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Biomedical subjects

P Oliver

Publications and source records attributed to P Oliver.

At least 19 recordsLinked to original sources
PubMed2006

Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm.

Resistin and adiponectin are adipokines with postulated opposite functions. Resistin has been related with insulin resistance in obesity, while adiponectin could be associated to higher insulin sensitivity. We have determined whether the production of these two adipokines during the day is related to the feeding rhythm in rats. Resistin mRNA levels in adipose tissue correlated positively with the gastric contents and serum insulin concentration, showing higher levels during the dark phase (period of the highest food intake), especially in the mesenteric depot, while levels decreased during the light phase. The diurnal pattern of resistin expression was not directly reflected in the circulating levels, but it showed a 6-h delay and correlated negatively with the gastric contents and serum insulin. Adiponectin expression followed an opposite pattern, not apparently related to feeding or insulin release, and not translated into changes in circulating levels. Moreover, considering that insulin stimulates resistin expression and that circulating resistin follows a contrary circadian pattern in comparison to insulin, resistin, apart from its role in the increased insulin resistance associated to obesity, could also act as a putative modulator of insulin in the daily feeding/fasting rhythm through a negative feedback regulation of its action.

Adiponectin↗
PubMed2004

Fitness and life-history traits of the two major mitochondrial DNA haplotypes of Drosophila subobscura.

Mitochondrial DNA restriction site analyses on natural populations of Drosophila subobscura have proved the existence of two common, coexisting haplotypes (I and II), as well as a set of less frequent ones derived from them. To explain this distribution, experiments to date point practically to all possible genetic mechanisms being involved in the changes of gene frequencies (cytonuclear coadaptation, direct natural selection on mtDNA and genetic drift). In an attempt to find differences that help to understand the dynamics of these haplotypes and to detect the effect of selection, we measured certain fitness components and life-history traits (egg-larva and larva-adult viabilities and developmental times, longevity, resistance to desiccation and optimal density) of the two main haplotypes I and II when maintained in laboratory population cages. As a general trend, haplotype II showed a higher net fitness than haplotype I, which explains the superiority of haplotype II over haplotype I in experimental populations but not their coexistence in nature, where additional factors must be considered.

Animals↗
PubMed2002

Linkage disequilibria between mtDNA haplotypes and chromosomal arrangements in a natural population of Drosophila subobscura.

The association between mtDNA haplotypes and chromosomal arrangements in a natural population of Drosophila subobscura from Calvia (Balearic Islands, Spain) was studied in order to search for linkage disequilibria, in an attempt to explain the populational dynamics of the mtDNA haplotypes of this species in nature. The presence of Wolbachia was not detected. Two main haplotypes (I and II) were found, as well as a series of less common ones. The Tajima D-test seemed to indicate some kind of seasonal population bottleneck. An analysis of linkage disequilibrium and factorial analysis of correspondences detected an association between haplotype I and the J(ST) inversion and haplotype II and the J(1) inversion.

Animals↗
PubMed2001

Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense.

Bacterial pneumonia is an increasing complication of HIV infection and inversely correlates with the CD4(+) lymphocyte count. Interleukin (IL)-17 is a cytokine produced principally by CD4(+) T cells, which induces granulopoiesis via granulocyte colony-stimulating factor (G-CSF) production and induces CXC chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokine production and lung host defenses. To test this, we used a model of Klebsiella pneumoniae lung infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R-deficient mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO) mice displayed a significant delay in neutrophil recruitment into the alveolar space, and had greater dissemination of K. pneumoniae compared with control mice. This defect was associated with a significant reduction in steady-state levels of G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling is critical for optimal production of G-CSF and MIP-2 and local control of pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.

Animals↗
PubMed2001

Il-17 mobilizes peripheral blood stem cells with short- and long-term repopulating ability in mice.

