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Biomedical subjects

John Wilson

Publications and source records attributed to John Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Phagocytic efficiency of monocytes and macrophages obtained from Sydney blood bank cohort members infected with an attenuated strain of HIV-1.

Defective function of monocyte-derived macrophages contributes to HIV-1 pathogenesis. We found that phagocytosis of the opportunistic pathogens Mycobacterium avium complex and Toxoplasma gondii was impaired in monocytes obtained from individuals infected with wild-type strains of HIV-1 but generally not in monocytes collected over a 6-year period from Sydney Blood Bank Cohort (SBBC) members infected with nef/long terminal repeats (LTR) region-defective strains of HIV-1. However, longitudinal analysis of phagocytosis in 1 SBBC member, C54, showed the development of defective engulfment of opportunistic pathogens at the most recent time points, coincident with the development of further molecular deletions in the nef/LTR region. Another SBBC member, C98, underwent bronchoscopy, which provided material to examine phagocytic signaling in alveolar macrophages. In contrast to normal phagocytic efficiency of C98's monocytes (over a 6-year period), defective signaling events during FcgammaR-mediated phagocytosis by C98's alveolar macrophages were observed. High basal phosphorylation within HIV-infected macrophages correlated with colocalization of tyrosine-phosphorylated proteins with HIV-1 p24 antigen rather than around the phagocytic targets as observed in uninfected cells. Thus, although phagocytic efficiency appears to be generally unimpaired in monocytes from SBBC members, evidence of impairment in recent samples from 1 SBBC member, coincident with further genetic changes within the virus, and abnormal phagocytic signaling in alveolar macrophages from another SBBC member may herald loss of attenuation of those strains.

Anticoagulants↗
PubMed2003

Older women with breast carcinoma are less likely to receive adjuvant chemotherapy: evidence of possible age bias?

BACKGROUND: Older women with breast carcinoma are less likely than younger women to receive adjuvant chemotherapy. The authors hypothesized that after controlling for confounders (i.e., variables related to both age and chemotherapy use) and effect modifiers (i.e., variables that have a significant interaction with age), age would become a less significant factor for predicting adjuvant chemotherapy use. METHODS: Data on 480 women with localized breast carcinoma were entered into the National Comprehensive Cancer Network database at The Ohio State University Medical Center. Women were divided into 3 groups: women age < 50 years (n = 143 [30%]), women ages 50-65 years (n = 216 [45%]), and women age > 65 years (n = 121 [25%]). Chi-square and Wilcoxon rank sum tests were used for univariate analyses of the variables of interest, and logistic regression was used for multivariate analyses. RESULTS: After adjustment for confounders (stage, tumor size, progesterone receptor status, and lymph node involvement) and effect modifiers (namely, estrogen receptor [ER] status), the odds of not receiving chemotherapy for women ages 50-65 years and women age > 65 years with ER-positive breast carcinoma were approximately 6 (odds ratio [OR], 6.4; 95% confidence interval [CI], 3.1-13.3; P < 0.001) and 62 (OR, 62.4; 95% CI, 21.8-178.7; P < 0.001) times greater, respectively, than the odds for women age < 50 years. Women ages 50-65 years with ER-negative breast carcinoma were not significantly different from women age < 50 years with respect to chemotherapy use (OR, 1.9; 95% CI, 0.5-7.3; P = 0.374). However, the odds of not receiving chemotherapy for women age > 65 years with ER-negative breast carcinoma were 7 times (OR, 6.7; 95% CI, 1.5-30.6; P = 0.013) greater than the odds for women age < 50 years. CONCLUSIONS: The results of the current study indicate that based on older age alone, women are less likely to receive adjuvant chemotherapy. In addition, the results suggest that age bias may contribute to undertreatment and lack of accrual of older women into clinical trials.

Age Factors↗
PubMed2003

Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging.

