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A Barnes

Publications and source records attributed to A Barnes.

At least 19 recordsLinked to original sources
PubMed2006

Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele.

Dogs exhibit a range of immune-mediated conditions including a lymphocytic thyroiditis which has many similarities to Hashimoto's thyroiditis in man. We have recently reported an association in Doberman Pinschers between canine hypothyroidism and a rare DLA class II haplotype that contains the DLA-DQA1*00101 allele. We now report a further series of 173 hypothyroid dogs in a range of breeds where a significant association with DLA-DQA1*00101 is shown.

Alleles↗
PubMed2006

Association of a common dog leucocyte antigen class II haplotype with canine primary immune-mediated haemolytic anaemia.

Immune-mediated haemolytic anaemia (IMHA) is the commonest immune-mediated disease of the dog, representing a major health concern to this species. The aim of this investigation was to determine whether genetic susceptibility to IMHA is associated with genes of the canine major histocompatibility complex (MHC; dog leucocyte antigen system, DLA). Samples were collected from 108 dogs with primary idiopathic, Coombs' positive IMHA. This diseased population was subdivided on the basis of Coombs' test results into two groups: 1) dogs with dominant warm-reactive immunoglobulin (Ig) G haemagglutinins and (2) dogs with an additional or dominant cold-reactive IgM haemagglutinin. The DLA class II alleles and haplotypes of the diseased population were characterised, and these data were compared with those derived from a breed-matched control cohort and a much larger group of DLA-typed dogs. Two haplotypes were increased in the patient group: DLA-DRB1*00601/DQA1*005011/DQB1*00701 (in the group with warm-reactive IgG haemagglutinins only) and DLA-DRB1*015/DQA1*00601/DQB1*00301 (in both groups, but more so in the group with cold-reactive IgM haemagglutinins). One haplotype, DLA-DRB1*001/DQA1*00101/DQB1*00201, was decreased in the total patient group, but this decrease was limited to the warm-reactive IgG haemagglutinins group, and it was actually increased in the cold-reactive IgM haemagglutinins group. A second haplotype, DLA-DRB1*015/DQA1*00601/DQB1*02301, was also decreased in the total patient group, and this decrease was found in both subgroups. In addition, all haplotypes carrying DLA-DRB1*001 were significantly increased in the cold-reactive IgM haemagglutinins group. When the overall patient group was divided on the basis of individual breeds with more than six animals represented, each of the haplotypes could be shown to be implicated in one of the breeds. Thus, it was apparent that different breeds had different MHC associations with canine IMHA, which is similar to the observation that different human ethnic groups can have different HLA associations with the same immune-mediated disease.

Alleles↗
PubMed2006

Identification of susceptibility and protective major histocompatibility complex haplotypes in canine diabetes mellitus.

Diabetes mellitus occurs spontaneously in dogs, which is believed to have an autoimmune component and to be a model of human latent autoimmune diabetes of adults (LADA). Some dog breeds (e.g. Samoyed) are particularly predisposed, whereas others (e.g. Boxer) are highly resistant. With the completion of the Dog Genome Assembly, comparative genomic studies of complex diseases in dogs, including diabetes, could provide an important investigative approach into such disorders. Type 1 diabetes in humans is strongly associated with major histocompatibility complex (MHC) class II polymorphisms. We have investigated whether canine dog leucocyte antigen (DLA) class II haplotypes are associated with diabetes. DNA from 460 cases and 1047 controls were genotyped for DLA-DRB1, DLA-DQA1 and DLA-DQB1 using sequence-based typing. Three DLA haplotypes, DRB1*009/DQA1*001/DQB1*008, DRB1*015/DQA1*0061/DQB1*023 and DRB1*002/DQA1*009/DQB1*001, were found at significantly increased frequency in cases with diabetes compared with controls. One DLA-DQ haplotype, DQA1*004/DQB1*013, was significantly reduced in cases with diabetes. Further analysis showed that DQA1 alleles carrying arginine at codon 55 of DQA1 were increased in dogs with diabetes. To our knowledge, this is the first report of a comparative study of MHC and diabetes in a non-rodent species. Since no laboratory model of LADA exists and dogs and humans share similar environments, further research into canine diabetes is warranted.

Alleles↗
PubMed2006

Physiological responses of Bos taurus and Bos indicus cattle to prolonged, continuous heat and humidity.

