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Biomedical subjects

S Taylor

Publications and source records attributed to S Taylor.

At least 19 recordsLinked to original sources
PubMed2006

A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii.

Toxoplasma gondii strains differ dramatically in virulence despite being genetically very similar. Genetic mapping revealed two closely adjacent quantitative trait loci on parasite chromosome VIIa that control the extreme virulence of the type I lineage. Positional cloning identified the candidate virulence gene ROP18, a highly polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion. Transfection of the virulent ROP18 allele into a nonpathogenic type III strain increased growth and enhanced mortality by 4 to 5 logs. These attributes of ROP18 required kinase activity, which revealed that secretion of effectors is a major component of parasite virulence.

Alleles↗
PubMed2006

Polymorphic secreted kinases are key virulence factors in toxoplasmosis.

The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify the responsible genes, we mapped virulence in F(1) progeny derived from crosses between type II and type III strains, which we introduced into mice. Five virulence (VIR) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule. Both are hypervariable rhoptry proteins that are secreted into the host cell upon invasion. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction.

Alleles↗
PubMed2006

Quartet states of the acetylene cation: electronic structure calculations and spin-orbit coupling terms.

Highly correlated ab initio methods have been used to generate one-dimensional cuts of the six-dimensional potential energy surfaces of the quartet and lowest doublet states for the HCCH(+) ion along the CH, CC, and cis and trans bending coordinates. Transition dipole moments and spin-orbit matrix elements are deduced. For the lowest 1 (4)Sigma(u) (+) state, the calculations predict a possible photon emission through the 1 (4)Pi(g)<--1 (4)Sigma(u) (+) transition competing with internal conversion and predissociation processes. The potential surfaces are used together with spin-orbit matrix elements to discuss the metastability and the predissociation processes forming the C(2)HC(2)H(+)+H(+)H products. Multistep spin-orbit induced predissociation pathways are suggested.

Journal Article↗
PubMed2006

Determination of the androgenic potency of whole effluents using mosquitofish and trout bioassays.

This study combined bioassay-derived and direct chemical analysis of steroidal compounds in pulp and paper and municipal sewage effluent in order to determine the cause of masculinization of female mosquitofish. The bioassays used in this study consisted of androgen and estrogen receptor binding, and aromatase inhibition using tissues from rainbow trout. This study observed no masculinization of female mosquitofish from a pulp and paper mill effluent that was previously observed to cause this effect. Mosquitofish sampled from the receiving environment of the same mill verified that masculinization was not occurring in the wild. The municipal sewage effluent also had no masculinizing effect. In vitro bioassays indicated significant sources of both androgens and estrogens in the effluents tested with sewage effluent having both the highest estradiol (41 ng/L) and testosterone (182 ng/L) equivalent concentration. These results could not be attributed to any particular compounds measured in the effluents. Two compounds implicated in the masculinization of mosquitofish by pulp and paper effluent, androstenedione and androstadienedione required relatively large (10-100 microg/L) waterborne concentrations to elicit a masculinizing effect and neither of these compounds are likely to occur at levels this high in the natural environment. The potent aromatase inhibitor, 4-hydroxyandrostenedione also did not cause masculinization at 100 microg/L indicating that masculinization did not occur through this mechanism. The mammalian anti-androgen, cyproterone acetate was only partially effective in mosquitofish and reduced the severity of masculinization in the presence of methyl testosterone. While neither effluent masculinized mosquitofish, there was a significant reduction of in vitro ovarian steroid production with the most severe effects observed with the sewage effluent. Overall, this study found the disappearance of a masculinizing effect that had been previously observed; concluded that based on 21 days aqueous exposures androstenedione and androstadienedione are not likely candidates for mosquitofish masculinization, and showed that masculinization and in vitro steroid production are unrelated biological endpoints.

Androgens↗
PubMed2006

Pharmacy diabetes care program: analysis of two screening methods for undiagnosed type 2 diabetes in Australian community pharmacy.

OBJECTIVE: To compare the efficacy and cost-effectiveness of two methods of screening for undiagnosed type 2 diabetes in Australian community pharmacy. METHODS: A random sample of 30 pharmacies were allocated into two groups: (i) tick test only (TTO); or (ii) sequential screening (SS) method. Both methods used the same initial risk assessment for type 2 diabetes. Subjects with one or more risk factors in the TTO group were offered a referral to their general practitioner (GP). Under the SS method, patients with risk factors were offered a capillary blood glucose test and those identified as being at risk referred to a GP. The effectiveness and cost-effectiveness of these approaches was assessed. RESULTS: A total of 1286 people were screened over a period of 3 months. The rate of diagnosis of diabetes was significantly higher for SS compared with the TTO method (1.7% versus 0.2%; p=0.008). The SS method resulted in fewer referrals to the GP and a higher uptake of referrals than the TTO method and so was the more cost-effective screening method. CONCLUSIONS: SS is the superior method from a cost and efficacy perspective. It should be considered as the preferred option for screening by community based pharmacists in Australia.

