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Biomedical subjects

D W Taylor

Publications and source records attributed to D W Taylor.

At least 73 records · Page 4Linked to original sources
PubMed1992

Analysis of antibody responses directed against two Onchocerca volvulus antigens defined by monoclonal antibodies.

Monoclonal antibodies, reactive with antigens solubilised from the body wall of intact female Onchocerca volvulus using 2% 2-beta-mercaptoethanol, have been characterised. Two IgG1 antibodies, Cam1 and Cam28, recognised antigens of apparent molecular weights of 18,000 and 28,000; and 120,000, respectively. The target antigens of Cam1 and Cam28 could be localised in the cuticle. Inhibition ELISAs showed that target epitopes of both monoclonal antibodies induce an antibody response in onchocerciasis patients. 153 sera from Sierra Leonean patients were tested for their individual antibody levels against antigen epitopes recognised by Cam1 and Cam28. Patients within the age of 5-8 years had the highest levels of antibodies against the Cam28-epitope, whereas patients above 60 years had almost none. Amicrofilaremic patients had higher anti-Cam28 antibody levels than microfilaremic patients and there was a significant difference between groups with no chronic skin disease and those with mild or severe signs. A high percentage of patients (80.4%) recognised the Cam1-epitope, highest antibody levels being found in patients within the age group of 15 to 45 years and in microfilaremic patients. However, levels of antibodies inhibiting monoclonal antibody Cam1 could not be correlated with presence or absence of skin disease.

Adolescent↗
PubMed1992

Immunological studies on onchocerciasis in Sierra Leone. 2. Cell-mediated immune responses after repeated treatment with ivermectin.

Cell mediated responses of peripheral blood lymphocytes were tested by incorporation of I-125 dideoxyuridine in a standard proliferation assay. The cells were collected from age and sex-matched patients selected on the basis of their clinical and parasitological status. These patients were treated with either ivermectin or placebo at 6-monthly intervals for two years. For the purpose of comparison, the patients were divided into three groups: children aged 5-9 years; 10-19 year olds; and, those older than 20 years. Repeated drug treatment over the two year period had no effect on either mitogenic or non-parasite antigen (PPD) responses in a majority of individuals. However, in younger children (5-9 years) repeated treatment with ivermectin resulted in some enhancement of Onchocerca-specific responses measured 6 months after administration of the drug. This effect was more pronounced in children presenting with positive skin-snips. An age related decline in mitogenic responses was observed.

Adolescent↗
PubMed1991

Effects of repeated doses of ivermectin on ocular onchocerciasis: community-based trial in Sierra Leone.

Ivermectin seems to be a safe and effective treatment for onchocerciasis when given in a single dose, but less is known about the effects of repeated doses. Also, there seem to be differences in its effectiveness in anterior and posterior segment ocular disease. The ocular effects of ivermectin were studied in 586 villagers who were taking part in a double-blind, placebo-controlled, randomised trial in Sierra Leone. Only those who had received four doses, with 6-month intervals, of ivermectin or placebo were eligible. The 296 ivermectin-treated subjects and the 272 who received placebo were comparable with respect to age, sex, Onchocerca infection, blindness, and visual impairment before treatment. After treatment, the ivermectin group had less anterior segment disease than the placebo group, with significantly lower prevalences of microfilariae in the anterior chamber and cornea, and punctate keratitis (all p less than 0.001), and iritis (p less than 0.05). There was no significant difference in the prevalence of sclerosing keratitis, optic atrophy, or chorioretinitis between the groups. Visual acuities tended to be better in the ivermectin group, but the difference was not significant. There was a small but significant (p less than 0.01) excess of vascular sheathing in the ivermectin group. These differences persisted when subjects who were blind or visually impaired at baseline were excluded from analysis. The long-term effects of ivermectin, particularly on posterior segment disease, need further evaluation. In the mean time, the mass distribution of ivermectin should be promoted for all communities with hyperendemic onchocerciasis at risk of anterior segment disease.

Adolescent↗
PubMed1991

Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis.

BACKGROUND: Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. METHODS: We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. RESULTS: Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). CONCLUSIONS: Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery.

Aged↗
PubMed1991

Immunological crossreactivity between a cloned antigen of Onchocerca volvulus and a component of the retinal pigment epithelium.