Two experiments were conducted to investigate the physiological responses of Bos taurus (Angus cross, n = 6) and Bos indicus (Brahman, n = 6) cattle to prolonged heat and humidity, as can occur during live export by sea. Each experiment was carried out in climate-controlled rooms, where heifers were exposed to 15 d of sustained heat and humidity. The treatment was designed to be representative of a long-haul, live-export voyage leaving a southern Australian winter and traveling to a Middle Eastern summer. Wet bulb temperature (WBT) was used to give a combined measure of dry bulb temperature and relative humidity and was increased over several days, culminating in 5 d at 32 degrees C WBT between d 7 and 11. By d 11, the respiratory rate and core body temperature increased (P < 0.001) compared with values at lower ambient temperature on d 1 and 2 when climate-controlled rooms were not operating. Feed intake of Bos taurus was reduced (P < 0.001) by d 11, whereas that of Bos indicus did not change (P = 0.14). Despite no diurnal variation in climatic conditions, core body temperature of both Bos taurus and Bos indicus continued to show a circadian amplitude of approximately 1 degrees C throughout the hottest period. This amplitude increased during the recovery period after heat was removed (up to 1.8 degrees C for Bos indicus and 1.6 degrees C for Bos taurus). Water intake for both Bos taurus and Bos indicus increased when WBT increased (P < 0.01 on d 11). Significant acid-base and blood electrolyte imbalances occurred in both Bos taurus and Bos indicus, with changes in Bos taurus being more substantial and prolonged. The increase in respiratory rate coincided with a decrease in the partial pressures of carbon dioxide and bicarbonate in venous blood. However, during the hottest period, average daily venous blood pH remained unchanged. When the heat load was reduced after d 11, the blood pH decreased, indicating metabolic acidosis. Blood pH declined from 7.44 to 7.36 for Bos taurus (P < 0.001) and from 7.44 to 7.38 for Bos indicus (P < 0.001). Other parameters measured include heart rate; packed cell volume; plasma and urine Na, K, and Cl; urine pH; and specific gravity. Our results suggest that Bos taurus cattle experience significant physiological changes during exposure to prolonged and continuous high heat and humidity, with alterations persisting for some days after the heat-stress conditions subside. Bos indicus experience similar but less pronounced physiological changes.

Acclimatization↗
PubMed2005

Canine DNA subjected to whole genome amplification is suitable for a wide range of molecular applications.

Molecular and genetic studies of canine disease phenotypes can be limited by the amount of DNA available for analysis. New methods have been developed to amplify the genomic DNA of a species producing large quantities of DNA from small starting amounts. Whole genome amplification (WGA) of DNA is now being used in human studies, although this technique has not been applied extensively in veterinary research. We evaluated WGA of canine DNA for suitability in a range of molecular tests. DNA from 93 canine blood extracted and 18 buccal swab samples was subjected to WGA using the GenomiPhi kit (Amersham). Genomic DNA was compared with WGA product using a range of techniques, including reference strand-mediated conformation analysis, denaturing high-performance liquid chromatography analysis, microsatellite genotyping, direct DNA sequencing, and single nucleotide polymorphism allelic discrimination. All samples amplified well, giving an average yield of 3 mug of DNA from 2.5 ng of starting material. Extremely high levels of experimental reproducibility and concordance were observed between source and WGA DNA samples for all analyses used: greater than 95% for blood extracted DNA and greater than 80% for buccal swab DNA. These studies clearly demonstrate the usefulness of WGA of canine DNA as a means of increasing DNA quantities for canine studies. This technique will have major implications for future veterinary research.

Animals↗
PubMed2003

Expression of p27kip1 in breast cancer and its prognostic significance.

p27kip1 is a member of the KIP/CIP family of cyclin-dependent kinase inhibitors and is a negative cell-cycle regulator that is thought to play a role in tumour suppression. Reduced levels of this protein have been observed in a number of human cancers. However, evidence is conflicting as to whether p27kip1 has a role to play in breast cancer, including predicting behaviour and prognosis. The present investigation aimed to provide a definitive study of 830 breast cancer cases with median patient follow-up of 104 months to determine the true prognostic significance, if any. Immunohistochemical analysis of tissue microarrays and three scoring methods were used to assess p27kip1 expression. Univariate analysis showed a significant relationship between reduced p27kip1 expression and increasing tumour grade, nuclear pleomorphism, mitosis, and decreasing tubule formation (all p<0.001). Significant associations between reduced p27, negative oestrogen receptor status, and ductal/no special type tumours were also observed. Survival analysis demonstrated that patients with tumours with high p27kip1 levels had an improved survival compared with those with cancers with low expression. On multivariate analysis, when compared with existing factors, p27kip1 was not, however, an independent prognostic factor. It is concluded that the inverse relationship between p27kip1 levels and histological grade and individual grade components suggests a role for p27kip1 in both cell proliferation and differentiation, but is not clinically useful.