Autologous and allogeneic bone marrow transplantations have evolved as important cancer therapy modalities. For both indications, peripheral blood has been shown to have distinct advantages over bone marrow as the stem cell source. Cytokine combinations for mobilization have enhanced stem cell yield and accelerated engraftment. However, novel mobilizing agents and strategies are needed to further improve clinical outcomes. Within the donor graft, the dynamic equilibrium between T cells and stem cells critically influences engraftment and transplantation results. IL-17 is a cytokine produced almost exclusively from activated T cells. IL-17 was expressed in vivo with adenovirus technology. Here, proof-of-principle studies demonstrate that IL-17 effectively mobilizes hemopoietic precursor cells (CFU-granulocyte-erythrocyte-macrophage-monocyte, CFU-high proliferative potential) and primitive hemopoietic stem cells (Lin(-/low)c-kit(+)Sca1(+)). Moreover, mouse IL-17 adenovirus-mobilized peripheral blood stem cells rescued lethally irradiated mice. Bone marrow was found to be 45-75% of donor origin at 1 year. In secondary recipients, donor-derived bone marrow cells ranged from 45 to 95%. These data show that IL-17 mobilizes stem cells in mice with short- and long-term reconstituting capacity. Additional comparative studies are needed as well as studies in tumor models to refine distinct potential clinical applications for IL-17-mobilized peripheral blood stem cells.

Animals↗
PubMed2001

Differential expression of genes for uncoupling proteins 1, 2 and 3 in brown and white adipose tissue depots during rat development.

The different expression patterns of genes for uncoupling proteins (UCPs) 1, 2 and 3 (ucp1, ucp2 and ucp3) were studied in interscapular brown adipose tissue (BAT) and in four white adipose tissue (WAT) depots (epididymal, inguinal, mesenteric and retroperitoneal) in male rats of different ages (18 days-12 months). UCP mRNA expression levels were determined by Northern blotting. In BAT, there were high levels of expression of UCP1 and UCP3 mRNA, but no detectable levels of UCP2 mRNA. Both ucp1 and ucp3 followed a similar expression pattern with age, with high levels in suckling rats which decreased to 50% or less in rats just under 2 months old, declining thereafter until 5 months and then recovering with age. However, an additional peak of expression was observed for ucp3 at the age of 3 months. In WAT, ucp1 expression was rare: occasional expression was found for UCP1 mRNA in the retroperitoneal depot in suckling rats and in the epididymal and inguinal depots in suckling and mature adult rats. ucp2 and ucp3 had different developmental expression patterns, but these were similar for each gene in the different depots studied. UCP3 mRNA was highly expressed in rats soon after birth, it decreased until 3 months, and increased thereafter, except for the mesenteric WAT where ucp3 expression decreased until 7 months before recovering. The fact that changes with age of both ucp1 and ucp3 expression have a similar profile in BAT, which is also similar to the ucp3 and also ucp1 profiles in some WAT depots, might reflect a common regulatory pattern for the expression of these genes, and also a common function. In contrast to ucp1 and ucp3, ucp2 had a peak of expression at about 2 months, and lower expression at 3 months, suggesting different regulation and probably a different role for this UCP.

Adipose Tissue↗
PubMed2001

Ontogenesis of leptin expression in different adipose tissue depots in the rat.

Serum leptin levels and leptin mRNA expression by adipose tissue increase with age and are mainly associated with an increase in adiposity. Regional changes in both leptin production and fat distribution contribute to circulating leptin levels and may play a role in the regulation of body weight. a capacity that changes during development. Here, we have studied leptin mRNA expression in four different white adipose tissue depots (epididymal, retroperitoneal, mesenteric, inguinal; namely, EWAT, RWAT, MWAT, IWAT) and in interscapular brown adipose tissue (IBAT). We have also studied their relationship with lipid content and adiposity changes, together with serum leptin levels in male rats at different ages (18, 55, 93, 159, 212, 294 and 355 days). Serum leptin levels increased during development, reaching stable levels at the age of 7 months, and, as expected, were highly correlated with both the adiposity index (r=0.908, P<0.01) and body weight (r=0.906, P<0.01). Leptin mRNA expression also increased with age, following characteristic ontogenic patterns in every adipose tissue depot. The patterns were similar in EWAT and RWAT: leptin expression increased very rapidly during the first 55 days for EWAT and 3 months for RWAT, with a peak in the latter at 7 months, and high expression levels were retained for the rest of the study period. In IWAT and IBAT, leptin expression increased steadily during the 12-month period studied and was significantly lower than levels in EWAT and RWAT. Leptin expression in MWAT increased progressively with age to reach levels close to those of EWAT and RWAT in 10-month-old animals. The pattern of leptin expression in both EWAT and RWAT paralleled their lipid content, and leptin mRNA expression per unit of tissue lipid content was maintained high and constant from a very young age (about 2 and 3 months, respectively). However, the expression of mRNA for leptin (expressed per unit of tissue lipid concentration) in MWAT, IWAT and IBAT increased steadily during the whole period studied, without attaining the maximal levels observed in EWAT and RWAT. MWAT, IWAT and IBAT maintained their capacity to increase leptin mRNA expression in response to an additional accumulation of lipids. Our data demonstrate that there are regional-specific differences and different rates of increase of leptin gene expression within distinct depots of WAT and BAT. These changes cannot be uniquely explained by changes in adiposity or lipid content, implying that there are regional-specific regulatory mechanisms that may depend on the attenuation with age of the beta-adrenergic inhibitory signalling pathway upon leptin expression or on other factors.

