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Biomedical subjects

Peter Taylor

Publications and source records attributed to Peter Taylor.

29 records · Page 2Linked to original sources
PubMed2003

Cardiac homeobox gene NKX2-5 mutations and congenital heart disease: associations with atrial septal defect and hypoplastic left heart syndrome.

OBJECTIVES: We sought to examine the importance of mutations in the cardiac transcription factor gene NKX2-5 in patients with an atrial septal defect (ASD), patent foramen ovale (PFO), or hypoplastic left heart syndrome (HLHS). BACKGROUND: Mutations in NKX2-5 have been found in families showing secundum ASD and atrioventricular (AV) conduction block and in some individuals with tetralogy of Fallot. The prevalence of NKX2-5 mutations in sporadic cases of ASD/PFO and other forms of congenital heart disease is unknown. METHODS: A cohort of 146 individuals with secundum ASD, PFO complicated by paradoxical embolism, or HLHS were evaluated. Patients with ASD or PFO were ascertained irrespective of family history or associated cardiac abnormalities. The coding region of the NKX2-5 locus was amplified by polymerase chain reaction and sequenced. RESULTS: Among 102 ASD and 25 PFO patients screened, 13 patients (10%) had a positive family history and 5 patients (4%) had AV conduction block. We found one previously documented NKX2-5 missense mutation, T178M, in members of a family with ASD without AV conduction block. One NKX2-5 mutation-positive child from this family had HLHS, although no mutations were subsequently found in 18 patients with sporadic or familial HLHS. In a second ASD family without AV conduction block, we found a missense change, E21Q, previously reported as pathogenic. Because this change did not segregate with disease status, we propose that it is a non-disease-causing polymorphism. CONCLUSIONS: Our findings suggest that NKX2-5 mutations are a relatively infrequent cause of sporadic ASD and HLHS. Screening for NKX2-5 mutations may be warranted in individuals with ASD and a positive family history, irrespective of the presence or absence of AV conduction block.

Adolescent↗
PubMed2003

A comparison between pre- and posthibernation morphometry, hematology, and blood chemistry in viperid snakes.

Snakes from temperate climates are often made to hibernate in zoos to stimulate reproduction. Unfortunately, deaths have occurred during and after hibernation. This study evaluated the health status, pre- and posthibernation, of 31 adult viperid snakes. It included morphometric measurements, hematology, and blood chemistry. No differences were seen in body weights and weight to length ratios between pre- and posthibernation examinations, suggesting that the overall condition of the snakes did not change. No differences were seen in hematologic and blood chemistry parameters, except that bile acids (3alpha-hydroxybile acids) decreased, the implications of which are unknown. Three individuals had markedly high plasma uric acid levels posthibernation; of these, two individuals died from extensive visceral gout and one recovered with fluid therapy. Viperid snakes should be clinically healthy, well hydrated, and in good body condition when they are put into hibernation. They should be maintained in an environment with sufficient humidity and should have access to water. Blood samples should be collected on arousal for measuring plasma uric acid levels. Changes in morphometry, hematology, and blood chemistry appear to be abnormal and should be investigated thoroughly.

Animals↗
PubMed2003

[Molecular and serological diagnosis of a dengue outbreak in Coro, Falcón state, Venezuela].

Dengue virus (DV) is responsible for a spectrum of diseases, from a self-limited fever disease (DF, dengue fever) to the more severe forms of hemorrhagic fever/dengue shock syndrome (DHF/DSS). The aim of this study was the serological and molecular confirmation of an outbreak of dengue in Falcon state, Venezuela. A total of 54 sera from patients with clinical diagnosis of DV infection were analyzed by an enzyme immunoassays developed in Venezuela (ELISA -IgM e -IgG) and by PCR. From them, 78% exhibited DV infection (PCR+ y/o IgM+), 48% exhibited viremia by PCR and 57% were positive to IgM. An interesting observation was the high percent (76%) of patients with past or secondary infection (IgG positive), which included all the patients exhibiting clinical symptoms of DHF (n = 8). From the PCR positive sera, serotype 1 was found in 27%, serotype 2 in 54% and serotype 4 in 19%. No serotype 3 was found circulating in this population, although this serotype was already circulating in the nearby island of Aruba. The combination of serological and molecular methods allow us to obtain a fairly precise information of this outbreak.

Adolescent↗
PubMed2002

Extracorporeal photopheresis reduces the number of mononuclear cells that produce pro-inflammatory cytokines, when tested ex-vivo.