Adult↗
PubMed2003

Cancer in Indigenous Australians: a review.

OBJECTIVES: To summarize for the first time evidence of the impact of cancer on Indigenous Australians. METHODS: Medline search of peer-reviewed scientific journals, and extensive search of reports of government agencies, publications of cancer registries and non-government organizations, and other non-peer-reviewed sources. RESULTS: Indigenous Australians have much higher incidence rates than other Australians of cancers of the lung, liver, and cervix; but much lower rates of cancers of the breast, colon and rectum, prostate, melanoma of skin, and lymphoma. Some of these differences can be explained, in part at least, by differences in risk factor prevalence. Indigenous Australians also have higher mortality and lower survival from cancer as a whole than other Australians. More advanced disease at diagnosis, and possibly poorer treatment, are partly responsible for these differences, but other factors may also be involved. CONCLUSIONS: Less accessible and less effective health programs are as great a problem for cancer control as for other aspects of Indigenous health in Australia. Major improvements in preventive services, screening, primary care, and specialist treatment services are required to reduce cancer incidence and improve cancer outcomes for Australia's Indigenous people.

Alcohol Drinking↗
PubMed2003

Complex chimeras to map ligand binding sites of GPCRs.

Family 1a GPCRs are thought to bind small molecule ligands in a pocket comprising sequences from non-contiguous transmembrane helices. In this study, receptor-ligand binding determinants were defined by building a series of complex chimeras where multiple sequences were exchanged between related G-protein coupled receptors. Regions of P2Y(1), P2Y(2) and BLT(1) predicted to interact with nucleotide and leukotriene ligands were identified and receptors were engineered within their transmembrane helices to transpose the ligand binding site of one receptor on to another receptor. Ligand-induced activation of chimeras was compared with wild-type receptor activation in a yeast reporter gene assay. Binding of ligand to a P2Y(2)/BLT(1) chimera confirmed that the ligand binding determinants of BLT(1) are located in the upper regions of the helices and extracellular loops of this receptor and that they had been successfully transferred to a receptor that normally binds unrelated ligands.

Amino Acid Sequence↗
PubMed2002

Effects of levodopa infusion on motor activation responses in Parkinson's disease.

BACKGROUND: Clinical improvement with levodopa therapy for PD is associated with specific regional changes in cerebral glucose metabolism. However, it is unknown how these effects of treatment in the resting state relate to alterations in brain function that occur during movement. In this study, the authors used PET to assess the effects of levodopa on motor activation responses and determined how these changes related to on-line recordings of movement speed and accuracy. METHODS: Seven right-handed PD patients were scanned with H(2)15O/PET while performing a predictable paced sequence of reaching movements and while observing the same screen displays and tones. PET studies were performed during "on" and "off" states with an individually titrated constant rate levodopa infusion; movements were kinematically controlled across treatment conditions. RESULTS: Levodopa improved "off" state UPDRS motor ratings (34%; p < 0.006) and movement time (18%; p = 0.001). Spatial errors worsened during levodopa infusion (24%; p = 0.02). Concurrent regional cerebral blood flow (rCBF) recordings revealed significant enhancement of motor activation responses in the posterior putamen bilaterally (p < 0.001), left ventral thalamus (p < 0.002), and pons (p < 0.005). Movement time improvement with treatment correlated with rCBF increases in the left globus pallidus and left ventral thalamus (p < 0.01). By contrast, the increase in spatial errors correlated with rCBF increases in the cerebellar vermis (p < 0.01). CONCLUSION: These results suggest that levodopa infusion may improve aspects of motor performance while worsening others. Different components of the motor cortico-striato-pallido-thalamo-cortical loop and related pathways may underlie motor improvement and adverse motoric effects of levodopa therapy for PD.

Aged↗
PubMed2002

Delta opioid receptor localization in the rat cerebellum.