Onchocerciasis (river blindness) is a major blinding disease in Africa, Central America, and South America. Loss of vision can be due to corneal change, optic atrophy, or chorioretinal disease. It has been suggested that autoimmunological reactions resulting from crossreactivity between parasite antigens and components of eye tissues contribute to development of ocular pathology. Using sera collected from onchocerciasis patients as a screening reagent, a cDNA clone (Ov39) has been isolated from a lambda gt11 expression library of Onchocerca volvulus. This antigen exhibits immunological crossreactivity with a component of retinal pigment epithelium cells (RPE). Antiserum raised against this recombinant peptide immunoprecipitates a 22,000 Mr antigen of adult O. volvulus and recognizes a 44,000 Mr component of bovine RPE by Western blotting. A 44,000 Mr antigen of cultured human RPE metabolically labeled with 35S-methionine can be immunoprecipitated with the same antiserum. An antigen of the same size is recognized by a rabbit antiserum raised against whole O. volvulus extract. Immunocytochemical studies on cryostat sections of the bovine eye using the antirecombinant sera localizes this antigen to the RPE.

Amino Acid Sequence↗
PubMed1991

Schistosome vaccines.

Schistosomiasis control currently relies primarily on chemotherapy which is both expensive and temporary. There is an urgent need for an effective vaccine. Studies in animal models and man have demonstrated the existence of protective immunity. Antibody-dependent cell-mediated cytotoxicity mechanisms involving eosinophils and macrophages have been implemented in destruction of the parasites. Antigens expressed on the surface of the schistosomulum are among the targets of protective immune responses. Vaccines comprising recombinant antigens are now being tested in vivo for their capacity to evoke protective responses. Live oral vaccines based on attenuated Salmonella expressing schistosomular surface antigens are being developed.

Animals↗
PubMed1991

A comparison of evaluative indices of quality of life and cognitive function in hemodialysis patients.

In the setting of end-stage renal disease, the reproducibility and responsiveness of three health-related quality-of-life instruments were evaluated. The Time Trade Off instrument (TTO) is a generic instrument used to evaluate the utility of a health state. The Hemodialysis Quality-of-Life questionnaire (HQL) is a disease-specific instrument. A series of function-specific tests evaluated neurocognitive function. The TTO and HQL instruments are patient centric in that patient values define the health status while the neurocognitive function tests reflect the values of healthcare professionals. Forty-seven chronic hemodialysis patients participated. Those with adequate dialysis, defined as a Kt/V (a measure of small solute removal during hemodialysis) above 1.0 were maintained at the level for two administrations of the three instruments separated by six to eight weeks. The test-retest intraclass correlation coefficient exceeded 0.90 for all five domains of the HQL questionnaire and exceeded 0.70 for nine neurocognitive function tests. Patients with inadequate dialysis (Kt/V less than 0.8) had Kt/V increased to above 1.0. The TTO was not responsive. For the HQL questionnaire, an item was considered responsive if a 1-point improvement, on a 7-point Likert type scale, occurred significantly more often among those with an improvement in hemodialysis treatment compared to those without improvement. Only one item had such a change and therefore the HQL cannot be considered responsive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Partial characterization of 2-beta-mercaptoethanol-soluble surface-associated antigens of Onchocerca volvulus.

Antigens were extracted from the epicuticle/cuticle of intact female Onchocerca volvulus using 2% 2-beta-mercaptoethanol and 1% SDS. In Western blot analysis a human infection serum selected for its high antibody titre against whole worm homogenates did not recognize any component solubilized by 1% SDS. However, the same serum did bind at least 7 antigens among the material extracted with 2-beta-mercaptoethanol. These antigens have apparent molecular weights (Mr) of: 15,000, 18,000, 28,000, 78,000, 98,000, 120,000 and 200,000. In ELISA using this preparation as target antigen, 151 out of 153 human infection sera gave positive results. An Onchocerca-specific IgG1 monoclonal antibody, designated Cam1, recognized the 28,000 Mr antigen, which is the most prominent antigen detected by Western blot analysis using human infection sera. In ELISA, using material affinity-purified with Cam1 as target antigen, 149 out of 153 human infection sera gave a positive IgG response. From a cDNA library three expressing clones were isolated with a rabbit serum raised against 2-beta-mercaptoethanol solubilized material. One of these clones was recognized by the monoclonal antibody Cam1.

