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Biomedical subjects

J M Hughes

Publications and source records attributed to J M Hughes.

At least 19 recordsLinked to original sources
PubMed2007

Phylogeographic structure in an Australian freshwater shrimp largely pre-dates the geological origins of its landscape.

The phylogeographic structure of cryptic lineages within the freshwater shrimp Caridina indistincta Calman, 1926 (Decapoda: Atyidae) was investigated in an attempt to unravel any potential genetic influences of Quaternary sea-level oscillations. The study was based on mitochondrial DNA sequences from specimens from lakes and creeks in the sand dune areas of southeast Queensland, eastern Australia. Four divergent lineages were identified, two of which were from Moreton and North (N.) Stradbroke Islands. Lineage 'C1' has been found only on Moreton Island and the western part of N. Stradbroke Island, whereas 'C2' was found on the eastern side of N. Stradbroke Island and a few locations on the mainland. These diverged from each other during the Late Miocene/Pliocene and so are older than the current landscape in which they are found. Small-scale phylogeographic analysis of C1 identified four separate geographic areas, within the two islands, whose divergences date to the Pleistocene (approximately 100-300 thousand years ago ('kya')). The N. Stradbroke Island population of C2 also diverged from the mainland during the Pleistocene, as did a sympatric freshwater fish Rhadinocentrus ornatus Regan, 1914 (Melanotaeniidae). This implies that the ice-age sea-level changes may have structured these populations, although there is little observable influence of the last glacial maximum (approximately 18 kya). Most estimates for the age of the landscape (dunes, lakes) also fall within the Pleistocene and so the effect of sea-level change may be seen both in biology and geology.

Animals↗
PubMed2006

Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics.

BACKGROUND: Mast cell microlocalisation within the airway smooth muscle (ASM) bundle is an important determinant of the asthmatic phenotype. We hypothesised that mast cells migrate towards ASM in response to ASM derived chemokines. METHODS: Primary ASM cultures from subjects with and without asthma were stimulated with interleukin (IL)-1beta, IL-4, and IL-13 alone and in combination. Mast cell chemotaxis towards these ASM supernatants was investigated, and the chemotaxins mediating migration by using specific blocking antibodies for stem cell factor (SCF) and the chemokine receptors CCR3, CXCR1, 3 and 4 as well as the Gi inhibitor pertussis toxin and the tyrosine kinase inhibitor genistein were defined. The concentrations of CCL11, CXCL8, CXCL10, TGF-beta, and SCF in the supernatants were measured and the effect of non-asthmatic ASM supernatants on the mast cell chemotactic activity of asthmatic ASM was examined. RESULTS: Human lung mast cells and HMC-1 cells migrated towards Th2 stimulated ASM from asthmatics but not non-asthmatics. Mast cell migration was mediated through the combined activation of CCR3 and CXCR1. CCL11 and CXCL8 expression by ASM increased markedly after stimulation, but was similar in those with and without asthma. ASM supernatants from non-asthmatics inhibited mast cell migration towards the asthmatic ASM supernatant. CONCLUSION: Th2 stimulated ASM from asthmatics is chemotactic for mast cells. Non-asthmatic ASM releases a mediator or mediators that inhibit mast cell migration towards stimulated asthmatic ASM. Specifically targeting mast cell migration into the ASM bundle may provide a novel treatment for asthma.

Asthma↗
PubMed2006

The prevalence of Neospora caninum and co-infection with Toxoplasma gondii by PCR analysis in naturally occurring mammal populations.

Neospora caninum and Toxoplasma gondii are closely related intracellular protozoan parasites associated with bovine and ovine abortion respectively. Little is known about the extent of Neospora/Toxoplasma co-infection in naturally infected populations of animals. Using nested PCR techniques, based on primers from the Nc5 region of N. caninum and SAG1 for T. gondii, the prevalence of N. caninum and its co-infection with T. gondii were investigated in populations of Mus domesticus, Rattus norvegicus and aborted lambs (Ovis aries). A low frequency of infection with N. caninum was detected in the Mus domesticus (3%) and Rattus norvegicus (4.4%) populations. A relatively high frequency of infection with N. caninum was detected in the brains of aborted lambs (18.9%). There was no significant relationship between N. caninum and T. gondii co-infection. Investigation of the tissue distribution of Neospora, in aborted lambs, showed that Neospora could not be detected in tissues other than brain and this was in contrast to Toxoplasma where the parasite could be frequently detected in a range of tissues.