Extracorporeal photopheresis (ECP) has been shown to be clinically effective in the treatment of many T cell-mediated conditions. ECP's mechanism of action includes the induction of apoptosis and the release of pro-inflammatory cytokines. Recently, we have observed early lymphoid apoptosis, detectable immediately post ECP. We were interested to determine what influence ECP has on pro-inflammatory cytokine secretion at this early pre-infusion stage. Samples from 6 cutaneous T cell lymphoma (CTCL) and 5 graft versus host disease (GvHD) patients were taken pre ECP and immediately post ECP, prior to re-infusion. Following separation, the PBMCs were added to a cell culture medium and stimulated with PMA, Ionomycin, and Brefeldin A for 6 hours. Using flow cytometry, intracellular cytokine expression of IFNgamma and TNFalpha was determined in the T cell population. The monocytes were evaluated for IL6, IFNgamma, IL12, and TNFalpha. For both patient groups, the number of IFNgamma-expressing T cells fell significantly at re-infusion, whilst both T cell- and monocyte-expressing TNFalpha levels were reduced at re-infusion. All other cytokines tested showed no significant change post ECP. For GvHD, pro-inflammatory cytokines have a pathological role. Their down-regulation may have a direct clinical benefit. However, the reduction in the number of IFNgamma- and TNFalpha-expressing mononuclear cells means, at this early stage, it is unlikely that these cytokines assist in the removal of the malignant Th2 cells present in CTCL.

Case-Control Studies↗
PubMed2002

The impact of theoretical errors on velocity estimation and accuracy of duplex grading of carotid stenosis.

Two potential errors in velocity estimation, Doppler angle misalignment and intrinsic spectral broadening (ISB), were determined and used to correct recorded blood velocities obtained from 20 patients (38 bifurcations). The recorded and corrected velocities were used to grade stenoses of greater than 70% using two duplex classification schemes. The first scheme used a peak systolic velocity (PSV) of > 250 cm/s in the internal carotid artery (ICA), and the second a PSV ratio of > 3.4 (ICA PSV/common carotid artery PSV). The "gold standard" was digital subtraction angiography (DSA). The maximum error in velocity estimation due to Doppler angle misalignment was 33 cm/s, but this did not alter sensitivity of stenosis detection. ISB correction caused a reduction in PSV that decreased the sensitivity of the PSV scheme from 65% to 45%. The PSV ratio classification was not affected by ISB errors. Centres using a PSV criterion for grading stenosis should use a fixed Doppler angle and should establish velocity thresholds in-house.

Aged↗
PubMed2002

Production of human monoclonal antibodies against Galalpha(1-3)Gal.

The hyperacute rejection observed in models of pig-to-human xenotransplantation is mainly because of the presence of natural antibodies in human blood with specificity for the Galalpha(1-3)Gal (Gal) carbohydrate moiety present on the surface of porcine endothelial cells. Human monoclonal anti-Gal antibodies could be of use both in the study of the basic mechanisms of hyperacute rejection as well as in its clinical prevention. In the present study we prepared 42 heterohybridomas (human-mouse) secreting antibodies with specificity for the Gal epitope. All of the antibodies produced were of the IgM isotype, according to a dot-blot assay. Twenty-seven antibodies were further characterized, and shown to be specific for Gal by different methods, including an enzyme-linked immunosorbent assay, in which the plates were sensitized with mouse laminin as a source of Gal. Specificity was also confirmed using purified Gal carbohydrate in a hemagglutination inhibition assay. The antibodies were shown to mediate lysis of Gal-expressing rabbit erythrocytes in the presence of complement. However, the heterohybridomas themselves were shown to express Gal, a result of the mouse P3x63Ag8.653 hybridoma cells used during hybridoma generation. The presence of this epitope on the surface of anti-Gal-producing cells, and on the antibody itself, represents a limitation to the production of high affinity anti-Gal antibodies.

Animals↗
PubMed2002

Effect of Burkholderia cepacia infection in the clinical course of patients with cystic fibrosis: a pilot study in a Sydney clinic.

BACKGROUND: Colonisation with Burkholderia cepacia complex in patients with cystic fibrosis (CF) has been associated with adverse outcomes. The aim of the present study was to determine the actuarial survival of CF patients colonized with B. cepacia and to evaluate the efficacy of the Royal Prince Alfred Hospital segregation policy. A secondary aim was to characterize the specific genomovars and strains of B. cepacia isolated in an Australian clinic. METHODS: Retrospective review of spirometric and microbiological data on all patients colonized with B. cepacia. Each B. cepacia-colonized subject was matched with three case-control subjects. Phenotype and genomovar typing, random amplified polymorphic DNA strain type and B. cepacia epidemic strain marker analyses were performed. The effect of B. cepacia colonization on transplant-free survival was estimated by Cox's proportional hazards regression using the entire clinic population. RESULTS: Fifteen patients were colonized with B. cepacia, of whom six (40%) had died from CF-related disease by August 1998, compared with 30 of 173 (17.3%) of the entire clinic population. Cepacia status had a significant adverse effect on survival, with a hazard ratio of 2.16 (95% confidence interval 1.0-4.69; P = 0.05). The outcome was variable in subgroups of B. cepacia. DISCUSSION: Colonization with B. cepacia had a significant adverse effect on survival within the study population. Genomovar and strain typing contributed usefully in accessing the effectiveness of the hospital's segregation policy in preventing cross-colonization.

