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Biomedical subjects

M Gill

Publications and source records attributed to M Gill.

At least 55 records · Page 3Linked to original sources
PubMed2000

Genetic characterization of type 2 porcine circovirus (PCV-2) from pigs with postweaning multisystemic wasting syndrome in different geographic regions of North America and development of a differential PCR-restriction fragment length polymorphism assay to detect and differentiate between infections with PCV-1 and PCV-2.

Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in swine. Increasing evidence indicates that a variant strain of porcine circovirus (PCV), designated type 2 PCV (PCV-2), is responsible for PMWS. To determine the extent of genetic heterogeneity of PCV-2 isolates, the complete genomes of six PCV-2 isolates from different regions of North America were amplified by PCR and sequenced. Sequence and phylogenetic analyses confirmed that two distinct genotypes of PCV exist: nonpathogenic genotype PCV-1 and PMWS-associated genotype PCV-2. However, within the PCV-2 genotype, several minor branches that have been identified appear to be associated with geographic origins. The genomic sequences of two French PCV-2 isolates diverge the most from those of other PCV-2 isolates and form a distinct branch. Other minor but distinguishable branches have also been identified for a Taiwan PCV-2 isolate and two of the Canadian PCV-2 isolates. All the U.S. PCV-2 isolates are closely related, but the Canadian isolates vary, to some extent, in their genomic sequences. The data from this study indicate that although the genome of PCV-2 is generally stable among different isolates, PCV-2 isolates from different geographic regions vary in their genomic sequences. This variation may have important implications for PCV-2 diagnosis and research. On the basis of genetic analyses of available PCV strains, a universal PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed to detect and differentiate between infections with PCV-1 and PCV-2. This PCR-RFLP assay should be useful for studying the pathogenesis of PCV-2, for detecting PCV-2 infection in pigs from different geographic regions, and for screening donor pigs for use in xenotransplantation.

Amino Acid Sequence↗
PubMed2000

Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration.

Emerging data suggest that VEGF receptors are expressed by endothelial cells as well as hematopoietic stem cells. Therefore, we hypothesized that functional VEGF receptors may also be expressed in malignant counterparts of hematopoietic stem cells such as leukemias. We demonstrate that certain leukemias not only produce VEGF but also express functional VEGFR-2 in vivo and in vitro, resulting in the generation of an autocrine loop that may support leukemic cell survival and proliferation. Approximately 50% of freshly isolated leukemias expressed mRNA and protein for VEGFR-2. VEGF(165) induced phosphorylation of VEGFR-2 and increased proliferation of leukemic cells, demonstrating these receptors were functional. VEGF(165) also induced the expression of MMP-9 by leukemic cells and promoted their migration through reconstituted basement membrane. The neutralizing mAb IMC-1C11, specific to human VEGFR-2, inhibited leukemic cell survival in vitro and blocked VEGF(165)-mediated proliferation of leukemic cells and VEGF-induced leukemic cell migration. Xenotransplantation of primary leukemias and leukemic cell lines into immunocompromised nonobese diabetic mice resulted in significant elevation of human, but not murine, VEGF in plasma and death of inoculated mice within 3 weeks. Injection of IMC-1C11 inhibited proliferation of xenotransplanted human leukemias and significantly increased the survival of inoculated mice. Interruption of signaling by VEGFRs, particularly VEGFR-2, may provide a novel strategy for inhibiting leukemic cell proliferation.

Animals↗
PubMed2000

[Lack of gender effect on familial schizophrenia. A Brazilian study].

Epidemiological studies on schizophrenia have showed different age at onset between gender, in which male schizophrenics present symptoms earlier than females. However this gender effect is not observed within familial schizophrenia. The present study investigates the age at onset in 31 RDC-schizophrenics from 13 Brazilian families. No differences in age at onset were found between gender, confirming previous studies in other populations. This result may indicate genetic influences on age at onset in a subgroup of patients affected by schizophrenia and can be explored by molecular genetic studies.

Adolescent↗
PubMed1999

Presenilin 1 and alpha-1-antichymotrypsin polymorphisms in Down syndrome: no effect on the presence of dementia.

As people with Down syndrome (DS) age, they are at greater risk for Alzheimer disease (AD) than the general population. It has been suggested that polymorphisms at the genes for presenilin-1 (PS-1) and alpha-1-antichymotrypsin (ACT) confer an increased risk for AD in the general population, and therefore potentially to AD in people with DS. We obtained DNA from 231 individuals with DS and 233 population controls. People with DS were evaluated for dementia. Allele frequencies at PS-1 and ACT polymorphisms in people with DS were compared to those in age-matched controls. There were no frequency differences between the control sample and DS sample for PS-1 or ACT alleles or genotypes. Similarly, there were no differences in allele frequencies between the demented and age-matched non-demented DS samples. However a higher frequency of PS-1 heterozygotes in the demented DS group was noted. We conclude that unlike the general population, neither PS-1 nor ACT polymorphisms appear to have a similar detrimental effect on dementia in DS. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:616-620, 1999.

Adult↗
PubMed1999

Linkage studies of bipolar disorder with chromosome 18 markers.

