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Biomedical subjects

D W Taylor

Publications and source records attributed to D W Taylor.

At least 37 records · Page 2Linked to original sources

Detection of the Plasmodium falciparum antigen histidine-rich protein 2 in blood of pregnant women: implications for diagnosing placental malaria.

Pregnant women have an increased susceptibility to infection by Plasmodium falciparum. Parasites may be present in the placenta yet not detectable in peripheral blood smears by routine light microscopy. In order to determine how frequently misdiagnosis occurs, peripheral blood and placental samples were collected from 1,077 Cameroonian women at the time of giving birth and examined for the presence of malarial parasites by using light microscopy. Results showed that 20.1% of the women who had placental malaria were peripheral blood smear negative. Thus, malarial infection was not detected by microscopic examination of peripheral blood smears from approximately one out of five malaria-infected women. Since P. falciparum parasites secrete histidine-rich protein 2 (HRP-2), we sought to determine if detecting HRP-2 in either peripheral plasma or whole blood might be used to diagnose the presence of parasites "hidden" in the placenta. Samples of peripheral plasma from 127 women with different levels of placental malarial infection were assayed by HRP-2-specific enzyme-linked immunosorbent assay. HRP-2 was detected in 88% of the women with placental malaria who tested negative by blood smear. Additionally, whole blood was obtained from 181 women and tested for HRP-2 with a rapid, chromatographic strip test (ICT). The ICT test accurately detected malarial infection in 89.1% of P. falciparum-infected women. Furthermore, 94% of women with malaria were accurately diagnosed by using a combination of microscopy and the ICT test. Thus, detection of HRP-2 in conjunction with microscopy should improve diagnosis of malaria in pregnant women.

Animals↗

The North American Symptomatic Carotid Endarterectomy Trial : surgical results in 1415 patients.

BACKGROUND AND PURPOSE: This study reports the surgical results in those patients who underwent carotid endarterectomy in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). METHODS: The rates of perioperative stroke and death at 30 days and the final assessment of stroke severity at 90 days were calculated. Regression modeling was used to identify variables that increased or decreased perioperative risk. Nonoutcome surgical complications were summarized. The durability of carotid endarterectomy was examined. RESULTS: In 1415 patients there were 92 perioperative outcome events, for an overall rate of 6.5%. At 30 days the results were as follows: death, 1.1%; disabling stroke, 1.8%; and nondisabling stroke, 3.7%. At 90 days, because of improvement in the neurological status of patients judged to have been disabled at 30 days, the results were as follows: death, 1.1%; disabling stroke, 0.9%; and nondisabling stroke, 4.5%. Thirty events occurred intraoperatively; 62 were delayed. Most strokes resulted from thromboembolism. Five baseline variables were predictive of increased surgical risk: hemispheric versus retinal transient ischemic attack as the qualifying event, left-sided procedure, contralateral carotid occlusion, ipsilateral ischemic lesion on CT scan, and irregular or ulcerated ipsilateral plaque. History of coronary artery disease with prior cardiac procedure was associated with reduced risk. The risk of perioperative wound complications was 9.3%, and that of cranial nerve injuries was 8.6%; most were of mild severity. At 8 years, the risk of disabling ipsilateral stroke was 5.7%, and that of any ipsilateral stroke was 17.1%. CONCLUSIONS: The overall rate of perioperative stroke and death was 6.5%, but the rate of permanently disabling stroke and death was only 2.0%. Other surgical complications were rarely clinically important. Carotid endarterectomy is a durable procedure.

Aged↗

Vessel-bearing stems of ASOVINEA TIANIIgen. et sp. nov. (Gigantopteridales) from theUpper Permian of Guizhou Province, China.

Permineralized gigantopterid stems of Vasovinea tianii Li et Taylor gen. et sp. nov. were collected from the Upper Permian of Guizhou Province, China. They are slender and bear prickles, trichomes, and compound hooks. Internally, the stems have a sparganum cortex, eustele, and secondary xylem. The mesarch protoxylem tracheids have annular to helical thickenings, and metaxylem tracheary elements have scalariform and/or transversely elongated, bordered pits, while those of the secondary xylem have scalariform to circular bordered pits. Importantly, the inner part of the secondary xylem has large vessel elements with foraminate-like perforation plates. The hooks and other morphological and anatomical characteristics are similar to those found in gigantopterids, suggesting that Vasovinea is a member of the Gigantopteridales. The vegetative plant is reconstructed from permineralized stems and Gigantopteris-type leaves based on the anatomical similarities and intimate association. The eustele, secondary xylem, and other features support the placement of the order among the seed plants. Ecologically, Vasovinea is suggested to have been a vine or liana that used compound hooks to climb among the trees in a Permian tropical rain forest. The occurrence of vessels could have been an efficient adaptation to allow the slender stems to conduct sufficient water to the large Gigantopteris-type leaves.