Animals↗
PubMed1991

MHC-restriction of antibody responses to an 86 kilodalton antigen of Schistosoma mansoni.

The previously observed MHC-restriction of the antibody response to an 86kDa S. mansoni antigen has been investigated in more detail. The I-A locus of the H-2 complex has been implicated as conferring responder or non-responder status on mice expressing the k and b alleles respectively. Inheritance of responsiveness was dominant over non-responsiveness. An additional level of complexity was observed in the p86 antibody responder status of individuals within a responding inbred strain. This could not be accounted for directly by the level of patent infection, but showed an inverse correlation with the level of egg output in H-2k mice. Differential antibody responsiveness to other antigens, between individuals of the same strain, occurred independently of the differential responsiveness to p86.

Animals↗
PubMed1991

Antimalarial antibodies of the immunoglobulin G2a isotype modulate parasitemias in mice infected with Plasmodium yoelii.

Previous studies have demonstrated the importance of antibodies in mediating immunity to malaria, but the relative contribution of the different immunoglobulin isotypes has not been assessed. In this study, hyperimmune plasma was generated against Plasmodium yoelii and separated by protein A-Sepharose chromatography into fractions containing immunoglobulin G1 (IgG1), IgG2a, IgG2b, or IgG3 antibodies and the remaining nonbinding plasma proteins, including IgM. Following concentration, the antimalarial titer of each isotypic fraction was approximately equivalent to the corresponding isotype in hyperimmune plasma. The isotypic fractions were passively transferred to BALB/c and outbred ICR mice prior to challenge with virulent P. yoelii 17XL and to CBA/CaJ mice challenged with avirulent P. yoelii 17XNL. Only mice receiving IgG2a antibodies experienced an altered course of infection. Immunoprecipitation studies showed that all four IgG isotypes appear to recognize a similar set of antigens. These results suggest that antimalarial antibodies of the IgG2a isotype play a dominant role in modulating P. yoelii parasitemias.

Animals↗
PubMed1991

Detection of antigens and antibodies in the urine of humans with Plasmodium falciparum malaria.

Humans infected with Plasmodium falciparum frequently have elevated levels of proteins in their urine, but it is unclear if any of these proteins are parasite antigens or antimalarial antibodies. To resolve this question, urine samples from malaria patients and controls living in Thailand and Ghana were evaluated. Urine samples from 85% of the patients had elevated protein levels and contained proteins with Mrs ranging from less than 29,000 to greater than 224,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antisera were produced against urine from infected and control subjects. Antisera raised against infected, but not control, urine were positive by indirect immunofluorescence on P. falciparum parasites and immunoprecipitated approximately 12 unique bands from extracts of parasites metabolically labeled with 35S-methionine. These data suggest that a variety of P. falciparum antigens are released into urine during acute infection. It is also likely that anti-P. falciparum antibodies are present in the urine of malaria patients because samples from these patients, but not controls, were positive in indirect immunofluorescence assays and immunoprecipitated at least 19 P. falciparum antigens from extracts of metabolically labeled parasites. The detection of malarial antigens and antibodies in urine may lead to a new approach for the diagnosis of malaria.

Adult↗
PubMed1991

Identification of Plasmodium falciparum histidine-rich protein 2 in the plasma of humans with malaria.

Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) is a water-soluble protein released from parasitized erythrocytes into in vitro culture supernatants. This study sought to determine whether PfHRP-2 could be detected in the plasma of humans with P. falciparum malaria. A monoclonal antibody (1E1) is described that binds to PfHRP-2. By using monoclonal antibody 1E1, PfHRP-2 was identified by Western blot (immunoblot) analysis in the plasma of 37 of 39 (95%) patients experiencing either a first or repeat episodes of P. falciparum malaria and by dot blot analysis in the plasma of 40 of 41 patients tested. PfHRP-2 was not detected in 30 control, uninfected subjects. The current demonstration of PfHRP-2 in plasma, plus the fact that it is a structurally well-characterized molecule present in all natural isolates of P. falciparum tested, makes PfHRP-2 of interest for its potential effects on the host immune system and as an antigen for specific diagnosis of malaria.