Abortion, Veterinary↗
PubMed2006

Biogeographic history of an Australian freshwater shrimp, Paratya australiensis (Atyidae): the role life history transition in phylogeographic diversification.

The widespread distribution of the freshwater shrimp Paratya australiensis in eastern Australia suggests that populations of this species have been connected in the past. Amphidromy is ancestral in these shrimps, although many extant populations are known to be restricted to freshwater habitats. In this study, we used a fragment of the cytochrome c oxidase I mitochondrial DNA (mtDNA) gene to examine diversity within P. australiensis and to assess the relative importance of amphidromy in its evolutionary history. We hypothesized that if transitions from an amphidromous to a freshwater life history were important, then we would find a number of divergent lineages restricted to single or groups of nearby drainages. Alternatively, if amphidromy was maintained within the species historically, we expected to find lineages distributed over many drainages. We assumed that the only way for divergence to occur within amphidromous lineages was if dispersal was limited to between nearby estuaries, which, during arid periods in the earth's history, became isolated from one another. We found nine highly divergent mtDNA lineages, estimated to have diverged from one another in the late Miocene/early Pliocene, when the climate was more arid than at present. Despite this, the geographic distribution of lineages and haplotypes within lineages did not support the notion of a stepping-stone model of dispersal between estuaries. We conclude that the extensive divergence has most likely arisen through a number of independent amphidromy-freshwater life history transitions, rather than via historical isolation of amphidromy populations. We also found evidence for extensive movement between coastal and inland drainages, supporting the notion that secondary contact between lineages may have occurred as a result of drainage rearrangements. Finally, our data indicate that P. australiensis is likely a complex of cryptic species, some of which are widely distributed, and others geographically restricted.

Animal Migration↗
PubMed2005

High levels of congenital transmission of Toxoplasma gondii in longitudinal and cross-sectional studies on sheep farms provides evidence of vertical transmission in ovine hosts.

Recent research suggests that vertical transmission may play an important role in sustaining Toxoplasma gondii infection in some species. We report here that congenital transmission occurs at consistently high levels in pedigree Charollais and outbred sheep flocks sampled over a 3-year period. Overall rates of transmission per pregnancy determined by PCR based diagnosis, were consistent over time in a commercial sheep flock (69%) and in sympatric (60%) and allopatric (41%) populations of Charollais sheep. The result of this was that 53.7 % of lambs were acquiring an infection prior to birth: 46.4% of live lambs and 90.0% of dead lambs (in agreement with the association made between T. gondii and abortion). No significant differences were observed between lamb sexes. Although we cannot distinguish between congenital transmission occurring due to primary infection at pregnancy or reactivation of chronic infection during pregnancy, our observations of consistently high levels of congenital transmission over successive lambings favour the latter.

Abortion, Veterinary↗
PubMed2005

Significant familial differences in the frequency of abortion and Toxoplasma gondii infection within a flock of Charollais sheep.

A study was carried out to investigate the frequencies of abortion and congenital Toxoplasma gondii infection within 27 families (765 individuals) of a pedigree Charollais sheep flock maintained on a working farm in Worcestershire, UK, since 1992. Pedigree lambing records were analysed to establish the frequency of abortion for each family. The frequency of congenital infection was determined for each family by PCR analysis of tissue samples taken from newborn lambs. A total of 155 lambs were tested for congenital T. gondii infection, which were all born during the study period 2000-2003. Significant differences in the frequency of abortion between sheep families within this flock were observed with frequencies ranging between 0% and 48% (P < 0.01). Significantly different infection frequencies with T. gondii were also observed for different families and ranged between 0% and 100% (P<0.01). Although the actual cause of each abortion was not verified, a highly significant positive correlation was found to exist between the frequency of abortion and the frequency of T. gondii infection in the same families (P<0.01). The data presented here raise further questions regarding the significance of congenital transmission of T. gondii within sheep populations, the possible successive vertical transmission of T. gondii within families of sheep, and the potential role of inherited genetic susceptibility to abortion with respect to T. gondii infection. This work invites further study into the epidemiology of ovine toxoplasmosis and may have implications for sheep husbandry methods in the future.

