Search PubMed⌕ Search

Biomedical subjects

L Jones

Publications and source records attributed to L Jones.

At least 55 records · Page 3Linked to original sources

Studies on dental erosion: An in vivo-in vitro model of endogenous dental erosion--its application to testing protection by fluoride gel application.

BACKGROUND: The objective in this study was to develop an in vivo-in vitro model of endogenous erosion, with a view to exploring the potential for some degree of its control by the use of topical fluoride gel application to teeth. METHODS: Six volunteers each wore a small clasp retained palatal acrylic appliance to which six sterilized enamel tiles were bonded. Three tiles on each appliance were coated extra-orally with either 1.23 per cent acidulated phosphate fluoride (APF) or 2.2 per cent sodium fluoride (NaF) neutral gel for four minutes prior to multiple periods of exposure to the simulated gastric acid, cumulating in 16, 36, 80 and 150 minutes of exposure. Impressions of the enamel tiles prior to and following acid exposure permitted dies to be prepared. These were sectioned through the exposed areas and examined under a stereomicroscope to assess maximum depths of erosion. RESULTS: The depth of erosive demineralization of enamel was found to be greatly reduced with increased frequency of APF gel application. The reduction in enamel loss was less following topical application of NaF gel. CONCLUSIONS: It was concluded that fluoride gels significantly reduced enamel erosion using this in vivo-in vitro model and therefore, if prescribed appropriately, should help reduce tooth tissue loss from endogenous erosion.

Acidulated Phosphate Fluoride↗

Photodynamic therapy for cancer of the pancreas.

BACKGROUND: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. AIMS: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. PATIENTS: Sixteen patients with inoperable adenocarcinomas (2.5-6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. METHODS: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. RESULTS: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4-30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. CONCLUSIONS: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.

Adenocarcinoma↗

Substantial linkage disequilibrium across the insulin-degrading enzyme locus but no association with late-onset Alzheimer's disease.

Insulin-degrading enzyme (IDE; insulysin; EC 3.4.24.56) is a 110-kDa neutral metallopeptidase that can degrade a number of peptides including beta-amyloid. The gene encoding IDE is located on chromosome 10 close to a region of linkage for late-onset Alzheimer's disease (LOAD) and thus is a functional and positional candidate for this disorder. We analysed all of the coding exons, untranslated regions and 1000 bp of 5'-flanking sequence of IDE by using denaturing high-performance liquid chromatography and sequencing. We detected eight single nucleotide polymorphisms (SNPs), three in the 5' flanking sequence and five in the coding sequence, of which three were found at lower than 5% frequency. None of them changed the amino acid sequence. We genotyped the five SNPs with allele frequencies of more than 5% in 133 Caucasian LOAD cases and 135 controls collected in the UK and 95 cases and 117 controls collected at the Mayo Clinic, Rochester, USA. Two of the SNPs were analysed in a further independent case-control sample (Washington University, St. Louis: 86 cases, 94 controls). No significant association was found with any individual SNP in any of the samples or with any haplotypes. Analysis of the marker D10S583, which maps 36 kb upstream of IDE, also failed to show association in 134 cases and 111 matched controls from the UK ( P=0.63). Strong linkage disequilibrium was detected between the five SNPs that spanned the whole of the 120-kb genomic region of IDE and one major and a number of minor haplotypes were detected in the populations studied. We conclude that IDE does not make a substantial contribution to the aetiology of LOAD and therefore cannot account for the linkage between LOAD and 10q.

Age of Onset↗

Primary health care services provided by nurse practitioners and family physicians in shared practice.

BACKGROUND: Collaborative practice involving nurse practitioners (NPs) and family physicians (FPs) is undergoing a renaissance in Canada. However, it is not understood what services are delivered by FPs and NPs working collaboratively. One objective of this study was to determine what primary health care services are provided to patients by NPs and FPs working in the same rural practice setting. METHODS: Baseline data from 2 rural Ontario primary care practices that participated in a pilot study of an outreach intervention to improve structured collaborative practice between NPs and FPs were analyzed to compare service provision by NPs and FPs. A total of 2 NPs and 4 FPs participated in data collection for 400 unique patient encounters over a 2-month period; the data included reasons for the visit, services provided during the visit and recommendations for further care. Indices of service delivery and descriptive statistics were generated to compare service provision by NPs and FPs. RESULTS: We analzyed data from a total of 122 encounters involving NPs and 278 involving FPs. The most frequent reason for visiting an NP was to undergo a periodic health examination (27% of reasons for visit), whereas the most frequent reason for visiting an FP was cardiovascular disease other than hypertension (8%). Delivery of health promotion services was similar for NPs and FPs (11.3 v. 10.0 instances per full-time equivalent [FTE]). Delivery of curative services was lower for NPs than for FPs (18.8 v. 29.3 instances per FTE), as was provision of rehabilitative services (15.0 v. 63.7 instances per FTE). In contrast, NPs provided more services related to disease prevention (78.8 v. 55.7 instances per FTE) and more supportive services (43.8 v. 33.7 instances per FTE) than FPs. Of the 173 referrals made during encounters with FPs, follow-up with an FP was recommended in 132 (76%) cases and with an NP in 3 (2%). Of the 79 referrals made during encounters with NPs, follow-up with an NP was recommended in 47 (59%) cases and with an FP in 13 (16%) (p < 0.001). INTERPRETATION: For the practices in this study NPs were underutilized with regard to curative and rehabilitative care. Referral patterns indicate little evidence of bidirectional referral (a measure of shared care). Explanations for the findings include medicolegal issues related to shared responsibility, lack of interdisciplinary education and lack of familiarity with the scope of NP practice.

