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Biomedical subjects

R C Thompson

Publications and source records attributed to R C Thompson.

At least 19 recordsLinked to original sources
PubMed2006

CXCR4 expression mediates glioma cell invasiveness.

Glioblastoma multiforme is a highly invasive tumor bearing a dismal prognosis. Experimental strategies that focus on the specific biological cues governing the invasive capacity of these tumors may hold significant therapeutic promise. In this context, we describe the in vitro and in vivo association of the cell surface chemokine receptor, CXCR4, with the development of an invasive phenotype in malignant glioblastoma. We demonstrate that invasive populations of glioma cells overexpress CXCR4 at the message and protein levels, and that this expression ranges from 25- to 89-fold higher than that found in noninvasive tumor cells. Furthermore, neutralization of CXCR4 significantly impairs the in vitro invasive capacity of malignant glial cells. In addition, glioma cells secrete CXCL12 and demonstrate robust invasive capacity toward a CXCL12 gradient in vitro. These findings underscore the importance of CXCR4 as a potential therapeutic target for the treatment of invasive glioblastoma.

Animals↗
PubMed2005

Arcuate nucleus transcriptome profiling identifies ankyrin repeat and suppressor of cytokine signalling box-containing protein 4 as a gene regulated by fasting in central nervous system feeding circuits.

The arcuate nucleus of the hypothalamus is a primary site for sensing blood borne nutrients and hormonal messengers that reflect caloric status. To identify novel energy homeostatic genes, we examined RNA extracts from the microdissected arcuate nucleus of fed and 48-h fasted rats using oligonucleotide microarrays. The relative abundance of 118 mRNA transcripts was increased and 203 mRNA transcripts was decreased during fasting. One of the down-regulated mRNAs was ankyrin-repeat and suppressor of cytokine signalling box-containing protein 4 (Asb-4). The predicted structure of Asb-4 protein suggested that it might encode an intracellular regulatory protein, and therefore its mRNA expression was investigated further. Reverse transcription quantitative polymerase chain reaction was used to validate down-regulation of Asb-4 mRNA in the arcuate nucleus of the fasted Sprague-Dawley rat (relative expression of Asb-4 mRNA: fed = 4.66 +/- 0.26; fasted = 3.96 +/- 0.23; n = 4, P < 0.01). Down-regulation was also demonstrated in the obese fa/fa Zucker rat, another model of energy disequilibrium (relative expression of Asb-4 mRNA: lean Zucker = 3.91 +/- 0.32; fa/fa = 2.93 +/- 0.26; n = 5, P < 0.001). In situ hybridisation shows that Asb-4 mRNA is expressed in brain areas linked to energy homeostasis, including the arcuate nucleus, paraventricular nucleus, dorsomedial nucleus, lateral hypothalamus and posterodorsal medial amygdaloid area. Double in situ hybridisation revealed that Asb-4 mRNA colocalises with key energy homeostatic neurones. In the fed state, Asb-4 mRNA is expressed by 95.6% of pro-opiomelanocortin (POMC) neurones and 46.4% of neuropeptide Y (NPY) neurones. By contrast, in the fasted state, the percentage of POMC neurones expressing Asb-4 mRNA drops to 73.2% (P < 0.001). Moreover, the density of Asb-4 mRNA per fasted POMC neurone is markedly decreased. Conversely, expression of Asb-4 mRNA by NPY neurones in the fasted state is modestly increased to 52.7% (P < 0.05). Based on its differential expression, neuroanatomical distribution and colocalisation, we hypothesise that Asb-4 is a gene involved in energy homeostasis.

Animals↗
PubMed2004

Dysregulation of the fibroblast growth factor system in major depression.

