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Biomedical subjects

M Contreras

Publications and source records attributed to M Contreras.

At least 145 records · Page 8Linked to original sources
PubMed1991

Effect of ciprofibrate on the activation and oxidation of very long chain fatty acids.

The effect of ciprofibrate, a hypolipidemic drug, was examined in the metabolism of palmitic (C16:0) and lignoceric (C24:0) acids in rat liver. Ciprofibrate is a peroxisomal proliferating drug which increases the number of peroxisomes. The palmitoyl-CoA ligase activity in peroxisomes, mitochondria and microsomes from ciprofibrate treated liver was 3.2, 1.9 and 1.5-fold higher respectively and the activity for oxidation of palmitic acid in peroxisomes and mitochondria was 8.5 and 2.3-fold higher respectively. Similarly, ciprofibrate had a higher effect on the metabolism of lignoceric acid. Treatment with ciprofibrate increased lignoceroyl-CoA ligase activity in peroxisomes, mitochondria and microsomes by 5.3, 3.3 and 2.3-fold respectively and that of oxidation of lignoceric acid was increased in peroxisomes and mitochondria by 13.4 and 2.3-fold respectively. The peroxisomal rates of oxidation of palmitic acid (8.5-fold) and lignoceric acid (13.4-fold) were increased to a different degree by ciprofibrate treatment. This differential effect of ciprofibrate suggests that different enzymes may be responsible for the oxidation of fatty acids of different chain length, at least at one or more step(s) of the peroxisomal fatty acid beta-oxidation pathway.

Activation Analysis↗
PubMed1991

A new canine model for evaluating blood prosthetic arterial graft interactions.

Various models have been proposed to examine blood-prosthetic materials interactions in terms of the effect of the prosthetic material on platelet structure and function, blood coagulation and fibrinolysis, and tissue infiltrates (cellular or acellular). In addition, these models have been used to examine the change in the graft surface over time. Particular difficulties in examining graft-materials interactions include species differences, short residence time for blood-materials interactions with commonly employed short grafts, and length of study limitations with ex vivo shunts. In this paper we report a canine, carotid-aorta subcutaneous prosthetic graft model. The specific advantages of this model are the length of the graft, which allows prolonged contact of blood with the prosthetic surface; the subcutaneous location of the graft, which allows repeated sampling of blood along the graft; and the healing characteristics of canine grafts. We selected the canine model because the healing characteristics are morphologically similar to those in humans in that endothelialization of the prosthetic surface is limited. Other models, such as the pig, are favored for use when examining blood coagulation, platelet, or fibrinolytic studies; however, these models can fully endothelialize prosthetic surfaces.

Animals↗
PubMed1991

Rhizomelic chondrodysplasia punctata: biochemical studies of peroxisomes isolated from cultured skin fibroblasts.

Peroxisomes isolated from cultured skin fibroblasts of two patients with rhizomelic chondrodysplasia punctata (RCDP) and two controls were compared for biochemical studies. These experiments provided the following results: (1) peroxisomes isolated from RCDP-cultured skin fibroblasts had the same density (1.175 g/ml) as control peroxisomes; (2) dihydroxyacetone phosphate acyltransferase activity, the first enzyme in the synthesis of plasmalogens, was deficient (0.5% of control) in RCDP peroxisomes and this activity was not observed in any other region of the gradient; (3) the rate of activation (lignoceroyl-CoA ligase) and oxidation of lignoceric acid was normal in RCDP peroxisomes; and (4) peroxisomes from RCDP contained 3-ketoacyl-CoA thiolase in the unprocessed form (44-kDa protein), whereas control peroxisomes had both processed (41-kDa protein) and unprocessed forms of 3-ketoacyl-CoA thiolase. The presence of both processed and unprocessed 3-ketoacyl-CoA thiolase in control peroxisomes and the unprocessed form in RCDP peroxisomes suggests that processing of 3-ketoacyl-CoA thiolase takes place in peroxisomes. Although the specific activity and percentage of activity of 3-ketoacyl-CoA thiolase in RCDP peroxisomes was only 22-26% of control, the normal oxidation of lignoceric acid in RCDP peroxisomes indicates that unprocessed 3-ketoacyl-CoA thiolase is active. The remaining peroxisomal 3-ketoacyl-CoA thiolase activity in RCDP was observed in a protein fraction (peroxisome ghosts) lighter than peroxisomes. The normal oxidation of fatty acids in peroxisomes and the absence of such activity in peroxisome ghosts (d = 1.12 g/ml) containing peroxisomal proteins in RCDP suggest that RCDP has only one population of functional peroxisomes (d = 1.175 g/ml).