Adipose Tissue↗
PubMed2001

Sexual dimorphism in age-related changes in UCP2 and leptin gene expression in subcutaneous adipose tissue in humans.

The influence of age and gender on uncoupling protein 2 (UCP2) expression and its relationship with leptin expression in subcutaneous adipose tissue has been studied in humans. Samples of subcutaneous adipose tissue were obtained from 41 adult subjects (20 women and 21 men), with an age range of 28 to 84 years, and body mass index (BMI) of 19 to 36 Kgm(minus sign2). UCP2 and leptin mRNA expression was determined by northern blot. In women, both leptin and UCP2 expression in the subcutaneous adipose tissue increased significantly with age (r = 0.490 p < 0.05 and r = 0.475 p < 0.05, respectively). In men, in contrast, a negative correlation was found between leptin expression and age (r = minus sign0.678 p < 0.001), while no significant correlation was apparent between UCP2 expression and age (r = minus sign0.077). In addition, there was a positive correlation between UCP2 and leptin expression in women (r = 0.656 p < 0.01). These data show important gender dependent differences in the age-related changes in leptin and UCP2 expression in subcutaneous adipose tissue in humans.

Journal Article↗
PubMed2001

Improved radioiodination of biomolecules using exhaustive Chloramine-T oxidation.

To improve standardization in analytical reagents we investigated Chloramine-T radioiodination (125I) of several biomolecules based on the use of a single amount of the oxidizing agent Chloramine-T as the limiting reagent being exhausted during the course of the reaction. Whenever the labeling yield resulted in less than one atom 125I/molecule, a second amount of the oxidizing agent was added. Thereafter, the integrity of the various biomolecules was assessed using radioimmunoassays, radioreceptor binding assays, or radioimmunometric assays. Purification yields were done by gel permeation (56% +/- 19%, n=230) or by precipitation with trichloroacetic acid (59% +/- 19%, n=230). Specific activity (117 +/- 61 MBq/nmol) and the degree of iodine incorporation (1.4 +/- 0.8 atoms of 125I/molecule) were achieved after 300 sec of incubation. A second addition of Chloramine-T resulted in an increased labeling yield of all biomolecules tested by a mean factor of 1.8 +/- 0.9. After the second addition of Chloramine-T, we observed for some biomolecules a significant (p<0.001) decreased effect in biological performance. In conclusion, the use of Chloramine-T as a limiting reagent resulted in molecules with appropriate immunological and biological performance. In general, tracers were minimally damaged and assessment of the shelf life as well as storing conditions showed the usefulness of the standardization of biomolecule labeling.

Animals↗
PubMed2001

Residential rehabilitation for drug users: a review of 13 months' intake to a therapeutic community.

BACKGROUND: Residential rehabilitation based on 'therapeutic community' treatment for drug users is a treatment option which is attractive to GPs and others referring drug users for treatment. Whilst there is evidence that maintenance-based programmes for drug users are effective, there have been fewer attempts to evaluate the effectiveness of abstinence-based programmes which are relatively more intensive and expensive interventions. OBJECTIVE: This paper reports and evaluates the outcomes for 13 months' intake of 138 drug users to a residential community. METHODS: We carried out a retrospective cohort study using existing clinical and residential record data. The setting is a residential rehabilitation centre run by the charity Phoenix House in Sheffield, UK, offering a 1-year programme for heroin addicts including community detoxification overseen by primary care specialist doctors and residential rehabilitation. Participants were all patients who entered treatment between 1 February 1998 and 28 February 1999 inclusive. An analysis was carried out of clinical records and other records kept by clinicians and staff at the centre. Outcome measures were numbers of days of retention in treatment and reasons for departure, categorized as completed treatment, planned or unplanned departure and expulsion from the programme. For patients who underwent in-house detoxification, a further outcome measure was whether or not detoxification was complete at discharge. RESULTS: Heroin was the main drug of abuse in 85% of admissions. Mean length of time for which individuals had been drug dependent was 8 years (range 1.3-20.1 years). The mean length of stay was 80.2 days (range 1-394, 95% confidence interval 61.8-98.6). Thirty-four individuals (25%) completed 90 days or more. No association was found between length of stay and age, sex, route of administration, polydrug use, length of time addicted or age of first addiction. Sixty-five per cent of those who received in-house detoxification completed the detoxification period. When patients were classified as 'successes' or 'failures' by reason for departure from the programme, 94 (68.1%) were classified as failures and 18 (13.0%) as successes. Data were unavailable for 26 patients. Success was not associated with any characteristic at entry apart from being drug free as opposed to requiring detoxification (P = 0.048, chi-square = 6.06, df = 2). CONCLUSION: This study shows overall low levels of programme completion and high levels of unplanned departure and eviction from the programme amongst these long-term drug users. On the other hand, the importance of abstinence for those who achieve it in residential rehabilitation should not be underestimated, nor should the possibility that long-term outcomes are influenced by the learning process involved in the intervention. It may be possible to operate better selection procedures in order to optimize outcomes.