Opioid receptors have been localized to a number of brain regions in rats as well as in other species. In situ hybridization has demonstrated the presence of mRNA for the delta receptor subtype in adult rat cerebellar cortex and in several deep nuclei, but there are no reports on localization of the delta receptor protein in cerebellar regions. In the present study, both quantitative immunohistochemistry and Western blots reveal the presence of delta receptors in the adult rat cerebellum, using a specific affinity-purified antibody. Purkinje cells and processes, as well as cells in the granule cell layer, were positively stained with the antibody. Quantitation of confocal microscopy images illustrated a lower relative level of delta receptor immunoreactivity in cerebellar cortical neurons as compared to neurons in hippocampal regions, striatum and cerebral cortex. Stimulation of delta receptors with a selective agonist, DPDPE, in frozen sections of rat brain, induced a significant increase in binding of [35S]-GTPgammaS in the cerebellar cortex as compared to basal binding levels, thereby demonstrating coupling of the receptor subtype to G-protein. Functional implications for the delta receptor in the cerebellum are discussed, particularly in light of evidence for the presence of a cerebellar opioid receptor for the endogenous opioid methionine enkephalin during early postnatal life.

Animals↗
PubMed2002

Extensive interbreed, but minimal intrabreed, variation of DLA class II alleles and haplotypes in dogs.

The DLA class II genes in the dog major histocompatibility complex are highly polymorphic. To date, 52 DLA-DRB1, 16 DLA-DQA1 and 41 DLA-DQB1 allelic sequences have been assigned. The aim of this study was to examine the intrabreed and interbreed variation of DLA allele and haplotype frequencies in dogs, and to ascertain whether conserved DLA class II haplotypes occur within and between different breeds. One thousand and 25 DNA samples from over 80 different breeds were DLA class II genotyped, the number of dogs per breed ranging from 1 to 61. DNA sequence based typing and sequence specific oligonucleotide probing were used to characterize dogs for their DLA-DRB1, DQA1 and DQB1 alleles. The high frequency of DLA class II homozygous animals (35%), allowed the assignment of many haplotypes despite the absence of family data. Four new DLA alleles were identified during the course of this study. Analysis of the data revealed considerable interbreed variation, not only in allele frequency, but also in the numbers of alleles found per breed. There was also considerable variation in the number of breeds in which particular alleles were found. These interbreed variations were found in all three DLA class II loci tested, and also applied to the three-locus haplotypes identified. Within this data set, 58 different DLA-DRB1/DQA1/DQB1 three-locus haplotypes were identified, which were all found in at least two different animals. Some of the haplotypes appeared to be characteristic of certain breeds. The high interbreed, and relatively low intrabreed, variation of MHC alleles and haplotypes found in this study could provide an explanation for reports of interbreed variation of immune responses to vaccines, viruses and other infections.

Alleles↗
PubMed2002

Evidence for extensive DLA polymorphism in different dog populations.

Many of the genes within the Canine Major Histocompatibility Complex are highly polymorphic. Most of the alleles defined to date for DLA-DRB1, DQA1 and DQB1 come from the analysis of European or North American pure bred dogs. Little is known about DLA gene polymorphisms in other dog populations. We have studied Alaskan Husky dogs and Brazilian mongrel dogs and compared them with a panel of 568 European dogs and 40 Alaskan gray wolves. DNA sequence based typing was used to characterize a series of 12 Alaskan Huskies and 115 Brazilian mongrels for their DLA-DRB1, DQA1 and DQB1 alleles. Within these dogs, 22 previously undescribed DLA class II alleles were identified: 10 DRB1, 5 DQA1 and 7 DQB1 alleles. All these alleles were found in more than one animal, and, in some cases, as a homozygote. Several alleles initially observed in Alaskan gray wolves were found in these dogs. Each new allele was found in specific haplotypic combinations. Many new DLA class II haplotypes were identified. Several of the new alleles and haplotypes were also identified in the European dogs used for comparison. One new haplotype, containing a previously unknown DLA-DRB1 allele together with DQA1 and DQB1 alleles only seen before in gray wolves, was found in 20 Brazilian dogs, including three homozygous animals. It appears likely that the extent of polymorphism of the DLA genes will increase substantially as dogs from a wider geographic distribution are studied. This has major implications for the study of disease susceptibility and immune responsiveness in dogs.

Alleles↗
PubMed2002

Decreased lung ischemia-reperfusion injury in rats after preoperative administration of cyclosporine and tacrolimus.