Abortion, Veterinary↗
PubMed2005

The head and body lice of humans are genetically distinct (Insecta: Phthiraptera, Pediculidae): evidence from double infestations.

Little is known about the population genetics of the louse infestations of humans. We used microsatellite DNA to study 11 double infestations, that is, hosts infested with head lice and body lice simultaneously. We tested for population structure on a host, and for population structure among seven hosts that shared sleeping quarters. We also sought evidence of migration among louse populations. Our results showed that: (i) the head and body lice on these individual hosts were two genetically distinct populations; (ii) each host had their own populations of head and body lice that were genetically distinct to those on other hosts; and (iii) lice had migrated from head to head, and from body to body, but not between heads and bodies. Our results indicate that head and body lice are separate species.

Animals↗
PubMed2004

Detection of high levels of congenital transmission of Toxoplasma gondii in natural urban populations of Mus domesticus.

The relative importance of different transmission routes of Toxoplasma gondii has been a matter for debate. This ubiquitous parasite is generally thought to be transmitted by infective oocysts excreted by the definitive host, the cat. Ingestion of undercooked meat has also been considered an important route of transmission in many mammals while congenital transmission has generally been considered relatively rare. Experimental studies demonstrate the ability of T. gondii to be transmitted congenitally, but few studies have investigated the frequency of this transmission route in natural populations. We use PCR amplification of the SAG1 gene to investigate the frequency of congenital transmission in a wild population of mice (Mus domesticus) and show that congenital transmission is occurring in 75% of pregnancies in this population. Furthermore, for infected pregnant mice, transmission occurs to at least one foetus in 100% of cases while variable penetrance of congenital infection is observed. These high levels of congenital transmission in this wild population of mice, taken together with other recent data on congenital transmission in sheep, suggests that this phenomenon might be more widespread than previously thought.

Animals↗
PubMed2004

Mitochondrial DNA signatures of restricted gene flow within divergent lineages of an atyid shrimp (Paratya australiensis).

We measured spatial genetic structure within three previously described mitochondrial lineages of the atyid shrimp, Paratya australiensis, occurring in upland streams of two major catchments within the Sydney Water Supply Catchment, New South Wales, Australia. In all three lineages, there was significant spatial structuring of genetic variation between catchments. In two lineages, recurrent but restricted maternal gene flow has apparently predominated in shaping within-catchment genetic structure, although this framework may be overlaid with episodic contiguous/long-distance expansion events. In the third lineage, there was no evidence of spatial genetic structuring within one of the catchments, because one haplotype was both common and widespread throughout the sampled area. High-frequency haplotypes were also shared among subcatchments in the other two lineages, and we discuss both historical and contemporary processes that may have left these genetic signatures. Our results are generally concordant with previous reports of significant population structuring in P. australiensis, occurring in upland river reaches elsewhere in eastern Australia. We propose that restricted dispersal and gene flow among upland populations of P. australiensis is linked to dramatic architectural structuring within and among mountain streams.

Analysis of Variance↗
PubMed2004

Population structure of Macrobrachium australiense (Decapoda: Palaemonidae) in Western Queensland, Australia: the role of contemporary and historical processes.