Adult↗
PubMed2001

Current best practice for the health surveillance of enzyme workers in the soap and detergent industry.

This study defines current best practice for the health surveillance of workers who are potentially exposed to enzymes in the manufacture of enzymatic detergent products. It is recommended that health surveillance is performed 6-monthly for the first 2 years and annually thereafter. The health surveillance programme should include a respiratory questionnaire to detect symptoms, assessment of lung function to detect pre-symptomatic changes and an immunological test to detect specific immunoglobulin E (IgE) to enzymes. The International Union Against Tuberculosis and Lung Disease respiratory questionnaire should be used since it has been validated extensively for detecting asthma. Operators should observe the American Thoracic Society performance criteria for spirometers and standardized procedures for conducting spirometry. Since current airborne monitoring techniques for enzymes do not detect short-duration peak exposures, the incidence of employee sensitizations remains the most reliable measure of the integrity of environmental control. The Pepys skin prick test has been validated as a sensitive, specific and practical test for detecting specific IgE to many inhalant allergens including enzymes. For newly sensitized workers, a multi-cause investigation should be conducted to identify potential sources of exposure. Group results of immunological test results assist in the evaluation of workplace control measures, and should be used to monitor the effectiveness of hygiene and engineering programmes and to help prioritize areas for improvement. Positive responses to a questionnaire or abnormal spirometry should be assessed further. Occupational asthma should be excluded in any case of adult-onset asthma that starts or deteriorates during working life. This is particularly important because an accurate diagnosis of occupational asthma with early avoidance of exposure to its cause can result in remission of symptoms and restoration of lung function.

Asthma↗
PubMed2001

Poly-L-lysine-based molecular conjugate vectors: a high efficiency gene transfer system for human progenitor and leukemia cells.

BACKGROUND: Targeted, specific receptor mediated gene transfer is a major goal of gene therapy research to accomplish gene transfer exclusively to the desired cell population. METHODS: First, the use of natural receptor for stem cell factor and transferrin receptor-targeted gene transfer using poly-L-lysine-based molecular conjugate vectors was evaluated in a panel of hematopoietic progenitor cell lines. Second, the ability of poly-L-lysine to enhance adenovirus mediated gene transfer efficiency was examined in different cell lines by using recombinant adenovirus-poly-L-lysine molecular conjugate conglomerates (recMCVEGFP). RESULTS: Despite effective ligand internalization receptor, gene expression amplification in receptor positive cell lines was not uniformly observed. Therefore, using a poly-L-lysine-based, receptor-targeted vector, neither transferrin nor natural receptor for stem cell factor mediated gene transfer can be considered a universally applicable procedure that exclusively depends on the presence of receptors on the cell surface; rather, it is a cell specific phenomenon. In our model, poly-L-lysine is the major contributor for gene transfer to hematopoietic progenitor cells, mediating the initial vector-cell binding. Human progenitor cell lines are poorly transduceable with recombinant adenovirus vectors. This new poly-L-lysine-modified, adenovirus-based vector could overcome virus tropism restrictions and consistently achieve very high transduction efficiency (>90%) in cells otherwise refractory to adenovirus gene transfer. CONCLUSIONS: Polylysine-based adenovirus vectors may have promise for situations in which high-efficiency gene transfer with transient high level transgene expression in hematopoietic cells is needed, such as leukemia vaccine protocols or for purging strategies in leukemia cell contaminated stem cell preparations.