Adolescent↗
PubMed1990

Characterisation of Sm20, a 20-kilodalton calcium-binding protein of Schistosoma mansoni.

A cDNA clone encoding part of a 20-kDa antigen of Schistosoma mansoni (Sm20) has been isolated. The amino acid sequence of this antigen, as predicted from the sequence of the cDNA, has significant homology to the family of calcium binding proteins which include calmodulin, troponin C and the light chain of myosin. Although we have been unable to show any immunological cross-reactivity between Sm20 and calmodulins from a range of other species, we have verified that Sm20 is a functional calcium binding protein. Sm20 is encoded by a small multigene family and is expressed in schistosomula and adult worms but not in eggs. The 20-kDa nascent polypeptide appears to be post-translationally modified to give a 38-kDa species. Sm20 is present in preparations of tegumental membranes and is easily removed from intact schistosomula by detergent treatment, suggesting that it is associated with the tegument. However, the cloned portion does not appear to be exposed on the surface.

Amino Acid Sequence↗
PubMed1990

Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors?

The entry characteristics of 1367 patients enrolled into the Extracranial/Intracranial Bypass Study were examined to determine if site differences in intracranial and extracranial arterial lesions among racial groups could be explained by differences in risk factors. Blacks were more often hypertensive, diabetic, or cigarette smokers, while whites had higher systolic blood pressure and hemoglobin values. Orientals had the lowest prevalence of vascular risk factors. Despite these differences in risk factors, multivariate analysis showed race to be an independent and strong predictor of the location of cerebrovascular lesions. To our knowledge, this study is unique in documenting risk factors prospectively and systematically in three racial groups simultaneously. Although generalization is limited by possible biases related to patient selection, the results affirm previous tentative conclusions about the role of race in determining the location of cerebrovascular disease.

Asian People↗
PubMed1990

CTS: a clinical trials simulator.

We describe an interactive clinical trial simulation program (CTS), which provides continuous graphical and numerical output as a simulation runs. CTS is capable of simulating trials with two treatment groups and a binary outcome with options for: (1) up to five prognostic subgroups; (2) one of three methods of randomization; (3) equal or unequal allocation of patients to treatment groups; (4) a null or alternative hypothesis; (5) common methodological problems including biased referrals, false positive and false negative outcome reports, non-compliance, dropouts, crossovers, and co-interventions; (6) six methods of dealing with each of these problems; (7) the type I error rate, and (8) stratified or unstratified analysis. In addition, the current results of a trial in progress may be used as the starting point of the simulation to estimate the power of the trial if carried to completion. A few thousand simulations of a user specified scenario is typically entered and executed in about 5 minutes, permitting a student or clinical investigator to explore a variety of scenarios.

Algorithms↗
PubMed1990

Antibodies to a histidine-rich protein (PfHRP1) disrupt spontaneously formed Plasmodium falciparum erythrocyte rosettes.

Cerebral involvement in Plasmodium falciparum malaria is associated with sequestration of infected red blood cells and occlusion of cerebral vessels. Adhesion of infected erythrocytes along the vascular endothelium as well as binding of uninfected erythrocytes to cells infected with late-stage asexual parasites (rosetting) may be important in erythrocyte sequestration. We report that the recently discovered rosetting phenomenon shares characteristics with other human cell-cell interactions (heparin sensitivity, temperature independence, Ca2+/Mg2+ and pH dependence). Mono- and polyclonal antibodies specific for PfHRP1, a histidine-rich protein present in the membrane of P. falciparum-infected erythrocytes, disrupt rosettes but do not affect attachment of infected erythrocytes to endothelial cells. The inhibitory anti-PfHRP1 antibodies reacted with rosetting parasites in indirect immunofluorescence and with P. falciparum polypeptides of Mr 28,000 and Mr 90,000 in immunoprecipitation and immunoblotting, respectively. No inhibitory effects on erythrocyte rosetting were obtained with antibodies to related histidine-rich or other antigens of P. lophurae or P. falciparum. Whether the epitope that mediates rosetting, and is recognized by the anti-PfHRP1 antibodies, is located on PfHRP1 or on a crossreactive antigen remains to be established. The results suggest that endothelial cytoadherence and erythrocyte rosetting involve different molecular mechanisms.

Animals↗