Rivers of Western Queensland, Australia, represent a discontinuous and variable aquatic habitat for the freshwater fauna of the region. Rivers periodically fluctuate between being highly fragmented, with numerous disconnected waterholes and ephemeral channels, and being highly connected by a dominant system of anastomosing channels. We used mitochondrial sequences to investigate the genetic structure and inferred patterns of dispersal associated with this flow regime for the freshwater prawn, Macrobrachium australiense (Decapoda: Palaemonidae), sampling 28 localities throughout eight catchments. Based on a 505 base pair fragment of mitochondrial cytochrome c oxidase subunit I, we identified 98 haplotypes in a sample of 402 individuals. The haplotypes clustered into two main clades corresponding geographically to the major drainages: the Lake Eyre and Murray-Darling basins. Populations of M. australiense inhabiting the two basins appear to have diverged around 800,000 years ago (estimated sequence divergence of 1.6%). Analysis of population differentiation indicated contemporary high levels of genetic subdivision and restricted gene flow among populations within and among catchments. Phylogenetic analysis detected a series of historical range expansions in the region and we suggest that climate fluctuations during the Pleistocene have resulted in extensive floods that have promoted historical movements of aquatic organisms across catchment boundaries.

Animals↗
PubMed2004

Stability of an epidural analgesic admixture containing epinephrine, fentanyl and bupivacaine.

The addition of epinephrine to solutions containing fentanyl and bupivacaine for epidural infusion has been shown to improve the quality of analgesia. However, this admixture is not available commercially in the United Kingdom. Moreover, stability data applicable to UK practice for this admixture are limited. This study investigated the stability of fentanyl 2 microg.ml(-1) plus bupivacaine 1 mg.ml(-1) in PVC bags with and without epinephrine 2 microg.ml(-1) over a period of 184 days both at room temperature and at 4 degrees C. All infusions were found to be stable over the study period (> 90% remaining) using stability-indicating High Performance Liquid Chromatography (HPLC) methods, with no changes in physical appearance or pH (range 4.5-4.2). The infusions were prepared using standard pharmaceutical products, so facilitating the batch preparation of epinephrine, fentanyl and bupivacaine epidural solutions by hospital pharmacy departments.

Analgesia, Epidural↗
PubMed2004

Vascular leucocyte adhesion molecules unaltered in the human retina in diabetes.

BACKGROUND/AIMS: Capillary occlusion is believed to have a critical role in the development of diabetic retinopathy (DR). The exact mechanism by which it occurs, however, remains unclear. Several in vitro and animal model studies have suggested increased adhesion of leucocytes to the endothelium via upregulated ICAM-1 on the retinal microvasculature as a possible mechanism. In this comparative immunohistochemical study the expression of ICAM-1 was compared in the retinal vasculature of 41 eyes obtained from 37 diabetic people with 19 eyes from 19 non-diabetic controls. METHODS: Serial cryosections of postmortem posterior tissue from 41 diabetic eyes and 19 non-diabetic eyes were stained with the monoclonal antibodies ICAM-1 (two clones), CD31(panendothelial marker), and PAL-E (vascular leakage marker). RESULTS: A similar pattern of vascular ICAM-1 staining was observed between diabetic and non-diabetic eyes. A diffuse ICAM-1 staining of the retina was also observed that was significantly more intense in the diabetic subjects (p = 0.001). CONCLUSION: These results indicate that ICAM-1 is constitutively expressed on retinal and choroidal vasculature of non-diabetic, control subjects and that this level of expression is not significantly altered by the diabetic environment. Taken together, these results do not support the prevalent paradigm of increased adhesion molecule expression as a primary mechanism responsible for capillary occlusion reported in diabetic individuals.

Adolescent↗
PubMed2004

Changing trends in US mesothelioma incidence.

AIMS: To report the temporal pattern and change in trend of mesothelioma incidence in the United States since 1973. METHODS: The Surveillance, Epidemiology, and End Results (SEER) programme of the National Cancer Institute has since 1973 provided annual age adjusted incidence for mesothelioma in representative cancer registries dispersed throughout the USA. SEER data are analysed to describe the trend of male mesothelioma incidence in the USA. RESULTS: The US male mesothelioma incidence data indicate that after two decades of increasing incidence, a likely decline has been observed since the early 1990s, when a highly significant change in the upward course occurred. CONCLUSIONS: Increasing male mesothelioma incidence for many years was undoubtedly the result of exposure to asbestos. The high mesothelioma risk was prominently influenced by exposure to amphibole asbestos (crocidolite and amosite), which reached its peak usage in the 1960s and thereafter declined. A differing pattern in some other countries (continuing rise in incidence) may be related to their greater and later amphibole use, particularly crocidolite. The known latency period for the development of this tumour provides biological plausibility for the recent decline in mesothelioma incidence in the USA. This favourable finding is contrary to a widespread fear that asbestos related health effects will show an inevitable increase in coming years, or even decades.