In this report we describe findings that imply dysregulation of several fibroblast growth factor (FGF) system transcripts in frontal cortical regions of brains from human subjects with major depressive disorder (MDD). This altered gene expression was discovered by microarray analysis of frontal cortical tissue from MDD, bipolar, and nonpsychiatric control subjects and was verified by quantitative real-time PCR analysis and, importantly, in a separate cohort of MDD subjects. Furthermore, we show, through a separate analysis of specific serotonin reuptake inhibitor (SSRI)-treated and non-SSRI-treated MDD subjects that the observed changes in expression of FGF transcripts are not secondary to drug treatment. Rather, changes in specific FGF transcripts are attenuated by SSRIs and may thus be partially responsible for the mechanism of action of these drugs. We also make available the gene-expression profile of all of the other growth factors and growth factor receptors detected in these postmortem samples.

Adult↗
PubMed2003

DNA microarray analysis of functionally discrete human brain regions reveals divergent transcriptional profiles.

Transcriptional profiles within discrete human brain regions are likely to reflect structural and functional specialization. Using DNA microarray technology, this study investigates differences in transcriptional profiles of highly divergent brain regions (the cerebellar cortex and the cerebral cortex) as well as differences between two closely related brain structures (the anterior cingulate cortex and the dorsolateral prefrontal cortex). Replication of this study across three independent laboratories, to address false-positive and false-negative results using microarray technology, is also discussed. We find greater than a thousand transcripts to be differentially expressed between cerebellum and cerebral cortex and very few transcripts to be differentially expressed between the two neocortical regions. We further characterized transcripts that were found to be specifically expressed within brain regions being compared and found that ontological classes representing signal transduction machinery, neurogenesis, synaptic transmission, and transcription factors were most highly represented.

Aged↗
PubMed2002

Axialization of laser cooled magnesium ions in a penning trap.

We report the first demonstration of the axialization of laser cooled ions in a Penning trap. Axialization involves the application of a small radial quadrupole drive which couples the cyclotron and magnetron motions. This enhances the laser cooling, allowing tighter confinement of the ions to the central axis of the trap than is otherwise possible. Using an intensified charge-coupled device (ICCD) camera we have imaged the axialization process for the first time. For a single ion, we recorded a large decrease of the magnetron amplitude corresponding to a reduction in ion temperature of approximately 2 orders of magnitude to an upper limit of order 10 mK. We have discovered dynamics specific to the laser cooled system which depend critically on the axial drive frequency and amplitude.

Journal Article↗
PubMed2002

Enteric parasitic zoonoses of domesticated dogs and cats.

Dogs and cats are important members of many families; however, they can harbour gastrointestinal parasites that may infect their owners. Some of these parasites, e.g. Echinococcus sp., can have a significant impact on human health. However, with appropriate education, management and anthelmintic regimes, zoonotic transmission of these parasites can be minimised.

Animals↗
PubMed2001

The future of veterinary parasitology: a time for change?

The future of veterinary parasitology is discussed at a time when R&D funding from the pharmaceutical industry is declining, yet the opportunities for veterinary parasitologists to diversify their activities has never been greater. Emerging and re-emerging areas requiring input from veterinary parasitologists include: veterinary public health; conservation and wildlife diseases; emerging and exotic infectious diseases; surveillance strategies; economic effects of parasitic diseases; aquaculture; molecular epidemiology; dietary and biological control of parasitic diseases; animal welfare; organic agricultural systems; novel vaccination strategies; drug target characterisation and rational drug design. Without change, the survival of veterinary parasitology as a viable, distinct discipline is under threat. In this environment, veterinary parasitologists must be adaptable, imaginative and pro-active in terms of setting the agendas for establishing strategic alliances, promoting research needs and developing research programs.

Animals↗
PubMed2001

Towards the eradication of hookworm in an isolated Australian community.

Hookworm (Ancylostoma duodenale) and other enteric parasites such as Giardia and Hymenolepis are common in Aboriginal communities in northem Australia, and their presence is associated with iron deficiency, anaemia, and failure to thrive. We report the outcome of a sustained, community-based control programme that used regular albendazole in one isolated community. Whereas hookworm has been effectively controlled by the programme, no sustained effect on the prevalence of Giardia and Hymenolepis was seen; the control of these parasites will depend on improvements in health education. This programme might serve as a model for community-based or population-based drug treatment programmes elsewhere.

