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Biomedical subjects

S Parker

Publications and source records attributed to S Parker.

At least 37 records · Page 2Linked to original sources
PubMed2001

Identification of four new translocations involving FGFR1 in myeloid disorders.

The 8p11 myeloproliferative syndrome (EMS) is associated with three translocations, t(8;13)(p11;q12), t(8;9)(p11;q33), and t(6;8)(q27;p11), that fuse unrelated genes (ZNF198, CEP110, and FOP, respectively) to the entire tyrosine kinase domain of FGFR1. In all cases thus far examined (n = 10), the t(8;13) results in an identical mRNA fusion between ZNF198 exon 17 and FGFR1 exon 9. To determine if consistent fusions are also seen in the variant translocations, we performed RT-PCR on four cases and sequenced the products. For two patients with a t(8;9), we found that CEP110 exon 15 was fused to FGFR1 exon 9. For two patients with a t(6;8), we found that FOP exon 5 (n = 1) or exon 7 (n = 1) was fused to FGFR1 exon 9. To determine if FGFR1 might be involved in other myeloid disorders with translocations of 8p, we developed a two-color FISH assay using two differentially labeled PAC clones that flank FGFR1. Disruption of this gene was indicated in a patient with a t(8;17)(p11;q25) and Ph-negative chronic myeloid leukemia in association with systemic malignant mast cell disease, a patient with acute myeloid leukemia with a t(8;11)(p11;p15), and two cases with T-cell lymphoma, myeloproliferative disorder, and marrow eosinophilia with a t(8;12)(p11;q15) and ins(12;8)(p11;p11p21), respectively. For the patient with the t(8;11), the chromosome 11 breakpoint was determined to be in the vicinity of NUP98. We conclude that 1) all mRNA fusions in EMS result in splicing to FGFR1 exon 9 but breakpoints in FOP are variable, 2) two-color FISH can identify patients with EMS, and 3) the t(8;17)(p11;q25), t(8;11)(p11;p15), t(8;12)(p11;q15), and ins(12;8)(p11;p11p21) are novel karyotypic changes that most likely involve FGFR1.

Chromosomes, Human, Pair 11↗
PubMed2001

The effect of particle size on the gelation of tissue conditioners.

Tissue conditioner materials comprise a methacrylate polymer powder, usually poly(ethyl methacrylate) (PEM), and a plasticiser that also contains ethanol. The aim of this study was to investigate the effect of ball milling the PEM on gelation time. PEM was used as received and after ball milling for 2, 4, 8 and 16 h. Particle size was measured in each case and gelation time at 37 degrees C when mixed with butyl phthalyl butyl glycollate (BPBG). Gelation time reduced with increasing milling time of the powder, however it was found that increase in the fines initially had a more significant affect than overall reduction in average particle size. The gelation time of unmilled and 16 h milled PEM were also measured when mixed with BPBG and various levels of ethanol. Unmilled PEM with 4% ethanol had a gelation time of 13.5 +/- 2.0 min compared to 5.5 +/- 1.0 min for the 16h milled PEM which was similar to that for the commercial material, Viscogel (6.0 +/- 1.0 min). Ball milling the PEM reduces the level of ethanol required to produce a clinically acceptable gelation time.

Biocompatible Materials↗
PubMed2001

Blends of isoprene-styrene/methacrylate monomer systems as denture soft lining material.

This work further develops the concept of using an elastomer gelled with methacrylate monomers to produce a methacrylate-based soft lining material without the use of a plasticizer. An isoprene-styrene (SIS) block copolymer was mixed with methyl methacrylate (MMA) and 1,6-hexandiol dimethacrylate (HDMA). The HDMA was used as a cross-linking agent. The elastomer/monomer ratios were maintained at 50/50 whereas the monomers ranged from 0 to 100%) HDMA. Mechanical properties and water absorption/desorption characteristics were used to assess the effect of varying the monomer compositions. The results indicated that phase separation took place, in particular at high HDMA content. This significantly increased the Young's modulus and decreased the elongation to break. Generally, the water uptake tended to decrease with increasing HDMA content, reflecting the effect of modulus. Second absorption cycles gave higher uptake values compared to the first. Formulations with a high amount of HDMA gave materials with modulus values too high for soft lining applications. This suggests that the optimum formulation requires a compromise between modulus and water uptake.