PURPOSE: Combretastatin A4 phosphate (CA4P) is a novel vascular targeting agent. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) studies were performed to examine changes in parameters related to blood flow and vascular permeability in tumor and normal tissue after CA4P treatment. MATERIALS AND METHODS: Changes in kinetic DCE-MRI parameters (transfer constant [Ktrans] and area under contrast medium-time curve [AUC]) over 24 hours after treatment with CA4P were measured in 18 patients in a phase I trial and compared with those obtained in the rat P22 carcinosarcoma model, using the same imaging technique. Rats were treated with 30 mg/kg of CA4P; patients received escalating doses from 5 to 114 mg/m2. RESULTS: A similar pattern and time course of change in tumor and normal tissue parameters was seen in rats and humans. Rat tumor Ktrans was reduced by 64% 6 hours after treatment with CA4P (30 mg/kg). No significant reductions in kidney or muscle parameters were seen. Significant reductions were seen in tumor Ktrans in six of 16 patients treated at >or= 52 mg/m2, with a significant group mean reduction of 37% and 29% at 4 and 24 hours, respectively, after treatment. The mean reduction in tumor initial area under the gadolinium-diethylenetriamine pentaacetic acid concentration-time curve (AUC) was 33% and 18%, respectively, at these times. No reduction was seen in muscle Ktrans or in kidney AUC in group analysis of the clinical data. CONCLUSION: CA4P acutely reduces Ktrans in human as well as rat tumors at well-tolerated doses, with no significant changes in kidney or muscle, providing proof of principle that this drug has tumor antivascular activity in rats and humans.

Animals↗
PubMed2003

Antioxidant properties of bran extracts from "Akron" wheat grown at different locations.

Bran extracts of Akron wheat grown at four nonirrigated and one irrigated testing locations were examined and compared for their free radical scavenging properties against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*)) and the radical cation ABTS(*)(+), chelating capacities, and total phenolic content (TPC) to determine the potential effects of environmental factors on the antioxidant properties of hard winter wheat. The environmental factors included total solar radiation, average daily solar radiation, and number of hours exceeding 32 degrees C. The results showed that bran samples from different growing locations may significantly differ in their radical scavenging activities against both DPPH(*) and ABTS(*)(+), chelating capacities, and TPC. A significant negative correlation was detected between the chelating activities of the bran samples from the four nonirrigated locations and total solar or daily average solar radiation (r = -0.999 and P = 0.001). These data suggest potential influences of growing conditions on the antioxidant properties of hard winter wheat and the possibility of producing wheat that is strong in a selected antioxidant property by optimizing the growing conditions of a selected wheat variety. More research is required to further investigate the relationship among antioxidant properties and environmental factors using different wheat varieties and larger sample sizes.

Altitude↗
PubMed2003

Impact of a novel neoadjuvant and adjuvant hormone-deprivation approach on quality of life, voiding function, and sexual function after prostate brachytherapy.

BACKGROUND: Data demonstrate a benefit from neoadjuvant and adjuvant hormone-deprivation therapy with luteinizing hormone-releasing hormone agonists in patients who are treated with radiotherapy for localized prostate carcinoma; however, this approach has detrimental effects on quality of life (QOL). A cross-sectional study was undertaken to evaluate the impact on QOL, voiding function, and sexual function of an alternative hormone-deprivation approach. METHODS: Three hundred fifty patients with clinical T1c-T2b prostate carcinoma were treated from March 1997 to August 2000 either with palladium 103 brachytherapy (BTM) without hormone therapy or with 8 months of adjuvant and neoadjuvant hormone-deprivation therapy with an antiandrogen and finasteride (BTM+H), were mailed the Functional Assessment of Cancer Therapy (FACT) global well being QOL instrument (FACT-G), the American Urological Association symptom score (AUASS), and specific items addressing urinary control and sexual function from validated instruments. Differences between treatment groups were assessed as a function of time since treatment. RESULTS: Seventy-two percent of patients responded to the questionnaire. No differences in overall FACT-G scores, AUASS scores, or AUASS subscale scores between the BTM group and the BTM+H group were found. The BTM+H group initially had lower personal well being FACT-G subscale scores, more urinary incontinence, and lower odds of attaining an erection sufficient for intercourse initially, although these differences disappeared with longer follow-up. CONCLUSIONS: The use of neoadjuvant and adjuvant antiandrogen and finasteride with brachytherapy is associated with QOL equal to that of brachytherapy alone for the treatment of patients with localized prostate carcinoma, allowing the advantages of hormone manipulation in terms of tumor control without its downside.