Actuarial Analysis↗
PubMed2000

Discriminant and multiple regression analysis of anemia and opportunistic infection in Fell pony foals.

A condition resembling acquired immunodeficiency with anemia has been described in British Fell pony foals. The pathogenesis is unknown. The present study involved 322 foals of which 164 were of Fell breed and 12 were affected. Discriminant and multiple regression analyses were used to test the results of all clinical pathology parameters from these foals for statistical association with (1) breed origin and (2) presence of disease. Only hematocrit associated significantly with presence of disease. However, significant associations were found with Fell breed origin, including serum albumin concentration and lymphocyte count. The unexpected discovery of sporadic lymphocytosis in the breed indicates the value of this kind of analysis and may be evidence that Fell foal immunodeficiency is associated with retroviral infection.

Journal Article↗
PubMedDate not supplied

Does leaf water efficiency vary among eucalypts in water-limited environments?

There is a need to generalize water use behavior of eucalypts to facilitate bioengineering and landscape remediation programs in a wide range of Australian environments. A critical question can be stated as a null hypothesis: tree water use per unit leaf area (leaf efficiency) is independent of eucalypt species. This is implicitly equivalent to the hydrological equilibrium hypothesis that states that leaf area is a function of climate, at least in cases where transpiration and growth are limited by soil water. Failure to reject this null hypothesis simplifies (a) the selection of tree species for water balance management, (b) the generation of regional-scale expectations of leaf area index, and (c) the estimation (monitoring) of the effectiveness of plantations in controlling site water balance. The hypothesis was tested with tree water use data collected in natural multi-species stands across Australia, including sites in the wet-dry season tropical woodlands of the Northern Territory, the Mediterranean climate forests of Western Australia, and a woodland system in southern New South Wales receiving an even distribution of rainfall throughout the year. We also tested the hypothesis in a multi-species tree plantation growing on a saline gradient. In each case, we could not reject the hypothesis of constant leaf efficiency among eucalypts. In every case there was a common, strong, linear relationship among tree leaf area and mean daily water use by all tree species in a sample. Single factor (species) analysis of variance did not detect significant differences between leaf water efficiencies of species. For the jarrah forest (Eucalyptus marginata J. Donn ex Sm., E. calophylla R. Br. ex Lindl.), the null hypothesis held in both spring (wet) and autumn (dry) conditions. The null hypothesis held in the mixed species woodland of New South Wales (E. macrorhynca F.J. Muell. ex Benth., E. blakelyi Maiden., E. polyanthemos Schauer.) under summer and autumn conditions, and across five species in the wet-dry tropical woodland (E. miniata A. Cunn. ex Schauer, E. tetrodonta F.J. Muell., E. porecta S.T. Blake, Erythrophleum chlorostachys F.J. Muell., and Terminalia ferdinandiana Exell.). The null hypothesis also held for a plantation of E. occidentalis Endl. and provenances of E. camaldulensis Dehnh. growing on a shallow saline gradient; i.e., leaf water efficiency remained constant across species and varieties despite obvious effects of salinity on the size of individual canopies. We conclude that there is little evidence for rejecting the hypothesis that leaf efficiency does not vary significantly among sympatric eucalypt species in rainfall-limited (soil-water-limited) systems. These findings open the way for useful bioengineering generalities about the hydrological role of trees in the Australian landscape.

Journal Article↗
PubMedDate not supplied

Interleukin-2 induces peroxide production by primed normodense eosinophils of patients with asthma.

In this study we assessed, by flow cytometry, the effect of interleukin 2 (IL-2) on the oxidative burst of normodense eosinophils (Eos's) isolated from 15 patients with moderately severe extrinsic asthma and 17 controls. We found that IL-2 significantly induced peroxide (H2O2) production in normodense Eos's from patients with asthma on a time kinetics study. This rise was higher in patients with immunoglobulin E levels > 180 IU/mL versus normal immunoglobulin E values. The effect of IL-2 was partially blocked by using anti-Tac antibody. In contrast, IL-2 decreased H2O2 production in normodense Eos's from controls. Cell surface expression of CD25, CD122, CD132, and CD69 were also determined and no statistical differences were found between both groups. In conclusion, IL-2 is able to increase H2O2 production by normodense Eos's isolated from patients with asthma and it may contribute to bronchial epithelium damage and chronic inflammation.

Adolescent↗