Absorption↗
PubMed2001

Isoprene-styrene copolymer elastomer and tetrahydrofurfuryl methacrylate mixtures for soft prosthetic applications.

Novel elastomer/methacrylate systems have been developed for potential soft prosthetic applications. Mixtures of varying compositions of an isoprene-styrene copolymer elastomer and tetrahydrofurfuryl methacrylate (SIS/THFMA) formed one-gel systems and were heat cured with a peroxide initiator. The blends were characterised in terms of sorption in deionised water and simulated body fluids (SBF), tensile properties and viscoelastic parameters of storage modulus and tan delta, as well as glass transition temperatures using dynamic mechanical analysis (DMA). DMA data gave two distinct peaks in tan delta, a lower temperature transition due to the isoprene phase in SIS and one at high temperature thought to be a combination of THFMA and the styrene phase in SIS. The tensile data showed a clear phase inversion within the mid range compositions changing from plastic to elastomeric behaviour. The sorption studies in deionised water showed a two stage uptake with an initial Fickian region that was linear to t 1/2 followed by a droplet growth/clustering system. The slope of the linear region was dependent on the composition ratio. The extent of overall uptake was osmotically dependent as all materials equilibrated at a much lower uptake in SBF. The diffusion coefficients were found to be concentration dependent.

Absorption↗
PubMed2001

Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo.

STI571 targets p210(BCR-ABL) in chronic myeloid leukaemia (CML). In vitro, STI571 reduces self-replication (replating ability) by chronic-phase CML CFU-GM. Here, we studied CFU-GM in advanced-phase (accelerated and blast crisis) CML. The numbers and self-replication of CFU-GM in advanced phase were greater than in the chronic phase. Self-replication by CFU-GM from advanced phase patients was reduced by STI571 or IFN alfa to the same extent as in the chronic phase. The reduced replating ability induced by STI571 correlated with that induced by IFN alpha (r=0.73). STI571 treatment in vivo also reduced replating ability and the numbers of CFU-GM/ml of blood.

Antineoplastic Agents↗
PubMed2001

Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels have been associated with vascular disease and higher mortality in patients with coronary artery disease. Graft coronary disease is a major cause of mortality in long-term survivors of heart transplantation, and hyperhomocysteinemia may be one of its causes. The objectives of our study were to establish the effectiveness of a 3 stage homocysteine-lowering algorithm in a group of 84 heart transplant (HTx) patients and to evaluate the effect of renal function on the response to homocysteine-lowering therapy. METHODS: Prospective treatment of 84 Htx patients (64 male; mean age, 48 +/- 13 years) with tHcy > 75th percentile consisted of a 3-stage treatment algorithm: Stage 1, folic acid (FA) 2 mg + vitamin (vit) B(12) 500 mcg daily; Stage 2, addition of vit B(6) 100 mg daily; Stage 3, increase FA to 15 mg daily. Serum creatinine (Cr) and tHcy levels were measured before treatment and 21 +/- 19 weeks after each stage of treatment. RESULTS: All 3 stages of treatment significantly lowered mean tHcy from 22.4 +/- 16.3 (mean +/- SD) micromol/liter to 16.3 +/- 6.7 micromol/liter (p < 0.00001), from 17.6 +/- 6.1 micromol/liter to 15.2 +/- 5.3 micromol/liter (p < 0.0001), and from 16.8 +/- 5.2 micromol/liter to 15.6 +/- 5.3 micromol/liter (p < 0.05), respectively. The average reduction from baseline was 38%. Creatinine levels did not change significantly during the study period. Total plasma homocysteine levels decreased below the 75th percentile in 55% of patients, with Cr levels significantly lower in this group of patients (126 +/- 36 micromol/liter vs 182 +/- 65 micromol/liter, p < 0.00001). However, we found no significant relationship between % change in tHcy and baseline Cr. CONCLUSIONS: In a group of 84 heart transplant patients with tHcy levels >75th percentile, treatment with FA and vit B(6) and B(12) according to a 3-stage algorithm resulted in statistically significant declines in mean tHcy levels. Overall, tHcy levels decreased 38%, with target tHcy levels <75th percentile achieved in 55% of the patients. The % change in tHcy was not related to Cr. Further studies are needed to correlate treatment of hyperhomocysteinemia with clinical endpoints, such as the time to development of transplant vasculopathy and long-term survival, and to define the most appropriate targets for therapy.

