Biomedical subjects

Graham Jones

Publications and source records attributed to Graham Jones.

9 recordsLinked to original sources

PubMed2006

Genetic association studies between the T cell immunoglobulin mucin (TIM) gene locus and childhood atopic dermatitis.

BACKGROUND: The T cell immunoglobulin mucin (TIM) gene family is involved in T cell proliferation and differentiation and has been implicated in allergic disease. We have tested whether TIM gene polymorphisms are associated with atopic dermatitis (AD) in an Australian cohort. METHODS: Transmission disequilibrium testing of 15 single nucleotide polymorphisms across TIM-1, TIM-3 and TIM-4 in 93 Caucasian families, and of a tri-allelic (0, 15 and 18 base pairs) TIM-1 insertion polymorphism in 123 Caucasian and Asian families, was carried out in proband-parent trio families. RESULTS: Transmission of the 18-base pair variant of this insertion was significantly under-represented in the childhood AD cohort (p = 0.02), which is in agreement with a previous study on asthma in an African-American cohort. We also found a novel association between AD and the major haplotype of TIM-4 (p = 0.016). There was no evidence for an association between AD and TIM-3. CONCLUSIONS: In addition to confirming the importance of genetic variation in TIM-1, our results also suggest that genetic variants in the ligand for TIM-1, TIM-4, also contribute to the presentation of AD and related disorders.

Child↗

PubMed2006

Surface functionalization of gold nanoparticles using hetero-bifunctional poly(ethylene glycol) spacer for intracellular tracking and delivery.

For the development of surface-functionalized gold nanoparticles as cellular probes and delivery agents, we have synthesized hetero-bifunctional poly(ethylene glycol) (PEG, MW 1500) having a thiol group on one terminus and a reactive functional group on the other for use as a flexible spacer. Coumarin, a model fluorescent dye, was conjugated to one end of the PEG spacer and gold nanoparticles were modified with coumarin-PEG-thiol. Surface attachment of coumarin through the PEG spacer decreased the fluorescence quenching effect of gold nanoparticles. The results of cellular cytotoxicity and fluorescence confocal analyses showed that the PEG spacer-modified nanoparticles were essentially non-toxic and could be efficiently internalized in the cells within 1 hour of incubation. Intracellular particle tracking using a Keck 3-D Fusion Microscope System showed that the functionalized gold nanoparticles were rapidly internalized in the cells and localized in the peri-nuclear region. Using the PEG spacer, the gold nano-platform can be conjugated with a variety of biologically relevant ligands such as fluorescent dyes, antibodies, etc in order to target, probe, and induce a stimulus at the target site.

Breast Neoplasms↗

PubMed2005

Prophylaxis of Thromboembolism in Critical Care (PROTECT) Trial: a pilot study.

PURPOSE: There is no randomized trial comparing low-molecular weight heparin (LMWH) and unfractionated heparin (UFH) for thromboprophylaxis in medical-surgical ICU patients. The primary objective of this randomized pilot study on LMWH vs UFH was to assess the feasibility of conducting a large randomized trial with respect to timely enrollment and blinded study drug administration, practicality of twice-weekly lower limb ultrasounds to screen for deep venous thrombosis, LMWH bioaccumulation and dose adjustment in renal insufficiency, and recruitment rates for a future trial in medical-surgical intensive care unit (ICU) patients. Its additional goals were to evaluate the suitability of the exclusion criteria and to document the range of research activities that precede accrual of patients into a trial to plan multisite management. MATERIALS AND METHODS: By computerized telephone randomization, we allocated 129 medical-surgical ICU patients to treatment with dalteparin 5,000 IU QD SC or that with UFH 5,000 IU BID SC. Within each clinical center, only the study pharmacist was not blinded. We performed bilateral lower limb compression ultrasounds within 48 hours of ICU admission, twice weekly, on suspicion of deep venous thrombosis, and 7 days after ICU discharge. Research coordinators and investigators at 7 centers reported the time they engaged in all research activities before the first patient was randomized. RESULTS: Timely complete study drug administration occurred after enrollment. More than 99% of scheduled doses were administered in a blinded fashion. Scheduled ultrasounds were performed without exception. No bioaccumulation of dalteparin was observed when creatinine clearance decreased to lower than 30 mL/min. Average recruitment was 2 patients/center per month before the study exclusion criteria were modified. Study startup activities required, on average, 65.5 hours of combined investigator and research coordinator time at each center. Careful examination of the accrual in the pilot study led to a reexamination of the Prophylaxis of Thromboembolism in Critical Care Trial (PROTECT) study exclusion criteria. CONCLUSIONS: This pilot study suggests that a multicenter randomized clinical trial comparing LMWH with UFH in critically ill medical-surgical patients is feasible. Pilot studies can improve the design of larger trials and may enhance successful timely completion.