OBJECTIVES: Calcineurin inhibitors reduce experimental reperfusion injury in the liver, brain, heart, kidney, and small bowel. These studies were undertaken to determine whether these agents are similarly protective against lung ischemia-reperfusion injury. METHODS: Left lungs of male rats were rendered ischemic for 90 minutes and reperfused for as long as 4 hours. Treated animals received cyclosporine A (INN: ciclosporin; 1 or 5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before ischemia, at reperfusion, or 2 hours after reperfusion. Injury was quantitated in terms of tissue polymorphonuclear leukocyte accumulation (myeloperoxidase content), vascular permeability (iodine 125-labeled bovine serum albumin extravasation), and bronchoalveolar lavage leukocyte content. Separate tissue samples were processed for nuclear protein and cytokine messenger RNA. RESULTS: Treatment with cyclosporine (5 mg/kg) or tacrolimus (0.2 mg/kg) 6 hours before reperfusion reduced lung vascular permeability by 54% and 56% relative to control animals (P <.03). The protective effects of cyclosporine and tacrolimus treatment before reperfusion correlated with 42% and 43% reductions in tissue polymorphonuclear leukocyte (myeloperoxidase) content (P <.008) and marked reductions in bronchoalveolar lavage leukocyte accumulation (P <.01). Administration of cyclosporine or tacrolimus at the time of reperfusion or 2 hours into the reperfusion period offered little or no protection. Animals treated before reperfusion also demonstrated marked reductions in nuclear factor kappaB activation and expression of proinflammatory cytokine messenger RNA. CONCLUSION: Cyclosporine and tacrolimus treatment before reperfusion was protective against lung ischemia-reperfusion injury in rats. The mechanism of these protective effects may involve the inhibition of nuclear factor kappaB, a central transcription factor mediating inflammatory injury. The decreased expression of cytokine messenger RNA indicates that both cyclosporine and tacrolimus may exert their protective effects at the pretranscriptional level.

Animals↗
PubMed2001

Activity of diadenosine polyphosphates at P2Y receptors stably expressed in 1321N1 cells.

The selectivities of the diadenosine polyphosphates (Ap(n)As, n=2-6) at the human P2Y(1), P2Y(2), P2Y(4), P2Y(6) and P2Y(11) receptors stably expressed in 1321N1 human astrocytoma cells was determined using a Fluorescence Imaging Plate Reader (FLIPR) to measure intracellular Ca(2+) mobilisation. The rank order of agonist potencies at P2Y(1) were: ADP>P(1),P(3)-diadenosine triphosphate (Ap(3)A)>P(1),P(3)-diadenosine hexaphosphate (Ap(6)A)=P(1),P(3)-diadenosine diphosphate (Ap(2)A)>>P(1),P(3)-diadenosine pentaphosphate (Ap(5)A). P(1),P(3)-diadenosine tetraphosphate (Ap(4)A) was inactive up to 1 mM. The rank order of agonist potencies at P2Y(2) were: UTP>Ap(4)A>>Ap(6)A>Ap(5)A>Ap(3)A>>Ap(2)A. The Ap(4)A concentration response curve appeared to be bi-phasic. At P2Y(4) all the Ap(n)As tested were inactive as agonists. At P2Y(6), only Ap(3)A and Ap(5)A showed significant agonist activity. At P2Y(11), only Ap(4)A showed significant agonist activity. Ap(n)As were inactive as antagonists of the P2Y(1), P2Y(2), P2Y(4), P2Y(6) and P2Y(11) receptors. At P2Y(4), however, the Ap(n)As potentiated the UTP response.

Adenosine Diphosphate↗
PubMed2001

Maintaining contact with people with severe mental illness: 5-year follow-up of assertive outreach.

BACKGROUND: Assertive outreach is a central strand of Government mental health policy in England. Are different long-term models of mental health care which include assertive outreach associated with different service user outcomes and cost? METHOD: We conducted a multi-site 5-year follow-up study of people with severe mental illness. From 0 to 18 months all three sites had Intensive Case Management (ICM) teams practising assertive outreach. From 18 to 60 months one team sustained ICM, one team merged and another was disbanded. All 131 original ICM team clients were the study participants. Outcome was measured in terms of sustained engagement with statutory mental health services, psychiatric symptoms, social functioning, resource use and cost. RESULTS: All 120 live participants were traced. Only four people had no service contact; when contacted by a researcher they appeared to be coping well. No incidents of serious violence were discovered. No differences existed between teams in the mean total symptom or total social functioning change scores at follow-up, after controlling for baseline differences. No differences existed in mean cost between teams during the first 18 months. Mean (standard deviation) annualised costs varied considerably in the 18-60 month period: sustained team Pound Sterling13,734 (10,820); integrated team Pound Sterling11,037 (13,603); disbanded team Pound Sterling5,742 (7,007) (F=4.4, 105 df, p=0.015). CONCLUSION: Continued specialist assertive outreach service models have higher costs than non-specialist services for no apparent benefit. In the long term new assertive outreach services should have procedures in place to transfer people to lower intensity and lower cost care.

Case Management↗