and Asian clients. Therapists were serving clients from up to four different cultural and linguistic backgrounds, yet access to interpreter services was poor. Therapists were on the whole poorly trained and equipped to treat Asian clients. A range of changes to working practices are described, but no cohesive approach was apparent. The issues involved in appropriate and accessible service delivery are discussed.

Adolescent↗
PubMed1994

Stuttering therapy with British-Asian children. II: Speech and language therapists' perceptions of their effectiveness.

This paper tested hypotheses arising from the literature on the treatment of stuttering in British-Asian children and adolescents, using data obtained from a postal questionnaire completed by 87 therapists. The results showed therapists treating lower numbers of Asian clients than expected, but perceiving their therapy to be less effective with their Asian clients than with their British ones. The variables affecting therapists' perceived success were not those expected. Greater experience with Asian clients did not increase perceived success, nor did Asian therapist and client sharing broadly the same cultural background guarantee success. A satisfactory interpreter service did not lead to a higher perceived success rate, nor did postgraduate training or making special changes to usual working practices. On the contrary, therapists in the last two categories were less likely to perceive success with their Asian clients. Therapists identified a very wide range of cultural factors needing special consideration in therapy, but consensus centred around parental attitudes to stuttering and to therapy.

Adolescent↗
PubMed1994

Differences between American Indian and non-Indian children referred for psychological services.

The physical and social characteristics of 60 American Indian children referred for psychological services were compared to those of 60 matched, non-Indian controls. Data were obtained from detailed records available in a multidisciplinary, medical school-related child study clinic. Indian children exhibited more health and social risk factors, but were superior to non-Indians on a variety of motor variables. Interpretations are offered concerning better psychological services for American Indian children based on better understanding of their possible exposure to physical health and social risks which may be related to psychological development.

Adolescent↗
PubMed1994

Detection and prevention of treatable visual failure in general practice: room for improvement?

An ageing population, the introduction of sight test charges and a problem that has never been adequately addressed since the inception of the National Health Service presents general practitioners with the increasing burden of detecting and preventing visual failure which they feel poorly equipped to deal with. Ophthalmology in general practice is a fundamental requirement for the reduction of avoidable visual failure and this is probably especially true for elderly patients and diabetic patients. A postal survey of general practitioners in Brent and Harrow suggests that there is potential for major improvements in the delivery of eye care by general practitioners, often without much additional expenditure (the equipment is there but it is not used) and with minimal training requirements. Simple changes in already existing screening programmes could potentially have an immediate effect on the visual well-being of the community.

Aged↗
PubMed1992

Effect of serotonin and thromboxane A2 on blood flow through moderately well developed coronary collateral vessels.

This study was performed to determine whether thromboxane A2 (as the analogue U46619) and serotonin can cause vasoconstriction of moderately well developed coronary collateral vessels. Studies were carried out in seven adult mongrel dogs 2 to 4 months after embolic occlusion of the left anterior descending coronary artery had been performed to stimulate collateral vessel growth. At the time of study this artery was cannulated to determine interarterial collateral flow from measurements of retrograde blood flow. Radioactive microspheres were administered during retrograde flow collection to determine continuing tissue flow for evaluation of microvascular collateral communications. Serotonin (50 micrograms/min) resulted in a 48 +/- 11% decrease in retrograde flow (p less than 0.01), with a 36 +/- 10% decrease in total collateral blood flow (p less than 0.02). Infusion of U46619 (0.01 microgram/kg per min) caused a 38 +/- 13% decrease in retrograde blood flow (p less than 0.01), with a 34 +/- 13% decrease in total collateral flow (p less than 0.05). Serotonin caused a significant increase in tissue flow to the subepicardium of the collateral-dependent region, whereas U46619 caused no change in tissue blood flow. These data demonstrate that both serotonin and thromboxane A2 can cause vasoconstriction of interarterial coronary collateral vessels. The findings suggest that platelet activation in coronary arteries from which collateral vessels originate has potential for causing collateral vasoconstriction, thereby compromising blood flow to the dependent myocardium.

Animals↗
PubMed1992

A factor analytic study of physical risk variables for CHD.

The scores of 40 hospitalized male coronary heart disease (CHD) patients, for seven traditionally employed physical CHD risk factors, were subjected to a confirmatory factor analysis that employed a LISREL program. An attempt was made to confirm a two-factor solution that involved family history as one factor, and smoking, serum cholesterol level, blood pressure, physical exercise, diet, and weight control as the second. The obtained goodness-of-fit index (.84) suggests that the two-factor solution is a moderately valid one. These findings raise the question whether many of the physical risk factors for CHD simply may be manifestations of a single behavioral characteristic, perhaps best described as "lack of self-control."

Adult↗
PubMed1992

Are the physical and TABP risk factors for heart disease unique to CHD?

Scores of 40 hospitalized CHD patients on 11 Type A-related and 7 physical CHD risk factors were compared to those of 40 hospitalized non-CHD patients. Family history for CHD was the only physical risk factor for which a significant difference was found. CHD patients scored significantly higher on all seven interview-measured Type A and Type A subcomponent variables. Only two of the four Jenkins Activity Survey-measured Type A variables produced significant differences, with one higher for non-CHD subjects. It was concluded that some CHD risk scores also may be associated with other diseases, to the experience of being seriously ill, and/or to the experience of hospitalization.

Adult↗
PubMed1992

On the validity of an Augmented Structured Interview for measuring subcomponents of the Type A behavior pattern.

This study was designed to provide validity data for the Augmented Structured Interview (ASI), which has been developed to measure subcomponents (as opposed to the global) Type A behavior pattern (TABP). Eighty subjects from a large private southwestern medical center were administered a self-report measure of the TABP (the Jenkins Activity Survey--JAS) and the ASI. Forty of the subjects were being treated for post-infarction coronary heart disease (CHD). The remaining forty subjects did not possess documented CHD. The obtained ratings for all the six ASI-measured Type A subcomponents were significantly higher for the CHD than for the non-CHD group. A discriminant functions analysis revealed that the ASI was superior to the JAS in correctly classifying CHD and non-CHD subjects. These outcomes are interpreted as providing initial support for the validity of the ASI.

Adult↗
PubMed1992

The OPQ: a proposed instrument for predicting poisoning accident recurrence in young children.

A 26-item self-report questionnaire for parents/guardians was constructed for potential use with first-exposure childhood poisoning victims to predict high risk for subsequent poisoning episodes. Data were obtained from 185 subjects served by 1 of 5 US regional poison control centers. The resulting device was labeled the OPQ. Its retrospective validity (R = 0.71) and test-retest reliability (0.81) are viewed as sufficient. The test itself, with accompanying scoring key and norms, are provided here in the hope that other clinicians and researchers will join in subjecting the OPQ to prospective validity studies and other forms of Scale refinement.

Child, Preschool↗