Anticoagulants↗

PubMed2005

Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement.

The systematic staging of chronic kidney disease (CKD) by glomerular filtration measurement and proteinuria has allowed the development of rational and appropriate management plans. One of the barriers to early detection of CKD is the lack of a precise, reliable and consistent measure of kidney function. The most common measure of kidney function is currently serum creatinine concentration. It varies with age, sex, muscle mass and diet, and interlaboratory variation between measurements is as high as 20%. The reference interval for serum creatinine concentration includes up to 25% of people (particularly thin, elderly women) who have an estimated glomerular filtration rate (eGFR) that is significantly reduced (< 60 mL/min/1.73 m). The recent publication of a validated formula (MDRD) to estimate GFR from age, sex, race and serum creatinine concentration, without any requirement for measures of body mass, allows pathology laboratories to "automatically" generate eGFR from data already acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine measurements would help to identify asymptomatic kidney dysfunction at an earlier stage. eGFR correlates well with complications of CKD and an increased risk of adverse outcomes such as cardiovascular morbidity and mortality. We recommend that pathology laboratories automatically report eGFR each time a serum creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in patients with normal or near-normal renal function, we recommend that calculated eGFRs above 60 mL/min/1.73 m be reported by laboratories as "> 60 mL/min/1.73 m", rather than as a precise figure.

Journal Article↗

PubMed2004

Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer.

PURPOSE: To evaluate the herbal combination, PC-SPES, and diethylstilbestrol (DES) in patients with androgen independent prostate cancer (AIPC). PATIENTS AND METHODS: A randomized phase II study was conducted with cross-over design. Patients were randomly assigned to receive either three PC-SPES capsules orally three times a day or DES 3 mg orally once a day. Prophylactic warfarin was administered. At clinical or prostate-specific antigen progression, patients received the other therapy. The study closed prematurely after PC-SPES was withdrawn from the market. Chemical analyses were performed on multiple lots of PC-SPES. RESULTS: Ninety patients were enrolled, of whom 85 were assessable for response. Prostate-specific antigen declines > or = 50% were noted in 40% (95% CI, 25% to 56%) with PC-SPES, and 24% (95% CI, 12% to 39%) with DES. Median response duration was not reached with PC-SPES, and was 3.8 months with DES. Median time to progression for randomly assigned patients was 5.5 months for PC-SPES and 2.9 months for DES. Common toxicities included mild fatigue, gynecomastia, and mastodynia. Five thromboembolic events occurred (one PC-SPES, four DES). Responses in the cross-over phase were inconclusive. Four lots of PC-SPES had measurable quantities of DES, ranging from 0.01% to 3.1% of the dose used in the DES arm. Ethinyl estradiol was also detected in PC-SPES lots. CONCLUSION: PC-SPES and DES demonstrate activity in AIPC and are well tolerated. However, the synthetic estrogens, DES and ethinyl estradiol, were detected in various lots of PC-SPES, including those used in this trial. Clinical trials that utilize herbal therapies must account for issues of purity and consistency.

Administration, Oral↗

PubMed2004

Continuous culture of photobacterium.