Australia↗
PubMed2006

Fluorescence and metastability of N2O2+: theory and experiment.

State-selective mass spectrometry has revealed one conclusive and another probable metastable state of the N2O2+ dication, assigned respectively as 1 3Pi at 38.5 eV and 2 3Pi at 42.5 eV. Photon coincidence experiments confirm that dissociation of 1 3Pi is preceded by a fluorescent transition to X 3Sigma- and also indicate that an identical mechanism occurs for 2 3Pi. Highly correlated MRCI calculations are performed at a range of N2O2+ geometries, from which both N-N and N-O bond stretching curves are generated. Substantial barriers along both coordinates are observed for 1 3Pi and 2 3Pi, although the increasing density of states at higher energy may allow spin-orbit or vibronic predissociation for 2 3Pi. Fragment emissions derived from N2O+ and N2O2+ are analyzed with the aid of glass filters, from which NO (X 2Pi<--A 2Sigma+) and vibrationally excited N2+ (X 2Sigmag+<--B 2Sigmau+) transitions are deduced.

Journal Article↗
PubMed2006

Increased levels of NAD(P)H: quinone oxidoreductase 1 (NQO1) in pancreatic tissues from smokers and pancreatic adenocarcinomas: A potential biomarker of early damage in the pancreas.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is elevated in several human tumors. This study was conducted to determine whether increased levels of NQO1 expression also occur in human pancreatic tumor tissue, and to compare expression levels in nontumorous tissue from smokers with those in nonsmokers. The expression of NQO1 was examined in pancreatic tissue samples from 82 human donors. These samples included normal (n = 20), smokers (n = 25), pancreatitis (n = 7), and adenocarcinomas of the pancreas (n = 30). Genotyping for the C609T polymorphism in NQO1 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was also performed. Polymorphic variants were confirmed by automatic sequencing. Higher levels of NQO1 expression were demonstrated in pancreatic adenocarcinomas (0.831 +/- 0.021) compared to those in nontumorous tissues from nonsmokers (0.139 +/- 0.024). These high levels were also found in smokers (0.729 +/- 0.167) and in pancreatitis tissues (0.923 +/- 0.184). NQO1 activity was also higher in smokers (2.43 +/- 0.61 nmol/min per mg protein) compared to nonsmokers (0.44 +/- 0.05 nmol/min per mg protein; p < 0.05). No differences were found in genotype distribution and frequencies of the variant alleles between normal and cancer tissues in this relatively small sample pool. Seventy-five percent of the normal pancreatic tissues showed 609(C/C) and 25% 609(C/T). In pancreatic adenocarcinomas the frequency distribution was 65% C/C, 30% C/T and 5% T/T. The increased expression in noncancer pancreatic tissue from smokers and the fact that smoking is a moderate risk factor for pancreatic cancer suggest that NQO1 expression may be a good candidate as a biomarker for pancreatic cancer, especially in risk groups such as smokers.

Adenocarcinoma↗
PubMed2006

Video capsule endoscopy in peutz-jeghers syndrome: a blinded comparison with barium follow-through for detection of small-bowel polyps.

BACKGROUND AND STUDY AIMS: Video capsule endoscopy has shown promise for the surveillance of significant small-bowel polyps in patients with Peutz-Jeghers syndrome. In this study the yield of significant small-bowel polyps by capsule endoscopy was compared to the yield of these polyps by barium follow-through in adults with Peutz-Jeghers syndrome. PATIENTS AND METHODS: A total of 19 adults with Peutz-Jeghers syndrome who were undergoing surveillance underwent both capsule endoscopy and barium follow-through examinations, and the number of small-bowel polyps of at least 1 cm in diameter that were detected was recorded for each method. The two methods were assessed in terms of comfort and convenience for the patients and their preferred future surveillance method, using a questionnaire. RESULTS: Capsule endoscopy detected a median of four significant small-bowel polyps while barium follow-through detected a median of one (P = 0.008). There was a trend towards more participants having at least one significant small-bowel polyp detected by capsule endoscopy than was the case with barium follow-through, though capsule endoscopy seemed to be less reliable for accurate sizing of polyps that were at the limit of clinical significance. Most participants expressed a preference for capsule endoscopy for future surveillance. CONCLUSIONS: Capsule endoscopy should replace barium follow-through for the surveillance of small-bowel polyps in adults with Peutz-Jeghers syndrome, but the findings of this study should be interpreted with caution until a more reliable means of sizing polyps by capsule endoscopy is available.