Acetyl-CoA C-Acetyltransferase↗
PubMed1991

A comparison of four enzyme immunoassays for the simultaneous detection of HIV-1- and HIV-2-specific antibody.

The performance of four HIV 1 and 2 combined assays has been compared with current type-specific assays using three panels of sera. The first panel comprised single samples from 19 HIV-1-infected persons; the second panel comprised 19 sera from 16 HIV-2-infected persons. Samples from both these panels were titrated across interpolated end points of detectability. The third panel comprised sera from 5200 consecutive blood donors. The four combined assays, manufactured by Abbott Laboratories, Behring Laboratories, Diagnostics Pasteur and Wellcome Diagnostics Laboratories detected all anti-HIV-1 sera at high dilution; the immunometric assay from Wellcome was particularly proficient. All assays were broadly similar in their ability to detect sera from recently infected persons. The same assays were also effective in detecting anti-HIV 2 in sera both from seropositive individuals and from a single recently-infected person, though none was as sensitive as an inhouse competitive EIA. When used for donor screening the repeat reactive rates for donors negative for HIV 1 and 2 antibodies ranged between 1.80% for Elavia Mixt from Pasteur, 0.27% Abbott combined and 0.15% for the Wellcome combined assays.

Antibodies, Viral↗
PubMed1991

Post-transfusion NANBH in the light of a test for anti-HCV.

The incidence of post-transfusion hepatitis (PTH) varies over an order of magnitude in different parts of the world. For example, prospective studies from Spain and the UK reveal rates of PTH of approximately 10 and 0.5% respectively. Similarly the association of a history of transfusion in patients with chronic liver disease varies widely; in Japan, with high rates of PTH, the association appears obvious whereas in the UK less obvious. These factors must be taken into account when assessing the cost-effectiveness of pre-transfusion screening for anti-HCV. A useful approach to assessing the value of screening donors for anti-HCV is to study prospectively the correlation of anti-HCV and PTH. In carefully selected cases of PTH, the correlation of anti-HCV and PTH in donor-recipient sets of samples may be very high. However, the predictive value of 'first-generation' assays for anti-HCV in routine studies of unselected cases of PTH may be less than 20% in countries with low rates of transfusion-transmitted non-A, non-B hepatitis (NANBH). The anti-HCV screening tests and supplementary assays are continually evolving. More recent assays incorporate structural as well as non-structural antigens in both types of ELISA used for screening and in the supplementary tests such as the recombinant based immunoblots.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗
PubMed1991

Is there a wastage of resources due to non-specificity of anti-HIV ELISAs?

A library of anti-HIV ELISA 'grey-area' and repeatably reactive samples sent for confirmatory testing, were retested using a second technique, the modified (Fujirebio Gelatin Particle) agglutination test (MAT). On testing 224 grey-area reactive samples, only four were found to be reactive with this second test. On retesting a further 259 ELISA repeatably reactive samples, of which only 33 were confirmed to be anti-HIV-1, only 45 were reactive by MAT; these included the 33 confirmed as positive samples, thereby reducing the false-positive from 226 to 12. The introduction of this second technique supported our decision to cease the referral of grey-area samples. It also demonstrated the high prevalence of non-specificity of repeatable reactivity associated with some of the most specific ELISA kits currently available.

Enzyme-Linked Immunosorbent Assay↗
PubMed1991

Non-A, non-B hepatitis and the anti-HCV assay.