Adolescent↗
PubMed2001

Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration.

In this Phase I trial, patients' peripheral blood dendritic cells were pulsed with peptides eluted from the surface of autologous glioma cells. Three biweekly intradermal vaccinations of peptide-pulsed dendritic cells were administered to seven patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. Dendritic cell vaccination elicited systemic cytotoxicity in four of seven tested patients. Robust intratumoral cytotoxic and memory T-cell infiltration was detected in two of four patients who underwent reoperation after vaccination. This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous peptide-pulsed dendritic cell vaccine for patients with malignant glioma.

Adult↗
PubMed2001

Genotyping Cryptosporidium parvum by single-strand conformation polymorphism analysis of ribosomal and heat shock gene regions.

Polymerase chain reaction (PCR)-coupled single-strand conformation polymorphism (SSCP) approaches utilizing nuclear DNA regions of the small subunit (SSU) of ribosomal RNA and heat shock protein 70 gene (HSP70) were established for genotyping Cryptosporidium parvum. The regions were amplified (individually or in a multiplex reaction) by PCR from DNA extracted from oocysts from ruminant or human hosts, then denatured and subjected to electrophoresis in a mutation detection enhancement (nondenaturing) gel matrix. Single-strand profiles produced in SSCP allowed the unequivocal identification/differentiation of the two common (human, 1 and cattle, 2) genotypes of C. parvum and the direct display of sequence variability within some samples, reflecting population variation. As these are considered among the most closely related genotypes (based on SSU and HSP70 sequence data), these findings and other preliminary results for C. felis (from cat) C. serpentis (from snake) and C. baileyi (from bird) indicate that the SSCP approaches established could be employed to identify any of the currently recognised genotypes and species of Cryptosporidium.

Animals↗
PubMed2001

Expression of Giardia duodenalis beta-tubulin as a soluble protein in Escherichia coli.

The beta-tubulin gene of the parasitic protozoan Giardia duodenalis has been expressed for the first time using a novel and direct method. The protein was expressed in both soluble and insoluble forms in an Escherichia coli-based expression system. The level of expression was found to be affected by several variables including the incubation temperature, length of time for which expression was carried out, and the E. coli culture volume. The protein expression system contributed no additional amino acids to the final fusion protein and the polyhistidine fusion sequence was easily removed from the beta-tubulin protein using a specific enterokinase enzyme. The expression system also provided a means of preparing a soluble protein and purifying it by a relatively straightforward affinity chromatography method to give a very high level of protein purity. This makes the protein suitable for a number of applications for characterization including beta-tubulin antibody assays, alpha-/beta-tubulin-binding regions, and beta-tubulin folding intermediates.

Animals↗
PubMed2001

Molecular and phylogenetic characterisation of Cryptosporidium from birds.

Avian isolates of Cryptosporidium species from different geographic locations were sequenced at two loci, the 18S rRNA gene and the heat shock gene (HSP-70). Phylogenetic analysis of the sequence data provided support for the existence of a new avian species of Cryptosporidium infecting finches and a second species infecting a black duck. The identity of Cryptosporidium baileyi and Cryptosporidium meleagridis as valid species was confirmed. Also, C. baileyi was identified in a number of isolates from the brown quail extending the host range of this species.

Animals↗
PubMed2001

The future impact of societal and cultural factors on parasitic disease -- some emerging issues.

A variety of societal and cultural factors will increase host exposure or susceptibility to infectious agents, particularly parasites. Such factors have already had a major impact on the emergence of infectious diseases and the situation is likely to worsen further as we enter the new millennium. The changes that are enhancing the spread and transmission of parasitic diseases, as well as those which are adversely affecting host responsiveness, are examined with reference to specific parasites.

