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Biomedical subjects

J M Jones

Publications and source records attributed to J M Jones.

At least 19 recordsLinked to original sources
PubMed2002

Adenoviral gene transfer to the heart during cardiopulmonary bypass: effect of myocardial protection technique on transgene expression.

OBJECTIVE: Adenoviral gene transfer to the arrested heart during cardiopulmonary bypass (CPB) is a novel method of allowing prolonged vector contact with the myocardium. In this model we investigated the importance of temperature, duration of arrest and cardioplegia on transgene expression. METHODS: First-generation adenoviral vector (1 x 10(12) total viral particles) containing the transgene for the human beta2-adrenoceptor (Adeno-beta(2)AR) or beta-galactosidase (Adeno-beta(gal)) was delivered to neonatal piglets via the proximal aorta, during simulated cardiac surgery, and allowed to dwell for the cross-clamp duration. Four treatment groups received Adeno-beta(2)AR. Groups A (n=4) and B (n=6) underwent cold crystalloid cardioplegia arrest for 10 and 30 min, respectively, Group C (n=5) underwent warm crystalloid cardioplegia arrest for 10 min, and Group D (n=5) underwent warm fibrillatory arrest for 10 min. Group E (n=6) received Adeno-beta(gal) and underwent cold crystalloid cardioplegia arrest (30 min). Animals were weaned off CPB and recovered for 2 days. Receptor density was assessed in membrane fractions using radioligand binding and compared using the Mann-Whitney U-test. RESULTS: Left ventricular transgene overexpression, as evidenced by elevated betaAR density, following Adeno-beta(2)AR treatment was greatest with cold cardioplegia (Group A 588+/-288.8 fmol/mg; P=0.002 and Group B 520+/-250.9 fmol/mg; P=0.01) versus control (Group E 109+/-8.4 fmol/mg). Overexpression also occurred with warm cardioplegia (Group C 274+/-69.5 fmol/mg; P=0.05) and ventricular fibrillation (Group D 215+/-48.4 fmol/mg; P=0.02) versus control. Comparison of the combined cold cardioplegia groups versus those treated with warm conditions showed a trend towards increased expression with cold conditions (P=0.1). Receptor density was also significantly increased in the right ventricle of animals in Group B (165+/-18.1 fmol/mg; P=0.03) and Group D (181+/-23.4 fmol/mg; P=0.02) versus control (Group E 118+/-5.8 fmol/mg). CONCLUSIONS: Cold crystalloid cardioplegia is not detrimental to gene transfer in vivo. In fact, there was a trend towards increased left ventricular transgene expression when the adenoviral vector was delivered following cold versus warm cardioplegia. Shorter periods of contact with the vector may reduce transgene overexpression. Therefore, gene transfer is possible during cardiac surgery with clinically used myocardial protection techniques.

Adenoviridae↗
PubMed2001

Correlating cell cycle with apoptosis in a cell line expressing a tandem green fluorescent protein substrate specific for group II caspases.

BACKGROUND: We describe a rapid flow cytometric assay that correlates cell cycle with apoptotic cell death in a cell line expressing a tandem green fluorescent protein (GFP). METHODS: A Jurkat cell line was transfected with a gene construct coding for constitutive expression of a tandem GFP molecule carrying a consensus cleavage site (DEVD) for group II caspases (C-2-Y). Cells were treated with CD95 antibody (Ab), then incubated with annexin V-phycoerythrin (PE), propidium iodide (PI), and Hoechst 33342. RESULTS: After CD95 treatment, the C-2-Y cell line had twice the number of nonapoptotic cells compared with both control cell lines. This proportion of viable, nonapoptotic cells after treatment was unaffected by the level of GFP (DEVD) expression in the cells, as confirmed by sorted populations. The early apoptotic cells in the C-2-Y cell line had an increased G0-G1 phase population compared with the control cell lines. CONCLUSIONS: Apoptosis is delayed in the C-2-Y cell line and the early apoptotic cells have a higher G0-G1 cell cycle frequency. The artificial substrate competes with the natural substrate(s), thereby slowing the apoptotic process. The expression level of DEVD-GFP does not alter the delayed induction of apoptosis. Caspase activation occurs prior to phosphatidylserine translocation.

Antibodies, Monoclonal↗
PubMed2001

Intermediates in V(D)J recombination: a stable RAG1/2 complex sequesters cleaved RSS ends.