5-alpha Reductase Inhibitors↗
PubMed2003

Volunteering and depression: the role of psychological and social resources in different age groups.

There are a number of reasons why volunteering might yield mental health benefits, especially to older people. Volunteer work improves access to social and psychological resources, which are known to counter negative moods such as depression and anxiety. Analysis of three waves of data from the Americans' Changing Lives data set (1986, 1989, 1994) reveals that volunteering does lower depression levels for those over 65, while prolonged exposure to volunteering benefits both populations. Some of the effect of volunteering on depression among the elderly is attributable to the social integration it encourages, but the mediating effect of psychological resources is very small. Volunteering for religious causes is more beneficial for mental health than volunteering for secular causes but, again, the effect is confined to the elderly.

Age Factors↗
PubMed2003

Detection of protein tyrosine-kinase (PTK) gene expression pattern in normal and malignant T lymphocytes by combined PTK-specific polymerase chain reaction and parallel denaturing gradient gel electrophoresis.

Protein tyrosine kinases (PTKs) control key functions of normal and malignant cells. Comparison of PTK gene expression among various cell populations may be achieved by amplification of the PTK cDNAs using degenerate primers which recognize two relatively invariable regions within their catalytic domain. This approach produces a mixture of PTK cDNA fragments with identical or very similar lengths which are difficult to separate by standard gel electrophoresis. These mixed products are then analyzed in a random fashion which leads to redundant cloning of some and potential omission of other PTKs. By using parallel denaturing gradient gel electrophoresis (DGGE) we have been able to separate the amplified PTK cDNAs derived from the same T-lymphocyte population and compare their expression between various types of normal and malignant T lymphocytes. One such PTK is the type I receptor for insulin-like growth factor, which we found to be preferentially expressed by neoplastic T cells on the both mRNA and protein levels. The combination of PCR which uses PTK-specific primers and parallel DGGE of the amplified PTK cDNAs may prove useful in studying mechanisms of cell activation and malignant transformation and in identifying targets for therapies based on selective inhibition of oncogenic PTKs.

Blotting, Northern↗
PubMed2003

Chronic fatigue syndrome: new evidence for a central fatigue disorder.

Considerable evidence points towards a prominent role for central nervous system (CNS) mechanisms in the pathogenesis of chronic fatigue syndrome (CFS), a disorder characterized chiefly by persistent, often debilitating, fatigue. We wished to characterize circulating profiles of putative amino acid modulators of CNS 5-hydroxytryptamine (5-HT; serotoninergic) and dopaminergic function in CFS patients at rest, as well as during symptom-limited exercise and subsequent recovery. Groups of 12 CFS patients and 11 age- and sex-matched sedentary controls, with similar physical activity histories, underwent ramp-incremental exercise to the limit of tolerance. Plasma amino acid concentrations, oxygen uptake and ratings of perceived exertion were measured at rest, and during exercise and recovery. Peak oxygen uptake was significantly lower in the CFS patients compared with controls. Rating of perceived exertion in the patients was higher at all time points measured, including at rest, relative to controls. Levels of free tryptophan (free Trp), the rate-limiting 5-HT precursor, were significantly higher in CFS patients at exhaustion and during recovery, whereas concentrations of branched-chain amino acids (BCAA) and large neutral amino acids (LNAA) were lower in CFS patients at exhaustion, and for LNAA also during recovery. Consequently, the [free Trp]/[BCAA] and [free Trp]/[LNAA] ratios were significantly higher in CFS patients, except at rest. On the other hand, levels of tyrosine, the rate-limiting dopaminergic precursor, were significantly lower at all time points in the CFS patients. The significant differences observed in a number of key putative CNS 5-HT and dopaminergic modulators, coupled with the exacerbated perception of effort, provide further evidence for a potentially significant role for CNS mechanisms in the pathogenesis of CFS.