Adult↗
PubMed2001

Development of novel elastomer/methacrylate monomer soft lining materials.

An earlier study identified a formulation comprising a butadiene/styrene copolymer (PBS) gelled with ethyl hexyl methacrylate (5 + formulation) as a potential denture soft lining material. It had good mechanical properties but water uptake was high as a result of the presence of a separating agent. This study has compared the tensile and water absorption properties of four elastomers free from separating agent (three butadiene/styrene, HBS, EBS, SBS, and one isoprene/styrene, SIS) with those of PBS all using the 5 + formulation. HBS is emulsion polymerized; the others are solution polymerized. SIS5 + had the better tensile properties whereas HBS5 + had the lowest water uptake. All the other 5 + formulations had higher uptakes than PBS5 +, which is thought to be due to the presence of hydrophilic groups from the solution polymerization process. All materials showed some sign of oxidation. Emulsion polymerized elastomers are regarded as less suitable for medical uses than the solution polymerized alternatives. Of these, SIS5 + seems to be less prone to oxidation and has the better mechanical properties so was considered to be the most suitable material for further development.

Journal Article↗
PubMed2001

Regions in the carboxy terminus of alpha-bENaC involved in gating and functional effects of actin.

Gating differences occur between the alpha-subunits of the bovine and rat clones of an amiloride-sensitive epithelial Na+ channel (ENaC). Deletion of the carboxy terminus of bovine alpha-ENaC (alpha-bENaC) at R567 converted the gating properties to that of rat alpha-ENaC (alpha-rENaC). The equivalent truncation in alpha-rENaC was without effect on the gating of the rat homologue. The addition of actin to ENaC channels composed of either alpha-rENaC or alpha-bENaC alone produced a twofold reduction in conductance and an increase in open probability. Neither alpha-rENaC (R613X) nor alpha-bENaC (R567X) was responsive to actin. Using a chimera consisting of alpha-rENaC1-615 and alpha-bENaC570-650, we examined several different carboxy-terminal truncation mutants plus and minus actin. When incorporated into planar bilayers, the gating pattern of this construct was identical to wild-type (wt) alpha-bENaC. Premature stop mutations proximal to E685X produced channels with gating patterns like alpha-rENaC. Actin had no effect on the E631X truncation, whereas more distal truncations all interacted with actin, as did wt alpha-bENaC. Key findings were confirmed using channels expressed in Xenopus oocytes and studied by cell-attached patch-clamp recording. Our results suggest that the site of actin regulation at the carboxy terminus of the chimera is located between residues 631 and 644.

Actins↗
PubMed2001

Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.

We tested the hypothesis that an arginine-rich region immediately following the second transmembrane domain may constitute part of the inner mouth of the epithelial Na+ channel (ENaC) pore and, hence, influence conduction and/or selectivity properties of the channel by expressing double point mutants in Xenopus oocytes. Double point mutations of arginines in this post-M2 region of the human alpha-ENaC (alpha-hENaC) led to a decrease and increase in the macroscopic conductance of alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, respectively, but had no effect on the single-channel conductance of either double point mutant. However, the apparent equilibrium dissociation constant for Na+ was decreased for both alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, and the maximum amiloride-sensitive Na+ current was decreased for alphaR586E,R587Ebetagamma-hENaC and increased for alphaR589E,R591Ebetagamma-hENaC. The relative permeabilities of Li+ and K+ vs. Na+ were increased 11.25- to 27.57-fold for alphaR586E,R587Ebetagamma-hENaC compared with wild type. The relative ion permeability of these double mutants and wild-type ENaC was inversely related to the crystal diameter of the permeant ions. Thus the region of positive charge is important for the ion permeation properties of the channel and may form part of the pore itself.

Animals↗
PubMed2001

Application of a PCR assay to enhance the detection and identification of Tritrichomonas foetus in cultured preputial samples.