Administration, Oral↗
PubMed2006

Coeliac disease and oats: a systematic review.

A systematic review of the literature related to the inclusion of oats in the gluten-free diet for patients with coeliac disease to assess whether oats can be recommended. A computerised literature review of multiple databases was carried out, identifying 17 primary studies, 6 of which met the criteria for inclusion in this review. None of the six studies found any significant difference in the serology between the oats and control groups. Two studies, however, identified a significant difference (p<0.001; p = 0.039) in intraepithelial lymphocyte counts between the oats and control groups. Oats can be symptomatically tolerated by most patients with coeliac disease; however, the long-term effects of a diet containing oats remain unknown. Patients with coeliac disease wishing to consume a diet containing oats should therefore receive regular follow-up, including small bowel biopsy at a specialist clinic for life.

Antibodies↗
PubMed2006

Non-invasive distal femoral expandable endoprosthesis for limb-salvage surgery in paediatric tumours.

We report our early experience with the use of a non-invasive distal femoral expandable endoprosthesis in seven skeletally immature patients with osteosarcoma of the distal femur. The patients had a mean age of 12.1 years (9 to 15) at the time of surgery. The prosthesis was lengthened at appropriate intervals in outpatient clinics, without anaesthesia, using the principle of electromagnetic induction. The patients were functionally evaluated using the Musculoskeletal Tumour Society scoring system. The mean follow-up was 20.2 months (14 to 30). The prostheses were lengthened by a mean of 25 mm (4.25 to 55) and maintained a mean knee flexion of 110 degrees (100 degrees to 120 degrees ). The mean Musculoskeletal Tumour Society score was 68% (11 to 29). Complications developed in two patients; one developed a flexion deformity of 25 degrees at the knee joint, which was subsequently overcome and one died of disseminated disease. The early results from patients treated with this device have been encouraging. The implant avoids multiple surgical procedures, general anaesthesia and assists in maintaining leg-length equality.

Adolescent↗
PubMed2006

T-lymphocyte profiles in FIV-infected wild lions and pumas reveal CD4 depletion.

Feline immunodeficiency virus (FIV) is a lentivirus related to human immunodeficiency virus (HIV) that causes feline AIDS in the domestic cat (Felis catus). Serological surveys indicate that at least 25 other species of cat possess antibodies that cross-react with domestic cat FIV. Most infected nondomestic cat species are without major symptoms of disease. Long-term studies of FIV genome variation and pathogenesis reveal patterns consistent with coadaptation of virus and host in free-ranging FIV-Ple-infected African lions (Panthera leo) and FIV-Pco-infected pumas (Puma concolor) populations. This report examined correlates of immunodeficiency in wild and captive lions and pumas by quantifying CD5(+), CD4(+), and CD8(+) T-cell subsets. Free-ranging FIV-Ple-infected lions had immunofluorescence flow cytometry (IFC) profiles marked by a dramatic decline in CD4(+) subsets, a reduction of the CD4(+)/CD8(+) ratio, reduction of CD8(+)beta(high) cells, and expansion of the CD8(+)beta(low) subset relative to uninfected lions. An overall significant depletion in CD5(+) T-cells in seropositive lions was linked with a compensatory increase in total CD5(-) lymphocytes. The IFC profiles were altered significantly in 50% of the seropositive individuals examined. The FIV-Pco-infected pumas had a more generalized response of lymphopenia expressed as a significant decline in total lymphocytes, CD5(+) T-cells, and CD5(-) lymphocytes as well as a significant reduction in CD4(+) T-cells. Like lions, seropositive pumas had a significant decline in CD8(+)beta(high) cells but differed by not having compensatory expansion of CD8(+)beta(low) cells relative to controls. Results from FIV-infected lions and pumas parallel human and Asian monkey CD4(+) diminution in HIV and SIV infection, respectively, and suggest there may be unrecognized immunological consequences of FIV infection in these two species of large cats.

Adaptation, Physiological↗
PubMed2005

Synthesis and biological evaluation of novel hexahydro-pyrido[3',2':4,5]pyrrolo[1,2-a]pyrazines as potent and selective 5-HT(2C) receptor agonists.

Further lead optimization efforts on previously described 1,2,3,4,10,10a-hexahydro-1H-pyrazino[1,2-a]indoles led to the new class of 5,5a,6,7,8,9-hexahydro-pyrido[3',2':4,5]pyrrolo[1,2-a]pyrazines culminating in the discovery of (5aR,9R)-2-[(cyclopropylmethoxy)methyl]-5,5a,6,7,8,9-hexahydro-9-methyl-pyrido[3', 2':4,5]pyrrolo[1,2-a]pyrazine 18 as a potent, full 5-HT(2C) receptor agonist with an outstanding selectivity profile and excellent hERG and phospholipidosis properties.