Journal Article↗

Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up. METHODS: Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis (ipsilateral) within 180 days before study entry were stratified according to the degree of stenosis (50 to 69 percent or <50 percent) and randomly assigned either to undergo carotid endarterectomy (1108 patients) or to receive medical care alone (1118 patients). The average follow-up was five years, and complete data on outcome events were available for 99.7 percent of the patients. The primary outcome event was any fatal or nonfatal stroke ipsilateral to the stenosis for which the patient underwent randomization. RESULTS: Among patients with stenosis of 50 to 69 percent, the five-year rate of any ipsilateral stroke (failure rate) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically (P=0.045); to prevent one ipsilateral stroke during the five-year period, 15 patients would have to be treated with carotid endarterectomy. Among patients with less than 50 percent stenosis, the failure rate was not significantly lower in the group treated with endarterectomy (14.9 percent) than in the medically treated group (18.7 percent, P=0.16). Among the patients with severe stenosis who underwent endarterectomy, the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent; this rate increased to only 6.7 percent at 8 years. Benefit was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms. CONCLUSIONS: Endarterectomy in patients with symptomatic moderate carotid stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke. Decisions about treatment for patients in this category must take into account recognized risk factors, and exceptional surgical skill is obligatory if carotid endarterectomy is to be performed. Patients with stenosis of less than 50 percent did not benefit from surgery. Patients with severe stenosis (> or =70 percent) had a durable benefit from endarterectomy at eight years of follow-up.

Aged↗

Monocrotaline pyrrole interacts with actin and increases thrombin-mediated permeability in pulmonary artery endothelial cells.

One of the earliest morphologic changes evident in the monocrotaline (MCT) model of pulmonary hypertension in rats is microvascular leak. Whether this represents a direct effect of MCT metabolites or is secondary to inflammatory and thrombotic changes remains uncertain. To determine whether MCT directly affects endothelial cell permeability barrier function, we characterized the interaction of the reactive pyrrole intermediate of MCT (MCTP) with endothelial cell actin and characterized its effects on thrombin-mediated signal transduction and monolayer permeability. Bovine pulmonary endothelial cells (BPAEC) treated with MCTP had altered distribution of filamentous actin evident by fluorescence microscopy. Correlative Western blots and autoradiography of actin isolated from BPAEC treated with 14C-MCTP showed comigration of actin and MCTP-derived 14C. MCTP treatment did not alter cellular free Ca2+ concentrations nor did it interfere with thrombin-mediated intracellular Ca2+ signal. Pretreatment with MCTP significantly augmented the thrombin-mediated transudation of Evan's blue albumin in BPAEC monolayers apparently by increasing the size of intercellular gaps. We conclude that MCTP directly interacts with actin to alter its polymerization state but does not significantly affect endothelial cell response to contractile stimulus. Our results suggest that MCTP may affect endothelial cell barrier function through alterations in intracellular junctions.

Actins↗

Comparative cytotoxicity of monocrotaline and its metabolites in cultured pulmonary artery endothelial cells.

Metabolites of the pyrrolizidine alkaloid monocrotaline cause progressive development of pulmonary hypertension in rats. The putative reactive intermediate monocrotaline pyrrole (MCTP) has been shown to cause cytotoxicity, hypertrophy, decreased proliferation, and altered synthetic capability in cultured pulmonary endothelial cells. We compared effects of monocrotaline (MCT) at 60 micrograms/ml (0.185 mM) with previously identified metabolites, MCTP 10 micrograms/ml (0.031 mM) and glutathione-conjugated dihydropyrrolizine (GSH-DHP) 60 micrograms/ml (0.135 mM), in cultured bovine pulmonary artery endothelial cells (BPAECs). To determine whether endothelial metabolism might contribute to the mechanism of this toxicity, we used markers of cytotoxicity (LDH release), synthetic activity (PGI2 synthesis), hypertrophy (planimetry), cell density (cell count/area), and Evans blue albumin (EBA) transudation as a marker for loss of fluid barrier integrity. We found changes in all endothelial markers with MCTP only. MCTP caused increased LDH release by 48 hr, augmented PGI2 synthesis by 96 hr, and resulted in hypertrophy and decreased cell density by 48 hr that persisted at least 21 days. There was increased EBA transudation at 24 hr posttreatment. We concluded that, based on markers of endothelial damage, BPAECs showed no apparent ability to metabolize MCT to a reactive intermediate nor to further metabolize GSH-DHP to a toxic species. We also concluded that MCTP can cause a direct effect on fluid barrier integrity of endothelial cell monolayers in the absence of inflammation.