The design and performance characteristics of a small volume (20 ml) continuous culture device for the cultivation of luminous bacteria are described. This simply constructed device can be used to supply luminescent bacteria with constant properties for either laboratory use or the assay of environmental pollutants. Furthermore, bacteria can be deployed to make sensitive (<1 nM) oxygen measurements. The culture device may be configured, alone or in combination, as a chemostat, turbidostat or a "bioluminostat" where bacterial bioluminescence becomes the controlling variable. Over extended periods (>1 week) it was possible to maintain steady-state luminescence within 5% of a pre-set value, although occasionally a non-bioluminescent "mutant" became dominant; in this case light emission was irreversibly lost. A secondary chamber provided additional flexibility and easy manipulation of the cultivated bacteria for testing. The continuous culture system is also suitable for the growth of recombinant microorganisms that either constitutively express luciferase, or do so in response to stress promoter activity. The non-standard control methodologies reported may have important research and industrial applications, for example in providing immediate process control or as an inferential method to optimize biomass: product yield ratios.

Aliivibrio fischeri↗

PubMed2004

Nuclear import of N-terminal FAK by activation of the FcepsilonRI receptor in RBL-2H3 cells.

As FAK integrates membrane receptor signalling, yet is also found in the nucleus, we investigated whether nuclear FAK is regulated by membrane receptor activation. Activation of the mast cell FcepsilonRI receptor leads to the release and synthesis of inflammatory mediators as well as increased proliferation and survival. Using RBL-2H3 basophilic leukaemia cells, FAK and the FcepsilonRI receptor were co-localised following cross-linking of IgE with antigen. This also resulted in a significant increase in the nucleus of several N-terminal FAK fragments, the largest of which included the kinase domain but not the focal adhesion targeting domain. This was confirmed using cells that stably expressed recombinant EGFP-FAK. Furthermore, treatment of EGFP-FAK expressing cells with Leptomycin B, an inhibitor of nuclear export, resulted in increased nuclear localisation of EGFP-FAK. Therefore, FAK can shuttle between the nuclear and cytoplasmic compartments and the cellular distribution of N-terminal FAK is regulated by membrane receptor activation.

Active Transport, Cell Nucleus↗

PubMed2004

Phosphorylcholine-containing polymers for use in cell encapsulation.

A model system for encapsulation of pancreatic islets which has potential properties for improving biocompatibility and immunosuppression was investigated. In vitro and in vivo studies have shown that phosphorylcholine-containing polymers have high biocompatibility due to low adsorption of proteins and reduced thrombus formation. Encapsulation of islets isolated from rats with a compound membrane composed of phosphorylcholine-containing polymers and cellulose acetate led to rapid insulin production and diffusion across the membrane in response to glucose challenge. The phosphorylcholine-containing polymer had a molecular weight of about 1.3 x 10(4) Da. The polymer-coated membrane excluded larger molecules such as IgG (molecular weight 150 kDa), thereby acting as a physical immuno-barrier, but allowed smaller molecules such as glucose and insulin to pass through.

Animals↗

PubMed2002

Application of affinity capillary electrophoresis for the determination of binding and thermodynamic constants of enediynes with bovine serum albumin.

The binding constants and thermodynamic properties of a series of novel enediyne compounds with bovine serum albumin (BSA) were determined. The enediynes were synthesized, characterized, and then studied by affinity capillary electrophoresis (ACE) methods to derive these recognition parameters. Change in electrophoretic mobility of BSA as a function of enediyne concentration was determined at 25 degrees C providing binding constants of 1.76 x 10(5), 1.14 x 10(5), and 0.68 x 10(5) M(-1) for enediynephenylalanine carboxylic acid, enediynephenylalanine methyl ester, and enediyne carboxylic acid, respectively. The binding constant for the enediynephenylalanine carboxylic acid was in good agreement with that obtained using conventional methodology. Binding constants for the interaction of enediynes with BSA decreased with an increase in temperature. Van't Hoff plots showed a direct correlation between intensity of the binding constant and the sign and magnitude of various thermodynamic parameters (DeltaG, DeltaS, and/or DeltaH).

Alkynes↗