Animals↗
PubMed2001

Complete development and long-term maintenance of Cryptosporidium parvum human and cattle genotypes in cell culture.

This study describes the complete development (from sporozoites to sporulated oocysts) of Cryptosporidium parvum (human and cattle genotypes) in the HCT-8 cell line. Furthermore, for the first time the complete life cycle was perpetuated in vitro for up to 25 days by subculturing. The long-term maintenance of the developmental cycle of the parasite in vitro appeared to be due to the initiation of the auto-reinfection cycle of C. parvum. This auto-reinfection is characterised by the production and excystation of new invasive sporozoites from thin-walled oocysts, with subsequent maintenance of the complete life cycle in vitro. In addition, thin-walled oocysts of the cattle genotype were infective for ARC/Swiss mice but similar oocysts of the human genotype were not. This culture system will provide a model for propagation of the complete life cycle of C. parvum in vitro.

Animals↗
PubMed2001

Does pet helminth prophylaxis increase the rate of selection for drug resistance?

There is a growing tendency to control helminths in pets by the prophylactic use of broad-spectrum drug combinations (Allwormers), some of which are of low efficacy. If similar treatment regimes were applied to livestock, parasite strains resistant to chemotherapy would be expected to evolve. The rate of selection for resistance depends significantly on epidemiological parameters and strategic recommendations based on experience with farm animals might not be applicable to pets without critical examinations. Also, the routine use of Allwormers reduces the level of interaction between veterinarians and pet owners and the valuable contribution by veterinarians towards educating pet owners about animal and public health issues in addition to parasite treatment.

Animals↗
PubMed2001

Prevention of glucoprivic stimulation of corticosterone secretion by leptin does not restore high frequency luteinizing hormone pulses in rats.

We have previously determined that exogenous leptin prevents the inhibition of pulsatile luteinizing hormone (LH) release in the fasting rodent. The present study tested the hypothesis that the mechanism by which leptin facilitates high LH secretion is through an attenuation of the stress response produced by a deficit in energy. Because hypogonadotropism is associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis during both metabolic stress and nonmetabolic stress, our approach included a comparison of whether exogenous leptin could prevent the rise in corticosterone produced by a nonmetabolic stress (immobilization for 2 h), as well as by a widely used metabolic stress (transient glucoprivation by 2-deoxyglucose, 2DG; 400 mg/kg, b.w., i.v.). Each stressor was applied to well-fed ovariectomized rats (n = 4-6 per group), 2 h after leptin (3 microg/g, b.w., i.p.) or vehicle administration. Blood samples were collected through an indwelling atrial cannula every 6 min for 1 h before and for 2 h after the stress treatment to measure LH, leptin and corticosterone. During metabolic stress (acute glucoprivation), circulating leptin decreased, corticosterone increased and LH decreased; leptin administration abolished the increase in corticosterone, but pulsatile LH secretion remained inhibited. In contrast, during nonmetabolic stress (immobilization), leptin secretion was unaffected, but circulating corticosterone increased and LH decreased; leptin treatment did not prevent either the increase in corticosterone or the decrease in LH secretion. An important overall finding is that leptin can differentially alter the HPA axis depending upon the type of stress. In addition, whether the pattern of leptin is altered depends upon the type of stress. Although a glucoprivic-induced decrease in endogenous leptin can be a stressor responsible for the increase in corticosterone secretion, a nonmetabolic stress-induced increase in corticosterone is not mediated by leptin. Moreover, our results reveal that the depression of LH secretion when leptin is low during reduced energy availability is not due to activation of the HPA axis. During an energy deficit, exogenous leptin could not restore high frequency LH secretion when HPA function was restored to normal. Finally, the inability of leptin to increase LH secretion in the face of 2DG supports the notion that the action of leptin is dependent upon the degree of glucose availability.

Animals↗