Rearrangement of gene segments to generate antigen receptor coding regions depends on the RAG1/2 recombinase, which assembles a synaptic complex between two DNA signal sequences and then cleaves the DNA directly adjacent to the paired signals. After coupled cleavage of complementary signal sequences, virtually all of the cleaved signal ends remained associated with RAG1/2 in stable complexes. These signal end complexes were distinct from various precleavage RAG1/2 signal complexes in that they were resistant to treatment with heparin. A mammalian joining apparatus consisting of purified Ku70/86, XRCC4, and DNA ligase IV proteins was sufficient to join deproteinized cleaved ends, but retention of signal sequences within the signal end complex blocked access to the DNA ends and prevented their joining by these proteins. Sequestration of cleaved ends within the signal end complex would account for the persistence of these ends in the cell after cleavage and may explain why they do not normally activate the DNA-damage-dependent cell cycle checkpoint.

Antigens, Nuclear↗
PubMed2001

Escherichia coli PriA helicase: fork binding orients the helicase to unwind the lagging strand side of arrested replication forks.

Escherichia coli PriA is a primosome assembly protein with 3' to 5' helicase activity whose apparent function is to promote resumption of DNA synthesis following replication-fork arrest. Here, we describe how initiation of helicase activity on DNA forks is influenced by both fork structure and by single-strand DNA-binding protein. PriA could recognize and unwind forked substrates where one or both arms were primarily duplex, and PriA required a small (two bases or larger) single-stranded gap at the fork in order to initiate unwinding. The helicase was most active on substrates with a duplex lagging-strand arm and a single-stranded leading-strand arm. On this substrate, PriA was capable of translocating on either the leading or lagging strands to unwind the duplex ahead of the fork or the lagging-strand duplex, respectively. Fork-specific binding apparently orients the helicase domain to unwind the lagging-strand duplex. Binding of single-strand-binding protein to forked templates could inhibit unwinding of the duplex ahead of the fork but not unwinding of the lagging-strand duplex or translocation on the lagging-strand template. While single-strand-binding protein could inhibit binding of PriA to the minimal, unforked DNA substrates, it could not inhibit PriA binding to forked substrates. In the cell, single-strand-binding protein and fork structure may direct PriA helicase to translocate along the lagging-strand template of forked structures such that the primosome is specifically assembled on that DNA strand.

Base Sequence↗
PubMed2001

Disordered eating attitudes and behaviours in teenaged girls: a school-based study.

BACKGROUND: Disordered eating attitudes and behaviours are common in older teens and young women in Western countries. Recent evidence suggests that the prevalence of these disorders is rising and that the age of onset has fallen. In the present study, disturbed eating attitudes and behaviours were evaluated in a large school-based population in Ontario in order to determine their prevalence and demographic distribution. METHODS: Females, aged 12-18 years, from schools in Toronto, Hamilton and Ottawa were invited to complete questionnaires, including 3 subscales of the Eating Disorder Inventory (Drive for Thinness, Body Dissatisfaction, Bulimia), the Eating Attitudes Test-26 (EAT-26) and the Diagnostic Survey for Eating Disorders (DSED). RESULTS: Questionnaires were completed by 1739 (70%) of the 2483 adolescent females who were approached. The mean age of subjects in the sample was 14.6 (standard deviation 1.9) years. Thirteen percent of those aged 12-14 years and 16% of those aged 15-18 years had scores above the recommended cut-off (> or = 20) for disordered eating on the EAT-26. Current dieting to lose weight was reported by 23% of participants. Binge eating with associated loss of control was reported by 15% of participants, self-induced vomiting by 8.2% and the use of diet pills by 2.4%. Laxative and diuretic misuse were uncommon. Dieting was associated with an increased risk of binge-eating and purging behaviours. Older age and body mass index in the highest quartile were independently related to symptoms of eating disorders. INTERPRETATION: Disordered eating attitudes and behaviours were present in over 27% of girls aged 12-18 years and were seen to increase gradually throughout adolescence. Prevention programs to diminish the progression and impact of these disorders should be implemented and assessed.

Adolescent↗
PubMed2001

Handoff from recombinase to replisome: insights from transposition.