Adult↗
PubMed2003

Distal right ventricular coil position reduces defibrillation thresholds.

UNLABELLED: Distal RV Coil Position Reduces DFTs. INTRODUCTION: Understanding the factors that affect defibrillation thresholds (DFTs) has important implications both for optimization of defibrillation efficacy and for the design of new transvenous leads. The aim of this prospective study was to test the hypothesis that defibrillation efficacy is improved with the right ventricular (RV) coil in a distal position compared with a more proximal RV coil position. METHODS AND RESULTS: A novel defibrillation lead with three adjacent RV defibrillation coils (distal 0.8 cm, middle 3.7 cm, proximal 0.8 cm) was used for this study to permit comparison of DFTs with the proximal and distal RV coil positions without lead repositioning. In the distal RV configuration, the distal and middle RV coils were connected electrically as the anode for defibrillation. In the proximal RV configuration, the middle and proximal coils were the anode. A superior vena cava (SVC) coil and active can were connected electrically as the cathode (reversed polarity, RV-->Can+SVC). In each patient, the DFT was measured twice using a binary search protocol with the distal RV and proximal RV configurations, with the order of testing randomized. The study cohort consisted of 31 subjects (mean age 65 +/- 12 years, mean left ventricular ejection fraction 30% +/- 16%, 81% male predominance). The mean delivered energy (8.2 +/- 5.3 J vs 11.2 +/- 6.1 J), leading-edge voltage (335 +/- 109 V vs 393 +/- 118 V), and peak current (11.6 +/- 5.2 A vs 14.9 +/- 7.3 A) at DFT all were significantly lower with the distal RV configuration compared to the proximal RV configuration (P < 0.01 for all comparisons). CONCLUSION: DFTs are significantly reduced with the distal RV configuration compared to the proximal RV configuration. Defibrillation leads should be designed with the shortest tip to coil distance that can be achieved without compromising ventricular fibrillation sensing.

Aged↗
PubMed2003

Use of pulsed-field gel electrophoresis in infection control issues concerning Burkholderia cepacia.

There was concern that nosocomial person-to-person transmission of Burkholderia cepacia had occurred when two patients with cystic fibrosis shared a bathroom. Pulsed-field gel electrophoresis demonstrated that the two isolates were unrelated. Subsequent testing of 34 stored isolates of B. cepacia demonstrated that no particular clone predominated in our hospital.

Burkholderia Infections↗
PubMed2002

Selection of subjects for human milk surveillance and research studies.

Subject selection for studies investigating environmental chemicals in human milk requires thoughtful consideration of multiple factors. Studies often need to produce generalizable and representative data that can be compared to other similar studies. Goals of the study determine the selection of subjects. Exposure is only one factor that influences the levels of environmental chemicals in human milk. Many maternal and infant characteristics should be considered in subject selection. Collection procedures of human milk samples also affect subject selection, as subject burden may be enough to reduce compliance with the collection protocols. Decisions must be made about pooling of samples both within subjects and within populations. Guidelines for subject selection are provided by the World Health Organization for human milk monitoring, but distinct differences in the lactational practices, geography, and ethnic and racial diversity of the U.S. population require somewhat different approaches.

Adult↗
PubMed2002

External quality assessment schemes for toxicology.