6-Ketoprostaglandin F1 alpha↗

The pathogenesis of chorioretinal disease in onchocerciasis.

The pathogenesis of onchocercal chorioretinopathy is poorly understood. In this article, Philip Cooper, Ronald Guderian, Roberto Proaño and David Taylor discuss the important clinical, histological and epidemiological features of the resulting lesions that cause blindness, and review the numerous mechanisins that have been put forward to explain its pathogenesis. The pathogenesis of anterior segment disease, particulary sclerosing keratitis, has been reviewed in depth previously(1) and will not be discussed here.

Journal Article↗

Immune response to the filaria Litomosoides sigmodontis in susceptible and resistant mice.

Comparisons were made between the immune responses evoked during the course of chronic and patient infections of Litomosoides sigmodontis in susceptible BALB/c mice and non-patent infections in resistant B10.D2 mice. Early antigen specific responses of spleen cells were weak in both mouse strains. However, by day 58 post infection a strong Th2 response, as determined by production of IL-4, IL-5 and IL-10, was observed in BALB/c mice but not in B10.D2 mice. Antibody responses seemed to appear sooner in B10.D2 than in BALB/c mice, and these differentially recognised two antigens of 15 kD and 80 kD.

Animals↗

Early reduction of the challenge recovery rate following immunization with irradiated infective larvae in a filaria mouse system.

The filaria Litomosoides sigmodontis, which develops a patent infection in BALB/c mice, was used to determine the fate of a challenge inoculum following immunization of mice with irradiation attenuated infective larvae (3 subcutaneous inoculations at weekly intervals with 25 L3 irradiated at 60 krad, and challenge with 25 L3 two weeks after the final immunization). The adult worm burden of vaccinated mice was reduced to 50% of that of controls although the pattern of larval migration and microfilaraemia were not affected. Necropsies showed that the increased killing of the filariae of the challenge inoculum occurred at the L3 stage within the first 2 days of challenge. This result draws attention on the protective mechanisms operating very early and probably in the subcutaneous region.

Animals↗

Vitamin E-deficient diets enriched with fish oil suppress lethal Plasmodium yoelii infections in athymic and scid/bg mice.

Mice fed vitamin E-deficient diets containing omega-3 fatty acids survive infection with lethal Plasmodium yoelii. The current study sought to determine if antimalarial T- and B-cell responses were required for such dietary-mediated protection. In the first set of experiments, nu/nu mice (which lack alphabeta T-cell-receptor-positive T cells and do not produce antimalarial antibody) and nu/+ mice were fed casein-based diets containing 4% menhaden oil, with or without vitamin E supplementation, for 4 weeks prior to infection with lethal P. yoelii. All mice fed diets containing vitamin E developed fulminating parasitemias and quickly died, whereas both nu/nu and nu/+ mice fed diets deficient in vitamin E controlled their parasitemias for the first 18 days of infection. Thereafter, the nu/nu mice became anemic and died, whereas the nu/+ mice produced antimalarial antibodies and survived. In the second set of experiments, scid/scid.bg/bg mice (which lack B cells and alphabeta and gammadelta T cells and have reduced NK-cell activity) were fed the experimental diet for 6 weeks and then infected with the less virulent 17XNL strain of P. yoelii. Mice fed vitamin E-containing diets quickly died, whereas those fed the vitamin E-deficient diet survived without developing detectable parasitemias. Results from these experiments show that under prooxidant dietary conditions, mice were able to control and even survive malaria in the absence of malaria-primed T cells and antimalarial antibody. These results emphasize the importance of cellular oxidative processes in parasite elimination.

Animals↗

Bacterial cell division protein FtsZ assembles into protofilament sheets and minirings, structural homologs of tubulin polymers.

The bacterial cell division protein FtsZ is a homolog of tubulin, but it has not been determined whether FtsZ polymers are structurally related to the microtubule lattice. In the present study, we have obtained high-resolution electron micrographs of two FtsZ polymers that show remarkable similarity to tubulin polymers. The first is a two-dimensional sheet of protofilaments with a lattice very similar to that of the microtubule wall. The second is a miniring, consisting of a single protofilament in a sharply curved, planar conformation. FtsZ minirings are very similar to tubulin rings that are formed upon disassembly of microtubules but are about half the diameter. This suggests that the curved conformation occurs at every FtsZ subunit, but in tubulin rings the conformation occurs at either beta- or alpha-tubulin subunits but not both. We conclude that the functional polymer of FtsZ in bacterial cell division is a long thin sheet of protofilaments. There is sufficient FtsZ in Escherichia coli to form a protofilament that encircles the cell 20 times. The similarity of polymers formed by FtsZ and tubulin implies that the protofilament sheet is an ancient cytoskeletal system, originally functioning in bacterial cell division and later modified to make microtubules.