Evidence consistent with the existence of genetic linkage between bipolar disorder and three regions on chromosome 18, the pericentromeric region, 18q21, and 18q22-q23 have been reported. Some analyses indicated greater evidence for linkage in pedigrees in which paternal transmission of disease occurs. We have undertaken linkage analyses using 12 highly polymorphic markers spanning these three regions of interest in a sample of 48 U.K. bipolar pedigrees. The sample comprises predominantly nuclear families and includes 118 subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM IV) bipolar I disorder and 147 subjects with broadly defined phenotype. Our data do not provide support for linkage using either parametric or nonparametric analyses. Evidence for linkage was not significantly increased by analyses that allowed for heterogeneity nor by analysing the subset of pedigrees consistent with paternal transmission.

Bipolar Disorder↗
PubMed1999

HLA and schizophrenia: refutation of reported associations with A9 (A23/A24), DR4, and DQbeta1*0602.

The aim of this study was to test previous hypotheses of association between schizophrenia and human leukocyte antigen (HLA) specificities A9 (A23/24), DR4, and allele DQbeta1*0602. Using sequence-specific oligonucleotide probes, 256 familial schizophrenic patients and 261 unrelated controls were genotyped at polymorphisms for HLA-A, DRbeta1, and DQbeta1 loci. No significant (p < 0.05) differences in the allele frequencies between schizophrenics and controls were found, either when examining the sample as a whole or when subdivided by clinical subtype or gender. The present data do not support association between these HLA specificities and schizophrenia, and our review of previous studies suggests that reported associations may well be false positive results.

Case-Control Studies↗
PubMed1999

Schizophrenia and HLA: No association with PCR-SSOP typed classical loci in a large Irish familial sample.

Susceptibility to autoimmunity is strongly influence by genes clustered in the MHC region, particularly class I and class II antigens. It has been proposed that there is an immune component in the aetiology of schizophrenia, and the distribution of human leukocyte antigens (HLA) in schizophrenic patients and controls has been investigated in numerous studies. Positive associations have been reported between schizophrenia and the HLA-A1, A2, A9, B5, Cw4, and DR8 and negative associations with HLA-DR4 and HLA-DQbeta*0602. Small sample size, variable diagnostic methodology, unreliable laboratory and statistical procedures, and possible mismatching of cases and controls may have contributed to a lack of consistency of results to date. Therefore, in this investigation we used a large and carefully diagnosed homogeneous Irish familial schizophrenic sample compared with ethnically matched controls. All alleles were determined using polymerase chain reaction amplification followed by short specific oligoprobes. We found no evidence of association with 80 HLA alleles (some previously not examined) from 4 genes. Our data therefore do not support the involvement of these classical HLA loci in the aetiology of schizophrenia at least in these Irish families. The remaining classical HLA loci (HLA-B and HLA-C) should be typed when reliable DNA-based methods become available.

Alleles↗
PubMed1999

Serotonin syndrome in a child after a single dose of fluvoxamine.

Serotonin syndrome, a potentially fatal iatrogenic complication of psychopharmacologic therapy, is most commonly reported with combinations of serotonergic medications. Serotonin syndrome is characterized by alterations in cognition, behavior, autonomic, and central nervous system function as a result of increased postsynaptic serotonin receptor agonism. We present the first reported case of serotonin syndrome after a single dose of fluvoxamine in a pediatric patient after ingestion of a single supratherapeutic dose of fluvoxamine.

Attention Deficit Disorder with Hyperactivity↗
PubMed1999

Meat production in developing countries.

Developing countries have very diverse food consumption patterns and agricultural production systems. The proportion of meat in national diets varies from negligible in some countries in central Africa to 30-40% in some countries in Latin America and Mongolia. However, the demand for meat in developing countries is increasing rapidly (53%/year from 1982 to 1993), as the result of population growth and the trend for people to move to the cities. Growth rates in consumption are greatest in Asia, with China dominating the statistics, in view of the size of its population. Theoretically, livestock production can be increased to meet this demand, but the multiple roles of livestock in developing countries must be recognized if this is to be achieved in a sustainable manner. Resource-poor farmers who keep livestock may value more highly their contribution to livelihoods and to crop production, through provision of draught power and improvements in soil fertility through the recycling of manure, than the production of more meat. Recognition of the goals of the farmer and the wishes of the consumer regarding meat quality need to be reflected in the way in which opportunities for increasing meat production are identified and communicated to farmers. The impact of the global economy on cereal prices, for example, will also influence which interventions will be economically viable. Interpretation of information in an integral manner, using geographical information systems, mathematical models and/or simple spreadsheet models will be an important ingredient in turning scientific knowledge into increased meat production in developing countries.

Agriculture↗
PubMed1999

New xanthorin glycosides from a Dermocybe species.

A mixture of the 8-O-beta-D-glucopyranoside of omega-hydroxyxanthorin 1-O-methyl ether (3) and the 8-O-beta-D-gentiobioside of xanthorin 1-O-methyl ether (4) was isolated from the water-soluble extractives of the Australian toadstool Dermocybe sp. WAT 22963. Compounds 3 and 4 were identified by characterization of their respective peracetyl derivatives 5 and 6.