Cooperative Behavior↗

Stem cells: so what's in a niche?

Much effort is being invested in defining the intrinsic and extrinsic factors that control stem cell maintenance and proliferation. Recent studies have identified a signaling hierarchy involved in coordinating the proliferation of germ line and somatic stem cells in the Drosophila ovary.

Animals↗

RNA-directed transcriptional gene silencing in plants can be inherited independently of the RNA trigger and requires Met1 for maintenance.

BACKGROUND: The association between DNA methylation and gene silencing has long been recognized; however, signals that initiate de novo methylation are largely unknown. In plants, recognition of RNAs that are inducers of posttranscriptional gene silencing (PTGS) can result in sequence-specific DNA methylation, and the aim of this work was to investigate whether heritable epigenetic changes can occur by this mechanism and if the Met1 methyltransferase is required. RESULTS: RNA-directed DNA methylation (RdDM) was initiated in 35S-GFP transgenic plants following infection with plant RNA viruses modified to carry portions of either the 35S promoter or the GFP coding region. Targeting of the promoter sequence resulted in both methylation and transcriptional gene silencing (TGS) that was inherited independently of the RNA trigger. Targeting the coding region also resulted in methylation; however, this was not inherited. Expression of Met1 was suppressed in order to investigate its role in initiation and maintenance of RdDM. Initiation of RdDM was found to be Met1-independent, whereas maintenance of methylation and TGS in the subsequent generations in the absence of the RNA trigger was Met1-dependent. Maintenance of methylation associated with systemic PTGS was also found to be Met1-independent. CONCLUSIONS: RNA-triggered events can lead to heritable changes in gene expression, and it is possible that initiation of other epigenetic phenomena such as trans-silencing and paramutation may have an RNA component.

Base Sequence↗

Dysregulation of beta-chemokines in the lungs of HIV-1-infected patients.

The beta-chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, monocyte chemotactic protein (MCP)-1 and regulated-on-activation normal T cell, expressed and secreted (RANTES) are not only chemotactic for mononuclear cells but may be important in suppression of HIV-1 replication through competitive binding to the chemokine receptor, CCR5, which is critical to viral entry. In this study, bronchoalveolar cells (BACs) and autologous peripheral blood mononuclear cells (PBMCs) were obtained from HIV-1-infected participants who did not manifest clinical signs of lung disease with peripheral CD4 T-cell count >200/mm(3) (n = 7, group with high CD4 count), or CD4 T-cell count <200/mm(3) (n = 12, group with low CD4 count), and from healthy study subjects (n = 5). The capacity to express beta-chemokines and CCR5 was assessed. Induction of MIP-1 alpha by lipopolysaccharide (LPS) in BAC of HIV-1-infected study subjects from the low CD4 group was less than BAC from healthy study subjects (p <.001), and also was less than in BACs from the group with a high CD4 group (p <.001). Moreover, the intracellular expression of MIP-1 alpha in LPS-induced monocytes of HIV-1-infected patients was significantly less than that from healthy study subjects (p <.01). In addition, spontaneous expression of mRNAs for CCR5 and MIP-1 alpha in BAC was significantly lower in HIV-1-infected patients compared with in healthy study subjects (p <.03 and p <.02, respectively). In contrast to the findings with MIP-1 alpha, LPS stimulated MCP-1 in BAC from the group of HIV-1-infected patients with high CD4 count was significantly higher than healthy study subjects (p <.001). These dysregulations in the ability to express beta-chemokines by BAC may be important in the progression of HIV-1 infection in the lung.

Bronchoalveolar Lavage↗

Rehabilitation of a quadruple amputee subsequent to electrical burns sustained whilst hang gliding.