Animals↗
PubMed2005

Dissolution of composition B detonation residuals.

Composition B (Comp B) detonation residuals pose environmental concern to the U.S. Army because hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a constituent, has contaminated groundwater near training ranges. To mimic their dissolution on surface soils, we dripped water at 0.51 ml/h onto individual Comp B particles (0.1-2.0 mg) collected from the detonation of 81-mm mortars. Analyses of the effluent indicate thatthe RDX and 2,4,6-trinitrotoluene (TNT) in Comp B do not dissolve independently. Rather, the relatively slow dissolution of RDX controls dissolution of the particle as a whole by limiting the exposed area of TNT. Two dissolution models, a published steady-flow model and a drop-impingement model developed here, provide good agreementwith the data using RDX parameters for time scaling. They predict dissolution times of 6-600 rainfall days for 0.01-100 mg Comp B particles exposed to 0.55 cm/h rainfall rate. These models should bracket the flow regimes for dissolution of detonation residuals on soils, but they require additional data to validate them across the range of particle sizes and rainfall rates of interest.

Environmental Exposure↗
PubMed2005

Identification of 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5-HT2C receptor agonists.

Synthesis and evaluation of the activity of new 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5-HT(2C) receptor agonists are described. Appropriately substituted, several analogs displayed selectivity against the other 5-HT(2) receptor subtypes of 1 order of magnitude or more. Selectivity was improved for several compounds versus the lead 1, increasing the therapeutic interest in this series of 5-HT(2C) receptor agonists.

Animals↗
PubMed2005

Complementary roles of simple variables, NYHA and N-BNP, in indicating aerobic capacity and severity of heart failure.

AIMS: The extent of exercise intolerance in patients with chronic heart failure (CHF) is dependent on and representative of the severity of heart failure. However, few primary care physicians have direct access to facilities for formal exercise testing. We have therefore explored whether information readily obtainable in the community can reliably predict the functional capacity of patients. METHODS AND RESULTS: Ninety-six subjects with a wide range of cardiac function (10 healthy controls and 86 CHF patients with NYHA classes I-IV, LVEF 36.9+/-15.2%) were recruited into the study and had resting plasma N-BNP and cardiopulmonary exercise testing to measure peak oxygen consumption (VO2). Significantly higher N-BNP levels were found in the CHF group (299.3 [704.8] fmol/ml, median [IQR]) compared with the healthy control group (7.2 [51.2] fmol/ml), p<0.0001. There were significant correlations between peak VO2 and N-BNP levels (R=0.64, P<0.001), peak VO2 and NYHA class (R=0.76, P=0.001), but no significant correlation was seen between peak VO2 and LVEF (R=0.0788, P=0.33). Multivariate analysis identified plasma N-BNP (P<0.0001) and NYHA class (P<0.0001) as significant independent predictors of peak VO2. Logistic modelling with NYHA class and log N-BNP to predict peak VO2<20 ml/kg/min showed that the area under the curve of receiver-operating-characteristic (ROC) curve was 0.906 (95% CI 0.844-0.968). A nomogram based on the data has been constructed to allow clinicians to estimate the likelihood of peak VO2 to be <20 ml/kg/min for given values of plasma N-BNP and NYHA class. CONCLUSIONS: By combining information from a simple objective blood test (N-BNP) and a simple scoring of functional status (NYHA), a clinician can deduce the aerobic exercise capacity and indirectly the extent of cardiac dysfunction of patients with CHF.

Adult↗
PubMed2005

Evidence for strange-quark contributions to the nucleon's form factors at Q2=0.108 (GeV/c)2.

We report on a measurement of the parity violating asymmetry in the elastic scattering of polarized electrons off unpolarized protons with the A4 apparatus at MAMI in Mainz at a four momentum transfer value of Q(2)=0.108 (GeV/c)(2) and at a forward electron scattering angle of 30 degrees p)=[-1.36+/-0.29(stat)+/-0.13(syst)]x10(-6). The expectation from the standard model assuming no strangeness contribution to the vector current is A(0)=(-2.06+/-0.14)x10(-6). We have improved the statistical accuracy by a factor of 3 as compared to our previous measurements at a higher Q2. We have extracted the strangeness contribution to the electromagnetic form factors from our data to be G(s)(E)+0.106G(s)(M)=0.071+/-0.036 at Q(2)=0.108 (GeV/c)(2). We again find the value for G(s)(E)+0.106G(s)(M) to be positive, this time at an improved significance level of two sigma.

Journal Article↗