Animals↗

RANTES in onchocerciasis: changes with ivermectin treatment.

Adverse reactions are seen relatively frequently after treatment of onchocerciasis patients with ivermectin. The chemokines RANTES and IL-8, which have both chemotactic and activation properties for eosinophils and neutrophils, respectively, may have a role in the pathogenesis of post-treatment reactions. Circulating levels of the chemokines and the cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 were measured in the plasma of 22 Onchocerca volvulus-infected subjects. Peaks of mean circulating levels of RANTES and TNF-alpha were seen at 6 h after ivermectin administration. Peripheral eosinophil counts declined at 36 h post-treatment and an early peak in RANTES levels was associated with a delay in peripheral eosinopenia. RANTES levels were negatively correlated with severity of rash (P < 0.001) and lymphoedema (P < 0.05), suggesting that high circulating levels of RANTES may inhibit eosinophil sequestration. No changes in circulating levels of IL-8 were seen. These findings suggest a possible role of circulating RANTES in modulating eosinophil sequestration in vivo.

Adolescent↗

Human isotype antibody responses to an Onchocerca volvulus glutathione S-transferase.

Human isotype specific antibody responses to a recombinant pi-class glutathione S-transferase (Ov24) from Onchocerca volvulus were assessed by ELISA, using a large and well-characterized bank sera (n = 238) from an hyper-endemic area of moderate intensity from Sierra Leone. IgG1, IgG4 and IgA responses, but neither IgG2 nor IgE response, to Ov24 were detected in infected subjects. The relationships between Ov24 antibody levels and skin microfilarial density, number of nodules, age, sex, eosinophil counts and clinical sign of reactive and chronic pathology were analysed using Pearson's correlation coefficient. Significant correlations between both IgA and IgG3 antibody levels and age were found (P < 0.01). Although no firm conclusions could be drawn from this study sample regarding the relationships between antibody levels and parasite load or clinical status, a negative correlation (P = 0.06) between Ov24 IgG3 antibody levels and microfilarodermia was found.

Adolescent↗

The fate of the filaria Litomosoides sigmodontis in susceptible and naturally resistant mice.

The fate of Litomosoides sigmodontis was compared in susceptible BALB/c and resistant B10D2 mice, presenting the same major histocompatibility complex (H-2d), with an attempt to dissociate the different elements of the life cycle in order, later, to dissociate the different mechanisms involved. Each female mouse was inoculated once with a small dose of infective larvae (25 L3) or a large dose (100 or 200 L3). In total, 92 BALB/c and 49 B10D2 were studied. Necropsies were performed up to D85 following infection with 25 larvae. The early fate was similar in B10D2 and BALB/c mice; particularly the recovery rate of worms was almost identical during the first month p.i. and represented a quarter of the inoculated larvae. Resistance in B10D2 mice appeared progressively, as judged by retardation of growth and of the fourth moulting, the presence of very small sterile female worms and male worms with abnormal left spicule, and a high frequency of live filariae coated with inflammatory cells and encapsulated dead worms. The L. sigmodontis life span in B10D2 was about half that in BALB/c. Necropsies were carried out up to D20 following infection with 100-200 L3. The recovery rate was increased in BALB/c. Growth was retarded earlier in B10D2 mice, this crowding effect already apparent at D10; this may indicate a role for metabolic factors. The pattern of the life cycle in both mouse strains confirms recent conclusions on Onchocercinae: the recovery rate is established as soon as the second day during "phase 1 of massive destruction", then it is stable during "phase 2 of insignificant mortality". During phase 1, the infective larvae are immediately destroyed in the subcutaneous tissue if they are not able to escape the inflammatory process by penetrating in local lymphatic vessels. By contrast, phase 2, which is longer than the duration of the third larval stage, indicates there is no mortality linked to the third moulting, at least following a single inoculation.

Animals↗

Seasonal variation of western white pine (Pinus monticola D. Don) foliage proteins.