A variety of external quality assurance (EQA) schemes monitor quantitative performance for routine biochemical analysis of agents such as paracetamol, salicylate, ethanol and carboxyhaemoglobin. Their usefulness for toxicologists can be lessened where the concentrations monitored do not extend fully into the toxic range or where the matrix is synthetic, of animal origin or serum as opposed to whole human blood. A scheme for quantitative determinations of a wider range of toxicological analytes such as opioids, benzodiazepines and tricyclics in human blood has been piloted by the United Kingdom National External Quality Assessment Scheme (UKNEQAS). Specialist schemes are available for drugs of abuse testing in urine and for hair analysis. Whilst these programmes provide much useful information on the performance of analytical techniques, they fail to monitor the integrated processes that are needed in investigation of toxicological cases. In practice, both qualitative and quantitative tests are used in combination with case information to guide the evaluation of the samples and to develop an interpretation of the analytical findings that is used to provide clinical or forensic advice. EQA programs that combine the analytical and interpretative aspects of case studies are available from EQA providers such as UKNEQAS and the Dutch KKGT program (Stichting Kwaliteitsbewaking Klinische Geneesmiddelanalyse en Toxicologie).

Forensic Medicine↗
PubMed2002

Free radical scavenging properties of wheat extracts.

Three hard winter wheat varieties (Akron, Trego, and Platte) were examined and compared for their free radical scavenging properties and total phenolic contents (TPC). Free radical scavenging properties of wheat grain extracts were evaluated by spectrophotometric and electron spin resonance (ESR) spectrometry methods against stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH*) and radical cation ABTS*+ (2,2'-azino-di[3-ethylbenzthiazoline sulfonate]). The results showed that the three wheat extracts differed in their capacities to quench or inhibit DPPH* and ABTS*+. Akron showed the greatest activity to quench DPPH radicals, while Platte had the highest capacity against ABTS*+. The ED50 values of wheat extracts against DPPH radicals were 0.60 mg/mL for Akron, 7.1 mg/mL for Trego, and 0.95 mg/mL for Platte under the experimental conditions. The trolox equivalents against ABTS*+ were 1.31 +/- 0.44, 1.08 +/- 0.05, and 1.91 +/- 0.06 micromol/g of grain for Akron, Trego, and Platte wheat, respectively. ESR results confirmed that wheat extracts directly reacted with and quenched free radicals. The TPC were 487.9 +/- 927.8 microg gallic acid equivalents/g of grain. No correlation was observed between TPC and radical scavenging capacities for DPPH* and ABTS*+ (p = 0.15 and p > 0.5, respectively).

Benzothiazoles↗
PubMed2002

Evaluation of the anti-vascular effects of combretastatin in rodent tumours by dynamic contrast enhanced MRI.

The anti-vascular effects of the tubulin binding agent, disodium combretastatin A-4 3-O-phosphate (CA-4-P), have been investigated in the rat P22 carcinosarcoma by measurements of radiolabelled iodoantipyrine uptake and dynamic contrast-enhanced MRI. The iodoantipyrine estimates of absolute tumour blood flow showed a reduction from 0.35 to 0.04 ml g(-1) min(-1) 6 h after 10 mg kg(-1) CA-4-P and to <0.01 ml g(-1) min(-1) after 100 mg kg(-1). Tumour blood flow recovered to control values 24 h after 10 mg kg(-1) CA-4-P, but there was no recovery by 24 h after the higher dose. Dynamic contrast-enhanced MR images were obtained at 4.7 T, following injection of 0.1 mmol kg(-1) Gd-DTPA and analysed assuming a model arterial input function. A parameter, K(trans), which is related to blood flow rate and permeability of the tumour vasculature to Gd-DTPA, was calculated from the uptake data. K(trans) showed a reduction from 0.34 to 0.11 min(-1) 6 h after 10 mg kg(-1) CA-4-P and to 0.07 min(-1) after 100 mg kg(-1). Although the magnitude of changes in K(trans) was smaller than that in tumour blood flow, the time course and dose-dependency patterns were very similar. The apparent extravascular extracellular volume fraction, nu(e), showed a four-fold reduction 6 h after 100 mg kg(-1) CA-4-P, possibly associated with vascular shutdown within large regions of the tumour. These results suggest that K(trans) values for Gd-DTPA uptake into tumours could be a useful non-invasive indicator of blood flow changes induced by anti-vascular agents such as combretastatin.