Bacteriophage Mu replicates as a transposable element, exploiting host enzymes to promote initiation of DNA synthesis. The phage-encoded transposase MuA, assembled into an oligomeric transpososome, promotes transfer of Mu ends to target DNA, creating a fork at each end, and then remains tightly bound to both forks. In the transition to DNA synthesis, the molecular chaperone ClpX acts first to weaken the transpososome's interaction with DNA, apparently activating its function as a molecular matchmaker. This activated transpososome promotes formation of a new nucleoprotein complex (prereplisome) by yet unidentified host factors [Mu replication factors (MRF alpha 2)], which displace the transpososome in an ATP-dependent reaction. Primosome assembly proteins PriA, PriB, DnaT, and the DnaB--DnaC complex then promote the binding of the replicative helicase DnaB on the lagging strand template of the Mu fork. PriA helicase plays an important role in opening the DNA duplex for DnaB binding, which leads to assembly of DNA polymerase III holoenzyme to form the replisome. The MRF alpha 2 transition factors, assembled into a prereplisome, not only protect the fork from action by nonspecific host enzymes but also appear to aid in replisome assembly by helping to activate PriA's helicase activity. They consist of at least two separable components, one heat stable and the other heat labile. Although the MRF alpha 2 components are apparently not encoded by currently known homologous recombination genes such as recA, recF, recO, and recR, they may fulfill an important function in assembling replisomes on arrested replication forks and products of homologous strand exchange.

Adenosine Triphosphatases↗
PubMed2001

Cardiac gene delivery with cardiopulmonary bypass.

BACKGROUND: Cardiac gene therapy offers the possibility of enhancing myocardial performance in the compromised heart. However, current gene delivery techniques have limited myocardial transgene expression and pose the risk of extracardiac expression. Isolation of the coronary circulation during cardiac surgery may allow for more efficient and cardiac-selective gene delivery in a clinically relevant model. Methods and Results-- Neonatal piglets (3 kg) underwent a median sternotomy and cardiopulmonary bypass, followed by aortic cross-clamping with 30 minutes of cardioplegic arrest. Adenoviral vectors containing transgenes for either beta-galactosidase (adeno-beta-gal, n=11) or the human beta(2)-adrenergic receptor (adeno-beta(2)-AR, n=15) were administered through the cardioplegia cannula immediately after arrest and were allowed to dwell in the coronary circulation during the cross-clamp period. After 1 week, the animals were killed, and their heart, lungs, and liver were excised and examined for gene expression. Analysis of beta-galactosidase staining revealed transmural myocardial gene expression among animals receiving adeno-beta-gal. No marker gene expression was detected in liver or lung tissue. beta-AR density in the left ventricle after adeno-beta(2)-AR delivery was 396+/-85% of levels in control animals (P<0.01). Animals receiving adeno-beta(2)-AR and control animals demonstrated similar beta-AR density in both the liver (114+/-8% versus 100+/-9%, P=NS) and lung (114+/-7% versus 100+/-9%, P=NS). There was no evidence of cardiac inflammation. CONCLUSIONS: By using cardiopulmonary bypass and cardioplegic arrest, intracoronary delivery of adenoviral vectors resulted in efficient myocardial uptake and expression. Undetectable transgene expression in liver or lung tissue suggests cardiac-selective expression.

Adenoviridae↗
PubMed2001

Multiple distinct targeting signals in integral peroxisomal membrane proteins.

Peroxisomal proteins are synthesized on free polysomes and then transported from the cytoplasm to peroxisomes. This process is mediated by two short well-defined targeting signals in peroxisomal matrix proteins, but a well-defined targeting signal has not yet been described for peroxisomal membrane proteins (PMPs). One assumption in virtually all prior studies of PMP targeting is that a given protein contains one, and only one, distinct targeting signal. Here, we show that the metabolite transporter PMP34, an integral PMP, contains at least two nonoverlapping sets of targeting information, either of which is sufficient for insertion into the peroxisome membrane. We also show that another integral PMP, the peroxin PEX13, also contains two independent sets of peroxisomal targeting information. These results challenge a major assumption of most PMP targeting studies. In addition, we demonstrate that PEX19, a factor required for peroxisomal membrane biogenesis, interacts with the two minimal targeting regions of PMP34. Together, these results raise the interesting possibility that PMP import may require novel mechanisms to ensure the solubility of integral PMPs before their insertion in the peroxisome membrane, and that PEX19 may play a central role in this process.

Amino Acid Sequence↗
PubMed2001

Partial mitral valve replacement for acute endocarditis.

We present a case of acute endocarditis involving the posteromedial commissure and both leaflets of the mitral valve, including a vegetation on and perforation of the anterior leaflet, in a young man with active Crohn's disease. Repair was performed using glutaraldehyde-treated bovine pericardium. Competence of the valve was achieved with no recurrence of endocarditis. This case demonstrates that extensive destruction of both leaflets of the mitral valve does not prohibit repair.

Adult↗
PubMed2001

Induction of the P450 reporter gene system bioassay by polycyclic aromatic hydrocarbons in Ulsan Bay (South Korea) sediments.