Adenoviruses, Human↗
PubMed2001

Efficient c-kit receptor-targeted gene transfer to primary human CD34-selected hematopoietic stem cells.

We have previously reported effective gene transfer with a targeted molecular conjugate adenovirus vector through the c-kit receptor in hematopoietic progenitor cell lines. However, a c-kit-targeted recombinant retroviral vector failed to transduce cells, indicating the existence of significant differences for c-kit target gene transfer between these two viruses. Here we demonstrate that conjugation of an adenovirus to a c-kit-retargeted retrovirus vector enables retroviral transduction. This finding suggests the requirement of endosomalysis for successful c-kit-targeted gene transfer. Furthermore, we show efficient gene transfer to, and high transgene expression (66%) in, CD34-selected, c-kit(+) human peripheral blood stem cells using a c-kit-targeted adenovirus vector. These findings may have important implications for future vector development in c-kit-targeted stem cell gene transfer.

Adenoviridae↗
PubMed2001

Prolonged ethanol treatment enhances lipopolysaccharide/phorbol myristate acetate-induced tumor necrosis factor-alpha production in human monocytic cells.

BACKGROUND: Ethanol (EtOH) is known to alter host immune responses and cytokine production. Acute EtOH exposure can suppress tumor necrosis factor (TNF)-alpha production, which attenuates pulmonary defense against infection. Previous studies in our laboratory show that acute EtOH inhibited TNF-alpha production by a posttranscriptional process, namely suppression of TNF-alpha-converting, enzyme-mediated, ectodomain shedding. However, chronic EtOH has been shown to augment TNF-alpha production, and this has been associated with EtOH-induced liver injury. To further characterize this paradoxical effect of EtOH on TNF-alpha production, we developed an in vitro model by using Mono Mac 6 cells, a human monocytic cell line. METHODS: Mono Mac 6 cells were treated with EtOH (0-75 mM) for 1 to 7 days. TNF-alpha production was induced by lipopolysaccharide and phorbol myristate acetate and quantitated by enzyme-linked immunosorbent assay. Generation of reactive oxygen species (ROS) was assayed by using a specific fluorogenic reagent. RESULTS: Acute EtOH initially inhibited lipopolysaccharide/phorbol myristate acetate-induced TNF-alpha production in Mono Mac 6 cells. However, during chronic EtOH exposure, this inhibition was reversed gradually over time. By day 6 after EtOH treatment, Mono Mac 6 cells demonstrated significant up-regulation of TNF-alpha production. Moreover, chronic EtOH induced the generation of ROS in these Mono Mac 6 cells. Scavenging ROS by Mn(III)tetrakis(1-methyl-4pyridyl)porphyrin pentachloride and N-acetyl-L-cysteine attenuated chronic EtOH-enhanced TNF-alpha production. CONCLUSION: These results suggest that ROS induction is involved in EtOH-enhanced TNF-alpha production by monocytes. This study also provides insight into the mechanisms of alteration of TNF-alpha production in different EtOH exposure settings.

Carcinogens↗
PubMed2001

Deaths from drugs of abuse in Sheffield, 1998: the role of prescribed medication.

Characteristics of recent drug abuse-related deaths in the city of Sheffield were examined from the coroner's records. Almost all of those who died of poisoning from a drug of abuse were known to be dependent on heroin yet less than half were receiving treatment. Benzodiazepines were frequently detected alongside opiates during toxicology, the source of which was likely to be the deceased's own prescription.

Adult↗
PubMed2001

What makes catchment management groups "tick"?

The work of catchment management groups throughout Australia represents a significant economic and social investment in natural resource management. Institutional structures and policies, the role of on-ground coordinators, facilitation processes, citizen participation and social capital are critical factors influencing the success of catchment management groups. From a participant-researcher viewpoint, this paper signposts research directions and themes that are being pursued from the participant/coordinator, catchment group, and lead government/non-government agency perspective on the influence of these factors on the success of a catchment management group in the Pumicestone Region of Southeast Queensland, Australia. Research directions, themes and discussion/reflection points for practitioners include--the importance of understanding milieu; motivation; success; having fun; "networking networks"; involvement of "nontraditional" stakeholders; development of stakeholder/participant partnerships; learning from other practitioners; methods of stakeholder/participant representation; evaluation; the need for guiding principles or philosophy; the equivalence of planning, implementation, evaluation, and resourcing; catchments as fundamental units of Nature; continuity of support for groups; recognising a new role for government; working with existing networks; and the need for an eclectic approach to natural resource management.

Community-Institutional Relations↗