Carbohydrate Conformation↗
PubMed1999

Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children.

Attention deficit hyperactivity disorder (ADHD) is a common disorder of childhood characterized by inattention, excessive motor activity, impulsivity, and distractibility. It is associated with serious disability in children, adolescents and adults. The etiology of the disorder is unknown, but it has a strong genetic component. Pharmacological and biochemical studies have suggested that dopaminergic and noradrenergic systems are involved. Using a sample of affected children and their parents we have found preferential transmission of alleles at polymorphisms at the dopamine transporter (DAT1), RR=1.2 (1.05-1.37), P=0.006, re-confirming and extending our previous findings for DAT1 (new sample one-tailed P=0.039); dopamine-beta-hydroxylase (DBH), RR=1.31 (1.09-1.56), P=0.0027; and the dopamine D5 receptor (DRD5), RR=1.67 (1.29-2.15), P=0.00005. Transmission of the 'associated' alleles at DAT1 and DBH is stronger in familial cases, RR(DAT1)=1.29 (1.04-1.59), RR(DBH)=1.49 (1.10-2.00), but for DRD5, transmission is stronger in non-familial cases, RR=1.59 (1.05-2.42). TDT analysis of complete trios supports the HHRR analysis, with P<0.05, for DAT1 P<0.005 and DBH and P<0.01 for DRD5. Attributable fractions for DAT1, DBH and DRD5 are calculated at 0.08, 0.12 and 0.20 respectively.

Adolescent↗
PubMed1999

Autosome search for schizophrenia susceptibility genes in multiply affected families.

We have analysed 298 polymorphic markers in 13 families multiply affected with schizophrenia and related disorders using a combination of radiolabelled and fluorescent-based methodologies. The markers were distributed throughout the autosomes at an average spacing of 12.8 cM. The data were analysed with two-point linkage analysis (MLINK) and heterogeneity testing (HOMOG). Several genetic models were used ranging from near dominant to fully recessive. Multi-point analysis was performed for 27 regions demonstrating either contiguously positive lod scores in two or more consecutive markers, and in regions with two-point lod score(s) of 1.0 or above in a single marker. A proportion of the multi-point regions have been implicated in previous studies, thereby decreasing risk of false-positive results. However neither our two-point, nor multi-point scores reached the threshold value for significance of 3. 6. Nevertheless three regions were suggestive of linkage.

Chromosome Mapping↗
PubMed1999

No evidence to support the association of the potassium channel gene hSKCa3 CAG repeat with schizophrenia or bipolar disorder in the Irish population.

Anticipation has attracted much interest and has been demonstrated in several neuropsychiatric disorders. For some disorders, this phenomenon has been found to correlate with the repeat number in large and unstable repeats (CAG/CTG). In addition, case control studies have suggested an increase in triplet repeat size in the psychoses. Recently, it was reported that the larger alleles (longer than 19 repeats) of the second potassium channel gene hSKCa3 are associated with schizophrenia in European and American samples. A similar trend, though not statistically significant, was also seen in bipolar disorder samples. This was further supported by an independent UK study.1 In this investigation, we have examined Irish familial schizophrenic patients, bipolar affective disorder patients and ethnically matched controls in an effort to replicate these findings. No significant differences between the patients and the control groups were observed. In addition, linkage analyses in the multiplex schizophrenic families showed no evidence for linkage or linkage disequilibrium. We concluded that the polymorphism of the second CAG repeat of the hSKCa3 gene is not a risk factor in schizophrenia or bipolar disorder, at least in the Irish population.

Bipolar Disorder↗
PubMed1999

Age at onset of dementia and age of menopause in women with Down's syndrome.

Menstrual status and the age of menopause were investigated in 143 Irish females with Down's syndrome (DS). The average age of menopause in 42 subjects (44.7 years) was younger than in the general population. The age at onset of dementia correlated with the age of menopause. This finding may be a manifestation of accelerated ageing in DS or point to oestrogen deficiency being an independent risk factor for the development of Alzheimer's dementia in DS. The implications of this finding for possible treatments are discussed.

Adult↗
PubMed1999

Determinants of aggression, and adaptive and maladaptive behaviour in older people with Down's syndrome with and without dementia.

In a cross-sectional study of aggression, and adaptive and maladaptive behaviour in 128 subjects with Down's syndrome (DS), 29 of whom had dementia, the current authors found that the presence of dementia was not predictive of aggression or maladaptive behaviour. However, the level of adaptive behaviour was shown to be lower in subjects with dementia, and in those with lower levels of cognitive functioning, as measured on a rating instrument, the Test for Severe Impairment. Although the presence of aggressive behaviours is not higher in subjects with dementia and DS on cross-sectional review, it remains to be seen whether aggression will increase in individual cases with the onset or progression of dementia. The decline in adaptive behaviour shown in the present study confirms the findings of previous studies and indicates a direction for service development for persons with the dual diagnosis of dementia and DS.

Adult↗