Polycyclic aromatic hydrocarbons (PAHs) and induction of the P450 reporter gene system (RGS) for 6- and 16-h exposure periods were determined in organic extracts of Ulsan Bay (South Korea) sediments to assess the utility of this bioassay as a screening tool for PAH contamination. The sum of the concentrations of 23 individual PAHs in 30 sediment samples (sigma PAH) based on GC-MS analysis ranged from 0.05 to 6.1 micrograms/g dry wt. P450 RGS fold induction ranged from 4.0 to 320 micrograms/g based on benzo[a]pyrene toxic equivalents (BaPEq). P450 RGS BaPEq and the 'chemical BaPEq', defined as the sum of the products of individual PAH concentrations and pre-determined toxic equivalency factors, exhibited very strong positive correlations with sigma PAH (r2 > 0.90; P < 0.001). Fold induction did not increase (and in some cases decreased) after the optimal incubation period (6 h) for PAHs, indicating that other compounds known to induce the P450 RGS (e.g. chlorinated organics) were not present at levels effecting significant induction. This was supported by GC-ECD analysis where non-ortho and mono-ortho polychlorinated biphenyls (PCBs) known to be strong P450 RGS inducers were found to be at very low or non-detectable levels in samples with the highest P450 RGS responses. The profound difference in PAH profiles for the two most contaminated sites suggested that this assay is especially sensitive for selected PAHs with greater than four rings. Combined with previous results, the P450 RGS shows promise as a useful screening tool for predicting deleterious biological effects resulting from CYP1A1-inducing, sediment-associated chemicals, particularly high molecular weight PAHs.

Biological Assay↗
PubMed2001

More than just a pamphlet: development of an innovative computer-based education program for cancer patients.

Patients with cancer continue to lack practical information regarding their illness and report low levels of awareness and use of patient services. The challenge to educators is to find cost-effective and timely ways to deliver a complex mix of interesting and high-quality information and expertise to this large and diverse audience, while still tailoring the content to individual needs and situations. In the present article, we describe the Princess Margaret Hospital (PMH) computer-based patient education program. The program is aimed toward empowering those dealing with cancer and provides comprehensive medical information and support via an interactive Intranet web site containing information about cancer (the Oncology Interactive Education Series), library resources, Internet links, information about PMH services, and a hospital calendar of events. Preliminary evaluation results have provided valuable direction for on-going program development and suggest that the program is easy to use, informative, and enjoyable for patients, families, volunteers, and health professionals.

Computer Communication Networks↗
PubMed2001

A Ku bridge over broken DNA.

The Ku heterodimer is essential for the nonhomologous end-joining pathway of DNA double-strand break repair; it both protects the broken ends and recruits some of the many proteins required to complete repair. The recently determined structure of Ku provides insights into how it can both bind to the DNA ends and allow access by the other proteins required to rejoin them.

Animals↗
PubMed2001

A study of the reaction of oxygen with graphite: model chemistry.

A considerable amount of research has been directed towards the mechanism of oxidation of graphite as a model reaction system and because of its industrial importance. A number of recent studies have been concerned with ab initio molecular orbital calculations on graphite including model chemistry and the reactions with molecular oxygen. This study is concerned with oxidation steps involving the attachment of molecular oxygen to the graphene, the formation of carbon monoxide and, in particular, the subsequent oxidation reactions.

Journal Article↗
PubMed2001

Pre-operative sestamibi-technetium subtraction scintigraphy in primary hyperparathyroidism: experience with 156 consecutive patients.

AIM: The aim of this study was to assess the usefulness of pre-operative sestamibi-technetium subtraction scintigraphy in a large cohort of patients with primary hyperparathyroidism (HPT). MATERIALS AND METHODS: A group of 156 consecutive patients with biochemically proven HPT underwent sestamibi-technetium subtraction scintigraphy before cervical exploration. Images were interpreted and reported prospectively and influenced the extent of surgical exploration. The intraoperative findings were compared retrospectively with the pre-operative scintigram reports in 154 individuals with technically satisfactory scintigrams. RESULTS: Of the 154 patients with satisfactory scintigrams, 122 (78.2%) demonstrated a single focus of activity following subtraction, 31 (19.9%) had negative findings and the remaining scintigram showed four foci of activity. At operation 138 (89.6%) solitary adenomas were removed, 13 patients (8.4%) had multi-gland disease and in three individuals (2.0%) no abnormal parathyroid tissue was found. The pre-operative scintigram accurately localized 91 of 98 (92.9%) solitary tumours weighing > 500 mg but only 18 of 35 (51.4%) adenomas weighing < 500 mg, (P < 0.0001). Overall sensitivity of sestamibi-technetium scintigraphy for localizing single parathyroid adenomas was 83.7%. CONCLUSION: Sestamibi-technetium subtraction scintigraphy will accurately localize a high proportion of solitary parathyroid adenomas but its usefulness is diminished by its inability to consistently identify smaller tumours.