Recently, a western white pine protein, Pin m III, was shown to be associated with overwintering and frost hardiness of western white pine foliage. To examine whether Pin m III is directly involved in frost hardiness by functioning as an antifreeze protein, work is underway to clone the gene encoding this protein and to assess the function of this gene in freezing tolerance by incorporating the gene in a test plant, such as tobacco. Here, we examined in more detail, by SDS-PAGE and also by two dimensional gel electrophoresis, the seasonal variation of additional proteins in western pine foliage. SDS-PAGE analysis of three seedlots showed that different proteins reached a maximum level in different months, although most proteins (5 to 11) reached a maximum level in winter months (December, January and February). The 2-D gel analysis of foliage sampled on three harvest dates (October, January and April) of one seedlot revealed a seasonal variation of a large number proteins (76 to 184). Of the seasonally varied proteins, the amino terminal sequence of several proteins including Pin m III was determined. One of the sequences was identified by homology to that of the small subunit of ribulose biphosphate carboxylase, whose level increased substantially from fall to spring. The amino terminal sequence of Pin m III had 89% homology to a sugar pine protein, Pin l I. The anti-photosystem II antibody was used to monitor the annual variation of the extrinsic 23-kDa photosystem II protein. The level of the extrinsic 23-kDa photosystem II protein decreased slowly as fall progressed and reached its lowest level in December and then increased in early spring indicating that this variation is due to photosynthetic activity of the foliage during the season.

Amino Acid Sequence↗

Do the facts and figures warrant a 10-fold increase in the performance of carotid endarterectomy on asymptomatic patients?

The detailed results of the Asymptomatic Carotid Atherosclerosis Study (ACAS) have been published. Electrifying reports in the media suggested that 53% fewer strokes would occur if individuals with 60% or greater stenosis were submitted to endarterectomy. The burning question is whether the evidence from this trial, and those preceding it, is sufficiently compelling to persuade any or all individuals with carotid stenosis, but free of any hemisphere and retinal symptoms, to have carotid endarterectomy. Based on a variety of population samplings, it is reasonable to estimate that approximately two million people are living in North America and Europe with asymptomatic lesions comparable with those studied in the ACAS.

Carotid Stenosis↗

Rationale and design of a large study to evaluate the renal and cardiovascular effects of an ACE inhibitor and vitamin E in high-risk patients with diabetes. The MICRO-HOPE Study. Microalbuminuria, cardiovascular, and renal outcomes. Heart Outcomes Prevention Evaluation.

OBJECTIVE: To describe the rationale and design of a large international study (microalbuminuria, cardiovascular, and renal outcomes [MICRO] in the HOPE [Heart Outcomes Prevention Evaluation] study) of an ACE inhibitor and vitamin E for the prevention of diabetic nephropathy (DN) and cardiovascular disease (CVD) in patients with diabetes and microalbuminuria (MA). RESEARCH DESIGN AND METHODS: A total of 3,657 diabetic subjects, including 1,129 with MA, are randomly allocated to receive the ACE inhibitor ramipril (or placebo) and vitamin E (or placebo) for 4 years in a two-by-two factorial design. Diabetic subjects are a subset of the 9,541 subjects enrolled in the HOPE study. RESULTS: The development of DN in microalbuminuric diabetic subjects and the development of MA in normoalbuminuric subjects, as well as cardiovascular death, myocardial infarction, and storke, are the main outcomes. The correlation of changes in albuminuria with changes in carotid atherosclerosis documented in a subset of subjects will also be analyzed. CONCLUSIONS: The effect of both an ACE inhibitor and vitamin E on the progression of renal and CVD in patients with diabetes is being assessed in the MICRO-HOPE study.

Albuminuria↗

Absence of cellular responses to a putative autoantigen in onchocercal chorioretinopathy. Cellular autoimmunity in onchocercal chorioretinopathy.

PURPOSE: Onchocerciasis is a major cause of blindness in the developing world. An autoimmune pathogenesis for onchocercal chorioretinopathy was proposed after the identification of a recombinant Onchocerca volvulus antigen (designated Ov39) demonstrated immunologic crossreactivity with a component of the retinal pigment epithelium and other ocular tissues. The aim of this study was to determine whether patients with onchocercal chorioretinopathy have enhanced lymphoproliferative responses to Ov39 compared to those without chorioretinal disease. METHODS: Lymphocyte blastogenic assays were performed using peripheral blood mononuclear cells (PBMCs) from patients with and without evidence of chorioretinopathy. PBMCs were cultured with Ov39, and supernatant fluids from Ov39-stimulated PBMCs were used to determine levels of the cytokines, interferon-gamma, and interleukin-5. RESULTS: Lymphoproliferative responses to Ov39 were not enhanced in patients with onchocercal chorioretinopathy compared to those without clinical evidence of chorioretinal disease. CONCLUSIONS: A role for Ov39-specific cellular autoreactivity in the pathogenesis of onchocercal chorioretinopathy could not be demonstrated.

Adolescent↗