The traditional diagnostic test for Tritrichomonas foetus involves collection of preputial or vaginal samples followed by culture in a growth media and microscopic examination. Recently, polymerase chain reaction (PCR) techniques have been described for use as a diagnostic assay. The objective of this study was to evaluate a previously described PCR assay for detecting T. foetus in cultured preputial material. The detection limits of the assay for T. foetus organisms in a growth medium, in samples prepared from washing microscope slides, and in preputial material cultured in a growth medium were determined. Preputial samples were collected from 13 bulls uninfected with T. foetus. The PCR assay was able to detect 5 T. foetus organisms in the growth medium and the cultured preputial material. Amplification products were obtained from samples prepared from washes of microscope slides containing as few as 3 visualized organisms. The PCR assay was able to detect organisms in culture at a lower concentration than was possible by direct microscopic examination. This low detection limit may allow the PCR assay to be used to enhance the sensitivity of the current diagnostic test. In addition, the assay could be used to confirm the identification of T. foetus organisms observed by direct microscopic examination when other confirmation techniques, such as staining and phase microscopy, are not practical.

Animals↗
PubMed2001

A new approach to monitoring exercise training.

The ability to monitor training is critical to the process of quantitating training periodization plans. To date, no method has proven successful in monitoring training during multiple types of exercise. High-intensity exercise training is particularly difficult to quantitate. In this study we evaluate the ability of the session rating of perceived exertion (RPE) method to quantitate training during non-steady state and prolonged exercise compared with an objective standard based on heart rate (HR). In a 2-part design, subjects performed steady state and interval cycle exercise or practiced basketball. Exercise bouts were quantitated using both the session RPE method and an objective HR method. During cycle exercise, the relationship between the exercise score derived using the session RPE method and the HR method was highly consistent, although the absolute score was significantly greater with the session RPE method. During basketball, there was a consistent relationship between the 2 methods of monitoring exercise, although the absolute score was also significantly greater with the session RPE method. Despite using different subjects in the 2 parts of the study, the regression relationships between the session RPE method and the HR method were nearly overlapping, suggesting the broad applicability of this method. We conclude that the session RPE method is a valid method of quantitating exercise training during a wide variety of types of exercise. As such, this technique may hold promise as a mode and intensity-independent method of quantitating exercise training and may provide a tool to allow the quantitative evaluation of training periodization plans.

Adult↗
PubMed2001

Family Caregivers' Motives for Helping Scale derived from motivation-to-help theory.

The literature does not contain a measure of family caregivers' motives for helping provide daily complex home care. Such a measure will permit nurses to assess and provide interventions specific to each caregiver's motivation for helping. The purpose of this study was to apply Batson's empirically derived helping pathway theory to the measurement of caregiver motives for helping and develop a short form that does not add to the burden of caregiving. A Principal Components factor analysis (N = 93) of Family Caregivers' Motives for Helping Scale is used. Criterion-related validity is ascertained using a triangulated, independent validation procedure with qualitative data from a subsample (N = 41). Subsample subjects' interview data were categorized, based on Batson's theoretical pathway definitions, by coders blinded to caregiver Motives for Helping Scale scores. Three of Batson's four helping pathways (reward seeking, altruism, and punishment-avoidance) were extracted during factor analysis. This three-factor solution explained 66.6% of the variance and was confirmed by a 97% agreement between three of Batson's pathways and caregivers' helping motive score. The content analyses of the descriptive interview data also coincide with the 3-factor solution. The scale items representing Batson's fourth helping pathway, distress reaction, were not retained due to cross loading. The Family Caregivers' Motives for Helping Scale accurately measures three of four theoretically derived motivations for helping another. The scale should be reanalyzed in a larger sample of caregivers. Aligning nursing interventions to caregiver motives for helping can provide reinforcement for caregivers and potentially enhance home care outcomes.

Caregivers↗
PubMed2000

Efficient factorization with a single pure qubit and logN mixed qubits.

It is commonly assumed that Shor's quantum algorithm for the efficient factorization of a large number N requires a pure initial state. Here we demonstrate that a single pure qubit, together with a collection of log 2N qubits in an arbitrary mixed state, is sufficient to implement Shor's factorization algorithm efficiently.

Journal Article↗