Angiogenesis Inhibitors↗
PubMed2002

Effective gene transfer to solid tumors using different nonviral gene delivery techniques: electroporation, liposomes, and integrin-targeted vector.

In this study, we measured transfection efficiency in vitro and in vivo using the following nonviral approaches of gene delivery: injection of plasmid DNA, electroporation-assisted, liposome-enhanced, and integrin-targeted gene delivery, as well as the combination of these methods. Four histologically different tumor models were transfected with a plasmid encoding the green fluorescent protein (GFP) (B16 mouse melanoma, P22 rat carcinosarcoma, SaF mouse sarcoma, and T24 human bladder carcinoma) using adherent cells, dense cell suspensions, and solid tumors. Emphasis was placed on different electroporation conditions to optimise the duration and amplitude of the electric pulses, as well as on different DNA concentrations for effective gene delivery. In addition, transfection efficiency was correlated with cell density of the tumors. The major in vivo findings were: (a) electroporation-assisted gene delivery with plasmid DNA, employing long electric pulses with low amplitude, yielded significantly better GFP expression than short electric pulses with high amplitude; (b) electroporation combined with liposome-DNA complexes yielded the highest percentage of transfected tumor area in B16F1 tumor (6%); (c) transfection efficiency of electroporation-assisted plasmid DNA delivery was dependent on tumor type; (d) integrin-targeted vector, alone or combined with electroporation, was largely ineffective. In conclusion, our results demonstrate that some nonviral methods of gene delivery are feasible and efficient in transfecting solid tumors. Therefore, this makes nonviral methods attractive for further development.

Animals↗
PubMed2002

The vascular response of tumor and normal tissues in the rat to the vascular targeting agent, combretastatin A-4-phosphate, at clinically relevant doses.

The antivascular actions of disodium combretastatin A-4 3-O-phosphate (CA-4-P) were investigated in the rat P22 carcinosarcoma after single doses of 10 or 30 mg x kg(-1). Pharmacokinetic data showed that 10 mg x kg(-1) in the rat gave a plasma exposure similar to that achieved in the clinic. Blood flow rate to the tumor and normal tissues was measured using the uptake of radiolabelled iodoantipyrine (IAP). Quantitative autoradiography was used to determine changes in spatial distribution of tumor blood flow. Both doses caused an increase in mean arterial blood pressure (MABP) and a reduction in heart rate 1 h after treatment. Blood flow rate to the tumor decreased to below 15% of control for both doses at 1 h, whereas the normal tissues were much less affected. A further reduction (to 2% of control at 6 h) was found for 30 mg x kg(-1). Recovery was essentially complete by 24 h for both doses. Vascular resistance increased 80-fold in tumor at 6 h after 30 mg x kg(-1), compared with a maximum 5-fold increase in normal tissues. Analysis of the spatial distribution of tumor blood flow illustrated an overall reduction in all areas of the tumor at 1 h after 10 mg x kg(-1), with a tendency for blood flow in the peripheral regions of the tumor to recover more quickly than in central regions. Tumor blood flow reduction was related to vascular damage including vessel distension, coagulation and haemorrhage, and tumor cell damage culminating in necrosis. No pathology was evident in any of the normal tissues following treatment. The data provide an insight into the mechanisms underlying tissue blood flow changes occurring after clinically relevant doses of CA-4-P. It is currently being used to aid interpretation of pharmacodynamic data obtained from phase I/II clinical trials of CA-4-P and is relevant for future drug development in this area.

Animals↗