PURPOSE: The purpose of this article is to describe the management, difficulties encountered and level of independence achieved during the initial stage of a quadruple amputee's rehabilitation. METHOD: This is a case study of the rehabilitation of the first known person losing all four limbs due to electrocution whilst hang gliding. RESULTS: The patient became a successful upper limb prosthetic user and returned to work six hours a day. Full independence in activities of daily living was not achieved nor considered practical. Independent walking was accomplished in physiotherapy. however an electric wheelchair remains the only functional means of mobility. CONCLUSION: The rehabilitation is described in detail to assist those managing such a rare and complex case.

Activities of Daily Living↗

Simultaneous, two-color fluorescence detection of total protein profiles and beta-glucuronidase activity in polyacrylamide gel.

A dichromatic method for measuring the specific activity of beta-glucuronidase from complex cell homogenates or partially purified protein fractions is presented. Dual fluorescence is achieved by using the green emitting fluorogenic substrate ELF 97 beta-D-glucuronide to detect beta-glucuronidase activity, followed by the red emitting SYPRO Ruby protein gel stain or SYPRO Ruby IEF gel stain to detect the remaining proteins in the electrophoretic profile. Both ELF 97 alcohol, the highly fluorescent hydrolytic product generated from the enzyme substrate, and the SYPRO Ruby total protein stains are maximally excited by ultraviolet illumination. ELF 97 alcohol emits maximally at 525 nm while the SYPRO Ruby dyes emit maximally at 610 nm. Since ELF 97 beta-glucuronide is a precipitating substrate, it allows precise localization of beta-glucuronidase activity with minimal band diffusion. The staining method is simple and direct, without the requirement for ancillary coupling reactions. Dichromatic protein detection is demonstrated after sodium dodecyl sulfate(SDS)-polyacrylamide gel electrophoresis, carrier ampholyte-mediated isoelectric focusing or two-dimensional gel electrophoresis.

Electrophoresis↗

Rapid and simple single nanogram detection of glycoproteins in polyacrylamide gels and on electroblots.

The fluorescent hydrazide, Pro-Q Emerald 300 dye, may be conjugated to glycoproteins by a periodic acid Schiff's (PAS) mechanism. The glycols present in glycoproteins are initially oxidized to aldehydes using periodic acid. The dye then reacts with the aldehydes to generate a highly fluorescent conjugate. Reduction with sodium metabisulfite or sodium borohydride is not required to stabilize the conjugate. Though glycoprotein detection may be performed on transfer membranes, direct detection in gels avoids electroblotting and glycoproteins may be visualized within 2-4 h of electrophoresis. This is substantially more rapid than PAS labeling with digoxigenin hydrazide followed by detection with an antidigoxigenin antibody conjugate of alkaline phosphatase, or PAS labeling with biotin hydrazide followed by detection with horseradish peroxidase or alkaline phosphatase conjugates of streptavidin, which require more than eight hours to complete. Pro-Q Emerald 300 dye-labeled gels and blots may be poststained with SYPRO Ruby dye, allowing sequential two-color detection of glycosylated and nonglycosylated proteins. Both fluorophores are excited with mid-range UV illumination. Pro-Q Emerald 300 dye maximally emits at 530 nm (green) while SYPRO Ruby dye maximally emits at 610 nm (red). As little as 300 pg of alpha 1-acid glycoprotein (40% carbohydrate) and 1 ng of glucose oxidase (12% carbohydrate) or avidin (7% carbohydrate) are detectable in gels after staining with Pro-Q Emerald 300 dye. Besides glycoproteins, as little as 2-4 ng of lipopolysaccharide is detectable in gels using Pro-Q Emerald 300 dye while 250-1000 ng is required for detection with conventional silver staining. Detection of glycoproteins may be achieved in sodium dodecyl sulfate-polyacrylamide gels, two-dimensional gels and on polyvinylidene difluoride membranes.

Animals↗

The use of the linear quadratic model in radiotherapy: a review.

To be able to predict the impact of any radiotherapy treatment the physics of radiation interactions and the expected biological effect for any radiotherapy treatment situation (dose, fractionation, modality) must be both understood and modelled. This review considers the current use and accuracy of the linear quadratic model which can be used to consider the variation in tissue response with fraction size. Cell kill following radiation damage results from damage to the DNA which can take a variety of forms. In many cases the linear quadratic model is used to estimate the relative impact for different situations especially clinical studies relating to fraction size. This is mainly undertaken using parameters derived from the linear quadratic model such as biological effective dose and standard effective dose. The model has also been adapted to consider the effect of overall treatment time, repair during treatment (as occurs for brachytherapy treatments) and other situations. There are some concerns over its use, mainly in the small dose ranges (both total low doses and low doses per fraction) where studies have shown its inaccuracy. In other situations however it does appear to provide a reasonable estimate of relative clinical effect. As with all models, however results should never be considered out of clinical context.