The successful cloning of a non-structural antigen from the genome of what is now designated as the 'hepatitis C virus' (HCV) has transformed an erstwhile diagnosis of exclusion for non-A, non-B hepatitis (NANBH). The assay has been validated against panels of known infectivity for NANBH and sera from haemophiliac patients treated either with virally inactivated or uninactivated factor VIII. The predictive value of the assay is being assessed clinically in prospective studies of post-transfusion hepatitis and by using laboratory techniques such as polymerase chain reaction. While the assay shows good predictability in high-risk subjects, an appreciable number of false-positive results are likely in blood donor populations. Furthermore, the extent of infectivity of seropositive blood donors is still the subject of active research. The prevalence of anti-HCV in blood donors varies from approximately 0.2 to 1.5% around the world, based on repeat reactivity in the Ortho antiglobulin ELISA assay. These rates may be appreciably reduced following supplementary testing with recombinant immunoblot assay (RIBA). Prevalence data in African sera are as yet unreliable, pending assessment by RIBA, presumably because of high levels of IgG interfering with the assay. Presence of anti-HBc or elevated alanine aminotransferase associates to a greater or lesser extent with seropositivity, especially when both surrogate markers are present, but conversely many (unconfirmed) seropositive subjects lack these surrogate markers. An understanding of the modes of transmission of HVC is of obvious importance to transfusion practice. Intravenous drug use is a striking risk factor, but the contribution made by sexual transmission is not so clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Development of non-Rh antibodies in volunteers stimulated for the production of hyperimmune anti-D.

At the North London Blood Transfusion Centre, red cells from accredited Rh-D-positive donors, matched for all antigens capable of inducing clinically significant antibodies, are used to stimulate immune plasma donors to achieve higher anti-D levels. Despite such careful matching, antibody to the relatively non-immunogenic M antigen developed in 3 out of 20 NN donors (15%) stimulated with M-positive cells. In general, good responders to the Rh antigen D are good responders to other red cell antigens; our report exemplifies the importance of using fully matched accredited red cells for immune stimulation and the need to perform thorough antibody screening after each stimulation.

Antibody Formation↗
PubMed1991

Blood component treatment: a retrospective audit in five major London hospitals.

A retrospective audit of 200 transfusion episodes involving the use of platelets or fresh frozen plasma (FFP) was performed in five hospitals in London. It examined the currently used practices of transfusion and assessed the appropriateness of blood component treatment. It was necessary to search for an excess of case notes to provide a sufficient number of patients for review. In 61.5% of cases the reason for using the components was not stated. Inadequate documentation of the use of blood components occurred in 66% of cases. An accepted clinical indication for the use of components was evident in only 36% of the total; inappropriate use of FFP was particularly apparent. It is concluded that many aspects of transfusion practice need to be improved.

Blood Transfusion↗
PubMed1991

Hepatitis C virus screening: UK Blood Transfusion Service on the threshold.

The implications of testing all blood donations in the UK for antibody to hepatitis C virus (HCV) are considered. Although the risks of serious liver disease arising from transfusion-transmitted HCV are relatively low in the UK, the cost of such screening will be high in terms of financial outlay and lost donations. In the UK, at least, screening of all blood donations for anti-HCV is unlikely to be as cost effective as screening for HBsAg or anti-HIV.

Antigens, Viral↗
PubMed1991

Anti-HIV-1: extended validation of a modified gelatin particle agglutination assay, and its use with an image analyser.

Modification of a commercial gelatin particle agglutination assay for anti-HIV-1 (MAT) has increased sensitivity, reduced reaction time and lowered the cost by 90%. We tested over 10,000 blood donations in parallel with the ELISA currently in use, and found the modified test to be highly sensitive and to enhance cost-effectiveness as it substantially reduces false-positive rates. The patterns of agglutination are clearly reproducible and readable by the naked eye and/or Image Analyzer, which provides objectivity and hard-copy documentation of results.

Agglutination Tests↗
PubMed1990

Clearance of Rh D-positive red cells with monoclonal anti-D.

Two human monoclonal antibodies, one IgG3 and one IgG1, with anti-Rh D specificity, were tested for their ability to clear red cells. Samples of red cells from 12 D-positive subjects were sensitised in vitro with various amounts of antibody, the number of antibody molecules bound to the cells was estimated, and the cells were reinjected into the donor's circulation. Both antibodies mediated clearance but substantially fewer IgG3 than IgG1 antibody molecules were required to produce a given rate of clearance. The IgG3 antibody was slightly more effective than polyclonal anti-D, as judged by comparison with previously published results. Since there is believed to be an association between the rate of red cell clearance by anti-D and the ability of the antibody to suppress D immunisation, the IgG3 monoclonal antibody may prove suitable for the immunoprophylaxis of Rh D haemolytic disease.

Antibodies, Monoclonal↗