Adenoma↗
PubMed2001

Repeat heart valve surgery: risk factors for operative mortality.

BACKGROUND: Patients undergoing repeat heart valve operations are a diverse population. We assessed risk factors for operative mortality in patients undergoing a first heart valve reoperation. METHODS: A retrospective review of hospital records was performed for 671 patients who underwent first repeat heart valve operations between 1969 and 1998. Univariable and multivariable analyses were performed. RESULTS: Operative mortality was 8.6%. Mortality fell each decade to 4.8% in the most recent period (adjusted chi(2) for linear trend P <.0005). Mortality increased from 3.0% for reoperation for a failed repair or reoperation at a new valve site to 10.6% for prosthetic valve dysfunction or periprosthetic leak and to 29.4% for endocarditis or valve thrombosis. Concomitant coronary artery bypass grafting was associated with a mortality of 15.4% compared with 8.2% when it was not required. Mortality for aortic valve replacement was 6.4%, mitral valve replacement 7.4%, aortic and mitral valve replacement 11.5%, tricuspid valve replacement 25.6%, periprosthetic leak repair 9.1%, and isolated valve repair 2.2%. Among 336 patients requiring replacement of prosthetic valves, mortality was 26.1% for replacement of a mechanical valve compared with 8.6% for replacement of a tissue valve (P <.0005). Multivariable analyses identified year of reoperation, age, coronary artery bypass grafting, indication, and replacement of a mechanical valve rather than a tissue valve as significant explanatory variables for operative mortality. CONCLUSIONS: Heart valve reoperations can be performed with an acceptable operative mortality. However, we have identified several categories of patients in whom reoperation carries an increased risk.

Aortic Valve↗
PubMed2001

Can assessment of psychosocial orientation assist continuing education program development in psychosocial oncology?

BACKGROUND: A pilot study was designed to aid in the development of a formal, interdisciplinary curriculum in psychosocial oncology for front-line health care professionals. METHOD: A 190-item questionnaire was distributed to psychosocial (PP) and non-psychosocial (NPP) oncology professionals attending a psychosocial skills workshop. A 38-item attitudinal survey of psychosocial orientation was used in an attempt to identify unperceived needs of the learners. RESULTS: Of the 150 questionnaires distributed, 104 (69%) were completed and returned. Overall scores for satisfaction with the workshop were high, and significantly higher in the PP group. No interdisciplinary difference existed in the preferred learning formats for future events, and both groups preferred interactive, experiential forums for developing skills relevant to patient management. The two groups' perceived learning needs differed. NPPs wanted to focus on skills such as communication, counseling, crisis intervention, palliative care, and coping with life-threatening illness. The attitudinal survey results demonstrated a significant difference between the psychosocial orientations of PPs and NPPs and suggested that NPPs would benefit from: 1) information to correct misconceptions about patients' psychosocial needs and experiences, 2) demonstrations of how to overcome contextual barriers to the delivery of psychosocial care. CONCLUSIONS: Front-line oncology professionals in many disciplines are interested in continuing education in psychosocial oncology. The attitudinal survey provided insight into unperceived learning needs that can help in designing future curricula. Its value as a tool to measure impact of these programs is worthy of future study.

Adult↗
PubMed2001

A province-wide needs assessment of oncology health care professionals in psychosocial oncology.

BACKGROUND: Oncology professionals still lack the knowledge and skills to provide effective psychosocial care. Continuing education (CE) aimed at addressing this lack may improve the provision of psychosocial care to patients and their families. METHODS: The authors conducted a province-wide cross-sectional mail survey of oncology health care professionals [oncologists (MDs), nurses (RNs) and radiation therapists (RTs)] and assessed psychosocial orientation, self-assessed knowledge, and motivation to learn about psychosocial oncology. In addition, they sought factors that might influence professionals' willingness to attend CE programs. RESULTS: In total, 241 surveys were completed and returned. Psychosocial orientation was highest in the RN subgroup. MDs rated their knowledge to deal with specific psychosocial issues higher than did RNs and RTs, while their motivation to learn more about providing psychosocial care was significantly lower. Seventy-three percent of respondents indicated that they would like CE in psychosocial oncology. Self-reported motivation to learn was the most significant factor associated with this interest. CONCLUSION: These findings raise questions about perceived learning needs and aided in the development of an interprofessional curriculum in psychosocial oncology.

Adult↗