Biophysical Phenomena↗

Femoral pseudoaneurysm thrombinjection.

BACKGROUND: The risk of pseudoaneurysm (PSA) increases with the number of catheterizations performed for cardiovascular diagnosis and therapy. Thrombin injection, or "thrombinjection," is an alternative to ultrasound-guided compression or surgical repair. Thrombinjection is effective and economical, but the specter of systemic arterial thrombosis hinders its wide application. We report cautionary steps taken prior to injection and lessons learned during our first 20 cases. METHODS AND RESULTS: Thrombinjection was performed under ultrasound (US) guidance in 12 women and 8 men with PSA after femoral catheterization. PSA varied in size from 17 to 39 mm with neck openings from 1.5 to 3.9 mm. Under local anesthesia and US longitudinal view, a 20-gauge US needle tip was placed in the PSA away from the neck. With 12 cases under 600 units, 100 to 2,300 units of thrombin (1,000 U/mL) were injected slowly. Slow injection, positioning of the ball of thrombus formed at the needle tip, probe compression, and combined or interchangeable use of US color flow and B-mode were the essential techniques utilized. All PSA thrombosed successfully on the first treatment. One patient had fever and another returned for compression treatment of a second, not recurrent, PSA. CONCLUSIONS: Successful thrombinjection was accomplished by focusing on common femoral artery PSA with small neck openings, avoiding arteriovenous fistulas, and using standard thrombin concentration, US needle, state of the art ultrasonography, slow injection, thrombus ball positioning, and adjunctive probe compression.

Adult↗

Tautomeric energetics of xanthine oxidase substrates: xanthine, 2-oxo-6-methylpurine, and lumazine.

The stability of the tautomers of each of the three important substrates of xanthine oxidase, xanthine, 2-oxo-6-methylpurine, and lumazine, was examined by quantum mechanical calculations. The geometries of these tautomers were optimized at the AM1, Hartree-Fock (HF/6-31G), and hybrid Hartree-Fock/density functional theory (B3LYP/6-31G(d)) levels of theory. The single point energies of some of the more stable tautomers for each of the substrates were calculated at the B3LYP/6-311 +G(2d,p) level of theory. The Conductor Polarized Continuum Model (CPCM) was used to evaluate the solvent effects on the relative stabilities of these tautomers. The calculations clearly identify the lowest energy tautomeric form for xanthine and lumazine. On the other hand, there appear to be three tautomers for 2-oxo-6-methylpurine, with only minor energetic differences in vacuo. In water, however, only one of them predominates. The lowest energy tautomers presumably represent the predominant tautomeric forms at the molybdenum center of xanthine oxidase during catalysis. Implications of these computational results are discussed in the context of enzyme catalysis.

Catalysis↗

System, environmental, and policy changes: using the social-ecological model as a framework for evaluating nutrition education and social marketing programs with low-income audiences.

A variety of nutrition education interventions and social marketing initiatives are being used by the Food Stamp Program to improve food resource management, food safety, dietary quality, and food security for low-income households. The Social-Ecological Model is proposed as a theory-based framework to characterize the nature and results of interventions conducted through large public/private partnerships with the Food Stamp Program. In particular, this article suggests indicators and measures that lend themselves to the pooling of data across counties and states, with special emphasis on systems, environment, and public policy change within organizations at the community and state levels.

Food Services↗

Increased hepatic oxidative DNA damage in patients with hepatocellular carcinoma.

Since oxidative DNA damage plays a role in experimental carcinogen-induced cancers, the purpose of the present study was to determine if hepatic oxidative DNA damage was increased in patients with HCC compared to patients with benign hepatic tumors or hepatic metastases (non-HCC) or to patients with end-stage alcoholic liver disease undergoing liver transplantation. Oxidative DNA damage was assessed by 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Results showed that peritumoral 8-OH-dG was markedly increased in HCC (N= 51) (180 +/- 74 vs 32 +/- 58-OH-dG/10(6)dG for tumor, P < 0.005) in contrast to patients with non-HCC (N = 17), in whom the peritumoral 8-OH-dG did not differ from that in tumor (39 +/- 7 vs. 31 +/- 108-OH-dG/10(6)dG). Oxidative DNA damage can be both mutagenic and carcinogenic; our data suggested it will be important in future studies to determine the chronology of this type of liver injury relative to hepatocarcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