Asbestos↗
PubMed2004

Mechanisms of serum potentiation of GM-CSF production by human airway smooth muscle cells.

Inflammation and vascular leakage are prevalent in asthma. This study aimed to elucidate the mechanisms involved in serum potentiation of cytokine-induced granulocyte macrophage colony stimulating factor (GM-CSF) production by human airway smooth muscle cells and to identify possible factors responsible. Serum-deprived cells at low density were stimulated with TNF-alpha and IL-1beta for 24 h. Human AB serum (10%), inhibitors of RNA and protein synthesis or specific signaling molecules, or known smooth muscle mitogens were then added for 24 h. Culture supernatants were analyzed for GM-CSF levels, and cells were harvested to assess viability, cell cycle progression, GM-CSF-specific mRNA content, and p38 phosphorylation. Serum potentiated GM-CSF release when added before, together with (maximal), or after the cytokines. The potentiation involved both new GM-CSF-specific mRNA production and protein synthesis. The mitogens IGF, PDGF, and thrombin all potentiated GM-CSF release, and neutralizing antibodies for EGF, IGF, and PDGF reduced the serum potentiation. Inhibitor studies ruled as unlikely the involvement of p70(S6kinase) and the MAPK p42/p44, two signaling pathways implicated in proliferation, and the involvement of the MAPK JNK, while establishing roles for p38 MAPK and NF-kappaB in the potentiation of GM-CSF release. Detection of significant p38 phosphorylation in response to serum stimulation, through Western blotting, further demonstrated the involvement of p38. These studies have provided evidence to support p38 being targeted to interrupt the cycle of inflammation, vascular leakage and cytokine production in asthma.

Antibodies↗
PubMed2004

New partnerships between animal health services and public health agencies.

As Veterinary Services and animal health organisations attempt to respond to a new era of emerging and re-emerging zoonotic diseases, their ability and skill in forming new strategic partnerships will be paramount. While these new partnerships are likely to include many relationships outside traditional Veterinary Services and animal agriculture, none will become more important than the formation of new animal health and public health partnerships. Episodes of emerging zoonoses are being increasingly recognised around the world and the confluence of people, animals and animal products today is unprecedented. Concurrently, a wide array of complex factors are also converging that will not only ensure the continuous emergence of zoonoses, but are also likely to drive the further increase and expansion of these diseases. This article discusses the need for the creation of more effective and co-operative partnerships in the face of new microbial threats, the complexity of both the formation and expansion of zoonoses, and the collective abilities of both human and animal health services to respond to them. Lessons learned from recent zoonotic epidemics supportthe need for co-ordinated research, interdisciplinary centres, integrated surveillance systems, response systems and infrastructures, and workforce development strategies. While there are some excellent examples of collaborative animal and public health relationships, there is no question that more and stronger partnerships among national and international organisations, both academic and private, will be necessary to meet the future challenges of emerging zoonoses and to manage their profound implications.

Animals↗
PubMed2003

Prevalence of zoonotic important parasites in the red fox (Vulpes vulpes) in Great Britain.

A national necropsy survey of red foxes was carried out across Great Britain to record Echinococcus, Trichinella and Toxoplasma. The survey did not record directly, or indirectly using coproantigen/PCR tests, evidence for the presence of Echinococcus multilocularis in 588 animals, although E. granulosus was suspected in six animals. Parasitological evidence for Trichinella spp. could not be found in 587 fox muscle digests, and a specific PCR test also failed to detect Toxoplasma in a sub-set of 61 random fox tongue biopsies. The upper 95% confidence interval for the above parasites was 0.60% (E. multilocularis), 0.60% (Trichinella spp.) and 5.6% (Toxoplasma). The commonest gut parasites were the hookworm Uncinaria stenocephala (41.3%) and the ascarid Toxocara canis (61.6%). This study also reports the second occurrence of Trichuris vulpis in Great Britain.

Animals↗